text:
The Muon system of the run II D0 detector
Abazov, V.M.; Acharya, B.S.; Alexeev, G.D.; Alkhazov, G.; Anosov, V.A.; Baldin, B.; Banerjee, S.; Bardon, O.; Bartlett, J.F.; Baturitsky, M.A.; Beutel, D.; Bezzubov, V.A.; Bodyagin, V.; Butler, J.M.; Cease, H.; Chi, E.; Denisov, D.; Denisov, S.P.; Diehl, H.T.; Doulas, S.; Dugad, S.R.; /Beijing, Inst. High Energy Phys. /Charles U. /Prague, Tech. U. /Prague, Inst. Phys. /San Francisco de Quito U. /Tata Inst. /Dubna, JINR /Moscow, ITEP /Moscow State U. /Serpukhov, IHEP /St. Petersburg, INP /Arizona U. /Florida State U. /Fermilab /Northern Illinois U. /Indiana U. /Boston U. /Northeastern U. /Brookhaven /Washington U., Seattle /Minsk, Inst. Nucl. Problems
The authors describe the design, construction and performance of the upgraded D0 muon system for Run II of the Fermilab Tevatron collider. Significant improvements have been made to the major subsystems of the D0 muon detector: trigger scintillation counters, tracking detectors, and electronics. The Run II central muon detector has a new scintillation counter system inside the iron toroid and an improved scintillation counter system outside the iron toroid. In the forward region, new scintillation counter and tracking systems have been installed. Extensive shielding has been added in the forward region. A large fraction of the muon system electronics is also new.
The muon system of the Run II DØ detector
NASA Astrophysics Data System (ADS)
Abazov, V. M.; Acharya, B. S.; Alexeev, G. D.; Alkhazov, G.; Anosov, V. A.; Baldin, B.; Banerjee, S.; Bardon, O.; Bartlett, J. F.; Baturitsky, M. A.; Beutel, D.; Bezzubov, V. A.; Bodyagin, V.; Butler, J. M.; Cease, H.; Chi, E.; Denisov, D.; Denisov, S. P.; Diehl, H. T.; Doulas, S.; Dugad, S. R.; Dvornikov, O. V.; Dyshkant, A.; Eads, M.; Evdokimov, A.; Evdokimov, V. N.; Fitzpatrick, T.; Fortner, M.; Gavrilov, V.; Gershtein, Y.; Golovtsov, V.; Gómez, B.; Goodwin, R.; Gornushkin, Yu. A.; Green, D. R.; Gupta, A.; Gurzhiev, S. N.; Gutierrez, G.; Haggerty, H.; Hanlet, P.; Hansen, S.; Hazen, E.; Hedin, D.; Hoeneisen, B.; Ito, A. S.; Jayanti, R.; Johns, K.; Jouravlev, N.; Kalinin, A. M.; Kalmani, S. D.; Kharzheev, Y. N.; Kirsch, N.; Komissarov, E. V.; Korablev, V. M.; Kostritsky, A.; Kozelov, A. V.; Kozlovsky, M.; Kravchuk, N. P.; Krishnaswamy, M. R.; Kuchinsky, N. A.; Kuleshov, S.; Kupco, A.; Larwill, M.; Leitner, R.; Lipaev, V. V.; Lobodenko, A.; Lokajicek, M.; Lubatti, H. J.; Machado, E.; Maity, M.; Malyshev, V. L.; Mao, H. S.; Marcus, M.; Marshall, T.; Mayorov, A. A.; McCroskey, R.; Merekov, Y. P.; Mikhailov, V. A.; Mokhov, N.; Mondal, N. K.; Nagaraj, P.; Narasimham, V. S.; Narayanan, A.; Negret, J. P.; Neustroev, P.; Nozdrin, A. A.; Oshinowo, B.; Parashar, N.; Parua, N.; Podstavkov, V. M.; Polozov, P.; Porokhovoi, S. Y.; Prokhorov, I. K.; Rao, M. V. S.; Raskowski, J.; Reddy, L. V.; Regan, T.; Rotolo, C.; Russakovich, N. A.; Sabirov, B. M.; Satyanarayana, B.; Scheglov, Y.; Schukin, A. A.; Shankar, H. C.; Shishkin, A. A.; Shpakov, D.; Shupe, M.; Simak, V.; Sirotenko, V.; Smith, G.; Smolek, K.; Soustruznik, K.; Stefanik, A.; Steinberg, J.; Stolin, V.; Stoyanova, D. A.; Stutte, L.; Temple, J.; Terentyev, N.; Teterin, V. V.; Tokmenin, V. V.; Tompkins, D.; Uvarov, L.; Uvarov, S.; Vasilyev, I. A.; Vertogradov, L. S.; Vishwanath, P. R.; Vorobyov, A.; Vysotsky, V. B.; Willutzki, H.; Wobisch, M.; Wood, D. R.; Yamada, R.; Yatsunenko, Y. A.; Yoffe, F.; Zanabria, M.; Zhao, T.; Zieminska, D.; Zieminski, A.; Zvyagintsev, S. A.
We describe the design, construction, and performance of the upgraded DØ muon system for Run II of the Fermilab Tevatron collider. Significant improvements have been made to the major subsystems of the DØ muon detector: trigger scintillation counters, tracking detectors, and electronics. The Run II central muon detector has a new scintillation counter system inside the iron toroid and an improved scintillation counter system outside the iron toroid. In the forward region, new scintillation counter and tracking systems have been installed. Extensive shielding has been added in the forward region. A large fraction of the muon system electronics is also new.
Specific light exposure of galactosylated Zn(II) phthalocyanines for selective PDT effects on breast cancer cells
NASA Astrophysics Data System (ADS)
Mantareva, V. N.; Kril, A.; Angelov, I.; Avramov, L.
Photodynamic therapy (PDT) is a clinically approved non-invasive and curative procedure for different oncological and non-oncological applications. PDT is still under development due to several limitations which lead to partially successful photodynamic response. The crucial steps in PDT procedure are binding of the photosensitizer to outer cell membrane, its penetration and subcellular localization which envisage the target sites of reactive oxygen species generated during irradiation. Since the surrounding normal cells are also exposed to the photosensitizer and the ambient daylight can be harmful for healthy tissues after therapeutic light application, the challenging task in PDT research is to optimize the procedure in a way to reach tumor cell selectivity. The present study outlines the influence of a light exposure pre-treatment (prior therapeutic light) with specific wavelengths (365 nm and 635 nm) on the uptake, the localization and further re-localization of galactose-substituted Zn(II) phthalocyanines into MDA-MB-231 breast cancer cells. The in vitro photodynamic effect towards tumor cells was studied in comparison to the normal cell line Balb/c 3T3 (clone 31) after pre-irradiation with UV light (365 nm) and red LED (635 nm). The results suggest that the galactose functional groups of Zn(II) phthalocyanine and the harmless UV light at 365 nm favor the selective PDT response.
Photodynamic Therapy (PDT): PDT Mechanisms
Allison, Ron R.
Photodynamic therapy (PDT) is a light based therapy used to ablate tumors. As practiced in oncology a photosensitizing agent is applied and then activated by a specific wavelength and energy of light. This light energy in the presence of oxygen will lead to the creation of the photodynamic reaction which is cyto and vasculo toxic. This paper will review the mechanisms of action of PDT and how they may be manipulated to improve clinical outcome in cancer patients. PMID:23422955
Verteporfin, photofrin II, and merocyanine 540 as PDT photosensitizers against melanoma cells
Nowak-Sliwinska, Patrycja; Karocki, Andrzej; Elas, Martyna; Pawlak, Anna; Stochel, Grazyna . E-mail: email@example.com; Urbanska, Krystyna . E-mail: email@example.com
The efficiency of photodynamic effect (PDE) for Photofrin II (PfII), Verteporfin, and Merocyanine 540 (MC540) was compared against neoplastic cells. Triplet state lifetimes and singlet molecular oxygen quantum yields were correlated with biological effect. PfII triplet lifetime was two times longer than that of Verteporfin, however, its singlet molecular oxygen quantum yield was two times lower in comparison with Verteporfin. High singlet molecular oxygen quantum yield of Verteporfin resulted in high biological efficacy. To achieve 50% mortality of cells four times lower light dose and five times lower concentration of Verteporfin were applied in comparison with PfII. The same level of cell damage was reached using 10 times higher light dose and two times higher concentration of MC540 in comparison with PfII. Our results confirm that singlet molecular oxygen based mechanism, prevalent for Verteporfin and PfII, was highly effective against melanoma cells. Verteporfin can be used at small doses with high cellular damage efficiency.
Organometallic Ru(II) Photosensitizers Derived from π-Expansive Cyclometalating Ligands: Surprising Theranostic PDT Effects.
Sainuddin, Tariq; McCain, Julia; Pinto, Mitch; Yin, Huimin; Gibson, Jordan; Hetu, Marc; McFarland, Sherri A
The purpose of the present study was to investigate the influence of π-expansive cyclometalating ligands on the photophysical and photobiological properties of organometallic Ru(II) compounds. Four compounds with increasing π conjugation on the cyclometalating ligand were prepared, and their structures were confirmed by HPLC, 1D and 2D (1)H NMR, and mass spectrometry. The properties of these compounds differed substantially from their Ru(II) polypyridyl counterparts. Namely, they were characterized by red-shifted absorption, very weak to no room temperature phosphorescence, extremely short phosphorescence state lifetimes (<10 ns), low singlet oxygen quantum yields (0.5-8%), and efficient ligand-centered fluorescence. Three of the metal complexes were very cytotoxic to cancer cells in the dark (EC50 values = 1-2 μM), in agreement with what has traditionally been observed for Ru(II) compounds derived from small C^N ligands. Surprisingly, the complex derived from the most π-expansive cyclometalating ligand exhibited no cytotoxicity in the dark (EC50 > 300 μM) but was phototoxic to cells in the nanomolar regime. Exceptionally large phototherapeutic margins, exceeding 3 orders of magnitude in some cases, were accompanied by bright ligand-centered intracellular fluorescence in cancer cells. Thus, Ru(II) organometallic systems derived from π-expansive cyclometalating ligands, such 4,9,16-triazadibenzo[a,c]napthacene (pbpn), represent the first class of potent light-responsive Ru(II) cyclometalating agents with theranostic potential. PMID:26672769
The Performance and Long Term Stability of the D0 Run II Forward Muon Scintillation Counters
Bezzubov, V.; Denisov, D.; Evdokimov, V.; Lipaev, V.; Shchukin, A.; Vasilyev, I.
The performance of the D0 experiment forward muon scintillation counters system during Run II of the Tevatron from 2001 to 2011 is described. The system consists of 4214 scintillation counters in six layers. The long term stability of the counters amplitude response determined using LED calibration system and muons produced in proton-antiproton collisions is presented. The average signal amplitude for counters of all layers has gradually decreased over ten years by 11%. The reference timing, determined using LED calibration, was stable within 0.26 ns. Average value of muon timing peak position was used for periodic D0 clock signal adjustments to compensate seasonal drift caused by temperature variations. Counters occupancy for different triggers in physics data collection runs and for minimum bias triggers are presented. The single muon yields versus time and the luminosity dependence of yields were stable for the forward muon system within 1% over 10 years.
During the second stage of a future neutrino factory unprecedented numbers of bunched muons will become available. The cooled medium-energy muon beam could be used for a high sensitivity search for an electric dipole moment (EDM) of the muon with a sensitivity better than 10{sup -24}e {center_dot} cm. This will make the sensitivity of the EDM experiment to non-standard physics competitive and in many models more sensitive than the present limits on edms of the electron and nucleons. The experimental design exploits the strong motional electric field sensed by relativistic particles in a magnetic storage ring.
The concept of using a muon storage ring to provide a well characterized beam of muon and electron neutrinos (a Neutrino Factory) has been under study for a number of years now at various laboratories throughout the world. The physics program of a Neutrino Factoryis focused on the relatively unexplored neutrino sector. In conjunction with a detector located a suitable distance from the neutrino source, the facility would make valuable contributions to the study of neutrino masses and lepton mixing. A Neutrino Factory is expected to improve the measurement accuracy of sin{sup 2}(2{theta}{sub 23}) and {Delta}m{sup 2}{sub 32} and provide measurements of sin{sup 2}(2{theta}{sub 13}) and the sign of {Delta}m{sup 2}{sub 32}. It may also be able to measure CP violation in the lepton sector.
GPD physics with polarized muon beams at COMPASS-II
Ferrero, Andrea [CEA-Saclay, DSM Collaboration: COMPASS Collaboration
A major part of the future COMPASS program is dedicated to the investigation of the nucleon structure through Deeply Virtual Compton Scattering (DVCS) and Deeply Virtual Meson Production (DVMP). COMPASS will measure DVCS and DVMP reactions with a high intensity muon beam of 160 GeV and a 2.5 m-long liquid hydrogen target surrounded by a new TOF system. The availability of muon beams with high energy and opposite charge and polarization will allow to access the Compton form factor related to the dominant GPD H and to study the x{sub B}-dependence of the t-slope of the pure DVCS cross section and to study nucleon tomography. Projections on the achievable accuracies and preliminary results of pilot measurements will be presented.
NASA Astrophysics Data System (ADS)
Kessel, David
Cellular targets of photodynamic therapy include mitochondria, lysosomes, the endoplasmic reticulum (ER) and the plasma membrane. PDT can evoke necrosis, autophagy and apoptosis, or combinations of these, depending on the PDT dose, the site(s) of photodamage and the cellular phenotype. It has been established that loss of viability occurs even when the apoptotic program is inhibited. Studies assessing effects of ER or mitochondrial photodamage, involving loss of Bcl-2 function, indicate that low-dose PDT elicited a rapid autophagic response in L1210 cells. This was attributed to the ability of autophagy to recycle photodamaged organelles, and there was partial protection from loss of viability. This effect was not observed in L1210/Atg7, where autophagy was silenced. At higher PDT doses, apoptotic cells were observed within 60 min in both cell lines, but more so in L1210. The ability of L1210 cells to undergo autophagy did not offer protection from cell death at the higher PDT dose. Previous studies had indicated that autophagy can contribute to cell death, since L1210 cells that do not undergo an initial apoptotic response often contain multiple autophagic vacuoles 24 hr later. With L1210/Atg7, apoptosis alone may account for the loss of viability at an LD 90 PDT dose.
Multi-year search for a diffuse flxu of muon neutrinos with AMANDA-II
IceCube Collaboration; Klein, Spencer; Achterberg, A.; Collaboration, IceCube
A search for TeV-PeV muon neutrinos from unresolved sources was performed on AMANDA-II data collected between 2000 and 2003 with an equivalent livetime of 807 days. This diffuse analysis sought to find an extraterrestrial neutrino flux from sources with non-thermal components. The signal is expected to have a harder spectrum than the atmospheric muon and neutrino backgrounds. Since no excess of events was seen in the data over the expected background, an upper limit of E{sup 2}{Phi}{sub 90%C.L.} < 7.4 x 10{sup -8} GeV cm{sup -2} s{sup -1} sr{sup -1} is placed on the diffuse flux of muon neutrinos with a {Phi} {proportional_to} E{sup -2} spectrum in the energy range 16 TeV to 2.5 PeV. This is currently the most sensitive {Phi} {proportional_to} E{sup -2} diffuse astrophysical neutrino limit. We also set upper limits for astrophysical and prompt neutrino models, all of which have spectra different than {Phi} {proportional_to} E{sup -2}.
Multiyear search for a diffuse flux of muon neutrinos with AMANDA-II
NASA Astrophysics Data System (ADS)
Achterberg, A.; Ackermann, M.; Adams, J.; Ahrens, J.; Andeen, K.; Auffenberg, J.; Bai, X.; Baret, B.; Barwick, S. W.; Bay, R.; Beattie, K.; Becka, T.; Becker, J. K.; Becker, K.-H.; Berghaus, P.; Berley, D.; Bernardini, E.; Bertrand, D.; Besson, D. Z.; Blaufuss, E.; Boersma, D. J.; Bohm, C.; Bolmont, J.; Böser, S.; Botner, O.; Bouchta, A.; Braun, J.; Burgess, T.; Castermans, T.; Chirkin, D.; Christy, B.; Clem, J.; Cowen, D. F.; D'Agostino, M. V.; Davour, A.; Day, C. T.; de Clercq, C.; Demirörs, L.; Descamps, F.; Desiati, P.; De Young, T.; Diaz-Velez, J. C.; Dreyer, J.; Dumm, J. P.; Duvoort, M. R.; Edwards, W. R.; Ehrlich, R.; Eisch, J.; Ellsworth, R. W.; Evenson, P. A.; Fadiran, O.; Fazely, A. R.; Filimonov, K.; Finley, C.; Foerster, M. M.; Fox, B. D.; Franckowiak, A.; Franke, R.; Gaisser, T. K.; Gallagher, J.; Ganugapati, R.; Geenen, H.; Gerhardt, L.; Goldschmidt, A.; Goodman, J. A.; Gozzini, R.; Griesel, T.; Groß, A.; Grullon, S.; Gunasingha, R. M.; Gurtner, M.; Ha, C.; Hallgren, A.; Halzen, F.; Han, K.; Hanson, K.; Hardtke, D.; Hardtke, R.; Hart, J. E.; Hasegawa, Y.; Hauschildt, T.; Hays, D.; Heise, J.; Helbing, K.; Hellwig, M.; Herquet, P.; Hill, G. C.; Hodges, J.; Hoffman, K. D.; Hommez, B.; Hoshina, K.; Hubert, D.; Hughey, B.; Hülß, J.-P.; Hulth, P. O.; Hultqvist, K.; Hundertmark, S.; Inaba, M.; Ishihara, A.; Jacobsen, J.; Japaridze, G. S.; Johansson, H.; Jones, A.; Joseph, J. M.; Kampert, K.-H.; Kappes, A.; Karg, T.; Karle, A.; Kawai, H.; Kelley, J. L.; Kislat, F.; Kitamura, N.; Klein, S. R.; Klepser, S.; Kohnen, G.; Kolanoski, H.; Köpke, L.; Kowalski, M.; Kowarik, T.; Krasberg, M.; Kuehn, K.; Labare, M.; Landsman, H.; Lauer, R.; Leich, H.; Leier, D.; Liubarsky, I.; Lundberg, J.; Lünemann, J.; Madsen, J.; Maruyama, R.; Mase, K.; Matis, H. S.; McCauley, T.; McParland, C. P.; Meli, A.; Messarius, T.; Mészáros, P.; Miyamoto, H.; Mokhtarani, A.; Montaruli, T.; Morey, A.; Morse, R.; Movit, S. M.; Münich, K.; Nahnhauer, R.; Nam, J. W.; Nießen, P.; Nygren, D. R.; Ögelman, H.; Olivas, A.; Patton, S.; Peña-Garay, C.; Pérez de Los Heros, C.; Piegsa, A.; Pieloth, D.; Pohl, A. C.; Porrata, R.; Pretz, J.; Price, P. B.; Przybylski, G. T.; Rawlins, K.; Razzaque, S.; Resconi, E.; Rhode, W.; Ribordy, M.; Rizzo, A.; Robbins, S.; Roth, P.; Rothmaier, F.; Rott, C.; Rutledge, D.; Ryckbosch, D.; Sander, H.-G.; Sarkar, S.; Satalecka, K.; Schlenstedt, S.; Schmidt, T.; Schneider, D.; Seckel, D.; Semburg, B.; Seo, S. H.; Sestayo, Y.; Seunarine, S.; Silvestri, A.; Smith, A. J.; Solarz, M.; Song, C.; Sopher, J. E.; Spiczak, G. M.; Spiering, C.; Stamatikos, M.; Stanev, T.; Stezelberger, T.; Stokstad, R. G.; Stoufer, M. C.; Stoyanov, S.; Strahler, E. A.; Straszheim, T.; Sulanke, K.-H.; Sullivan, G. W.; Sumner, T. J.; Taboada, I.; Tarasova, O.; Tepe, A.; Thollander, L.; Tilav, S.; Tluczykont, M.; Toale, P. A.; Tosi, D.; Turčan, D.; van Eijndhoven, N.; Vandenbroucke, J.; van Overloop, A.; Viscomi, V.; Voigt, B.; Wagner, W.; Walck, C.; Waldmann, H.; Walter, M.; Wang, Y.-R.; Wendt, C.; Wiebusch, C. H.; Wiedemann, C.; Wikström, G.; Williams, D. R.; Wischnewski, R.; Wissing, H.; Woschnagg, K.; Xu, X. W.; Yodh, G.; Yoshida, S.; Zornoza, J. D.
A search for TeV-PeV muon neutrinos from unresolved sources was performed on AMANDA-II data collected between 2000 and 2003 with an equivalent live time of 807 days. This diffuse analysis sought to find an extraterrestrial neutrino flux from sources with nonthermal components. The signal is expected to have a harder spectrum than the atmospheric muon and neutrino backgrounds. Since no excess of events was seen in the data over the expected background, an upper limit of E2Φ90%C.L.<7.4×10-8GeVcm-2s-1sr-1 is placed on the diffuse flux of muon neutrinos with a Φ∝E-2 spectrum in the energy range 16 TeV to 2.5 PeV. This is currently the most sensitive Φ∝E-2 diffuse astrophysical neutrino limit. We also set upper limits for astrophysical and prompt neutrino models, all of which have spectra different from Φ∝E-2.
Zhu, Timothy C.; Finlay, Jarod C.
Summary We provide a review of the current state of dosimetry in prostate photodynamic therapy (PDT). PDT of the human prostate has been performed with a number of different photosensitizers and with a variety of dosimetry schemes. The simplest clinical light dose prescription is to quantify the total light energy emitted per length (J/cm) of cylindrical diffusing fibers (CDF) for patients treated with a defined photosensitizer injection per body weight. However, this approach does not take into account the light scattering by tissue and usually underestimates the local light fluence rate, and consequently the fluence. Techniques have been developed to characterize tissue optical properties and light fluence rates in vivo using interstitial measurements during prostate PDT. Optical methods have been developed to characterize tissue absorption and scattering spectra, which in turn provide information about tissue oxygenation and drug concentration. Fluorescence techniques can be used to quantify drug concentrations and photobleaching rates of photosensitizers. PMID:25046988
Synthesis, DNA interactions and antibacterial PDT of Cu(II) complexes of phenanthroline based photosensitizers via singlet oxygen generation
NASA Astrophysics Data System (ADS)
Sudhamani, C. N.; Bhojya Naik, H. S.; Sangeetha Gowda, K. R.; Giridhar, M.; Girija, D.; Prashanth Kumar, P. N.
Cu(II) complexes [Cu(mqt)(B)H2O]ClO4(1-3) of 2-thiol 4-methylquinoline and phenanthroline bases (B), viz 1,10-phenanthroline (phen in 1), Dipyrido[3,2-d:2‧,3‧-f]quinoxaline (dpq in 2) and Dipyrido[3,2-a:2‧,3‧-c]phenazine (dppz in 3) have been prepared and characterized by elemental analysis, IR, UV-Vis, magnetic moment values, EPR spectra and conductivity measurements. The spectral data reveal that all the complexes exhibit square-pyramidal geometry. The DNA-binding behaviors of the three complexes were investigated by absorption spectra, viscosity measurements and thermal denaturation studies. The DNA binding constants for complexes (1), (2) and (3) were determined to 2.2 × 103, 1.3 × 104 and 8.6 × 104 M-1 respectively. The experimental results suggest that these complexes interact with DNA through groove-binding mode. The photo induced cleavage studies shows that the complexes possess photonuclease property against pUC19 DNA under UV-Visible irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy (PACT) assay against Escherichiacoli and all complexes exhibited significant reduction in bacterial growth on photoirradiation.
Synthesis, DNA interactions and antibacterial PDT of Cu(II) complexes of phenanthroline based photosensitizers via singlet oxygen generation.
Sudhamani, C N; Bhojya Naik, H S; Sangeetha Gowda, K R; Giridhar, M; Girija, D; Prashanth Kumar, P N
Cu(II) complexes [Cu(mqt)(B)H2O]ClO4(1-3) of 2-thiol 4-methylquinoline and phenanthroline bases (B), viz 1,10-phenanthroline (phen in 1), Dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 2) and Dipyrido[3,2-a:2',3'-c]phenazine (dppz in 3) have been prepared and characterized by elemental analysis, IR, UV-Vis, magnetic moment values, EPR spectra and conductivity measurements. The spectral data reveal that all the complexes exhibit square-pyramidal geometry. The DNA-binding behaviors of the three complexes were investigated by absorption spectra, viscosity measurements and thermal denaturation studies. The DNA binding constants for complexes (1), (2) and (3) were determined to 2.2×10(3), 1.3×10(4) and 8.6×10(4)M(-1) respectively. The experimental results suggest that these complexes interact with DNA through groove-binding mode. The photo induced cleavage studies shows that the complexes possess photonuclease property against pUC19 DNA under UV-Visible irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy (PACT) assay against Escherichiacoli and all complexes exhibited significant reduction in bacterial growth on photoirradiation. PMID:25544194
Endoscopic photodynamic therapy (PDT) for oesophageal cancer.
Moghissi, Keyvan
Endoscopic photodynamic therapy (PDT) is undertaken only when tumour is visible endoscopically with malignancy biopsy confirmed. Patients will be either Group A: inoperable cases with locally advanced cancer when the aim is palliation of dysphagia, or Group E: patients with early stage I-II disease who are unsuitable for surgery or decline operation, when the intent is curative. Following assessment for suitability for PDT and counselling, Photofrin 2mg/(kgbw) is administered 24-72h before endoscopic illumination using a Diode 630nm laser. Illumination may be either interstitial or intraluminal at a dose of 100-200J/cm. PMID:25049097
NASA Technical Reports Server (NTRS)
Wernet, M. P.
multiple frequency RGB monitor (EGA or better), a math co-processor, and a pointing device. The printers supported by the graphical analysis routines are the HP Laserjet+, Series II, and Series III with at least 1.5 MB memory. The data acquisition routines require the EPIX 4-MEG video board and optional 12.5MHz oscillator, and associated EPIX software. Data can be acquired from any CCD or RS-170 compatible video camera with pixel resolution of 600hX400v or better. PDT is distributed on one 5.25 inch 360K MS-DOS format diskette. Due to the use of required proprietary software, executable code is not provided on the distribution media. Compiling the source code requires the Microsoft C v5.1 compiler, Microsoft QuickC v2.0, the Microsoft Mouse Library, EPIX Image Processing Libraries, the Microway NDP-Fortran-386 v2.1 compiler, and the Media Cybernetics HALO Professional Graphics Kernal System. Due to the complexities of the machine requirements, COSMIC strongly recommends the purchase and review of the documentation prior to the purchase of the program. The source code, and sample input and output files are provided in PKZIP format; the PKUNZIP utility is included. PDT was developed in 1990. All trade names used are the property of their respective corporate owners.
DUMAND-II (deep underwater muon and neutrino detector) progress report
Young, K.K.; The DUMAND Collaboration
The DUMAND II detector will search for astronomical sources of high energy neutrinos. Successful deployment of the basic infrastructure, including the shore cable, the underwater junction box, and an environmental module was accomplished in December, 1993. One optical module string was also deployed and operated, logging data for about 10 hours. The underwater cable was connected to the shore station where we were able to successfully exercise system controls and log further environmental data. After this time, water leaking into the electronics control module for the deployed string disabled the string electrical system. The acquired data are consistent with the expected rate of downgoing muons, and our ability to reconstruct muons was demonstrated. The measured acoustical backgrounds are consistent with expectation, which should allow acoustical detection of nearby PeV particle cascades. The disabled string has been recovered and is undergoing repairs ashore. We have identified the source of the water leak and implemented additional testing and QC procedures to ensure no repetition in our next deployment. We will be ready to deploy three strings and begin continuous data taking in late 1994 or early 1995. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.
Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells.
Kim, Jisun; Lim, Haesoon; Kim, Sangwoo; Cho, Hyejung; Kim, Yong; Li, Xiaojie; Choi, Hongran; Kim, Okjoon
We previously reported that photodynamic therapy (PDT) induces cell death in head and neck cancer through both autophagy and apoptosis. Regulation of cell death by autophagy and apoptosis is important to enhance the effects of PDT. Autophagy maintains a balance between cell death and PDT resistance. Downregulation of heat shock protein 27 (HSP27) induces PDT resistance in head and neck cancer cells. Furthermore, HSP70 regulates apoptosis during oxidative stress. However, the role of HSPs in PDT-induced cell death through autophagy and apoptosis is unclear. Therefore, in the present study, we investigated the effects of HSP27 and HSP70 on PDT-induced cell death of oral cancer cells through autophagy and apoptosis. Cancer cells were treated with hematoporphyrin at varying doses, followed by irradiation at 635 nm with an energy density of 5 mW/cm2. We determined the changes in HSP expression by determining the levels of PARP-1 and LC3II in PDT-resistant cells. Furthermore, we assessed cell death signaling after downregulating HSPs by transfecting specific siRNAs. We observed that PDT decreased HSP27 expression but increased HSP70 expression in the head and neck cancer cells. Treatment of cells with LC3II and PARP-1 inhibitors resulted in upregulation of HSP70 and HSP27 expression, respectively. Downregulation of HSP27 and HSP70 induced cell death and PDT resistance through autophagy and apoptosis. Moreover, downregulation of HSP27 in PDT-resistant cells resulted in enhanced survival. These results indicate that the regulation of HSP27 and HSP70 plays a principal role in increasing the effects of PDT by inducing autophagic and apoptotic cell death. PMID:26820233
In vivo light dosimetry for pleural PDT
NASA Astrophysics Data System (ADS)
Dimofte, Andreea; Zhu, Timothy C.; Finlay, Jarod C.; Culligan, Melissa; Edmonds, Christine E.; Friedberg, Joseph S.; Cengel, Keith; Hahn, Stephen M.
In-vivo light Dosimetry for patients undergoing photodynamic therapy (PDT) is one of the important dosimetry quantities critical for predicting PDT outcome. This study examines the light fluence (rate) delivered to patients undergoing pleural PDT as a function of treatment time, treatment volume and surface area, and its accuracy as a function of the calibration accuracies of each isotropic detector and the calibration integrating sphere. The patients studied here were enrolled in Phase II clinical trial of Photofrin-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. The ages of the patients studied varied from 34 to 69 year old. All patients were administered 2mg per kg body weight Photoprin 24 hours before the surgery. Patients undergoing photodynamic therapy (PDT) are treated with laser light with a light fluence of 60 J/cm^2 at 630nm. Fluence rate (mW/cm^2) and cumulative fluence (J/cm^2) was monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors were used for in-vivo light dosimetry. The anisotropy of each isotropic detector was found to be within 30%. The mean fluence rate delivery varied from 37.84 to 94.05 mW/cm^2 and treatment time varied from 1762 to 5232s. We have established a correlation between the treatment time and the treatment volume. The results are discussed using an integrating sphere theory and the measured tissue optical properties. The result can be used as a clinical guideline for future pleural PDT treatment.
Measurement of the Flux and Zenith-Angle Distribution of Upward Through-Going Muons in Kamiokande II+III
NASA Astrophysics Data System (ADS)
Hatakeyama, S.; Hara, T.; Fukuda, Y.; Hayakawa, T.; Inoue, K.; Ishihara, K.; Ishino, H.; Joukou, S.; Kajita, T.; Kasuga, S.; Koshio, Y.; Kumita, T.; Matsumoto, K.; Nakahata, M.; Nakamura, K.; Okumura, K.; Sakai, A.; Shiozawa, M.; Suzuki, J.; Suzuki, Y.; Tomoeda, T.; Totsuka, Y.; Hirata, K. S.; Kihara, K.; Oyama, Y.; Koshiba, M.; Nishijima, K.; Horiuchi, T.; Fujita, K.; Koga, M.; Maruyama, T.; Suzuki, A.; Mori, M.; Suda, T.; Suzuki, A. T.; Ishizuka, T.; Miyano, K.; Okazawa, H.; Nagashima, Y.; Takita, M.; Yamaguchi, T.; Hayato, Y.; Kaneyuki, K.; Suzuki, T.; Takeuchi, Y.; Tanimori, T.; Tasaka, S.; Ichihara, E.; Miyamoto, S.; Nishikawa, K.
The flux of upward through-going muons of minimum (mean) threshold energy >1.6 (3.0) GeV is measured, based on a total of 372 events observed by the Kamiokande II+III detector during 2456 detector live days. The observed muon flux was Φobs = [1.94+/-0.10\\(stat.\\)+0.07-0.06sys.\\)]×10-13 cm-2 s-1 sr-1, which is compared to an expected value of Φtheo = [2.46+/-0.54\\(theo.\\)]×10-13 cm-2 s-1 sr-1. The observation is in agreement with the prediction within the errors. The zenith-angle dependence of the observed upward through-going muons supports the previous indication of neutrino oscillations made by Kamiokande using sub- and multi-GeV atmospheric neutrino events.
Photodynamic therapy (PDT) for perianal bowenoid papulosis
NASA Astrophysics Data System (ADS)
Gahlen, Johannes; Stern, Josef; Graschew, Georgi; Kaus, Michael R.; Tilgen, W.
HPV associated bowenoid papulosis of the anogenital region are classified as carcinoma in situ. The treatment can be difficult and recurrence rates are high. Extended surgical resections may have complications such as anal sphincter insufficiency. PDT does have some advantages and less side effects in the treatment of these tumors. We treated one female patient with an extended perianal bowenoid papulosis. Previous surgical resection led to local recurrence and partial sphincter insufficiency. Twenty-four hours before local laser light radiation (Ar-Dye laser, 630 nm wavelength), a systemic photosensitizer was applied (Photofrin II, 1.5 mg/kg BW). Four courses of PDT were performed within one year. We observed a total tumor necrosis in every radiation area. The previous sphincter insufficiency improved during the sessions. Side effects were rare. Pain in the radiation was stopped within 2 - 3 days under pain medication. PDT can induce a total local tumor necrosis in perianal bowenoid papulosis. Concerning local expansion, PDT can be a curable treatment.
Atomic effects in tritium beta-decay. II. Muon to electron conversion in atoms
Wampler, K.D.
I. The final-state, atomic effects in the low energy end of the tritium beta decay spectrum are studied in detail. The author treats the instantaneous, two-electron repulsion in the final state, effectively to all orders in perturbation theory, by solving the eigenvalue problem with a discretized and truncated form of the Hamiltonian. He finds that these effects fail to explain the distortion in the spectrum observed by Simpson (Phys. Rev. Lett. 54, 649 (1985)). Simpson attributed this distortion to the admixture of a heavy mass antineutrino in the outgoing electron antineutrino state. In fact, the final-state Coulomb effects enhance the distortion. This calculation clears up some of the ambiguities of other theoretical analyses based on considerations of screening functions and perturbation theory. II. He presents a phenomenological study of separate lepton number violating muon to electron conversion in atoms. Previous work on this process has concentrated on elastic transitions where the nucleus characteristics have the gate on the substrate and the source-drain contacts on the top of the sample. The first use as an FET dielectric is reported of hydrogenated amorphous silicon-carbon (prepared from silane and propane mixture), photo-oxidised by UV lamp or laser. These FETs have similar characteristics to those with silicon nitride gate insulator but without the difficulties of preparing good insulator/semiconductor interfaces. Using the same materials attempts have been made to produce charge coupled devices.
Cengel, Keith A; Simone, Charles B; Glatstein, Eli
Despite descriptions of light-mediated therapy in ancient texts and the discovery of photodynamic therapy (PDT) in the early 1900s, the landmark article in 1978 in Cancer Research by Dougherty and his colleagues at the Roswell Park Cancer Institute remains rightly viewed as the starting point for clinical PDT in modern medicine. As a large clinical series that explored many of the factors now viewed as critical determinates of PDT dose, efficacy, and toxicity, that study showed remarkable foresight, yet it also served to raise as many questions as it answered. Since its publication, PDT has been increasingly utilized in clinical practice for the treatment of both benign and malignant conditions, and many of their questions have yielded new technologies and areas of investigation, thus remaining highly relevant nearly 40 years after their initial asking. Moreover, continuing advances in our ability to measure physical properties such as absorbed light dose, photosensitizer concentration, tissue oxygen concentration, and singlet oxygen production in real-time may allow for adaptive modification of light delivery during PDT on a fine scale to optimize treatment response. Finally, combining molecularly targeted drugs and novel photosensitizers has the potential to improve further the therapeutic index and extend the spectrum of clinical PDT far beyond what was imagined when that sentinel manuscript was written. Cancer Res; 76(9); 2497-9. ©2016 AACRSee related article by Dougherty et al., Cancer Res 1978;38:2628-35Visit the Cancer Research 75(th) Anniversary timeline. PMID:27197260
A Diffusion Cloud Chamber Study of Very Slow Mesons. II. Beta Decay of the Muon
DOE R&D Accomplishments Database
Lederman, L. M.; Sargent, C. P.; Rinehart, M.; Rogers, K.
The spectrum of electrons arising from the decay of the negative mu meson has been determined. The muons are arrested in the gas of a high pressure hydrogen filled diffusion cloud chamber. The momenta of the decay electrons are determined from their curvature in a magnetic field of 7750 gauss. The spectrum of 415 electrons has been analyzed according to the theory of Michel.
Photodynamic therapy (PDT) for locally recurrent breast carcinoma
NASA Astrophysics Data System (ADS)
Gahlen, Johannes; Stern, Josef; Graschew, Georgi; Kaus, Michael R.; Herfarth, Christian
Locally recurrent breast carcinoma and skin metastasisses on the chest wall can be difficult to treat. Conventional treatments like radiation-, chemo- and hormonal therapy have shown poor results in these patients. In comparison to this, PDT has some advantages and less side effects. We can observe a tumor accumulation of a systemic applied photosensitizer (PS). The PS can be stimulated by light of a wavelength of 630 nm and a phototoxic effect in the tumor occurs. We treated 7 patients with locally recurrent breast carcinoma 15 times with PDT. The intravenous application of the PS (Photofrin II, 1.5 mg/kg BW) was done 24 - 96 hours before local laser light radiation. The light source was an Ar-Dye laser with a wavelength of 630 nm. Due to a local tumor necrosis we observed a tumor reduction in each case. In 5 patients we saw a complete local remission with a good cosmetic result. Side effects were rare. All patients suffered from pain in the treated area. No major phototoxicity effects were seen. PDT can induce complete local tumor remissions in patients with cutaneous metastasisses after locally recurrent breast carcinoma. In absence of other metastasisses PDT is possibly a curative treatment. One of the major advantages of this treatment are the rare side effects, rare complications and the possible repetition of the PDT.
In-vivo outcome study of HPPH mediated PDT using singlet oxygen explicit dosimetry (SOED)
NASA Astrophysics Data System (ADS)
Penjweini, Rozhin; Kim, Michele M.; Zhu, Timothy C.
Type II photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive singlet oxygen. However, the medical application of this technique has been limited due to inaccurate PDT dosimetric methods. The goal of this study is to examine the relationship between outcome (in terms of tumor growth rate) and calculated reacted singlet oxygen concentration [1O2]rx after HPPH-mediated PDT to compare with other PDT dose metrics, such as PDT dose or total light fluence. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration and tissue optical properties via fluorescence and absorption measurement with a contact probe before and after PDT were taken to then quantify total light fluence, PDT dose, and [1O2]rx based on a macroscopic model of singlet oxygen. In addition, photobleaching of photosenitizer were measured during PDT as a second check of the model. Changes in tumor volume were tracked following treatment and compared to the three calculated dose metrics. The correlations between total light fluence, PDT dose, reacted [1O2]rx and tumor growth demonstrate that [1O2]rx serves as a better dosimetric quantity for predicting treatment outcome and a clinically relevant tumor growth endpoint.
Photodynamic therapy (PDT) as a biological modifier
NASA Astrophysics Data System (ADS)
Obochi, Modestus; Tao, Jing-Song; Hunt, David W. C.; Levy, Julia G.
The capacity of photosensitizers and light to ablate cancerous tissues and unwanted neovasculature constitutes the classical application of photodynamic therapy (PDT). Cell death results from either necrotic or apoptotic processes. The use of photosensitizers and light at doses which do not cause death has been found to affect changes in certain cell populations which profoundly effect their expression of cell surface molecules and secretion of cytokines, thereby altering the functional attributes of the treated cells. Cells of the immune system and the skin may be sensitive to modulation by 'sub-lethal PDT.' Ongoing studies have been conducted to assess, at the molecular level, changes in both lymphocytes and epidermal cells (EC) caused by treatment with low levels of benzoporphyrin derivative monoacid ring A (BPD) (a photosensitizer currently in clinical trials for cancer, psoriasis, endometriosis and age-related macular degeneration) and light. Treatment of skin with BPD and light, at levels which significantly enhanced the length of murine skin allograft acceptance, have been found to down-regulate the expression of Langerhans cell (LC) surface antigen molecules [major histocompatibility complex (MHC) class II and intracellular adhesion molecule (ICAM)-1] and the formation of some cytokines (tumor necrosis factor-alpha (TNF- (alpha) ).
Apoptotic effects of Photofrin-Diomed 630-PDT on SHEEC human esophageal squamous cancer cells
Gao, Shegan; Zhang, Mengxi; Zhu, Xiaojuan; Qu, Zhifeng; Shan, Tanyou; Xie, Xuanhu; Wang, Ying; Feng, Xiaoshan
Photodynamic therapy (PDT) using photofrin-II is a clinically effective treatment for both non-neoplastic and neoplastic diseases. Herein, we performed an in vitro experiment to study the anti-tumor effect and mechanisms of photofrin-II mediated PDT for esophageal squamous cell carcinoma (ESCC) cell line, SHEEC. In this study, human ESCC cell line SHEEC and parental normal cell line SHEE were used. The anti-tumor effect of PDT was determined by evaluating cell viability using CCK-8 assay, apoptosis and generation of reactive oxygen species (ROS). PDT induced significant apoptosis in SHEEC and SHEE cells in a time- and photofrin-II dose-dependent manner. Furthermore, PDT treatment induced significant death of SHEEC, instead of SHEE cells. The apoptotic outcome was accompanied by concurrent generation of ROS. In summary, PDT shed light on therapy of ESCC, functioning as a useful tool for ESCC clinical treatment, providing a better understanding of Photofrin-Diomed 630-PDT in SHEEC cells. PMID:26628993
The role of DAMPS in ALA-PDT for skin squamous cell carcinoma (Conference Presentation)
NASA Astrophysics Data System (ADS)
Wang, Xiuli; Wang, Xiaojie; Ji, Jie; Zhang, Haiyan; Shi, Lei
5-Aminolevulinic acid mediated photodynamic therapy (ALA-PDT) is an established local approach for skin squamous cell carcinoma. It is believed that dangerous signals damage-associated molecular patterns (DAMPs) play an important role in ALA-PDT. In this study, we evaluated in vitro and in vivo expressions of major DAMPs, calreticulin (CRT), heat shock proteins 70 (HSP70), and high mobility group box 1 (HMGB1), induced by ALA-PDT using immunohistochemistry, western blot, and ELISA in a squamous cell carcinoma (SCC) mouse model. The role of DAMPs in the maturation of DCs potentiated by ALA-PDT-treated tumor cells was detected by FACS and ELISA. Our results showed that ALA-PDT enhanced the expression of CRT, HSP70, and HMGB1. These induced DAMPs played an important role in activating DCs by PDT-treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, CD80, and CD86) and functional maturation (enhanced capability to secrete IFN-γ and IL-12). Furthermore, injecting ALA-PDT-treated tumor cells into naïve mice resulted in complete protection against cancer cells of the same origin. Our findings indicate that ALA-PDT can upregulate DAMPs and enhance tumor immunogenicity, providing a promising strategy for inducing a systemic anticancer immune response.
Optical molecular imaging in PDT
NASA Astrophysics Data System (ADS)
Mitra, Soumya; Snyder, John W.; Foster, Thomas H.
Motivated by recent successes in fluorescence imaging of whole mount tissue preparations and by rapid progress in the fields of molecular imaging and molecular biology, we are exploring a number of applications of optical fluorescence imaging in superficial murine tumor models in vivo. Imaging the PDT-induced expression of the heat shock protein 70 (HSP70) in cells and in vivo is accomplished using stably transfected EMT6 cells in which the gene for GFP is under the control of the HSP70 promoter. These cells readily form solid tumors in BALB/c mice, enabling the direct imaging of the extent and time course of the activation of this promoter, with each mouse serving as its own control. Imaging of similarly transfected EMT6 cells with a HIF-1α/GFP fusion protein vector enables visualization of HIF-1α translocation to the nucleus. Recently, we have accomplished fluorescent labeling of surface antigens in vivo using intratumor and intravenous injection of fluorophore-conjugated antibodies. Injection of deep-red fluorophore-conjugated-anti-CD31 enables confocal fluorescence imaging of the tumor vasculature to depths of at least 100 microns. With the vessels rendered fluorescent in this way, a number of interesting studies become possible in the living mouse, including the direct visualization of photosensitizer distribution from perfused vessels. Using the appropriate fluorophore-conjugated antibodies, we have also been able to image infiltrating granulocytes in EMT6 tumors in response to PDT in vivo.
ALA-PDT mediated DC vaccine for skin squamous cell carcinoma
NASA Astrophysics Data System (ADS)
Ji, Jie; Fan, Zhixia; Zhou, Feifan; Wang, Xiaojie; Shi, Lei; Zhang, Haiyan; Wang, Peiru; Yang, Degang; Zhang, Linglin; Wang, Xiuli; Chen, Wei R.
Dendritic cell (DC) based vaccine has emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have only achieved limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secret INF-Υ and IL-12). ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumor in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing DC-based cancer vaccine, which could improve the clinical application of PDT- DC vaccines.
Naphthalocyanine-complexes as potential photosensitizers for PDT of tumors
NASA Astrophysics Data System (ADS)
Shopova, Maria; Woehrle, Dieter; Mantareva, Vanya; Mueller, Silke
In the present paper information about the synthesis and results on the pharmacokinetic and experimental photodynamic therapy (PDT) of naphthalocyanines are given. The photodynamic activity of differently substituted zinc(II)- and silicon(IV)-naphthalocyanines using liposomes or Cremophor EL as drug-delivery systems is shown on different tumor models. For the evaluation of the phototherapeutic effect different assessment criteria were used, including light and electron microscope observations. The main conclusions which can be arrived at on the basis of our findings are the following: silicon(IV)-naphthalocyanine seems to be not a very effective tumor sensitizer, especially in the treatment o pigmented melanoma, while zinc(II)-naphthalocyanines appear to be very promising for PDT of tumors. Their selective targeting and slow clearance from tumor tissue, fast clearance from skin and pronounced phototherapeutic effect on different tumor models and especially at melanotic tumors, even after application of low drug doses, make this group of photosensitizers very attractive for successful PDT of cancer.
Stimulation of dendritic cells by DAMPs in ALA-PDT treated SCC tumor cells
Zhang, Haiyan; Fan, Zhixia; Zhang, Linglin; Shi, Lei; Zhou, Feifan; Chen, Wei R.; Wang, Hongwei; Wang, Xiuli
Photodynamic therapy (PDT) not only kills tumor cells directly but also rapidly recruits and activates immune cells favoring the development of antitumor adaptive immunity. It is believed that Topical 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) can induce anti-tumor immune responses through dangerous signals damage-associated molecular patterns (DAMPs). In this study, we investigated the effect of ALA-PDT induced DAMPs on immune cells. We focused on the stimulation of dendritic cells by major DAMPs, enhanced the expression of calreticulin (CRT), heat shock proteins 70 (HSP70), and high mobility group box 1 (HMGB1), either individually or in combination. We evaluated in vitro and in vivo expressions of DAMPs induced by ALA-PDT using immunohistochemistry, western blot, and ELISA in a squamous cell carcinoma (SCC) mouse model. The role of DAMPs in the maturation of DCs potentiated by ALA-PDT-treated tumor cells was detected by FACS and ELISA. Our results showed that ALA-PDT enhanced the expression of CRT, HSP70, and HMGB1. These induced DAMPs played an important part in activating DCs by PDT-treated tumor cells, including phenotypic maturation (increase of surface expression of MHC-II, CD80, and CD86) and functional maturation (enhanced capability to secrete IFN-γ and IL-12). Furthermore, injecting ALA-PDT-treated tumor cells into naïve mice resulted in complete protection against cancer cells of the same origin. Our findings indicate that ALA-PDT can increase DAMPs and enhance tumor immunogenicity, providing a promising strategy for inducing a systemic anticancer immune response. PMID:26625309
Photosensitizer dosimetry controlled PDT treatment planning reduces inter-individual variability in response to PDT
NASA Astrophysics Data System (ADS)
Zhou, Xiaodong; Pogue, Brian W.; Chen, Bin; Demidenko, Eugene; Joshi, Rohan; Hoopes, Jack; Hasan, Tayyaba
Effective Photodynamic therapy (PDT) treatment depends on the amount of active photosensitizer and the delivered light in the targeting tissue. For the same PDT treatment protocol, variation in photosensitizer uptake between animals induces variation in the treatment response between animals. This variation can be compensated via control of delivered light dose through photodynamic dose escalation based on online dosimetry of photosensitizer in the animal. The subcutaneous MAT-LyLu Dunning prostate tumor model was used in this study. Photosensitizer BPD-MA uptake was quantified by multiple fluorescence micro-probe measurements at 3 hours after verteporfin administration. PDT irradiation was carried out after photosensitizer uptake measurement with a total light dose of 75 J/cm2 and a light dose rate of 50 mW/cm2. Therapeutic response of PDT treatments was evaluated by the tumor regrowth assay. Verteporfin uptake varied considerably among tumors (inter-tumor variation 56% standard deviation) and within a tumor (largest intra-tumor variation 64%). An inverse correlation was found between mean photosensitizer intensity and PDT treatment effectiveness (R2 = 37.3%, p < 0.005). In order to compensate individual PDT treatments, photodynamic doses were calculated on an individual animal basis, by matching the light delivered to provide an equal photosensitizer dose multiplied by light dose. This was completed for the lower-quartile, mean and upper-quartile of the photosensitizer distribution. The coefficient of variance in the surviving fraction decreased from 24.9% in non-compensated PDT (NC-PDT) treatments to 16.0%, 14.0% and 15.9% in groups compensated to the lower-quartile (CL-PDT), the median (CM-PDT) and the upper-quartile (CU-PDT), respectively. In terms of treatment efficacy, the CL-PDT group was significantly less effective compared with NC-PDT, CM-PDT and CU-PDT treatments (p < 0.005). No significant difference in effectiveness was observed between NC-PDT, CM-PDT
Targeted PDT agent eradicates TrkC expressing tumors via photodynamic therapy (PDT).
Kue, Chin Siang; Kamkaew, Anyanee; Lee, Hong Boon; Chung, Lip Yong; Kiew, Lik Voon; Burgess, Kevin
This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for (1)O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC- cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC--photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT (single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC- tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC- tumors or 2-PDT in TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n = 7) showed full tumor remission and survived until 90 days with no metastasis to key organs. PMID:25487316
Targeted PDT Agent Eradicates TrkC Expressing Tumors via Photodynamic Therapy (PDT)
This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for 1O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC– cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC–-photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT (single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC– tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC– tumors or 2-PDT in TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n = 7) showed full tumor remission and survived until 90 days with no metastasis to key organs. PMID:25487316
Palmer, R.B. |; Sessler, A.; Skrinsky, A.
Muon Colliders have unique technical and physics advantages and disadvantages when compared with both hadron and electron machines. They should thus be regarded as complementary. Parameters are given of 4 TeV and 0.5 TeV high luminosity {micro}{sup +}{micro}{sup {minus}}colliders, and of a 0.5 TeV lower luminosity demonstration machine. We discuss the various systems in such muon colliders, starting from the proton accelerator needed to generate the muons and proceeding through muon cooling, acceleration and storage in a collider ring. Problems of detector background are also discussed.
Effect of verteporfin-PDT on epithelial growth factor receptor (EGFR) signaling pathway in cholangiocarcinoma cell lines
NASA Astrophysics Data System (ADS)
Andreola, Fausto; Cerec, Virginie; Pereira, Stephen P.
EGFR, a member of the ERBB family, plays a pivotal role in carcinogenesis. EGFR overexpression is implicated in DNA repair and synergistic interactions between EGFR-targeting drugs and conventional chemo/radiotherapy have been reported in preclinical studies for different cancers but not cholangiocarcinoma (CCA). To date there are no in vitro data available on the cellular response and effect of either photodynamic therapy (PDT) or EGFR-targeting drugs on CCA. Therefore, we aimed to study the: (i) response to Verteporfin PDT and to EGFR-targeting drugs, as single agents; (ii) effect of PDT on ERBBs expression, phosporylation status and activation of its signaling pathways; (iii) response to combination of PDT and EGFR-targeting agents. We showed that two cholangiocarcinoma cell lines (HuCCT1 and TFK1 cells, intra- and extrahepatic, respectively) differentially respond to verteporfin-PDT treatment and are resistant to EGFR-targeting agents. A constitutive activation of EGFR in both cell lines was also observed, which could partly account for the observed resistance to EGFR-targeting drugs. In addition, verteporfin-PDT induced further phosphorylation of both EGFR and other Receptor Tyrosine Kinases. Mitochondria-independent apoptosis was induced by PDT in both CCA cell lines; in particular, PDT modulated the expression of members of the Inhibitor of Apoptosis (IAP) family of proteins. Interestingly, there was a PDT-induced EGFR nuclear translocation in both cell lines; co-treatment with either an EGFR-inhibitor (Cetuximab) or a nuclear import blocking agent (Wheat Germ Agglutinin) had an additive effect on PDT cell killing, thus implying a role of EGFR in repairing the potential PDT-induced DNA damage.
Palmer, R.
Parameters are given of muon colliders with center of mass energies of 1.5 and 3 TeV. Pion production is from protons on a mercury target. Capture, decay, and phase rotation yields bunch trains of both muon signs. Six dimensional cooling reduces the emittances until the trains are merged into single bunches, one of each sign. Further cooling in 6 dimensions is then applied, followed by final transverse cooling in 50 T solenoids. After acceleration the muons enter the collider ring. Ongoing R&D is discussed.
Assessing PDT response with diffuse optical spectroscopies
NASA Astrophysics Data System (ADS)
Rohrbach, Daniel J.
Photodynamic therapy (PDT) is used to treat a variety of conditions including cancer. Effective PDT requires three components: a photosensitizer (PS), light of a specific wavelength to activate the PS and oxygen. When all three are present in a lesion it leads to cell death and vascular destruction. Optical techniques such as diffuse reflectance spectroscopy (DRS), diffuse fluorescence spectroscopy (DFS) and diffuse correlation spectroscopy (DCS) can be used to quantify vascular parameters and photosensitizer content before and after PDT, providing valuable information for assessing response. For the quantification of vascular parameters, a probe-specific empirical light transport model was developed. A look-up-table was constructed using tissue simulating phantoms made of Intralipid to control the scattering, India Ink to control the absorption and water. The empirical model allowed the quantification of optical properties as well as the vascular parameters blood volume fraction (BVf) and blood oxygen saturation (SO2) with DRS. Blood flow was measured using DCS. For the quantification of PS content two techniques were used. DRS was used to fit the absorption of the PS and DFS measured the fluorescence of the PS. For quantification of PS content from measured fluorescence, a correction factor was developed using Monte Carlo simulations to account for the optical properties at the excitation and emission wavelengths. The three techniques were used to assess PDT response in pre-clinical and clinical studies. For the preclinical study, mice were treated with HPPH-PDT and blood flow was measured continuously with DCS. Blood flow variables were compared to STAT3 crosslinking (a molecular marker for PDT photoreaction) and CD31 staining (to visualize intact endothelial cells after PDT). For the clinical study, patients in a clinical trial for HPPH-PDT were measured with DRS, DFS and DCS before and after treatment. Multiple parameters were compared to the clinical response
PDT dose dosimeter for pleural photodynamic therapy
NASA Astrophysics Data System (ADS)
Kim, Michele M.; Darafsheh, Arash; Ahmad, Mahmoud; Finlay, Jarod C.; Zhu, Timothy C.
PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), a PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously in the same treatment location. Light fluence and spectral data were rigorously compared to other methods of measurement (e.g. photodiode, multi-fiber spectroscopy contact probe) to assess the accuracy of the measurements as well as their uncertainty. Photosensitizer concentration was obtained by measuring the fluorescence of the sensitizer excited by the treatment light. Fluence rate based on the intensity of the laser spectrum was compared to the data obtained by direct measurement of fluence rate by a fiber-coupled photodiode. Phantom studies were done to obtain an optical property correction for the fluorescence signal. Measurements were performed in patients treated Photofrin for different locations in the pleural cavity. Multiple sites were measured to investigate the heterogeneity of the cavity and to provide cross-validation via relative dosimetry. This novel method will allow for accurate real-time determination of delivered PDT dose and improved PDT dosimetry.
Can PDT be potentiated by immunotherapy?
NASA Astrophysics Data System (ADS)
Korbelik, Mladen; Krosl, Gorazd; Chaplin, David J.
Two principal aspects of interlinkage of the immune system with photodynamic therapy (PDT) treatment are discussed in detail: (1) participation of tumor associated macrophages (TAM) in tumor localization of photosensitizers, and (2) induction of an inflammatory immune response by phototoxic effects in endothelial cells, TAM and other cells in the tumor, leading to necrosis of the tumor tissue. It is illustrated how Photofrin levels in TAM, and consequently in the tumor as a whole, can be altered (increased or decreased) by specific agents that stimulate or impair physiological processes in TAM. It is suggested that the selectivity of tumor localization of some photosensitizers can be augmented by TAM targeted immunotherapy with agents that enhance the rate of tumor infiltration of these cells and stimulate their phagocytic activity. Preliminary results of ongoing studies suggest that PDT induces a massive infiltration of immune cells into the treated tumor. It is hypothesized that by combining PDT with an appropriate type of immunotherapy the immune reaction can be potentiated and directed against the surviving tumor cells. As as an example, it is shown that much better control of SCCVII tumor is achieved by combining PDT with the treatment by the immunoactivator SPG compared to PDT alone.
PD and PDT for hepatoblastoma? Preclinical considerations
NASA Astrophysics Data System (ADS)
Stepp, Herbert; Bergmann, Florian; Johansson, Ann; Heide, Michael; Metzger, Roman; Rolle, Udo; Till, Holger
Objective: Provide preclinical data on the feasibility of 5-aminolevulinic acid (5-ALA) -based photodetection (PD) and Photodynamic Therapy (PDT) of early childhood tumors. Methods: Hepatoblastoma (HuH6), neuroblastoma (MHH-NB11) and N1-fibroblast cell lines were tested for their relative capacities to synthesize Protoporphyrin IX (PpIX) from 5-ALA and for their susceptibility to PDT in vitro. HuH6-cells were also inoculated in the peritoneum of rats. The pharmacokinetics of porphyrin accumulation was measured in 9 rats by laparoscopic spectroscopy. 5-ALA was applied by i.p. injection of 500 mg/kg bw. In another 21 animals, tumors (n=20), liver (n=5) and peritoneum (n=4) were treated by PDT laparoscopically. 48 h after irradiation, animals were again incubated with 5-ALA and then sacrificed and tissues were removed for further investigation. Results: Both tumor cell lines showed higher levels of porphyrin fluorescence than the fibroblasts. Cell viability testing proved the HuH6 cells to be most susceptible to PDT. Pharmacokinetic measurements of PpIX in xenografted tumors showed a peak at 80-200 min after i.p. injection of 5-ALA. Irradiation resulted in pronounced photobleaching at all irradiated sites and necrosis of tumor and liver tissue, whereas peritoneum appeared to remain unaffected. Necrosis induced by PDT could be seen in fluorescence microscopy due to the lack of porphyrin synthesis in necrotic tissue after the re-incubation with 5-ALA.
Taking PDT into mainstream clinical practice
NASA Astrophysics Data System (ADS)
Bown, Stephen G.
Many individuals in the field are frustrated by the slow progress getting PDT established in mainstream clinical practice. The five key reasons are: 1. Lack of adequate evidence of safety and efficacy and optimization of dosimetry. These are fundamental. The number of randomized controlled studies is still small. For some cancer applications, it is difficult to get patients to agree to be randomised, so different approaches must be taken. Anecdotal results are not acceptable to sceptics and regulators. 2. The regulatory processes. The rules get more complex every day, but there is no choice, they must be met. The full bureaucratic strength of the pharmaceutical industry is needed to address these issues. 3. Conservatism of the medical profession. Established physicians are reluctant to change practice, especially if it means referring patients to different specialists. 4. Lack of education. It is amazing how few physicians have even heard of PDT and many that have, are sceptical. The profile of PDT to both the medical profession and the general public needs to be raised dramatically. Patient demand works wonders! 5. Money. Major investment is required to run clinical trials. Pharmaceutical companies may see PDT as a threat (eg reduced market for chemotherapy agents). Licensed photosensitisers are expensive. Why not reduce the price initially, to get the technique established and stimulate demand? PDT has the potential for enormous cost savings for health service providers. With appropriate motivation and resources these problems can be addressed. Possible routes forward will be suggested.
PDT Dose Dosimeter for Pleural Photodynamic Therapy
Kim, Michele M.; Darafsheh, Arash; Ahmad, Mahmoud; Finlay, Jarod C.; Zhu, Timothy C.
PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), a PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously in the same treatment location. Light fluence and spectral data were rigorously compared to other methods of measurement (e.g. photodiode, multi-fiber spectroscopy contact probe) to assess the accuracy of the measurements as well as their uncertainty. Photosensitizer concentration was obtained by measuring the fluorescence of the sensitizer excited by the treatment light. Fluence rate based on the intensity of the laser spectrum was compared to the data obtained by direct measurement of fluence rate by a fiber-coupled photodiode. Phantom studies were done to obtain an optical property correction for the fluorescence signal. Measurements were performed in patients treated Photofrin for different locations in the pleural cavity. Multiple sites were measured to investigate the heterogeneity of the cavity and to provide cross-validation via relative dosimetry. This novel method will allow for accurate real-time determination of delivered PDT dose and improved PDT dosimetry. PMID:27053825
Muon muon collider: Feasibility study
A feasibility study is presented of a 2 + 2 TeV muon collider with a luminosity of L = 10{sup 35} cm{sup {minus}2} s{sup {minus}1}. The resulting design is not optimized for performance, and certainly not for cost; however, it does suffice--the authors believe--to allow them to make a credible case, that a muon collider is a serious possibility for particle physics and, therefore, worthy of R and D support so that the reality of, and interest in, a muon collider can be better assayed. The goal of this support would be to completely assess the physics potential and to evaluate the cost and development of the necessary technology. The muon collider complex consists of components which first produce copious pions, then capture the pions and the resulting muons from their decay; this is followed by an ionization cooling channel to reduce the longitudinal and transverse emittance of the muon beam. The next stage is to accelerate the muons and, finally, inject them into a collider ring which has a small beta function at the colliding point. This is the first attempt at a point design and it will require further study and optimization. Experimental work will be needed to verify the validity of diverse crucial elements in the design.
Hyperglycemia enhances the effectiveness of PDT
NASA Astrophysics Data System (ADS)
Fan, Keichun; Huang, Yingcai; Li, Junheng
The effect of injection of 10 mg/g 50% glucose on photodynamic therapy of mouse transplantable S-180 sarcoma was studied. The concentration of hematoporphyrin monomethylether in plasma, skin, and tumor was measured by recording spectrofluorophotometer. tumor pathological section was made and necrosis area of tumor longitudinal section was measured by image processing after photoradiation of gold vapor laser. The results of this study suggested that the uptake of photosensitizer in tumor significantly increased while the uptake of photosensitizer in skin remained unchanged after glucose administration. Furthermore, glucose administration combined with PDT produced a greater tumor necrosis area than using PDT alone. The mechanisms and clinical significance were also discussed.
Comanche airframe design - The PDT approach
NASA Astrophysics Data System (ADS)
Kay, Bruce F.
The paper discusses the product development team (PDT) management approach adopted for the airframe design of the RAH-66 Comanche, a new helicopter for armed reconnaissance. One of the Comanche program's most important goals is cost control, and mechanisms for accomplishing this are firmly imbedded in all PDTs. Continuous evaluation of the supportability attributes is performed by PDT members representing different areas. Typical of the analyses used to influence the design is the predictions of maintenance requirements. These data are used, for example, to determine equipment locations; components requiring the most maintenance are placed in the most accessible positions.
ALA-mediated fluorescence-guided resection (FGR) and PDT of glioma
NASA Astrophysics Data System (ADS)
Johansson, Ann; Stepp, Herbert; Beck, Tobias; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Meinel, Thomas; Stummer, Walter; Kreth, Friedrich-Wilhelm; Tonn, Jörg-Christian; Baumgartner, Reinhold
A summary of clinical trials employing photodynamic diagnosis (PDD) and photodynamic therapy (PDT) for the diagnosis and treatment of brain malignancies is presented. Intra-cavity PDT has been performed within the surgical cavity following FGR, employing oral administration of 5-aminolevulinic acid (5-ALA), either targeting fluorescing tissue regions that were not removed during FGR due to safety reasons (referred to as focal PDT, n=20) or illuminating the entire resection cavity (referred to as integral PDT, n=9). Both approaches proved technically feasible and safe. Spectroscopic measurements performed pre-, during and post-PDT revealed Protoporphyrin IX (PpIX)-photobleaching of more than 95% after the delivery of 200 J/cm2. This light dose did not induce any side effects. Furthermore, interstitial PDT (iPDT) has been employed within one feasibility trial (n=10) and one Phase I/II trial (n=15). Here, three to six cylindrical light diffusors (20-30 mm length, 200 mW/cm, 720 J/cm) were positioned within the target tissue under stereotactic guidance. Pre-treatment planning was performed with the intent to target the entire tumour volume with a sufficient light dose while also minimising the risk of any light-induced temperature increase. For the feasibility trial patients with small, recurrent gliomas were included, resulting in a median survival of 15 months as well as some unexpected longterm survivals (up to 5 years). The Phase I/II trial employed the same clinical procedures. Here, the 12-month survival was 35% and the median progression-free survival was 6 months. In summary, stereotactic iPDT in combination with treatment-planning could be shown to be a safe and feasible treatment modality. These trials are presently being extended to also include on-line monitoring of PpIX fluorescence and photobleaching kinetics. Preliminary data has revealed dramatically different PpIX levels and photobleaching kinetics. Such data could possibly be employed for realtime
Muon Muon Collider: Feasibility Study
Gallardo, J.C.; Palmer, R.B.; Tollestrup, A.V.; Sessler, A.M.; Skrinsky, A.N.; Ankenbrandt, C.; Geer, S.; Griffin, J.; Johnstone, C.; Lebrun, P.; McInturff, A.; Mills, Frederick E.; Mokhov, N.; Moretti, A.; Neuffer, D.; Ng, K.Y.; Noble, R.; Novitski, I.; Popovic, M.; Qian, C.; Van Ginneken, A. /Fermilab /Brookhaven /Wisconsin U., Madison /Tel Aviv U. /Indiana U. /UCLA /LBL, Berkeley /SLAC /Argonne /Sobolev IM, Novosibirsk /UC, Davis /Munich, Tech. U. /Virginia U. /KEK, Tsukuba /DESY /Novosibirsk, IYF /Jefferson Lab /Mississippi U. /SUNY, Stony Brook /MIT /Columbia U. /Fairfield U. /UC, Berkeley
A feasibility study is presented of a 2 + 2 TeV muon collider with a luminosity of L = 10{sup 35} cm{sup -2}s{sup -1}. The resulting design is not optimized for performance, and certainly not for cost; however, it does suffice - we believe - to allow us to make a credible case, that a muon collider is a serious possibility for particle physics and, therefore, worthy of R and D support so that the reality of, and interest in, a muon collider can be better assayed. The goal of this support would be to completely assess the physics potential and to evaluate the cost and development of the necessary technology. The muon collider complex consists of components which first produce copious pions, then capture the pions and the resulting muons from their decay; this is followed by an ionization cooling channel to reduce the longitudinal and transverse emittance of the muon beam. The next stage is to accelerate the muons and, finally, inject them into a collider ring wich has a small beta function at the colliding point. This is the first attempt at a point design and it will require further study and optimization. Experimental work will be needed to verify the validity of diverse crucial elements in the design. Muons because of their large mass compared to an electron, do not produce significant synchrotron radiation. As a result there is negligible beamstrahlung and high energy collisions are not limited by this phenomena. In addition, muons can be accelerated in circular devices which will be considerably smaller than two full-energy linacs as required in an e{sup +} - e{sup -} collider. A hadron collider would require a CM energy 5 to 10 times higher than 4 TeV to have an equivalent energy reach. Since the accelerator size is limited by the strength of bending magnets, the hadron collider for the same physics reach would have to be much larger than the muon collider. In addition, muon collisions should be cleaner than hadron collisions. There are many detailed particle
Enhancing protoporphyrin IX-induced PDT
NASA Astrophysics Data System (ADS)
Curnow, Alison; Pye, Andrew; Campbell, Sandra
Photodynamic therapy (PDT) using porphyrin precursors is commonly used in dermatology. Evidence indicates that good clinical outcomes (associated with excellent cosmesis) can be achieved in superficial precancers and basal cell carcinoma (BCC), however, efficacy appears less favorable for thicker nodular BCC (nBCC) unless multiple PDT treatment cycles are performed. Enhancement is therefore required if nBCC lesions are to be treated effectively with a single PDT treatment. The most common technique currently being routinely employed clinically is the use of aminolevulinic acid (ALA) esters (usually methyl (MAL) or hexyl (HAL)). Standard dermatological PDT employing these porphyrin precursors already manipulates the normal heme biosynthesis pathway resulting in a temporary accumulation of the natural photosensitizer, protoporphyrin IX (PpIX). Further manipulation using iron chelating agents is possible however. In normal and malignant human cells in vitro, the novel iron chelating agent CP94 produced greater PPIX fluorescence when administered with ALA or MAL than either congener produced alone. CP94 was also significantly more effective than the clinically established iron chelating agent desferrioxamine (DFO). Topical application of ALA+CP94 to clinical nBCC lesions was a simple and safe treatment modification which produced a significant increase in clinical clearance when CP94 was included in the cream.
PDT dose dosimetry for pleural photodynamic therapy
NASA Astrophysics Data System (ADS)
Sharikova, Anna V.; Finlay, Jarod C.; Liang, Xing; Zhu, Timothy C.
PDT dose is the product of the photosensitizer concentration and the light fluence in target tissue. Although existing systems are capable of measuring the light fluence in vivo, the concurrent measurement of photosensitizer in the treated tissue so far has been lacking. We have developed and tested a new method to simultaneously acquire light dosimetry and photosensitizer fluorescence data via the same isotropic detector, employing treatment light as the excitation source. A dichroic beamsplitter is used to split light from the isotropic detector into two fibers, one for light dosimetry, the other, after the 665 nm treatment light is removed by a band-stop filter, to a spectrometer for fluorescence detection. The light fluence varies significantly during treatment because of the source movement. The fluorescence signal is normalized by the light fluence measured at treatment wavelength. We have shown that the absolute photosensitizer concentration can be obtained by an optical properties correction factor and linear spectral fitting. Tissue optical properties are determined using an absorption spectroscopy probe immediately before PDT at the same sites. This novel method allows accurate real-time determination of delivered PDT dose using existing isotropic detectors, and may lead to a considerable improvement of PDT treatment quality compared to the currently employed systems. Preliminary data in patient studies is presented.
A treatment planning system for pleural PDT
NASA Astrophysics Data System (ADS)
Sandell, Julia; Chang, Chang; Finlay, Jarod C.; Zhu, Timothy C.
Uniform light fluence distribution for patients undergoing photodynamic therapy (PDT) is critical to ensure predictable PDT outcome. However, common practice uses a point source to deliver light to the pleural cavity. To improve the uniformity of light fluence rate distribution, we have developed a treatment planning system using an infrared camera to track the movement of the point source. This study examines the light fluence (rate) delivered to chest phantom to simulate a patient undergoing pleural PDT. Fluence rate (mW/cm2) and cumulative fluence (J/cm2) was monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors were used for in-vivo light dosimetry. Light fluence rate in the pleural cavity is also calculated using the diffusion approximation with a finite-element model. We have established a correlation between the light fluence rate distribution and the light fluence rate measured on the selected points based on a spherical cavity model. Integrating sphere theory is used to aid the calculation of light fluence rate on the surface of the sphere as well as inside tissue assuming uniform optical properties. The resulting treatment planning tool can be valuable as a clinical guideline for future pleural PDT treatment.
Comparison of two phthalocyanines for PDT
NASA Astrophysics Data System (ADS)
Bachor, Ruediger; Reich, Ella D.; Graf, Peter; Rueck, Angelika C.; Hautmann, Richard E.
Photodynamic therapy (PDT) is a new treatment modality for bladder carcinoma, especially carcinoma in situ. The goal of our study was to compare two different phthalocyanines for PDT of bladder carcinoma cells and to evaluate phototoxic potential. Material and methods: For PDT hydrophilic chlor-aluminum sulfonated phthalocyanine (CASP) and lipophilic zinc- phthalocyanine (ZnP, CPG 55 847) were compared. For ZnP liposomes as drug carrier were used. The photosensitizer concentrations for both substances used for PDT experiments were 5, 10 and 20 (mu) g/ml. Irradiation was performed with a Penta lamp emitting at wavelengths between 590 and 900 nm at a fluence of up to 12 J/cm2. After irradiation cells were incubated for two days, counted and compared with a control group. Results: The cell survival rate was decreased depending on the light and drug dose. After incubation with the highest drug dose and irradiation with 12 J/cm2 cell survival was 0.03 and 5.5% after incubation with CASP or ZnP, respectively. Light, CASP or ZnP alone had no effect on cells. Studies of the PDT effect by electron microscopy showed intracellular vacuolization caused by mitochondrial damage after incubation with either photosensitizer. Conclusion: The hydrophilic and lipophilic phthalocyanine tested here showed very similar effects on our cell line. ZnP is a pure compound and hence has some advantage over CASP, which is a mixture of a tri- and tetrasulfonated phthalocyanine. In addition, ZnP is administered in liposomes which should enhance tumor selectivity by binding to low density lipoprotein receptors on tumor cells.
Mechanistic exploration of a bi-directional PDT-based combination in pancreatic cancer (Conference Presentation)
NASA Astrophysics Data System (ADS)
Huang, Huang-Chiao; Mallidi, Srivalleesha; Liu, Joyce; Chiang, Chun-Te; Mai, Zhiming; Goldschmidt, Ruth; Rizvi, Imran; Ebrahim-Zadeh, Neema; Hasan, Tayyaba
It is increasingly evident that the most effective cancer treatments will involve interactive regimens that target multiple non-overlapping pathways, preferably such that each component enhances the others to improve outcomes while minimizing systemic toxicities. Toward this goal, we developed a combination of photodynamic therapy and irinotecan, which mechanistically cooperate with each other, beyond their individual tumor destruction pathways, to cause synergistic reduction in orthotopic pancreatic tumor burden. A three-way mechanistic basis of the observed the synergism will be discussed: (i) PDT downregulates drug efflux transporters to increase intracellular irinotecan levels. (ii) Irinotecan reduces the expression of hypoxia-induced marker, which is upregulated by PDT. (iii) PDT downregulates irinotecan-induced survivin expression to amplify the apoptotic and anti-proliferative effects. The clinical translation potential of the combination will also be highlighted.
Polarized muon beams for muon collider
NASA Astrophysics Data System (ADS)
Skrinsky, A. N.
An option for the production of intense and highly polarized muon beams, suitable for a high-luminosity muon collider, is described briefly. It is based on a multi-channel pion-collection system, narrow-band pion-to-muon decay channels, proper muon spin gymnastics, and ionization cooling to combine all of the muon beams into a single bunch of ultimately low emittance.
Mitochondrion-mediated apoptosis induced by photofrin-PDT
NASA Astrophysics Data System (ADS)
Wu, Yunxia; Xing, Da
Apoptosis is an important cellular event that plays a key role in pathogeny and therapy of many diseases. The mechanisms of the initiation and regulation of PDT-induced apoptosis are complex. Some PDT-associated apoptosis pathways involved plasma membrane death receptors, mitochondria, lysosomes and endoplasmic reticulum (ER). In order to determine the apoptosis pathway induced by Photofrin-PDT, we used fluorescence resonance energy transfer (FRET) technique and probe SCAT3 to monitor the dynamics of caspase-3 activation after PDT treatment and also measured caspase-8 activity. With laser scanning confocal microscopy, we found that Photofrin were localized primarily in mitochondria, the primary targets of Photofrin-PDT. Formation of mitochondrial reactive oxygen species (ROS) was detected within minutes after PDT treatment. This was followed by mitochondrial membrane potential (ΔΨm), cytochrome c release, caspase-9 activity, caspase-3 activity and apoptosis. After PDT treatment, caspase-3 was activated rapidly while caspase-8 remained inactivated. Our results indicated that PDT-induced apoptosis was initiated from mitochondria pathway and independent of caspase-8 activation. The activation of caspase-3 by PDT started 20 minutes after treatment and completed in about 15 minutes. PDT-induced apoptosis is directly initiated from mitochondria pathway and not involved in the death receptors-dependent pathway. Our results demonstrated that FRET could be an effective tool to determine PDT-induced apoptosis and other cell death mechanism.
Mechanistic studies on a sequential PDT protocol
NASA Astrophysics Data System (ADS)
Kessel, David
A low (~LD15) PDT dose resulting in selective lysosomal photodamage can markedly promote photokilling by subsequent photodamage targeted to mitochondria. Experimental data are consistent with the proposal that cleavage of the autophagyassociated protein ATG5 to a pro-apoptotic fragment is responsible for this effect. This process is known to be dependent on the proteolytic activity of calpain. We have proposed that Ca2+ released from photodamaged lysosomes is the trigger for ATG5 cleavage. We can now document the conversion of ATG5 to the truncated form after lysosomal photodamage. Photofrin, a photosensitizer that targets both mitochondria and lysosomes, can be used for either phase of the sequential PDT process. The ability of Photofrin to target both loci may explain the well-documented efficacy of this agent.
Cell death pathways associated with PDT
NASA Astrophysics Data System (ADS)
Kessel, David; Reiners, John J., Jr.
Photodynamic therapy leads to both direct and indirect tumor cell death. The latter also involves the consequences of vascular shut-down and immunologic effects. While these factors are a major factor in tumor eradication, there is usually an element of direct cell killing that can reduce the cell population by as much as 2-3 logs. Necrosis was initially believed to represent the predominant PDT death mechanism. An apoptotic response to PDT was first reported by Oleinick in 1991, using a sensitizer that targets the anti-apoptotic protein Bcl-2. Apoptosis leads to fragmentation of DNA and of cells into apoptotic bodies that are removed by phagocytosis. Inflammatory effects are minimized, and the auto- catalytic elements of the process can amplify the death signal. In this study, we examined consequences of Bcl-2 photodamage by a porphycene sensitizer that targets the ER and causes photodamage to the anti-apoptotic protein Bcl-2. Death patterns after Bcl-2 inactivation by a small-molecular antagonist were also assessed. In addition to apoptosis, we also characterized a hitherto undescribed PDT effect, the initiation of autophagy. Autophagy was initially identified as a cell survival pathway, allowing the recycling of components as nutrients become scarce. We propose that autophagy can also represent both a potential survival pathway after PDT damage to cellular organelles, as well as a cell-death pathway. Recent literature reports indicate that autophagy, as well as apoptosis, can be evoked after down-regulation of Bcl-2, a result consistent with results reported here.
Animal models for photodynamic therapy (PDT)
Silva, Zenildo Santos; Bussadori, Sandra Kalil; Fernandes, Kristianne Porta Santos; Huang, Ying-Ying; Hamblin, Michael R.
Photodynamic therapy (PDT) employs non-toxic dyes called photosensitizers (PSs), which absorb visible light to give the excited singlet state, followed by the long-lived triplet state that can undergo photochemistry. In the presence of ambient oxygen, reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radicals are formed that are able to kill cancer cells, inactivate microbial pathogens and destroy unwanted tissue. Although there are already several clinically approved PSs for various disease indications, many studies around the world are using animal models to investigate the further utility of PDT. The present review will cover the main groups of animal models that have been described in the literature. Cancer comprises the single biggest group of models including syngeneic mouse/rat tumours that can either be subcutaneous or orthotopic and allow the study of anti-tumour immune response; human tumours that need to be implanted in immunosuppressed hosts; carcinogen-induced tumours; and mice that have been genetically engineered to develop cancer (often by pathways similar to those in patients). Infections are the second biggest class of animal models and the anatomical sites include wounds, burns, oral cavity, ears, eyes, nose etc. Responsible pathogens can include Gram-positive and Gram-negative bacteria, fungi, viruses and parasites. A smaller and diverse group of miscellaneous animal models have been reported that allow PDT to be tested in ophthalmology, atherosclerosis, atrial fibrillation, dermatology and wound healing. Successful studies using animal models of PDT are blazing the trail for tomorrow's clinical approvals. PMID:26415497
Direct imaging of macrophage activation during PDT treatment
NASA Astrophysics Data System (ADS)
Song, Sheng; Zhou, Feifan; Chen, Wei R.; Xing, Da
Mounting evidence describes a more complex progress of macrophage activation during photodynamic therapy (PDT), which performing distinct immunological functions and different physiologies on surrounding cells and tissues. Macrophage-targeted PDT has been applied in the selective killing of cells involved in inflammation and tumor. We have previously shown that PDT-mediated tumor cells apoptosis can induce a higher level immune response than necrosis, and enhance the macrophage activation. However, the molecular mechanism of macrophage activation during PDT-induced apoptotic cells (AC) still unclear. Here, we use confocal microscopy to image the phagocytosis of tumor cells by macrophages. We also observed that PDT-treated AC can activate Toll-like receptors (TLRs) which are present on macrophages surface. Besides, the increase in nitric oxide (NO) formation in macrophages was detected in real time by a laser scanning microscopy. This study provided more details for understanding the molecular mechanism of the immune response induced by PDT-treated AC.
Direct imaging of macrophage activation during PDT treatment
NASA Astrophysics Data System (ADS)
Song, Sheng; Zhou, Feifan; Chen, Wei R.; Xing, Da
Mounting evidence describes a more complex progress of macrophage activation during photodynamic therapy (PDT), which performing distinct immunological functions and different physiologies on surrounding cells and tissues. Macrophage-targeted PDT has been applied in the selective killing of cells involved in inflammation and tumor. We have previously shown that PDT-mediated tumor cells apoptosis can induce a higher level immune response than necrosis, and enhance the macrophage activation. However, the molecular mechanism of macrophage activation during PDT-induced apoptotic cells (AC) still unclear. Here, we use confocal microscopy to image the phagocytosis of tumor cells by macrophages. We also observed that PDT-treated AC can activate Toll-like receptors (TLRs) which are present on macrophages surface. Besides, the increase in nitric oxide (NO) formation in macrophages was detected in real time by a laser scanning microscopy. This study provided more details for understanding the molecular mechanism of the immune response induced by PDT-treated AC.
Effects of PDT on the endocytic pathway
NASA Astrophysics Data System (ADS)
Kessel, David
Two lines of evidence point to an early effect of photodamage on membrane trafficking. [1] Internalization of a fluorescent probe for hydrophobic membrane loci was impaired by prior photodamage. [2] Interference with the endocytic pathway by the PI-3 kinase antagonist wortmannin led to accumulation of cytoplasmic vacuoles suggesting a block in the recycling of plasma membrane components. Prior photodamage blocked this pathway so that no vacuoles were formed upon exposure of cells to wortmannin. In a murine hepatoma line, the endocytic pathway was preferentially sensitive to lysosomal photodamage. The role of photodamage to the endocytic pathway as a factor in PDT efficacy remains to be assessed.
An IR Navigation System for Pleural PDT
NASA Astrophysics Data System (ADS)
Zhu, Timothy; Liang, Xing; Kim, Michele; Finlay, Jarod; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles; Friedberg, Joseph; Cengel, Keith
Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for malignant pleural mesothelioma (MPM). In the current pleural PDT protocol, a moving fiber-based point source is used to deliver the light. The light fluences at multiple locations are monitored by several isotropic detectors placed in the pleural cavity. To improve the delivery of light fluence uniformity, an infrared (IR) navigation system is used to track the motion of the light source in real-time at a rate of 20 - 60 Hz. A treatment planning system uses the laser source positions obtained from the IR camera to calculate light fluence distribution to monitor the light dose uniformity on the surface of the pleural cavity. A novel reconstruction algorithm is used to determine the pleural cavity surface contour. A dual-correction method is used to match the calculated fluences at detector locations to the detector readings. Preliminary data from a phantom shows superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown with and without the correction method.
PDT of the endometrium using ALA
NASA Astrophysics Data System (ADS)
Gannon, Michael J.; Vernon, David I.; Holroyd, J. Andrew; Stringer, Mark R.; Johnson, Nick; Brown, Stanley B.
There is a widely recognized need for new approaches to effect endometrial ablation as an alternative to hysterectomy for treatment of menorrhagia. Photodynamic therapy (PDT) offers one such approach. We have investigated the use of 5-aminolaevulinic acid (ALA)-based PDT of the endometrium in model systems and in a series of patients. In all of this work, the ALA was administrated directly into the uterine cavity to reduce any possibility of systemic photosensitization. In a series of experiments in perfused ex vivo uteri, ALA was introduced into the cavity and protoporphyrin formation was measured in the endometrium, the underlying myometrium and the perfusate. ALA transfer into the perfusate was also measured. This work demonstrated that protoporphyrin formation in the endometrium was approximately ten fold that in the underlying myometrium and that systemic photosensitization would be unlikely to result form transfer of administered ALA from the uterus into the circulation. Similar results were found in studies carried out in vivo, where ALA was administered to patients scheduled for hysterectomy. Using a specially designed light source, the first patients have now been treated by giving intrauterine ALA followed by laser light. Two series of treatments - 10 in all - have been carried out. Eight patients have one year follow up. A reduction in measured menstrual blood loss was demonstrated in all but one patient. Complete symptomatic relief was obtained in tow women who did not require further treatment.
Development of an applicator for multiphoton PDT
NASA Astrophysics Data System (ADS)
Graschew, Georgi; Bastian, Matthias; Rakowsky, Stefan; Roelofs, Theo A.; Balanos, Evangelos; Schlag, Peter M.; Steinmeyer, Gunter; Elsaesser, Thomas
Multiphoton excitation of photosensitizers for laser induced fluorescence diagnosis (LIFD) and photodynamic therapy (PDT) of tumors has the advantage of greater tissue penetration due to the longer wavelength of irradiation. However, multiphoton LIFD and PDT are presently not clinically applicable as there are no applicators available for the delivery of the pulsed laser radiation to the operating room. As an approach, in this contribution the beam delivery through photonic crystal fibers has been investigated. Pulses of a Ti:sapphire laser of 100 fs pulse duration and an average power of 150 mW have been transported through such a fiber of 25 m length and the resulting pulses show the absence of nonlinear contributions but still a broadening of the pulse to 2 ps due to the dispersion of the fiber. It is planned to compensate this broadening by a grating in front of the fiber. Alternatively, the transport of laser radiation of 150 fs and 100 mW through a mirror-joint-arm used for conventional CO2 lasers has been tested showing no broadening of the laser pulses. Two-photon photodynamic activity of mTHPC-CMPEG4 shall serve as a test of the laser light transport system.
NASA Technical Reports Server (NTRS)
Stanev, T.; Vankov, C. P.; Halzen, F.
Muon production in gamma-induced air showers, accounting for all major processes. For muon energies in the GeV region the photoproduction is by far the most important process, while the contribution of micron + micron pair creation is not negligible for TeV muons. The total rate of muons in gamma showers is, however, very low.
PDT: special cases in front of legal regulations
NASA Astrophysics Data System (ADS)
Fischer, E.; Wegner, A.; Pfeiler, T.; Mertz, M.
Introduction: The classic indication for photodynamic therapy (PDT) in ophthalmology is currently represented by classic subfoveal choroidal neovascularisation (CNV) due to age-related macular degeneration (AMD). PDT is a method, which almost selectively causes endothelial damage in neovascular lesions, followed by vascular occlusion and involution of the CNV. The mechanistic aspect suggests that non AMD-related choroidal neovascularisations might also benefit from PDT. PDT in AMD: Within the German health system, PDT indications follow the criteria based on the inclusion criteria of the TAP studies. For instance the CNV should be predominantly classic and located under the center of the foveal avascular zone. In the diagnosis and follow-up of exudative AMD, visual acuity measurements and fluorescein angiography are the established parameters. Retinal thickness analyzer (RTA) measurements might give further information. Before PDT, they show a significant retinal thickening due to intra- and subretinal exudation. Following PDT, early RTA follow-ups show a clear decrease in retinal thickening accompanies by increasing or stable acuity. PDT in CNV of other origins than AMD: New studies support a new spectrum of indications for PDT, hopefully leading to general cost reimbursement for patients. PDT should be viewed as a general method for vascular occlusion and does not represent a causal therapy for progressive exudative AMD. We present patients with CNV due to pathologic myopia, angioid streaks and POHS. Conclusion: The selective vascular occlusion caused by PDT, besides CNV associated with AMD and pathologic myopia, may also allow the treatment of choroidal neovascularisations based on other entities. Careful individual evaluation of those cases is recommended. Despite this wide array of possible indications, cost reimbursement has been limited to classic subfoveal CNV in AMD, although single case reimbursements in choroidal neovascular lesions due to pathologic
Effect of verteporfin-PDT on the Notch signaling pathway in cholangiocarcinoma (CCA) cell lines
NASA Astrophysics Data System (ADS)
Cerec, Virginie; Andreola, Fausto; Pereira, Stephen P.
Accumulating preclinical and clinical evidence supports a pro-oncogenic function for Notch signaling in several solid tumors. Therefore, Notch inhibitory agents, such as gamma-secretase inhibitors (GSI), are being investigated as cancer therapeutic agents and a potential adjuvant to conventional chemo/radiotherapy. To date, no in vitro data are available on the cellular response and effect of either photodynamic therapy (PDT) or GSI on human cholangiocarcinoma (CCA). Consequently, we aimed to study the: (i) constitutive expression of Notch signaling pathway in CCA cell lines; (ii) response to Verteporfin-PDT and to GSI, as single agents on CCA cell lines; (iii) effect of Verteporfin-PDT on Notch signaling pathway expression. Expression of Notch signaling components was studied in two cholangiocarcinoma cell lines, HuCCT1 and TFK-1 (intra- and extrahepatic, respectively). No difference in basal expression of Notch1, 2 and Jagged1 was observed in either cell line. In contrast, Notch3 was found to be weakly and highly expressed in HuCCT1 and TFK-1 cells, respectively - supporting our recent microarray data which showed Notch3 overexpression in biliary brushings from patients with extrahepatic CCA. HuCCT1 and TFK-1 differentially responded to Verteporfin-PDT treatment; preliminary data showed no clear effect of GSI on proliferation/apoptosis in either cell line following short exposure (6 and 24h). Following Verteporfin-PDT, Notch1, 2 and Jagged-1 expression was down-regulated in both cell lines, while Notch3 expression was unaffected in HuCCT1 cells and down-regulated in TFK-1 cells. The Notch signaling pathway could represent a potential target for combination therapy in CCA treatment.
Host cell infiltration into PDT-treated tumor
NASA Astrophysics Data System (ADS)
Korbelik, Mladen; Krosl, Gorazd; Dougherty, Graeme J.; Chaplin, David J.
C3H mice bearing SCCVII squamous cell carcinoma were treated with photodynamic therapy (PDT) 24 hours after receiving Photofrin (25 mg/kg, i.v.). Single cell suspensions obtained by the enzymatic digestion of tumors excised either 30 minutes or 4 hours after PDT were analyzed for the content of host immune cells and colony forming ability of malignant cells. The results were compared to the data obtained with non-treated tumors. It is shown that there is a marked increase in the content of cells expressing Mac-1 (monocytes/macrophages or granulocytes) in the tumor 30 minutes post PDT, while a high level of other leucocytes are found within the tumors by 4 hours after PDT. As elaborated in Discussion, the infiltration rate of host immune cells, dying of malignant tumor cells, and yet unknown death rate of host cells originally present in PDT treated tumor occurring concomitantly during this time period complicates this analysis. The results of this study suggest a massive infiltration of macrophages and other leucocytes in PDT treated SCCVII tumor, supporting the suggestion that a potent immune reaction is one of the main characteristics of PDT action in solid tumors. It remains to be determined to what extent is the activity of tumor infiltrating immune cells responsible for its eradication by PDT.
Activity of glycated chitosan and other adjuvants to PDT vaccines
NASA Astrophysics Data System (ADS)
Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.
Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.
Squamous cell carcinoma of dogs and cats: an ideal test system for human head and neck PDT protocols
NASA Astrophysics Data System (ADS)
Lucroy, Michael D.
Photodynamic therapy (PDT) is ideally suited for the treatment of head and neck cancer (HNC) in humans. Developing useful PDT protocols for HNC is challenging due to the expense of Phase I and II clinical trials. Moreover, the often-poor predictive value of murine models means that photosensitizers may proceed far into development before problems are noted. Dogs and cats with spontaneous oral squamous cell carcinoma (SCC) share striking similarities with humans affected with oral SCC. These similarities include viral and environmental tobacco smoke as risk factors, location-dependent prognoses, and relative resistance to chemotherapy. The relatively large oral cancers encountered in veterinary patients allow for light and drug dosimetry that are directly applicable to humans. The irregular shape of oral SCC allows a rigorous evaluation of novel photodynamic therapy protocols under field conditions. Because spontaneous tumors in dogs and cats arise in an outbred animal population it is possible to observe an intact host response to PDT. The shorter lifespan of dogs and cats allows rapid accrual of endpoint data. External beam radiation therapy and chemotherapy are commonplace in veterinary medicine, making dogs and cats with spontaneous SCC a useful resource to study the interactions with PDT and other cancer treatment modalities. Our preliminary results demonstrate that PDT is well-tolerated by dogs with oral cancer, and a Phase II clinical trial of zinc-phthalocyanine-based photodynamic therapy is underway in dogs with oral SCC. The usefulness of 5-aminolevulinic acid methyl ester-based PDT is being investigated in cats with oral SCC.
Preparations for Muon Experiments at Fermilab
Syphers, M.J.; Popovic, M.; Prebys, E.; Ankenbrandt, C.; /Muons Inc., Batavia
The use of existing Fermilab facilities to provide beams for two muon experiments--the Muon to Electron Conversion Experiment (Mu2e) and the New g-2 Experiment--is under consideration. Plans are being pursued to perform these experiments following the completion of the Tevatron Collider Run II, utilizing the beam lines and storage rings used today for antiproton accumulation without considerable reconfiguration.
PDT: loss of autophagic cytoprotection after lysosomal photodamage
NASA Astrophysics Data System (ADS)
Kessel, David; Price, Michael
Photodynamic therapy is known to evoke both autophagy and apoptosis. Apoptosis is an irreversible death pathway while autophagy can serve a cytoprotective function. In this study, we examined two photosensitizing agents that target lysosomes, although they differ in the reactive oxygen species (ROS) formed during irradiation. With both agents, the 'shoulder' on the PDT dose-response curve was substantially attenuated, consistent with loss of a cytoprotective pathway. In contrast, this 'shoulder' is commonly observed when PDT targets mitochondria or the ER. We propose that lysosomal targets may offer the possibility of promoting PDT efficacy by eliminating a potentially protective pathway.
NASA Astrophysics Data System (ADS)
Giacomelli, P.
The muon detection system of the Compact Muon Solenoid experiment is described. It consists of three different detector technologies: drift tubes in the barrel region, cathode strip chambers in the endcap region and resistive plate chambers in both barrel and endcap regions. The CMS muon detection system ensures excellent muon detection and efficient triggering in the pseudorapidity range 0< η<2.4. The most recent developments and some results from the R&D program will also be discussed.
Johnson, Rolland P; Ankenbrandt, Charles; Bhat, Chandra; Popovic, Milorad; Bogacz, Alex; Derbenev, Yaroslav
The idea of coalescing multiple muon bunches at high energy to enhance the luminosity of a muon collider provides many advantages. It circumvents space-charge, beam loading, and wakefield problems of intense low energy bunches while restoring the synergy between muon colliders and neutrino factories based on muon storage rings. A sampling of initial conceptual design work for a coalescing ring is presented here.
Light dose verification for pleural PDT
NASA Astrophysics Data System (ADS)
Sandell, Julia L.; Liang, Xing; Zhu, Timothy
The ability to deliver uniform light dose in Photodynamic therapy (PDT) is critical to treatment efficacy. Current protocol in pleural photodynamic therapy uses 7 isotropic detectors placed at discrete locations within the pleural cavity to monitor light dose throughout treatment. While effort is made to place the detectors uniformly through the cavity, measurements do not provide an overall uniform measurement of delivered dose. A real-time infrared (IR) tracking camera is development to better deliver and monitor a more uniform light distribution during treatment. It has been shown previously that there is good agreement between fluence calculated using IR tracking data and isotropic detector measurements for direct light phantom experiments. This study presents the results of an extensive phantom study which uses variable, patient-like geometries and optical properties (both absorption and scattering). Position data of the treatment is collected from the IR navigation system while concurrently light distribution measurements are made using the aforementioned isotropic detectors. These measurements are compared to fluence calculations made using data from the IR navigation system to verify our light distribution theory is correct and applicable in patient-like settings. The verification of this treatment planning technique is an important step in bringing real-time fluence monitoring into the clinic for more effective treatment.
Role of PDT and lasers in the tracheobronchial tree
NASA Astrophysics Data System (ADS)
Beamis, John F.
Multiple centers in this country and throughout the world have documented the efficacy of Photodynamic Therapy (PDT) in the treatment of cancers of the tracheobronchial tree. While PDT can effectively achieve airway patency by treating bulky obstructing tumors, its most promising role for treating tracheobronchial cancers is in the treatment of superficial early stage tumors which can potentially be treated for cure with this technique. Unfortunately more widespread use of PDT awaits FDA approval which will be slow in coming due to the need for randomized controlled studies. Many improvements are needed in the thoracic application of the Nd:YAG Laser and PDT. However efforts to prevent lung cancer and detect early lung tumors may prove more beneficial than improvement of current systems which are all too often utilized on end stage tumors.
PDT for malignant tumors: a clinical analysis of 152 cases
NASA Astrophysics Data System (ADS)
Zhuang, Shi-Zhang; Wang, Yun-Zhen; Li, Xin; Zhang, Changjun; Wang, Jian-Zhao; Zhang, Da-Ren
Hematoporphyrin derivative (HPD) laser photodynamic therapy (PDT) was applied for the patients of 152 cases of malignant tumors, including tumors of the lip, tongue, esophagus, urinary bladder, skin, larynx, vagina, etc. Since early 1981 good results have been obtained.
[Use of nanoparticles (NP) in photodynamic therapy (PDT) against cancer].
Roblero-Bartolón, Gabriela Victoria; Ramón-Gallegos, Eva
Nanotechnology is a promising interdisciplinary field for developing improved methods of diagnosis and treatment of different diseases, including cancer. Give their optical, magnetic, and structural property, the nanoparticles have been proposed to be use in the development of unconventional treatments for cancer such as photodynamic therapy (PDT). In PDT, a photosensitizing agent is used that accumulates in tumor cells, generating reactive oxygen species that causes the death of malignant cells after irradiation with light at a particular wavelength. However, the use of PDT presents different problems in its application due to the characteristics of hydrophobicity of the photosensitizers, which hinder the efficiency of administration and treatment. It is here where the use of nanoparticles is proposed as a delivery vehicle to optimize treatment application. In this review we describe the use of nanoparticles coupled to PDT in the treatment of cancer and its molecular mechanism of action. PMID:25739488
NASA Astrophysics Data System (ADS)
Eaton, G. H.; Clarke-Gayther, M. A.; Scott, C. A.; Cox, S. F. J.; Kilcoyne, S. H.
The original pulsed surface muon facility was established at the Rutherford Appleton Laboratory's ISIS in 1987. The facility was then upgraded in 1993 from a single beam line and spectrometer to a triple beam facility with three spectrometers working independently. The layout of ISIS is shown. A plan of the ISIS experimental hall is shown, indicating the respective locations of the neutron beams, the KARMEN neutrino facility and the muon beam line complex. Other topics shown in the report include the following: (1) Muon production; (2) Transport of muons to the experimental areas; (3) Positron elimination from the ISIS muon beam; (4) Creation of three independent beam lines.
NASA Technical Reports Server (NTRS)
Armour, Edward A.G.
Muon catalyzed fusion is a process in which a negatively charged muon combines with two nuclei of isotopes of hydrogen, e.g, a proton and a deuteron or a deuteron and a triton, to form a muonic molecular ion in which the binding is so tight that nuclear fusion occurs. The muon is normally released after fusion has taken place and so can catalyze further fusions. As the muon has a mean lifetime of 2.2 microseconds, this is the maximum period over which a muon can participate in this process. This article gives an outline of the history of muon catalyzed fusion from 1947, when it was first realised that such a process might occur, to the present day. It includes a description of the contribution that Drachrnan has made to the theory of muon catalyzed fusion and the influence this has had on the author's research.
From molecular PDT damage to cellular PDT responses: attempts at bridging the gap on the role of Bcl-2
NASA Astrophysics Data System (ADS)
Usuda, Jitsuo; Xue, Liang-yan; Chiu, Song-mao; Azizuddin, Kashif; Morris, Rachel L.; Mulvihill, John; Oleinick, Nancy L.
Expression of the anti-apoptotic proteins Bcl-2 and/or Bcl-xL is greatly elevated in many advanced cancers, especially those resistant to standard therapies, such as radiation or chemotherapy. It has been suggested that those two proteins would be attractive targets for the development of new cancer treatments. Photodynamic therapy (PDT) with photosensitizers that localize in or target mitochondria, such as the phthalocyanine Pc 4, specifically attack the anti-apoptotic protein Bcl-2, generating a variety of oxidized, complexed, and cleaved photoproducts. The closely related protein Bcl-xL is also a target of Pc 4-PDT. In a recent study employing transient transfection of an expression vector encoding deletion mutants of Bcl-2, we identified the membrane anchorage regions of the protein that are required to form the photosensitive target. In spite of the demonstrated photodamage to Bcl-2 (and Bcl-xL), how the photodamage translates into changes in the sensitivity of cells to PDT-induced apoptosis or other modes of cell death is not clear, and it also remains unclear how elevated amounts of anti-apoptotic proteins in tumors might make them more or less responsive to PDT. In the present study, we have studied the PDT response of MCF7 human breast cancer cells overexpressing wild-type Bcl-2 or certain deletion mutants either in a transient or stable mode. We show that cells expressing modestly elevated amounts (<10-fold increase) of Bcl-2 and in which the pro-apoptotic protein Bax is not upregulated do not differ from the parental cells with respect to PDT-induced cell killing. In contrast, cells expressing higher amounts (>50-fold increase) of Bcl-2 or certain mutants are made significantly more resistant to the induction of apoptosis and the loss of clonogenicity upon exposure to Pc 4-PDT. In the presence of high levels of Bcl-2, extensive photodamage requires higher PDT doses. We conclude that Pc 4-PDT targets Bcl-2 and Bcl-xL, eliminating one mechanism that
Initial targets and cellular responses to PDT
NASA Astrophysics Data System (ADS)
Rodriguez, Myriam E.; Azizuddin, Kashif; Chiu, Song-mao; Delos Santos, Grace; Joseph, Sheeba; Xue, Liang-yan; Oleinick, Nancy L.
Pc 4, a photosensitizer first synthesized at Case Western Reserve University and now in clinical trial at University Hospitals of Cleveland, has been shown to bind preferentially and with high affinity to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components are photodamaged. In most cancer cells, apoptosis is triggered by the initial photodamage; however, in cells deficient in one of the critical intermediates of apoptosis, this process does not occur, although the cells remain as sensitive to the lethal effects of Pc 4-PDT as the apoptosis-competent cells, when cell death is determined by colony formation. Here we report that an alternative death process, autophagy, is induced in all cells tested and becomes the dominant pathway for elimination of lethally damaged cells when apoptosis is compromised. The anti-apoptotic protein Bcl-2, when overexpressed, protects only apoptosis-competent cells against loss of clonogenicity, while the autophagy inhibitor 3-methyladenine provides a markedly greater protection to apoptosis-deficient cells. The results suggest that the primary determinant of cell death is not the final pathway for elimination of the cells but the initial photodamage to critical membrane targets. In attempts to identify those targets, we have studied the role of different membrane phospholipids in the localization of Pc 4. Cardiolipin (CL) is a phospholipid found exclusively in the mitochondrial inner membrane and at the contact sites between the inner and outer membranes. Previous fluorescence resonance energy transfer studies revealed colocalization of Pc 4 and CL, which points to CL as a possible binding site and target for Pc 4. Unilamellar liposomes with different lipid compositions were used as membrane models to test the affinity of Pc 4. As revealed by the binding constants, Pc 4 does not display preferential binding to CL in these systems. Moreover, binding affinities appear to be
Biological consequences of PDT: tying up the loose ends
NASA Astrophysics Data System (ADS)
Kessel, David; Andrzejak, Michelle; Price, Michael
While many of the determinants of photodynamic tumor eradication have been identified, the story is not yet complete. Fluorescent probes for reactive oxygen species (ROS) are seldom specific, and the role of different ROS in apoptosis vs. autophagy are not fully delineated. Moreover, the conflicting roles of autophagy as both a death and a survival pathway remain to be explained. Most tissue-culture studies are carried out in 20% oxygen although this is far in excess of the environment of malignant cells in vivo. And while apoptotic and/or autophagic death appears to account for the lethal effects of PDT, an effect on membrane recycling has now been identified. In this report, we summarize some recent experiments designed to examine the specificity of fluorescent ROS probes. We also demonstrate the ability of hydrogen peroxide to accelerate the autophagic response to PDT in an adhering cell line, the 1c1c7 murine hepatoma. In this cell line, autophagy appears to be a pro-survival mechanism since a sub-line (KD) depleted in a critical autophagy protein (atg7) was more responsive to PDT than wild-type (WT) cells. There are clearly multiple determinants of direct tumor cell kill by PDT that depend on the PDT target, the ROS produced and phenotypic variations.
Fluorescence Guided PDT for Optimization of Skin Cancer Treatment
NASA Astrophysics Data System (ADS)
Blanco, Kate; Moriyama, Lilian; Inada, Natalia; Kurachi, Cristina; Salvio, Ana; Leite, Everson; Menezes, Priscila; Bagnato, Vanderlei
The photodynamic therapy (PDT) is an alternative technique that can be indicated for superficial basal cell carcinoma (sBCC), Bowen's disease and actinic keratosis with high efficiency. The objective of this study is to present the importance of fluorescence imaging for PDT guidance and monitoring in real time. Confirming that the lesion is well prepared and the photosensitizer shows a homogenous distribution, the outcome after few PDT sessions will be positive and the recurrence should be lower. Our proposition in this study is use the widefield fluorescence imaging to evaluate the PDT protocol in situ and in real time for each lesion. This evaluation procedure is performed in two steps: first with the monitoring of the production of protoporphyrin IX (PpIX) induced by methyl aminolevulinate (MAL), an derivative of 5-aminolevulinic acid (ALA) and second with the detection of PpIX photobleaching after illumination. The fluorescence images provide information correlated with distinct clinical features and with the treatment outcome. Eight BCC lesions are presented and discussed in this study. Different fluorescence patterns of PpIX production and photobleaching could be correlated with the treatment response. The presented results show the potential of using widefield fluorescence imaging as a guidance tool to customized PDT.
NASA Technical Reports Server (NTRS)
Heinz, R.
An analysis of the multiple muon events in the Monopole Astrophysics and Cosmic Ray Observatory detector was conducted to determine the cosmic ray composition. Particular emphasis is placed on the interesting primary cosmic ray energy region above 2000 TeV/nucleus. An extensive study of muon production in cosmic ray showers has been done. Results were used to parameterize the characteristics of muon penetration into the Earth to the location of a detector.
NASA Astrophysics Data System (ADS)
Jiang, Chunhua
Muons are an unmistakable signature of most of the LHC physics is designed to explore. The ability to trigger on and reconstruct muons at highest luminorsities is central to the concept of CMS. CMS is characterized by simplicity of design, with one magnet whose solenoideal field facilitates precision racking in the central barrel region and triggering on muons through their bending in the tharnverse and side views. The CMS muon system has three purpose: muon identification, muon trigger and nuon momentum measurement.
Brain PDD and PDT unlocking the mystery of malignant gliomas.
Eljamel, M Sam
Malignant brain tumours (MBTs) have one of the worst outcomes of human cancers today and their incidence is on the increase. Current treatment failure is usually due to local recurrence of the tumour rather than distant metastasis. In the last three decades we have seen many novel and potentially effective treatment strategies rise rapidly to the rescue. Sadly, however, the majority of these approaches were not good enough to withstand the harsh reality of the sceptical gaze of the scientific eye or the stringent health economics of this millennium. PDD and PDT, however, is one of the few therapies fighting back and still standing today. The results of its randomised controlled trials are eagerly awaited. To date the literature suggests that both PDD and PDT significantly prolong the time to tumour progression, reduce local recurrence, increase radical resection and prolong overall survival of MBTs. PDD and PDT are well tolerated by patients and worthwhile pursuing. PMID:25048434
Potential of systemic photosensitizers for PDT of skin malignancies
NASA Astrophysics Data System (ADS)
Philipp, Carsten M.; Müller, Ute; Urban, Peter; Berlien, H.-Peter
Usually systemic photosensitizers (PS) require a long period of incubation (48-96h) after systemic admission. On the other hand clearing from healthy skin needs weeks or months. Severe side effects on skin are possible in case of uncontrolled light exposure. Topical PDT may solve this problem, but deep portions may not be sufficiently sensitized, resulting in a survival of some tumor cell population after PDT and recurrence. The same problem counts for actinic keratosis and Bowen's disease, but with even worse consequences as a resulting infiltrating growing squamous cell carcinoma (SCC) is likely to produce metastatic lesions. Light dosimetry is crucial also. Wavelenght, fluence and total energy may influence outcome of any PDT substantially. 17 patients with Bowen's disease or BCC where treated using a novel systemic PS (Fotolon ®) and 665nm light from a diode laser. Follow up time ranges between 2.5 and 1 years after treatment. 2 patients received a second PDT, in 15 patients one treatment was efficient. We found a remissions in 1, local control in 2 and no evidence of disease in 14 patients. Significant fluorescence was noted in all lesions. With a light protection protocol for only 48 hours no severe side effects where seen. One patient developed mild redness of sunlight exposed skin sites 24h after being discharged from light protection protocol. In comparison with currently available topical PS Fotolon ® offers some important advantages as secure photosenzitation of deep portions, single treatment, high selectivity combined with a high cure rate. In comparison with currently available systemic PS Fotolon ® offers short incubation time, high selectivity and short time of elimination, while efficiency was comparable to HPD (hematoporphyrin-derivate) PDT combined with ALA-5 PDT and without need for additional local PS-application for PDD.
Simple optical theory for light dosimetry during PDT (Invited Paper)
NASA Astrophysics Data System (ADS)
Jacques, Steven L.
Photons are one of the three major reactants in the photodynamic reaction that yields toxic photoproduct for cell killing. Dosimetry of light is a major concern when planning a photodynamic therapy (PDT) protocol. This paper presents a very simple approach toward the tissue optics with a practical conclusion about how tissue optics affects planning of day-to-day PDT dosimetry. The paper does not address all the complexities of real tissue dosimetry, such as heterogeneous tissues, variable absorption due to changing tissue blood content, and variable tissue oxygen levels. The paper outlines the optical behavior in a homogeneous tissue, which is a starting point for understanding light dosimetry.
Rational design of a receptor-targeted photodynamic molecular beacon for the multilevel control of singlet oxygen production and PDT activity in cancer cells
NASA Astrophysics Data System (ADS)
Chen, Juan; Stefflova, Klara; Warren, Mike; Bu, Jiachuan; Wilson, Brian C.; Zheng, Gang
Photodynamic therapy (PDT) involves the combined action of light, oxygen and a photosensitizer (PS). It offers unique control in the PS's action because the key cytotoxic agent, singlet oxygen (1O II), is only produced in situ upon irradiation. The 1O II production can be controlled in three levels. The first level involves the judicious use of fiber optics to selectively deliver light to disease tissues. The second level is to exert control over the PS's localization by selectively delivering PS to cancer cells. The third level is to exert control of the PS's ability to generate 1O II in responding to specific cancer biomarkers. Here, we present two PDT agents based on the latter two levels of 1O II control. The first PDT agent "PPF" contains a PS (Pyro) and a tumor homing molecule (folate) and a peptide linker. PPF was found to be selectively accumulated in cancer cells via folate receptor (FR) pathway. The second PDT agent "PP MMP7B" is a matrix metalloproteinase-7 (MMP7)-triggered photodynamic molecular beacon (PMB) containing a PS (Pyro), a 1O II quencher (BHQ3) and a MMP7-cleavable peptide linker. Thus, the 1O II production of PP MMP7B is highly sequence-specific and its photodynamic cytotoxicity is MMP7-dependent. Since these agents are designed to share functional modules (PS and peptide linker) and common cancer cell model (KB cells overexpress both FR and MMP7), it forms the basis for rational design of receptor-targeted PMB for achieving a multi-level control of 1O II production in cancer cells, which in term, could provide a much higher level of PDT selectivity.
Diffractively produced Z bosons in the muon decay channel in p-pbar collisions at s**(1/2) = 1.96 TeV, and the measurement of the efficiency of the D0 Run II luminosity monitor
Edwards, Tamsin L
The first analysis of diffractively produced Z bosons in the muon decay channel is presented, using data taken by the D0 detector at the Tevatron at {radical}s = 1.96 TeV. The data sample corresponds to an integrated luminosity of 109 pb{sup -1}. The diffractive sample is defined using the fractional momentum loss {zeta} of the intact proton or antiproton measured using the calorimeter and muon detector systems. In a sample of 10791 (Z/{gamma})* {yields} {mu}{sup +}{mu}{sup -} events, 24 diffractive candidate events are found with {zeta} < 0.02. The first work towards measuring the cross section times branching ratio for diffractive production of (Z/{gamma})* {yields} {mu}{sup +}{mu}{sup -} is presented for the kinematic region {zeta} < 0.02. The first work towards measuring the cross section times branching ratio for diffractive production of (Z/{gamma})* {yields} {mu}{sup +}{mu}{sup -} is presented for the kinematic region {zeta} < 0.02. The systematic uncertainties are not yet sufficiently understood to present the cross section result. In addition, the first measurement of the efficiency of the Run II D0 Luminosity Monitor is presented, which is used in all cross section measurements. The efficiency is: {var_epsilon}{sub LM} = (90.9 {+-} 1.8)%.
NASA Technical Reports Server (NTRS)
Edwards, P. G.; Protheroe, R. J.
The result of a new calculation of the atmospheric muon and neutrino fluxes and the energy spectrum of muon-neutrinos produced in individual extensive air showers (EAS) initiated by proton and gamma-ray primaries is reported. Also explained is the possibility of detecting atmospheric nu sub mu's due to gamma-rays from these sources.
Telecommunication using muon beams
Arnold, Richard C.
Telecommunication is effected by generating a beam of mu mesons or muons, varying a property of the beam at a modulating rate to generate a modulated beam of muons, and detecting the information in the modulated beam at a remote location.
Critical dosimetry measures and surrogate tools that can facilitate clinical success in PDT (Conference Presentation)
NASA Astrophysics Data System (ADS)
Pogue, Brian W.; Davis, Scott C.; Kanick, Stephen C.; Maytin, Edward V.; Pereira, Stephen P.; Palanisami, Akilan; Hasan, Tayyaba
Photodynamic therapy can be a highly complex treatment with more than one parameter to control, or in some cases it is easily implemented with little control other than prescribed drug and light values. The role of measured dosimetry as related to clinical adoption has not been as successful as it could have been, and part of this may be from the conflicting goals of advocating for as many measurements as possible for accurate control, versus companies and clinical adopters advocating for as few measurements as possible, to keep it simple. An organized approach to dosimetry selection is required, which shifts from mechanistic measurements in pre-clinical and early phase I trials, towards just those essential dose limiting measurements and a focus on possible surrogate measures in phase II/III trials. This essential and surrogate approach to dosimetry should help successful adoption of clinical PDT if successful. The examples of essential dosimetry points and surrogate dosimetry tools which might be implemented in phase II and higher trials are discussed for solid tissue PDT with verteporfin and skin lesion treatment with aminolevulinc acid.
A photobleaching-based PDT dose metric predicts PDT efficacy over certain BPD concentration ranges in a three-dimensional model of ovarian cancer
NASA Astrophysics Data System (ADS)
Anbil, S.; Rizvi, I.; Celli, J. P.; Alagic, N.; Hasan, T.
Photodynamic therapy (PDT) dosimetry is an active area of study that is motivated by the need to reliably predict treatment outcomes. Implicit dosimetric parameters, such as photosensitizer (PS) photobleaching, may indicate PDT efficacy and could establish a framework to provide patient-customized PDT. Here, tumor destruction and benzoporphryin-derivative (BPD) photobleaching are characterized by systematically varying BPD-light combinations to achieve fixed PDT doses (M * J * cm-2) in a three-dimensional (3D) model of micrometastatic ovarian cancer (OvCa). It is observed that the BPD-light parameters used to construct a given PDT dose significantly impact nodule viability and BPD photobleaching. As a result, PDT dose, when measured by the product of BPD concentration and fluence, does not reliably predict overall efficacy. A PDT dose metric that incorporates a term for BPD photobleaching more robustly predicts PDT efficacy at low concentrations of BPD. These results suggest that PDT dose metrics that are informed by implicit approaches to dosimetry could improve the reliability of PDT-based regimens and provide opportunities for patient-specific treatment planning.
Preclinical evaluation of zinc phthalocyanine tetrasulfonate-based PDT
NASA Astrophysics Data System (ADS)
Borgatti-Jeffreys, Antonella; Hooser, Stephen B.; Miller, Margaret A.; Thomas, Rose M.; deGortari, Amalia; Lucroy, Michael D.
Photodynamic therapy (PDT) involves the light activation of a drug within a tumor causing selective tumor cell death. Unfortunately, some photosensitizing drugs have been associated with adverse reactions in veterinary patients. Zinc phthalocyanine tetrasulfonate (ZnPcS4) is a promising second-generation photosensitizer for use in veterinary medicine, however, it cannot be applied clinically until safety and efficacy data are available. ZnPcS4 was given to Swiss Webster mice to assess acute toxicity. Doses >100 mg/kg were associated with acute toxicity and mortality, and doses >100 mg/kg resulted in renal tubular nephrosis, suggesting that the minimum toxic dose is approximately 100 mg/kg. Based on these data, a Phase I clinical trial of ZnPcS4-based PDT in tumor-bearing dogs is underway, with ZnPcS4 doses up to 2 mg/kg producing no apparent toxicity. Tumor response has been observed after ZnPcS4-based PDT using doses as low as 0.25 mg/kg, suggesting that conventional phase I clinical trials may not be appropriate for PDT protocols.
PDT: Photometric DeTrending Algorithm Using Machine Learning
NASA Astrophysics Data System (ADS)
Kim, Dae-Won
PDT removes systematic trends in light curves. It finds clusters of light curves that are highly correlated using machine learning, constructs one master trend per cluster and detrends an individual light curve using the constructed master trends by minimizing residuals while constraining coefficients to be positive.
In vivo light dosimetry for HPPH-mediated pleural PDT
NASA Astrophysics Data System (ADS)
Dimofte, Andreea; Zhu, Timothy C.; Finlay, Jarod C.; Cullighan, Melissa; Edmonds, Christine E.; Friedberg, Joseph S.; Cengel, Keith; Hahn, Stephen M.
This study examines the light fluence (rate) delivered to patients undergoing pleural PDT as a function of treatment time, treatment volume and surface area. The accuracy of treatment delivery is analyzed as a function of the calibration accuracies of each isotropic detector and the calibration integrating sphere. The patients studied here are enrolled in a Phase I clinical trial of HPPH-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. Patients are administered 4mg per kg body weight HPPH 24-48 hours before the surgery. Patients undergoing photodynamic therapy (PDT) are treated with light therapy with a fluence of 15-60 J/cm2 at 661nm. Fluence rate (mW/cm2) and cumulative fluence (J/cm2) is monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors are used for in-vivo light dosimetry. The anisotropy of each isotropic detector was found to be within 15%. The mean fluence rate delivery and treatment time are recorded. A correlation between the treatment time and the treatment volume is established. The result can be used as a clinical guideline for future pleural PDT treatment.
Techport Input for Propulsive Descent Technologies (PDT) Project
NASA Technical Reports Server (NTRS)
Campbell, Charles H.
The PDT project will investigate the use of retro propulsion during the supersonic phase of atmospheric entry for Mars missions. The project technical approach involves a combination of procurement and evaluation of commercially provided flight data, development of candidate vehicle configurations, and engineering calibration of computational fluid dynamics models to the available flight data.
PDT in periodontal disease of HAART resistance patients
NASA Astrophysics Data System (ADS)
Giovani, Elcio M.; Noro-Filho, Gilberto A.; Caputo, Bruno V.; Casarin, Renato; Costa, Claudio; Salgado, Daniela; Santos, Camila C.
HIV/Aids patients present a change of microbiota associated with host immunodeficiency. Photodynamic therapy (PDT) showed as a promising and viable alternative in reducing microbiota. Present study evaluate effectiveness of photodynamic therapy in periodontal disease of AIDS patients with highly activity antiretroviral therapy (HAART) failure, measuring the clinical periodontal parameters and periodontal microbiota. Twelve patients with HARRT resistance (R group) divided into two groups (control and PDT) and 12 patients with no HAART resistance (NR group) divided into two groups (control and PDT). The results show the difference in baseline of CD4 cells count, NR group 640.0 +/- 176.2 cells/mm3 R group and 333.3 +/- 205.8 cells / mm3 (p<0.05), and in 8.3% detectable viral load in NR group and 75% detectable (p <0.001) in R group. As clinical periodontal parameters (PD and CAL), PDT was more effective than the control group only in the NR group (p <0.05%), moreover, there was no difference in the evaluation of clinical periodontal parameters between the both R groups (p>0.05%). Microbiological evaluation in R group presents a general reduction in the Aa at 3 and 6 months. Furthermore, demonstrated a reduction of Pg in all groups at 6 months and in R group at 3 months. The impact assessment of photodynamic therapy in patients with different levels of immunosuppression determined that the combination of mechanical periodontal treatment with photodynamic therapy in patients with HAART failure did not cause additional benefits. Therefore, PDT in this study could not been indicated in HAART resistance patients.
Underwater measurements of muon intensity
NASA Technical Reports Server (NTRS)
Fedorov, V. M.; Pustovetov, V. P.; Trubkin, Y. A.; Kirilenkov, A. V.
Experimental measurements of cosmic ray muon intensity deep underwater aimed at determining a muon absorption curve are of considerable interest, as they allow to reproduce independently the muon energy spectrum at sea level. The comparison of the muon absorption curve in sea water with that in rock makes it possible to determine muon energy losses caused by nuclear interactions. The data available on muon absorption in water and that in rock are not equivalent. Underground measurements are numerous and have been carried out down to the depth of approx. 15km w.e., whereas underwater muon intensity have been measured twice and only down to approx. 3km deep.
Muon Collider Progress: Accelerators
Zisman, Michael S.
A muon collider would be a powerful tool for exploring the energy-frontier with leptons, and would complement the studies now under way at the LHC. Such a device would offer several important benefits. Muons, like electrons, are point particles so the full center-of-mass energy is available for particle production. Moreover, on account of their higher mass, muons give rise to very little synchrotron radiation and produce very little beamstrahlung. The first feature permits the use of a circular collider that can make efficient use of the expensive rf system and whose footprint is compatible with an existing laboratory site. The second feature leads to a relatively narrow energy spread at the collision point. Designing an accelerator complex for a muon collider is a challenging task. Firstly, the muons are produced as a tertiary beam, so a high-power proton beam and a target that can withstand it are needed to provide the required luminosity of ~1 × 10{sup 34} cm{sup –2}s{sup –1}. Secondly, the beam is initially produced with a large 6D phase space, which necessitates a scheme for reducing the muon beam emittance ("cooling"). Finally, the muon has a short lifetime so all beam manipulations must be done very rapidly. The Muon Accelerator Program, led by Fermilab and including a number of U.S. national laboratories and universities, has undertaken design and R&D activities aimed toward the eventual construction of a muon collider. Design features of such a facility and the supporting R&D program are described.
Zisman, Michael S.
We describe the scientific motivation for a new type of accelerator, the muon collider. This accelerator would permit an energy-frontier scientific program and yet would fit on the site of an existing laboratory. Such a device is quite challenging, and requires a substantial R&D program. After describing the ingredients of the facility, the ongoing R&D activities of the Muon Accelerator Program are discussed. A possible U.S. scenario that could lead to a muon collider at Fermilab is briefly mentioned.
NASA Technical Reports Server (NTRS)
Stanev, T.
The first generation of large and precise detectors, some initially dedicated to search for nucleon decay has accumulated significant statistics on neutrinos and high-energy muons. A second generation of even better and bigger detectors are already in operation or in advanced construction stage. The present set of experimental data on muon groups and neutrinos is qualitatively better than several years ago and the expectations for the following years are high. Composition studies with underground muon groups, neutrino detection, and expected extraterrestrial neutrino fluxes are discussed.
Neutrino physics at muon colliders
King, B.J.
An overview is given of the neutrino physics potential of future muon storage rings that use muon collider technology to produce, accelerate and store large currents of muons. After a general characterization of the neutrino beam and its interactions, some crude quantitative estimates are given for the physics performance of a muon ring neutrino experiment (MURINE) consisting of a high rate, high performance neutrino detector at a 250 GeV muon collider storage ring.
Antimicrobial photodynamic therapy with RLP068 kills methicillin-resistant Staphylococcus aureus and improves wound healing in a mouse model of infected skin abrasion PDT with RLP068/Cl in infected mouse skin abrasion.
Vecchio, Daniela; Dai, Tianhong; Huang, Liyi; Fantetti, Lia; Roncucci, Gabrio; Hamblin, Michael R
Photodynamic therapy (PDT) is an alternative treatment for infections that can kill drug resistant bacteria without damaging host-tissue. In this study we used bioluminescent methicillin-resistant Staphylococcus aureus, in a mouse skin abrasion model, to investigate the effect of PDT on bacterial inactivation and wound healing. RLP068/Cl, a tetracationic Zn(II)phthalocyanine derivative and toluidine blue (TBO) were used. The light-dose response of PDT to kill bacteria in vivo and the possible recurrence in the days post-treatment were monitored by real-time bioluminescence imaging, and wound healing by digital photography. The results showed PDT with RLP068/Cl (but not TBO) was able to kill bacteria, to inhibit bacterial re-growth after the treatment and to significantly accelerate the wound healing process (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim). PMID:22987338
Susceptibility of representative dental pathogens to inactivation by the PDT with water-soluble photosensitizers
NASA Astrophysics Data System (ADS)
Angelov, Ivan; Mantareva, Vanya; Kussovski, Veselin; Worle, Diter; Kisov, Hristo; Belcheva, Marieta; Georgieva, Tzvetelina; Dimitrov, Slavcho
In the recent decade the applications of photodynamic therapy (PDT) rapidly increase in several topics and one of areas where the PDT in the future will be play significant role is dentistry. The different photosensitizing complexes with a good water solubility and with absorption with an intensive maximum in the red region (630-690 nm), which makes them suitable for photodynamic treatments, were investigated. The photochemical properties of complexes for singlet oxygen generation were investigated and were shown relations between uptake levels and light intensity to achieve increase in photodynamic efficacy. Photodynamic efficacy against fungi Candida albicans and bacteria's E. faecalis, MRSA and S. Mutans in planktonic media was evaluated. The high photodynamic efficacy was shown for SiPc at very low concentrations (0.9 μM) and light doses of 50 J cm-2 by intensity of light 60 mW cm-2. The photodynamic response for E. faecalis, MRSA and S. Mutans, after treatments with different photosensitizers show strong dependence on concentrations of photsensitzers and micro organisms. The level of inactivation of the pathogen bacteria's from 1-2 degree of initial concentration up to full inactivation was observed. The studied complexes were compared to the recently studied Methylene blue, Haematoporphyrine and tetra-methylpirydiloxy Zn(II)- phthalocyanines and experimental results show that some of them have a good potential for inactivation of representative pathogenic bacterial strains. Experimental results also indicate that photodynamic therapy appears an effective method for inactivation of oral pathogenic bacterias and fungi.
Susceptibility of representative dental pathogens to inactivation by the PDT with water-soluble photosensitizers
NASA Astrophysics Data System (ADS)
Angelov, Ivan; Mantareva, Vanya; Kussovski, Veselin; Worle, Diter; Kisov, Hristo; Belcheva, Marieta; Georgieva, Tzvetelina; Dimitrov, Slavcho
In the recent decade the applications of photodynamic therapy (PDT) rapidly increase in several topics and one of areas where the PDT in the future will be play significant role is dentistry. The different photosensitizing complexes with a good water solubility and with absorption with an intensive maximum in the red region (630-690 nm), which makes them suitable for photodynamic treatments, were investigated. The photochemical properties of complexes for singlet oxygen generation were investigated and were shown relations between uptake levels and light intensity to achieve increase in photodynamic efficacy. Photodynamic efficacy against fungi Candida albicans and bacteria's E. faecalis, MRSA and S. Mutans in planktonic media was evaluated. The high photodynamic efficacy was shown for SiPc at very low concentrations (0.9 μM) and light doses of 50 J cm-2 by intensity of light 60 mW cm-2. The photodynamic response for E. faecalis, MRSA and S. Mutans, after treatments with different photosensitizers show strong dependence on concentrations of photsensitzers and micro organisms. The level of inactivation of the pathogen bacteria's from 1-2 degree of initial concentration up to full inactivation was observed. The studied complexes were compared to the recently studied Methylene blue, Haematoporphyrine and tetra-methylpirydiloxy Zn(II)- phthalocyanines and experimental results show that some of them have a good potential for inactivation of representative pathogenic bacterial strains. Experimental results also indicate that photodynamic therapy appears an effective method for inactivation of oral pathogenic bacterias and fungi.
NASA Astrophysics Data System (ADS)
Clayden, N. J.
Positive muons have long been used as extrinsic probes in chemistry, offering unique properties for the investigation of local magnetism, dynamics, transport and radical kinetics. Exciting new developments in muon beam lines offer the opportunity of extending these studies selectively to surfaces permitting, for example, the detection of increased mobility of polymer chains at the surface of a polymer film. So called pump and probe methods, involving external perturbations by laser irradiation to manipulate vibrational and electronic states, can be followed by muon pulses allowing the probing of the properties of these states. Muoniated radical probes are finding greater use in soft matter. Selectivity is achieved in these complex systems through an appropriate target molecule giving the chance to measure partitioning and interfacial transfer in surfactant systems. Improvements in sample environments allow the observation of muons in increasingly extreme combinations of temperature and pressure, such as supercritical water, allowing the characterization of the chemistry in these systems.
Study of atmospheric muons using a cosmic ray telescope
NASA Astrophysics Data System (ADS)
Abdollahi, S.; Bahmanabadi, M.; Purmohammad, D.
The charge ratio of cosmic muons holds important information for both the atmospheric neutrino anomaly and hadronic interaction models. In this paper we measured the muon charge ratio (R_{\\mu }=N_{\\mu ^{+}}/N_{\\mu ^{-}}) in the cosmic ray flux in the momenta range 0.76-1.60 GeV/c by using a cosmic ray telescope. The delayed coincidence method is used based on the reduced mean lifetime of negative muons due to nuclear capture in matter. The systematic time-dependent effects of the muon charge ratio are considered by grouping the decay data into different time intervals. We compared the experimental data with the predictions of CORSIKA simulations using a high energy interaction model (QGSJET-II) and two low energy interaction models (UrQMD and GHEISHA) in the energy range 1011-1016 eV for primary particles. In addition, by considering the muon flux in different zenithal and azimuthal angles, the muon angular distribution is obtained as I(θ) = I(0)cos nθ with average n = 1.91 ± 0.07. Dependence of the muon flux on the azimuth angle (the East-West effect) is also observed, due to the influence of the geomagnetic field in particular on low energy muons.
Fast cooling, muon acceleration and the prospect of muon colliders
NASA Astrophysics Data System (ADS)
Palmer, Mark
Facilities based on stored muons offer unique potential for future high-energy physics capabilities. Three key characteristics of the muon make this possible: * The muon is a lepton; * The muon is roughly 200 times as massive as the electron; * The muon decays to an electron and two neutrinos. As the next heavier members of the lepton family with respect to the electron and positron, μ+ and μ-. beams can be collided to provide a precision lepton probe of the electroweak couplings. This makes a muon collider a suitable option for a lepton collider companion to a hadron collider discovery machine...
Ptochos, F.; /Cyprus U.
We report a study of multi-muon events produced at the Fermilab Tevatron collider and recorded by the CDF II detector. In a data set acquired with a dedicated dimuon trigger and corresponding to an integrated luminosity of 2100 pb{sup -1}, we isolate a significant sample of events in which at least one of the identified muons has large impact parameter and is produced outside the beam pipe of radius 1.5 cm. We are unable to fully account for the number and properties of the events through standard model processes in conjunction with our current understanding of the CDF II detector, trigger and event reconstruction. Several topological and kinematic properties of these events are also presented. In contrast, the production cross section and kinematics of events in which both muon candidates are produced inside the beam pipe are successfully modeled by known QCD processes which include heavy flavor production. The presence of these anomalous multi-muon events offers a plausible resolution to long-standing inconsistencies related to b{bar b} production and decay.
Endobronchial occlusive disease: Nd:YAG or PDT?
NASA Astrophysics Data System (ADS)
Regal, Anne-Marie; Takita, Hiroshi
Patients with endobronchial occlusion commonly experience dyspnea, cough, hemoptysis, pneumonitis, and atelectasis. If luminal patency is not re-established, obstructive symptoms may progress to sepsis and death. Although the overall survival of patients with lung cancer may not be altered by relief of airway obstruction, the prognosis for this subset of patients may be improved by eliminating the septic complications of bronchial occlusion. Techniques to treat occluded bronchi include electro-fulguration, cryotherapy, brachytherapy, laser (CO2, Nd-YAG) therapy, and photodynamic therapy (PDT). These represent local forms of treatment and are intended to be palliative. Nd-YAG and PDT are the modalities more frequently utilized in this setting. Comparison of the two treatment forms may furnish insight regarding the appropriate role for each as individual therapies and as part of the armamentarium of cancer therapies.
Ultrasound-guided interventional PDT of liver cancer
NASA Astrophysics Data System (ADS)
Zeng, Chaoying; Yang, Dong; Huang, Ping; Zhang, Huijuan; Huang, Muyin; Chen, Ji; Lu, Guorong
Thirty patients with advanced liver cancer were treated by interstitial photodynamic therapy (PDT). These included 28 hepatocellular carcinoma and two adenocarcinoma, 19 primary tumors and 11 recurred follow other treatments. The diameter of tumors were 7-10cm in 13 cases and 10-16cm in 17 cases. In this study, an argon laser pumped dye laser system was used to give a CW laser beam at 630 nm which was split and coupled into there optical fibers. The patients were injected intravenously with photosensitizer hematoporphyrin derivative at a dose of 5mg/kg body weight 48 hours before PDT. Then the fibers were inserted into tumor by ultrasound- guided percutaneous puncture. The inserted irradiation points were spaced in entire tumor with the light release power 300mW and the irradiation time 12 minutes per point. Total 52 treatments were performed in 30 patients. Among them, 14 cases were treated only one time and 16 cases via 2-3 times. The follow-up was carried out in 25 cases for 12- 24 months. The results show that significant remission was 22 percent in those patients by only one treatment and 62 percent in those via 2 to 3 treatments. The shrink rate of tumor size was over 90 percent in five of six cases after treatment 3. The survival time has been over one year in 12 cases. No obvious change to be found for all patients in liver function test, renal function test and blood routine examination. The level of AFP indicated a descending trend after PDT. This work indicate that PDT is effective and safe for the treatment of large liver cancers including those recurred follow hepatic resection and those failed in hepatic artery infusion embolic chemotherapy.
Mars Mission Scenario: Data Volume and PDT Notes
NASA Technical Reports Server (NTRS)
Hemmati, Hamid; Biswas, A.; Piazzolla, S.; Townes, S.
Objectives of this work are: (1) Investigate methods for quantifying the value of interoperability for deep space missions: A network of optical receive stations Each one potentially owned by a different space agency. Reduces overall cost to any individual agency Provides geographically diverse locations to mitigate weather problems (clouds, wind, rain, dust, etc.) (2) Metrics: a. Total data volume returned over mission duration b. Percent data transferred (PDT) or something similar.
Light dosimetry and dose verification for pleural PDT
NASA Astrophysics Data System (ADS)
Dimofte, Andreea; Sharikova, Anna V.; Meo, Julia L.; Simone, Charles B.; Friedberg, Joseph S.; Zhu, Timothy C.
In-vivo light dosimetry for patients undergoing photodynamic therapy (PDT) is critical for predicting PDT outcome. Patients in this study are enrolled in a Phase I clinical trial of HPPH-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. They are administered 4mg per kg body weight HPPH 48 hours before the surgery and receive light therapy with a fluence of 15-45 J/cm2 at 661 and 665nm. Fluence rate (mW/cm2) and cumulative fluence (J/cm2) are monitored at 7 sites during the light treatment delivery using isotropic detectors. Light fluence (rate) delivered to patients is examined as a function of treatment time, volume and surface area. In a previous study, a correlation between the treatment time and the treatment volume and surface area was established. However, we did not include the direct light and the effect of the shape of the pleural surface on the scattered light. A real-time infrared (IR) navigation system was used to separate the contribution from the direct light. An improved expression that accurately calculates the total fluence at the cavity wall as a function of light source location, cavity geometry and optical properties is determined based on theoretical and phantom studies. The theoretical study includes an expression for light fluence rate in an elliptical geometry instead of the spheroid geometry used previously. The calculated light fluence is compared to the measured fluence in patients of different cavity geometries and optical properties. The result can be used as a clinical guideline for future pleural PDT treatment.
Fractionated PDT with 5-aminolevulinic acid: effective, cost effective, and patient friendly
NASA Astrophysics Data System (ADS)
de Vijlder, Hannah C.; Middelburg, Tom A.; de Bruijn, Henriette S.; Robinson, Dominic J.; Neumann, H. A. Martino; de Haas, Ellen R. M.
PDT with ALA and MAL is established as a relatively effective treatment for non-melanoma skin cancer and premalignancies. PDT is often repeated, because a single treatment gives poor long term results. Preclinical studies showed that ALA-PDT applying a fractionated illumination scheme with a small first light fraction and a second larger light fraction separated by a dark interval of two hours resulted in a significant increase in efficacy. Whereas the efficacy was not enhanced by fractionating MAL-PDT, indicating that ALA-PDT mechanism is not the same as MAL-PDT mechanism. The increase in efficacy using fractionated PDT was confirmed clinically. A randomized comparative clinical study comparing fractionated ALA-PDT versus non-fractionated ALA-PDT in the treatment of superficial basal cell carcinoma showed a significant higher response rate in the lesions treated with fractionated ALA-PDT after a follow-up of one year ( p<0.002, log-rank test). The five year follow-up is studied at moment. So far the complete response in the group treated with fractionated ALA-PDT seems to be only a few percentages lower compared to the one year follow-up. Besides the gain in response rate, fractionated ALA PDT is cost effective. ALA gel is less expensive than the commercially available MAL (Metvix) and moreover fractionated ALA-PDT takes one treatment day, instead of two treatment days using the Metvix treatment protocol (two MAL-PDT treatments separated by one week), both reducing direct and indirect costs and the burden to the patient.
The in Vitro Antimicrobial Efficacy of PDT against Periodontopathogenic Bacteria
Haag, Philippe A.; Steiger-Ronay, Valerie; Schmidlin, Patrick R.
Periodontitis, an inflammatory disease, is caused by biofilms with a mixed microbial etiology and involves the progressive destruction of the tooth-supporting tissues. A rising number of studies investigate the clinical potential of photodynamic therapy (PDT) as an adjunct during active therapy. The aim of the present review was to evaluate the available literature for the in vitro antimicrobial efficacy of photodynamic therapy focusing on the periodontopathogenic bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. The focused question was: "Is it possible to decrease (at least 3 log steps or 99.9%) or even eliminate bacterial growth by photodynamic therapy in vitro when compared to untreated control groups or control groups treated by placebo?" In general, PDT resulted in a substantial reduction of surviving bacteria. However, not all studies showed the desired reduction or elimination. The ranges of log10-reduction were 0.38 (58%) to a complete eradication (100%) for P. gingivalis, 0.21 (39%) to 100% for A. actinomycetemcomitans and 0.3 (50%) to 100% for F. nucleatum. In conclusion, further and particularly more comparable studies are needed to evaluate if PDT can be clinically successful as an adjuvant in periodontal therapy. PMID:26580607
Using iron chelating agents to enhance dermatological PDT
NASA Astrophysics Data System (ADS)
Curnow, Alison; Dogra, Yuktee; Winyard, Paul; Campbell, Sandra
Topical protoporphyrin IX (PPIX) induced photodynamic therapy (PDT) of basal cell carcinoma (BCC) produces good clinical outcomes with excellent cosmesis as long as the disease remains superficial. Efficacy for nodular BCC however appears inferior to standard treatment unless repeat treatments are performed. Enhancement is therefore required and is possible by employing iron chelating agents to temporarily increase PPIX accumulation above the levels normally obtained using aminolevulinic acid (ALA) or the methyl ester of ALA (MAL) alone. In vitro studies investigated the effect of the novel iron chelator, CP94 on necrotic or apoptotic cell death in cultured human skin fibroblasts and epidermal carcinoma cells incubated with MAL. Furthermore, following a dose escalating safety study conducted with ALA in patients, an additional twelve nodular BCCs were recruited for topical treatment with standard MAL-PDT +/- increasing doses of CP94. Six weeks later following clinical assessment, the whole treatment site was excised for histological analysis. CP94 produced greater cell death in vitro when administered in conjunction with MAL than this porphyrin precursor could produce when administered alone. Clinically, PDT treatment using Metvix + CP94 was a simple and safe modification associated with a trend of reduced tumor thickness with increasing CP94 dose.
PDT-treated apoptotic cells induce macrophage synthesis NO
NASA Astrophysics Data System (ADS)
Song, S.; Xing, D.; Zhou, F. F.; Chen, W. R.
Nitric oxide (NO) is a biologically active molecule which has multi-functional in different species. As a second messenger and neurotransmitter, NO is not only an important regulatory factor between cells' information transmission, but also an important messenger in cell-mediated immunity and cytotoxicity. On the other side, NO is involving in some diseases' pathological process. In pathological conditions, the macrophages are activated to produce a large quantity of nitric oxide synthase (iNOS), which can use L-arginine to produce an excessive amount of NO, thereby killing bacteria, viruses, parasites, fungi, tumor cells, as well as in other series of the immune process. In this paper, photofrin-based photodynamic therapy (PDT) was used to treat EMT6 mammary tumors in vitro to induce apoptotic cells, and then co-incubation both apoptotic cells and macrophages, which could activate macrophage to induce a series of cytotoxic factors, especially NO. This, in turn, utilizes macrophages to activate a cytotoxic response towards neighboring tumor cells. These results provided a new idea for us to further study the immunological mechanism involved in damaging effects of PDT, also revealed the important function of the immune effect of apoptotic cells in PDT.
Approaches to a broad range of high performance PDT sensitizers
NASA Astrophysics Data System (ADS)
d'A. Rocha Gonsalves, António M.; Serra, Arménio C.; Pineiro, Marta; Botelho, M. Filomena
Starting from expertise in the area of chemical synthesis, particularly in tetrapyrrolic macrocycles and an interest in modelling structures for particular objectives, we came to the point of aiming at modelling photochemical sensitizers designed for photodynamic therapy (PDT) purposes. Our endeavours were gratifying when it was proved that our synthetic methodologies allowed for the easy availability of properly halogenated porphyrins with high quantum yield singlet oxygen efficiency. Joining the presence of this heavy atom and other functionalities as substituents in selected positions of macrocyclic structures we were able to generate novel porphyrin structures whose photophysical and photochemical properties, singlet oxygen formation quantum yields, photobleaching and logP were measured. Cellular uptake measurements and cytotoxicity assays on WiDr adenocarcinoma and A375 tumor cell lines were carried out and some of our porphyrins demonstrated very high performance as PDT sensitizers comparatively to known compounds approved for clinical use and in the market. Further developments of our studies allowed for the generation of different and more efficient structures, easily made available by our own synthetic methodologies. Our studies in this area allowed us to reach a stage which we believe to correspond to a significant knowledge and capacity to synthesise a broad range of simple structures, whose selectivity and efficiency as PDT sensitizers can be modulated for different cellular and tissue specificities. Our most recent developments in this area will be presented in this communication.
PDT-induced apoptosis in arterial smooth muscles cells
NASA Astrophysics Data System (ADS)
Nyamekye, Isaac; Renick, R.; Gilbert, C.; McEwan, Jean R.; Evan, G.; Bishop, Christopher C. R.; Bown, Stephen G.
PDT kills smooth muscle cells (SMC) in vivo and thus prevents intimal hyperplasia after angioplasty. It causes little inflammation and structural integrity of the artery is not compromised. We have studied the process of the SMC death in vitro. Cultured rat SMC (cell line sv40 ATCC) were sensitized with aluminum disulphonated phthalocyanine (AlS2Pc), and then irradiated with 675 nm laser light (2.5 J/cm2). Controls were studied using only sensitizer or laser for treatment. The cells were incubated and the dying process observed with a time lapse video and microscope system. PDT caused a characteristic pattern of death. Cells lost contact with neighbors, shrank, and showed hyperactivity and membrane ruffling. The cells imploded into active and condensed membrane bound vesicles which were terminally reduced to residual bodies. These are the morphological changes of apoptosis. The control cells which were given AlS2Pc alone or laser alone showed no death. PDT induced cultured arterial SMC death by apoptosis rather than necrosis. An apoptotic mechanism of cell death in vivo would explain the relative lack of inflammation and local tissue destruction in the face of massive death.
Balancing particle absorption with structural support of the muon beam stop in muons-to-electrons experimental chamber
Majewski, Ryan
The Mu2e experiment at Fermi National Accelerator Laboratory is seeking a full conversion from muon to electron. The design for Mu2e is based off MECO, another proposed experiment that sought a full conversion from muon to electron at Brookhaven National Laboratory in the 1990s. Mu2e will provide sensitivity that is four times the sensitivity of the previous experiment, SINDRUM II. Discovering muon to electron conversions could help explain physics beyond the standard model of the particle physics.
Adjuvant photodynamic therapy (PDT) with photosensitizer photosens for superficial bladder cancer: experimental investigations to treat prostate cancer by PDT with photosens
NASA Astrophysics Data System (ADS)
Apolikhin, Oleg I.; Chernishov, Igor V.; Sivkov, Andrey V.; Altunin, Denis V.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.
14 patients with transional-cell bladder cancer in stage T1N0M0G2 after transurethral bladder resection were offered adjuvant treatment with PDT. Adjuvant PDT was performed 1-1.5 months after transurethral bladder resection for superficial bladder cancer. Prior to PDT conventional and fluorescent cystoscopy were performed. In the absence of inflammation and after full epitalisation of postoperative wound a session of therapy was performed. 24 hours prior to PDT-session photosensitizer Photosens was injected intravenously in the dose of 0.8 mg per kg of body weight. Prior to PDT local anesthesia of urethra with lidocain-gel was performed. Cystoscopy was carried out. PDT was performed with diode laser "Biospec" (675 nm). During the session the place of standing diffuser and the volume of a bladder were controlled. After 7 months of observation no tumor recidivists were observed. Registered side effects were not life-threatened. 5 patients had pain or discomfort in suprapubic area, ceasing spontaneously or requiring administration of analgetics. No systemic side-effects or allergic reactions were observed. The method can be used in out-patient practice. Absence of early recidivists shows efficiency of PDT in the treatment of superficial bladder cancer. Further study is necessary to estimate optimal regimen of PDT. The further controlling of condition on the patients in this group is required. At the laboratory animals' experiment, we conducted the explorations devoted to the influence of the photodynamic effect at the prostate's tissues.
NASA Astrophysics Data System (ADS)
Gorringe, T. P.; Hertzog, D. W.
The muon is playing a unique role in sub-atomic physics. Studies of muon decay both determine the overall strength and establish the chiral structure of weak interactions, as well as setting extraordinary limits on charged-lepton-flavor-violating processes. Measurements of the muon's anomalous magnetic moment offer singular sensitivity to the completeness of the standard model and the predictions of many speculative theories. Spectroscopy of muonium and muonic atoms gives unmatched determinations of fundamental quantities including the magnetic moment ratio μμ /μp, lepton mass ratio mμ /me, and proton charge radius rp. Also, muon capture experiments are exploring elusive features of weak interactions involving nucleons and nuclei. We will review the experimental landscape of contemporary high-precision and high-sensitivity experiments with muons. One focus is the novel methods and ingenious techniques that achieve such precision and sensitivity in recent, present, and planned experiments. Another focus is the uncommonly broad and topical range of questions in atomic, nuclear and particle physics that such experiments explore.
Fukushima Daiichi Muon Imaging
NASA Astrophysics Data System (ADS)
Miyadera, Haruo
Japanese government announced cold-shutdown condition of the reactors at Fukushima Daiichi by the end of 2011, and mid- and long-term roadmap towards decommissioning has been drawn. However, little is known for the conditions of the cores because access to the reactors has been limited by the high radiation environment. The debris removal from the Unit 1 - 3 is planned to start as early as 2020, but the dismantlement is not easy without any realistic information of the damage to the cores, and the locations and amounts of the fuel debris. Soon after the disaster of Fukushima Daiichi, several teams in the US and Japan proposed to apply muon transmission or scattering imagings to provide information of the Fukushima Daiichi reactors without accessing inside the reactor building. GEANT4 modeling studies of Fukushima Daiichi Unit 1 and 2 showed clear superiority of the muon scattering method over conventional transmission method. The scattering method was demonstrated with a research reactor, Toshiba Nuclear Critical Assembly (NCA), where a fuel assembly was imaged with 3-cm resolution. The muon scattering imaging of Fukushima Daiichi was approved as a national project and is aiming at installing muon trackers to Unit 2. A proposed plan includes installation of muon trackers on the 2nd floor (operation floor) of turbine building, and in front of the reactor building. Two 7mx7m detectors were assembled at Toshiba and tested.
Muon Reconstruction and Identification in CMS
Everett, A.
We present the design strategies and status of the CMS muon reconstruction and identification identification software. Muon reconstruction and identification is accomplished through a variety of complementary algorithms. The CMS muon reconstruction software is based on a Kalman filter technique and reconstructs muons in the standalone muon system, using information from all three types of muon detectors, and links the resulting muon tracks with tracks reconstructed in the silicon tracker. In addition, a muon identification algorithm has been developed which tries to identify muons with high efficiency while maintaining a low probability of misidentification. The muon identification algorithm is complementary by design to the muon reconstruction algorithm that starts track reconstruction in the muon detectors. The identification algorithm accepts reconstructed tracks from the inner tracker and attempts to quantify the muon compatibility for each track using associated calorimeter and muon detector hit information. The performance status is based on detailed detector simulations as well as initial studies using cosmic muon data.
Photodynamic therapy (PDT) in advanced inoperable bronchial carcinoma
NASA Astrophysics Data System (ADS)
Moghissi, Keyvan; Dixon, Kate; Stringer, Mark R.; Brown, Stanley B.
Objective: To assess the efficacy of PDT to: Palliate symptoms, control disease and extend survival in patients with advanced inoperable cancer. Subject and Method: 55 Males and 23 females aged between 45-81 years (mean 66 years) with inoperable and advanced lung cancer with > 5O. obstructive lesions of the main, lobar or segmental bronchi. Patients had pre-treatment routine clinical radiological, functional and endoscopic assessment with proven histological diagnosis. Protocol of PDT was; Intravenous injection of 2 mg/Kg bodyweight Polyhaematoporphyrin (equivalent to Photofrin) or Photofrin followed 24-72 hours later by illumination of tumour using 630 nm light (Oxford Laser) delivered via an optical fibre with end diffuser. Treatments were carried out under general anaesthesia as a day case procedure. Patients were rebronchoscoped for debridement/retreatment 4-7 days later. Results: There was no treatment related mortality. Two patients developed mild photosensitivity reaction. All patients showed symptomatic improvement with good initial functional and radiological amelioration. Every patient responded to treatment. Seven patients had complete response and negative histology for 3-12 months. After the first treatment average Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) improvement was 0.5 litres and 0.4 litres respectively. Twenty five percent of patients (nr 19) survived more than 2 years, 10'. (nr=8) between 1-2 years and the remaining 51 patients less than a year. Conclusion: PDT should be considered as a therapeutic modality for all stages of lung cancer and is an excellent treatment modality for palliation in advanced bronchial malignancies.
PREFACE: Muon spin rotation, relaxation or resonance
NASA Astrophysics Data System (ADS)
Heffner, Robert H.; Nagamine, Kanetada
), is currently being built to replace the current Japanese muSR capability at KEK. These muSR institutions provide scientists a variety of sample environments, including a range of temperatures, magnetic fields and applied pressure. In addition, very low-energy muon beams (< 1 keV) have been developed for studies of thin films and nano-materials. In 2002 this world-wide community founded the International Society of muSR Spectroscopy (http://musr.org/~isms/) in order to promote the health of this growing field of research. The 20 papers presented in this volume are intended to highlight some of the current muSR research activities of interest to condensed matter physicists. It is not an exhaustive review. In particular, the active and exciting area of muonium chemistry is left to a future volume. The group of papers in section I addresses the physics of strongly correlated electrons in solids, one of the most active fields of condensed matter research today. Strong electron correlations arise from (Coulomb) interactions which render Landau's theory of electron transport for weakly interacting systems invalid. Included in this category are unconventional heavy-fermion superconductors, high-temperature copper-oxide superconductors, non-Fermi liquid (NFL) systems and systems with strong electron-lattice-spin coupling, such as the colossal magnetoresistance manganites. Two key properties often make the muon a unique probe of these materials: (1) the muon's large magnetic moment (~3 mup) renders it extremely sensitive to the tiny magnetic fields (~1 Gauss) found, for example, in many NFL systems and in superconductors possessing time-reversal-violating order parameters, and (2) the muon's spin 1/2 creates a simple muSR lineshape (no quadrupolar coupling), ideal for measuring spin-lattice-relaxation, local susceptibilities and magnetic-field distributions in ordered magnets and superconductors. Section II contains studies which exploit the unique sensitivities of muSR just
Baldini, W.
In this paper is described the design, the construction and the performances of several Multi Wire Proportional Chamber prototypes built for the LHCb Muon system. In particular we report results for detection efficiency, time resolution, high rate performances and ageing effect measured at the CERN T11 test beam area and at the high irradiation ENEA Casaccia Calliope Facility.
Experimental studies of combination of PDT and tumor chemotherapy or 60Co irradiation
NASA Astrophysics Data System (ADS)
Didziapetriene, Janina; Prasmickiene, Grazina; Sukeliene, Dalija; Rotomskis, Ricardas; Streckyte, Giedre; Atkocius, Vydmantas; Staciokiene, Laima; Smilgevicius, Valerijus
We present experimental results obtained by combining photodynamic therapy (PDT) with tumor chemotherapy or radiotherapy. Dimethoxyhematoporphyrin (DMHp) and photosan (PS) were used as photosensitizers, pharanoxi and vincristine as antitumor drugs. The therapeutic effect of the combination of PDT and antitumor drugs (pharanoxi, vincristine) slightly increases as compared to the treatment of PDT or antitumor drug alone. The additive therapeutic effect is achieved under the combination of PDT and 60Co irradiation. It seems that the sensitizers DMHp and PS regulate lipid peroxidation in blood serum of experimental animals, which becomes more active under the influence of alkylating antitumor drugs. Therefore, they could protect an organism from negative influence of tumor chemotherapy.
Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications.
Kim, Miri; Jung, Haw Young; Park, Hyun Jeong
Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects. PMID:26404243
PDT-induced apoptosis: investigations using two malignant brain tumor models
NASA Astrophysics Data System (ADS)
Lilge, Lothar D.; Menzies, Keir; Bisland, Stuart K.; Lin, Annie; Wilson, Brian C.
PDT included necrosis in brain tissue and an intracranial tumor has been quantified for various photosensitizers, and it has been shown to be dependent on the sub-cellular localization of these photosensitizers. In quantifying non- necrotic biological endpoints, such as PDT induced apoptosis, the expression and translation of apoptosis inhibiting or promoting genes is of considerable importance. We studied the susceptibility of two glioblastoma cell lines to under go apoptotic cell death following photodynamic treatment with either Photofrin or delta-aminolevulinic acid (delta) ALA) in vivo. Murine 9L Gliosarcoma cells or human U87 Glioblastoma cells were implanted into the cortex of rats, and following 12 or 14 days of growth respectively, subjected to either Photofrin-mediated PDT or ALA-mediated PDT. 9L gliosarcoma cells express the phosphatase Tensin homologue (PTEN) tumor suppressor gene while in U87 cells PTEN is mutated. Differences in the Photofrin mediated PDT induced apoptosis were noted between the two different cell lines in vivo, suggesting that Photofrin mediated PDT may be dependent on apoptotic pathways. ALA induced PPIX showed higher selectivity towards 9L than Photofrin mediated PDT. These studies suggests that PDT could be used as an effective treatment for intracranial neoplasm. Endogenous photosensitizers such as ALA could be used to promote apoptosis in tumor cells due to PDT treatment and thereby minimize the extent of necrotic infarction in the surrounding normal brain.
Molecular mechanisms associated with ALA-PDT of brain tumor cells
NASA Astrophysics Data System (ADS)
Alqawi, Omar; Espiritu, Myrna; Singh, Gurmit
Previous studies have shown that low-dose PDT using 5-aminolevulinic acid (ALA)-induced photoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis. In this study we investigated the molecular mechanisms associated with apoptosis after ALA-PDT treatment in two brain glioma cell lines: human U87, and rat CNS-1cells. We used high energy light at a short time (acute PDT) and low energy light at a long time of exposure (metronomic PDT) to treat both cell lines. The cells were treated with 0.25 mM ALA at 5 joules for energy. We found that CNS-1 cells were more resistant to ALA-PDT than U87 cells when treated by both acute and metronomic PDT. To screen possible apoptosis mechanisms associated with acute and metronomic PDT, microarray analysis of gene expression was performed on RNA from glioblastoma cells treated with either acute or metronomic ALA-PDT. Within the set of genes that were negatively or positively regulated by both treatments are tumor necrosis factor receptors. The expression of TNF receptors was investigated further by RT-PCR and western blotting. The apoptosis mechanism of the cell death occurred through different pathways including BCL-2 and TNF receptors, and in part caused by cleaving caspase 3. Interestingly, metronomic ALA-PDT inhibited the expression of LTβR and the transcription factor NFκB. This inhibition was ALA concentration dependent at low concentrations.
Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications
Kim, Miri; Jung, Haw Young; Park, Hyun Jeong
Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects. PMID:26404243
Overcoming therapeutic resistance in pancreatic cancer is not a simple mix of PDT and chemotherapy: Evaluation of PDT-chemotherapy combinations in 3D tumor models
NASA Astrophysics Data System (ADS)
Celli, Jonathan P.; Petrovic, Ljubica; Massdodi, Iqbal; Rizvi, Imran; Hasan, Tayyaba
The dismal survival statistics for pancreatic cancer are due in large part to the notoriously poor response of these tumors to conventional therapies. Here we examine the ability of photodynamic therapy (PDT), using the photosensitizer verteporfin to enhance of the efficacy of traditional chemotherapy agents and/or eradicate populations that are nonresponsive to these agents. Using an in vitro 3D tumor model of pancreatic cancer combined with an imaging-based methodology for quantifying therapeutic response, we specifically examine PDT combination treatments with gemcitabine and oxaliplatin. We show that our 3D cell culture model recapitulates a more clinically-relevant dose response to gemcitabine, with minimal cytotoxic response even at high doses. The same cultures exhibit modest response to PDT treatments, but are also less responsive to this modality relative to our previous reports of monolayer dose response in the same cells. In combination we found no evidence of any enhancement in efficacy of either PDT or gemcitabine treatment regardless of dose or sequence (PDT before gemcitabine, or gemcitabine before PDT). However, when oxaliplatin chemotherapy was administered immediately after treatment with 2.5J/cm2 verteporfin PDT, there was an observable enhancement in response that appears to exceed the additive combination of either treatment alone and suggesting there may be a synergistic interaction. This observation is consistent with previous reports of enhanced efficacy in combinations of PDT with platinum-based chemotherapy. The contrast in results between the combinations examined here underscores the need for rational design of mechanism-based PDT combinations.
Monte Carlo simulation of light fluence calculation during pleural PDT
NASA Astrophysics Data System (ADS)
Meo, Julia L.; Zhu, Timothy
A thorough understanding of light distribution in the desired tissue is necessary for accurate light dosimetry in PDT. Solving the problem of light dose depends, in part, on the geometry of the tissue to be treated. When considering PDT in the thoracic cavity for treatment of malignant, localized tumors such as those observed in malignant pleural mesothelioma (MPM), changes in light dose caused by the cavity geometry should be accounted for in order to improve treatment efficacy. Cavity-like geometries demonstrate what is known as the "integrating sphere effect" where multiple light scattering off the cavity walls induces an overall increase in light dose in the cavity. We present a Monte Carlo simulation of light fluence based on a spherical and an elliptical cavity geometry with various dimensions. The tissue optical properties as well as the non-scattering medium (air and water) varies. We have also introduced small absorption inside the cavity to simulate the effect of blood absorption. We expand the MC simulation to track photons both within the cavity and in the surrounding cavity walls. Simulations are run for a variety of cavity optical properties determined using spectroscopic methods. We concluded from the MC simulation that the light fluence inside the cavity is inversely proportional to the surface area.
Real-time treatment feedback guidance of Pleural PDT
NASA Astrophysics Data System (ADS)
Zhu, Timothy C.; Kim, Michele M.; Liang, Xing; Liu, Baochang; Meo, Julia L.; Finlay, Jarod C.; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles; Cengel, Keith; Friedberg, Joseph
Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for mesothelioma with remarkable results. In the current intrapleural PDT protocol, a moving fiber-based point source is used to deliver the light and the light dose are monitored by 7 detectors placed in the pleural cavity. To improve the delivery of light dose uniformity, an infrared (IR) camera system is used to track the motion of the light sources. A treatment planning system uses feedback from the detectors as well as the IR camera to update light fluence distribution in real-time, which is used to guide the light source motion for uniform light dose distribution. We have improved the GUI of the light dose calculation engine to provide real-time light fluence distribution suitable for guiding the surgery to delivery light more uniformly. A dual-correction method is used in the feedback system, so that fluence calculation can match detector readings using both direct and scatter light models. An improved measurement device is developed to automatically acquire laser position for the point source. Comparison of the effects of the guidance is presented in phantom study.
A real-time treatment guidance system for pleural PDT
NASA Astrophysics Data System (ADS)
Zhu, Timothy C.; Liang, Xing; Sandell, Julia; Finlay, Jarod C.; Dimofte, Andreea; Rodriguez, Carmen; Cengel, Keith; Friedberg, Joseph; Hahn, Stephen M.; Glatstein, Eli
Intrapleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for mesothelioma. In the current intrapleural PDT protocol, a moving fiber-based point source is used to deliver the light and the light dose are monitored by 7 detectors placed in the pleural cavity. To improve the delivery of light dose uniformity, an infrared (IR) camera system is used to track the motion of the light sources. A treatment planning system uses feedback from the detectors as well as the IR camera to update light fluence distribution in real-time, which is used to guide the light source motion for uniform light dose distribution. We have reported previously the success of using IR camera to passively monitor the light fluence rate distribution. In this study, the real-time feedback has been implemented in the current system prototype, by transferring data from the IR camera to a computer at a rate of 20 Hz, and by calculation/displaying using Matlab. A dual-correction method is used in the feedback system, so that fluence calculation can match detector readings. Preliminary data from a phantom showed superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown using the correction method dose model.
Noncoherent light for PDT of spontaneous animal tumors
NASA Astrophysics Data System (ADS)
Lucroy, Michael D.; Ridgway, Tisha D.; Higbee, Russell G.; Reeds, Kimberly
Cultured 9L cells were incubated with graded doses of pheophorbide-a-hexyl ether (HPPH) and exposed to 665 nm red light from either a noncoherent light source or a KTP-pumped dye laser. Cell death was observed after irradiation using either light source, with the noncoherent light being most effective at the highest HPPH concentrations. To determing the practicality of using the noncoherent light source for clinical PDT, dogs and cats with spontaneous tumors were injected intravenously with 0.15 mg/kg HPPH one hour before their tumors were irradiated with 665 nm noncoherent light (50 mW cm-2, 100 J cm-2). Of the 9 tumors treated, 8 complete responses were observed, all of which occurred in animals with squamous cell carcinoma. After 68 weeks of follow up, the median initial disease free interval had not been reached. These data support the use of noncoherent light sources for PDT of spontaneous tumors in animals, representing a cost-effective alternative to medical lasers in both veterinary and human dermatology and oncology.
Beta-lactamase targeted enzyme activatable photosensitizers for antimicrobial PDT
NASA Astrophysics Data System (ADS)
Zheng, Xiang; Verma, Sarika; Sallum, Ulysses W.; Hasan, Tayyaba
Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed.
Possible explanation for the low flux of high energy astrophysical muon neutrinos
Pakvasa, Sandip
I consider the possibility that some exotic neutrino property is responsible for reducing the muon neutrino flux at high energies from distant sources; specifically, (i) neutrino decay and (ii) neutrinos being pseudo-Dirac particles. This would provide a mechanism for the lack of high energy muon events in the Icecube detector.
On muon energy spectrum in muon groups underground
NASA Technical Reports Server (NTRS)
Bakatanov, V. N.; Chudakov, A. E.; Novoseltsev, Y. F.; Novoseltseva, M. V.; Stenkin, Y. V.
A method is described which was used to measure muon energy spectrum characteristics in muon groups underground using mu-e decays recording. The Baksan Telescope's experimental data on mu-e decays intensity in muon groups of various multiplicities are analyzed. The experimental data indicating very flat spectrum does not however represent the total spectrum in muon groups. Obviously the muon energy spectrum depends strongly on a distance from the group axis. The core attraction effect makes a significant distortion, making the spectrum flatter. After taking this into account and making corrections for this effect the integral total spectrum index in groups has a very small depencence on muon multiplicity and agrees well with expected one: beta=beta (sub expected) = 1.75.
Muon capture for the front end of a muon collider
Neuffer, D.; Yoshikawa, C.; /MUONS Inc., Batavia
We discuss the design of the muon capture front end for a {mu}{sup +}-{mu}{sup -} Collider. In the front end, a proton bunch on a target creates secondary pions that drift into a capture transport channel, decaying into muons. A sequence of rf cavities forms the resulting muon beams into strings of bunches of differing energies, aligns the bunches to (nearly) equal central energies, and initiates ionization cooling. The muons are then cooled and accelerated to high energy into a storage ring for high-energy high luminosity collisions. Our initial design is based on the somewhat similar front end of the International Design Study (IDS) neutrino factory.
NASA Technical Reports Server (NTRS)
The bulk of the muon spin rotation research work centered around the development of the muon spin rotation facility at the Alternating Gradient Synchrotron (AGS) of Brookhaven National Laboratory (BNL). The collimation system was both designed and fabricated at Virginia State University. This improved collimation system, plus improvements in detectors and electronics enabled the acquisition of spectra free of background out to 15 microseconds. There were two runs at Brookhaven in 1984, one run was devoted primarily to beam development and the other run allowed several successful experiments to be performed. The effect of uniaxial strain on an Fe(Si) crystal at elevated temperature (360K) was measured and the results are incorporated herein. A complete analysis of Fe pulling data taken earlier is included.
Noble, Robert J. FNAL
Recent progress in the study of muon colliders is presented. An international collaboration consisting of over 100 individuals is involved in calculations and experiments to demonstrate the feasibility of this new type of lepton collider. Theoretical efforts are now concentrated on low-energy colliders in the 100 to 500 GeV center-of-mass energy range. Credible machine designs are emerging for much of a hypothetical complex from proton source to the final collider. Ionization cooling has been the most difficult part of the concept, and more powerful simulation tools are now in place to develop workable schemes. A collaboration proposal for a muon cooling experiment has been presented to the Fermilab Physics Advisory Committee, and a proposal for a targetry and pion collection channel experiment at Brookhaven National Laboratory is in preparation. Initial proton bunching and space-charge compensation experiments at existing hadron facilities have occurred to demonstrate proton driver feasibility.
The role of impurities in molecular solids and biological materials. First-principles study of: I. Helium in solid hydrogen as an obstacle for efficiency of muon catalyzed fusion, and II. Muon and muonium in proteins and DNA as probes for electron transport
NASA Astrophysics Data System (ADS)
Scheicher, Ralph H.
The Hartree-Fock cluster procedure has been used to investigate the electronic structures and associated properties of helium in solid hydrogen and of muon and muonium in cytochrome c and DNA. Our study has shown that He+ is trapped about equally strongly at both tetrahedral and octahedral interstitial sites in solid hydrogen, with almost no dependence of the binding energy on the orientation of the surrounding H2 molecules. Neutral helium appears unbound in solid hydrogen. The results of our calculations provide an explanation for the stronger trapping of helium in the solid phase of hydrogen as compared to the liquid phase, observed in muon catalyzed fusion experiments. Regarding the phenomenon of helium nucleation, our calculations have shown that two He+ ions trapped at adjacent sites in solid hydrogen can substantially reduce their repulsion due to the influence of the H2 molecules. For muon and muonium trapping in cytochrome c, we have shown that the double-bonded oxygen in the carboxyl group is capable of trapping both muon and muonium. This suggests for the muon spin relaxation measurements which study the electron transfer path in cytochrome c, that the muon trapped at this type of oxygen atom is the main one that can sense the movement of the electron that leaves the trapped muonium. Our results provide valuable understanding of the differences between the properties associated with muon and muonium trapped in different amino acids in the protein chain of cytochrome c and the role of environmental effects. Our study of muon and muonium trapping in DNA has shown that significant differences exist in the magnetic hyperfine interaction of muonium trapped in the nucleic acid Adenine between the A-form and B-form DNA type, and the isolated molecule type. This result has potential importance for the interpretation of muon spin relaxation experiments which investigate the dependence of electron mobility upon base pair separation in DNA. The results of our study
ALA-PDT inhibits proliferation and promotes apoptosis of SCC cells through STAT3 signal pathway.
Qiao, Li; Mei, Zhusong; Yang, Zhiyong; Li, Xinji; Cai, Hong; Liu, Wei
Previous studies suggest that apoptosis of carcinoma cells led by photodynamics is mainly intrinsic apoptosis, but whether the extrinsic pathway is involved in the treatment of carcinoma by photodynamic therapy is not confirmed. This research investigated the effect of ALA-PDT on the proliferation and apoptosis of SCC cell A431 and COLO-16, and discussed the role played by JAK/STAT3 signal pathway in this process. Our data showed that the expression levels STAT3 and p-STAT3 protein in the cancer tissue are higher than the corresponding adjacent tissue to carcinoma. The expression level of p-STAT3 in cancerous tissue has a correlation with the tumor size and tissue histopathological differentiation. ALA-PDT could inhibit proliferation of A431 and COLO-16 cells, STAT3 knock down could enhance ALA-PDT's inhibition of cell proliferation, and promote apoptosis induced by ALA-PDT. On the other hand, overexpression of STAT3 has the opposite effect. In addition, ALA-PDT can weaken the protein expression of STAT3 and its target gene Bcl-2 mRNA, and ALA-PDT can strengthen the protein expression of STAT3's target gene Bax mRNA. Overexpression of STAT3 can offset the effect on Bcl-2 and Bax by ALA-PDT; on the other hand, STAT3 knocking down can strengthen ALA-PDT's effect on Bcl-2 and Bax. PMID:26805005
The US Muon Accelerator Program
Torun, Y.; Kirk, H.; Bross, A.; Geer, Steve; Shiltsev, Vladimir; Zisman, M.; /LBL, Berkeley
An accelerator complex that can produce ultra-intense beams of muons presents many opportunities to explore new physics. A facility of this type is unique in that, in a relatively straightforward way, it can present a physics program that can be staged and thus move forward incrementally, addressing exciting new physics at each step. At the request of the US Department of Energy's Office of High Energy Physics, the Neutrino Factory and Muon Collider Collaboration (NFMCC) and the Fermilab Muon Collider Task Force (MCTF) have recently submitted a proposal to create a Muon Accelerator Program that will have, as a primary goal, to deliver a Design Feasibility Study for an energy-frontier Muon Collider by the end of a 7 year R&D program. This paper presents a description of a Muon Collider facility and gives an overview of the proposal.
NASA Astrophysics Data System (ADS)
Malamova, E.; Angelov, I.; Kalapov, I.; Davidkov, K.; Stamenov, J.
: The Muon Cerenkov Telescope is a system of water cerenkov detectors, using the coincidence technique to register cosmic ray muons. It is constructed in order to study the variations of cosmic rays and their correlation with solar activity and processes in the Earth magnetosphere. 1 Basic design of the Muon Cerenkov Telescope The telescope has 18 water cerenkov detectors / 0.25 m2 each /, situated in two parallel planes. / Fig. 1/ Each detector /fig. 2/ consists of a container with dimensions 50x50x12.5 cm made of 3mm thick glass with mirror cover of the outer side. The container is filled with distilled water to 10cm level. A photomultiplier is attached to a transparent circle at the floor of the container and the discriminator is placed in its housing. When a charged particle with energy greater than the threshold energy for cerenkov radiation generation passes the radiator, cerenkov photons are initiated and a part of them reach the PMT cathode after multiple reflections from the mirror sides of the container.
Muon Colliders and Neutrino Factories
Geer, Steve; /Fermilab
Over the past decade, there has been significant progress in developing the concepts and technologies needed to produce, capture, and accelerate {Omicron}(10{sup 21}) muons per year. These developments have paved the way for a new type of neutrino source (neutrino factory) and a new type of very high energy lepton-antilepton collider (muon collider). This article reviews the motivation, design, and research and development for future neutrino factories and muon colliders.
Muon colliders and neutrino factories
Geer, S.; /Fermilab
Over the last decade there has been significant progress in developing the concepts and technologies needed to produce, capture and accelerate {Omicron}(10{sup 21}) muons/year. This development prepares the way for a new type of neutrino source (Neutrino Factory) and a new type of very high energy lepton-antilepton collider (Muon Collider). This article reviews the motivation, design and R&D for Neutrino Factories and Muon Colliders.
Muon Colliders and Neutrino Factories *
NASA Astrophysics Data System (ADS)
Geer, Steve
Over the past decade, there has been significant progress in developing the concepts and technologies needed to produce, capture, and accelerate O(1021) muons per year. These developments have paved the way for a new type of neutrino source (neutrino factory) and a new type of very high energy lepton-antilepton collider (muon collider). This article reviews the motivation, design, and research and development for future neutrino factories and muon colliders.
Sensitive detection of PDT-induced cell damages with luminescent oxygen nanosensors
NASA Astrophysics Data System (ADS)
Ma, Hong-Ru; Peng, Hong-shang; You, Fang-tian; Ping, Jian-tao; Zhou, Chao; Guo, Lan-ying
In this work luminescent nanosensors specifically created for intracellular oxygen (ic-O2) were utilized to assess photodynamic therapy (PDT) -induced cell damages. Firstly, ic-O2 was demonstrated to be consumed much faster than extracellular O2 with respective O2 nanosensors. Using the ic-O2 nanosensors, PDT-treated cells with different degree of impairment were then resolved according to the oxygen consumption rate (OCR). The evolving trend of cytotoxicity derived from OCRs was in agreement with cell viability obtained from 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Moreover, the direct damage of PDT on cell mitochondria was successfully detected by monitoring respiration instantly after PDT treatment, which is actually beyond the scope of MTT assay. These results suggest that fluorescence sensing of ic-O2-associated cell respiration is promising and even may become a standardized method, complementary to MTT assay, to evaluate PDT-induced cytotoxicity.
Glutamate-mediated protection of crayfish glial cells from PDT-induced apoptosis
NASA Astrophysics Data System (ADS)
Rudkovskii, M. V.; Romanenko, N. P.; Berezhnaya, E. V.; Kovaleva, V. D.; Uzdensky, A. B.
Photodynamic treatment that causes intense oxidative stress and kills cells is currently used in neurooncology. However, along with tumor it damages surrounding healthy neurons and glial cells. In order to study the possible role of glutamate-related signaling pathways in photodynamic injury of neurons and glia, we investigated photodynamic effect of alumophthalocyanine Photosens on isolated crayfish stretch receptor that consists of a single neuron surrounded by glial cells. The laser diode (670 nm, 0.4 W/cm2) was used for dye photoexcitation. Application of glutamate increased photodynamically induced necrosis of neurons and glial cells but significantly decreased glial apoptosis. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after cleavage in the extracellular space by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced apoptosis of glial cells. These data confirm the anti-apoptotic activity of glutamate. Application of NMDA or inhibition of NMDA receptors by MK801 did not influence photodynamic death of neurons and glial cells that indicated nonparticipation of NMDA receptors in these processes. Inhibition of metabotropic glutamate receptors by AP-3 decreased PDT-induced apoptosis. One can suggest that crayfish neurons naturally secrete NAAG, which being cleaved by GCOP produces glutamate. Glutamate prevents photoinduced apoptosis of glial cells possibly through metabotropic but not ionotropic glutamate receptors.
Glutamate-mediated protection of crayfish glial cells from PDT-induced apoptosis
NASA Astrophysics Data System (ADS)
Rudkovskii, M. V.; Romanenko, N. P.; Berezhnaya, E. V.; Kovaleva, V. D.; Uzdensky, A. B.
Photodynamic treatment that causes intense oxidative stress and kills cells is currently used in neurooncology. However, along with tumor it damages surrounding healthy neurons and glial cells. In order to study the possible role of glutamate-related signaling pathways in photodynamic injury of neurons and glia, we investigated photodynamic effect of alumophthalocyanine Photosens on isolated crayfish stretch receptor that consists of a single neuron surrounded by glial cells. The laser diode (670 nm, 0.4 W/cm2) was used for dye photoexcitation. Application of glutamate increased photodynamically induced necrosis of neurons and glial cells but significantly decreased glial apoptosis. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after cleavage in the extracellular space by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced apoptosis of glial cells. These data confirm the anti-apoptotic activity of glutamate. Application of NMDA or inhibition of NMDA receptors by MK801 did not influence photodynamic death of neurons and glial cells that indicated nonparticipation of NMDA receptors in these processes. Inhibition of metabotropic glutamate receptors by AP-3 decreased PDT-induced apoptosis. One can suggest that crayfish neurons naturally secrete NAAG, which being cleaved by GCOP produces glutamate. Glutamate prevents photoinduced apoptosis of glial cells possibly through metabotropic but not ionotropic glutamate receptors.
Light dosimetry technique for endoscopic PDT using microlens optical fiber
NASA Astrophysics Data System (ADS)
Jacques, Steven L.
A simple procedure is presented for determining the irradiance of light striking tissues during light delivery using a microlens optical fiber via an endoscope. The particular example is photodynamic therapy (PDT) of laryngeal cancer. A microlens optical fiber is an optical fiber with a small lens assembly at its terminus which magnifies the image of the end of the fiber yielding a uniform irradiance in a plane distant from the fiber. Prior to the therapy, the relation between fiber-target distance, h [cm], and the diameter of the uniform beam, d(h) [cm], was established and the area of the beam was calculated: A(h) equals (pi) d(h)2/4. The laser power P [W] required to achieve a desired irradiance E [W/cm2] was P(h) equals EA(h), and this relation was prepared as a simple graph for routine use in the clinic. During the therapy, the doctor advances the optical fiber through the working channel of the endoscope to touch the target tissue site while observing through the optical channel, and marks the fiber on the outside of the endoscope. The doctor then retracts the fiber until an aiming beam transmitted through the fiber fully illuminates the desired target area, and again marks the fiber on the outside of the endoscope. The difference in the two marks on the fiber outside the endoscope yields h, the height of the fiber above the target tissue. The laser operator then uses the P(h) equals EA(h) graph to select the proper laser power to achieve the desired E. Although trivially simple, this dosimetry procedure was critical to the proper implementation of PDT for laryngeal cancer.
From Neutrino Factory to Muon Collider
Geer, S.; /Fermilab
Both Muon Colliders and Neutrino Factories require a muon source capable of producing and capturing {Omicron}(10{sup 21}) muons/year. This paper reviews the similarities and differences between Neutrino Factory and Muon Collider accelerator complexes, the ongoing R&D needed for a Muon Collider that goes beyond Neutrino Factory R&D, and some thoughts about how a Neutrino Factory on the CERN site might eventually be upgraded to a Muon Collider.
Physical applications of muon catalysis: Muon capture in hydrogen
NASA Astrophysics Data System (ADS)
Filchenkov, V. V.
Results of theoretical and experimental research on capture of negative muons in hydrogen are reported with an emphasis on the accompanying phenomenon of muon catalysis in hydrogen and subtleties of the experimental method. A conclusion is drawn that precise determination of the capture rate is important for refining the standard model.
Muon Spin Rotation Spectroscopy - Utilizing Muons in Solid State Physics
Suter, Andreas
Over the past decades muon spin rotation techniques (mSR) have established themselves as an invaluable tool to study a variety of static and dynamic phenomena in bulk solid state physics and chemistry. Common to all these approaches is that the muon is utilized as a spin microprobe and/or hydrogen-like probe, implanted in the material under investigation. Recent developments extend the range of application to near surface phenomena, thin film and super-lattice studies. After briefly summarizing the production of so called surface muons used for bulk studies, and discussing the principle differences between pulsed and continuous muon beams, the production of keV-energy muon sources will be discussed. A few topical examples from different active research fields will be presented to demonstrate the power of these techniques.
Electron-muon ranger: performance in the MICE muon beam
NASA Astrophysics Data System (ADS)
Adams, D.; Alekou, A.; Apollonio, M.; Asfandiyarov, R.; Barber, G.; Barclay, P.; de Bari, A.; Bayes, R.; Bayliss, V.; Bene, P.; Bertoni, R.; Blackmore, V. J.; Blondel, A.; Blot, S.; Bogomilov, M.; Bonesini, M.; Booth, C. N.; Bowring, D.; Boyd, S.; Bradshaw, T. W.; Bravar, U.; Bross, A. D.; Cadoux, F.; Capponi, M.; Carlisle, T.; Cecchet, G.; Charnley, C.; Chignoli, F.; Cline, D.; Cobb, J. H.; Colling, G.; Collomb, N.; Coney, L.; Cooke, P.; Courthold, M.; Cremaldi, L. M.; Debieux, S.; DeMello, A.; Dick, A.; Dobbs, A.; Dornan, P.; Drielsma, F.; Filthaut, F.; Fitzpatrick, T.; Franchini, P.; Francis, V.; Fry, L.; Gallagher, A.; Gamet, R.; Gardener, R.; Gourlay, S.; Grant, A.; Graulich, J. S.; Greis, J.; Griffiths, S.; Hanlet, P.; Hansen, O. M.; Hanson, G. G.; Hart, T. L.; Hartnett, T.; Hayler, T.; Heidt, C.; Hills, M.; Hodgson, P.; Hunt, C.; Husi, C.; Iaciofano, A.; Ishimoto, S.; Kafka, G.; Kaplan, D. M.; Karadzhov, Y.; Kim, Y. K.; Kuno, Y.; Kyberd, P.; Lagrange, J.-B.; Langlands, J.; Lau, W.; Leonova, M.; Li, D.; Lintern, A.; Littlefield, M.; Long, K.; Luo, T.; Macwaters, C.; Martlew, B.; Martyniak, J.; Masciocchi, F.; Mazza, R.; Middleton, S.; Moretti, A.; Moss, A.; Muir, A.; Mullacrane, I.; Nebrensky, J. J.; Neuffer, D.; Nichols, A.; Nicholson, R.; Nicola, L.; Noah Messomo, E.; Nugent, J. C.; Oates, A.; Onel, Y.; Orestano, D.; Overton, E.; Owens, P.; Palladino, V.; Pasternak, J.; Pastore, F.; Pidcott, C.; Popovic, M.; Preece, R.; Prestemon, S.; Rajaram, D.; Ramberger, S.; Rayner, M. A.; Ricciardi, S.; Roberts, T. J.; Robinson, M.; Rogers, C.; Ronald, K.; Rothenfusser, K.; Rubinov, P.; Rucinski, P.; Sakamato, H.; Sanders, D. A.; Sandström, R.; Santos, E.; Savidge, T.; Smith, P. J.; Snopok, P.; Soler, F. J. P.; Speirs, D.; Stanley, T.; Stokes, G.; Summers, D. J.; Tarrant, J.; Taylor, I.; Tortora, L.; Torun, Y.; Tsenov, R.; Tunnell, C. D.; Uchida, M. A.; Vankova-Kirilova, G.; Virostek, S.; Vretenar, M.; Warburton, P.; Watson, S.; White, C.; Whyte, C. G.; Wilson, A.; Wisting, H.; Yang, X.; Young, A.; Zisman, M.
The Muon Ionization Cooling Experiment (MICE) will perform a detailed study of ionization cooling to evaluate the feasibility of the technique. To carry out this program, MICE requires an efficient particle-identification (PID) system to identify muons. The Electron-Muon Ranger (EMR) is a fully-active tracking-calorimeter that forms part of the PID system and tags muons that traverse the cooling channel without decaying. The detector is capable of identifying electrons with an efficiency of 98.6%, providing a purity for the MICE beam that exceeds 99.8%. The EMR also proved to be a powerful tool for the reconstruction of muon momenta in the range 100-280 MeV/c.
An intense low energy muon source for the muon collider
Taqqu, D.
A scheme for obtaining an intense source of low energy muons is described. It is based on the production of pions in a high field magnetic bottle trap. By ensuring efficient slowing down and extraction of the decay muons an intense intermediate energy muon beam is obtained. For the specific case of negative muons a novel technique called frictional accumulation provides efficient conversion into a 10 keV{mu}{sup {minus}} beam whose emittance is then reduced in a configuration providing extended frictional cooling. The result is a beam of very small transverse and longitudinal emittance that can be used together with an equivalent {mu}{sup +} beam as compact intense muon source for the {mu}{sup +}{mu}{sup {minus}} collider. A final luminosity around 10{sup 34} cm{sup {minus}2}s{sup {minus}1} is expected to be obtained at 2 TeV. {copyright} {ital 1996 American Institute of Physics.}
Electron-Muon Ranger: Performance in the MICE muon beam
Adams, D.
The Muon Ionization Cooling Experiment (MICE) will perform a detailed study of ionization cooling to evaluate the feasibility of the technique. To carry out this program, MICE requires an efficient particle-identification (PID) system to identify muons. The Electron-Muon Ranger (EMR) is a fully-active tracking-calorimeter that forms part of the PID system and tags muons that traverse the cooling channel without decaying. The detector is capable of identifying electrons with an efficiency of 98.6%, providing a purity for the MICE beam that exceeds 99.8%. Lastly, the EMR also proved to be a powerful tool for the reconstruction of muon momenta inmore » the range 100–280 MeV/c.« less
Electron-Muon Ranger: Performance in the MICE muon beam
Adams, D.
The Muon Ionization Cooling Experiment (MICE) will perform a detailed study of ionization cooling to evaluate the feasibility of the technique. To carry out this program, MICE requires an efficient particle-identification (PID) system to identify muons. The Electron-Muon Ranger (EMR) is a fully-active tracking-calorimeter that forms part of the PID system and tags muons that traverse the cooling channel without decaying. The detector is capable of identifying electrons with an efficiency of 98.6%, providing a purity for the MICE beam that exceeds 99.8%. Lastly, the EMR also proved to be a powerful tool for the reconstruction of muon momenta in the range 100–280 MeV/c.
Muon Cooling—emittance exchange
NASA Astrophysics Data System (ADS)
Parsa, Zohreh
Muon Cooling is the key factor in building of a Muon collider, (to a less degree) Muon storage ring, and a Neutrino Factory. Muon colliders potential to provide a probe for fundamental particle physics is very interesting, but may take a considerable time to realize, as much more work and study is needed. Utilizing high intensity Muon sources-Neutrino Factories, and other intermediate steps are very important and will greatly expand our abilities and confidence in the credibility of high energy muon colliders. To obtain the needed collider luminosity, the phase-space volume must be greatly reduced within the muon life time. The Ionization cooling is the preferred method used to compress the phase space and reduce the emittance to obtain high luminosity muon beams. We note that, the ionization losses results not only in damping, but also heating. The use of alternating solenoid lattices has been proposed, where the emittance are large. We present an overview of the cooling and discuss formalism, solenoid magnets and some beam dynamics.
High luminosity muon collider design
Palmer, R.; Gallardo, J.
Muon Colliders have unique technical and physics advantages and disadvantages when compared with both hadron and electron machines. They should be regarded as complementary. Parameters are given of 4 TeV high luminosity {mu}{sup +}{mu}{sup {minus}} collider, and of a 0.5 TeV lower luminosity demonstration machine. We discuss the various systems in such muon colliders.
Pathway-PDT: a flexible pathway analysis tool for nuclear families
Background Pathway analysis based on Genome-Wide Association Studies (GWAS) data has become popular as a secondary analysis strategy. Although many pathway analysis tools have been developed for case–control studies, there is no tool that can use all information from raw genotypes in general nuclear families. We developed Pathway-PDT, which uses the framework of Pedigree Disequilibrium Test (PDT) for general family data, to perform pathway analysis based on raw genotypes in family-based GWAS. Results Simulation results showed that Pathway-PDT is more powerful than the p-value based method, ALIGATOR. Pathway-PDT also can be more powerful than the PLINK set-based test when analyzing general nuclear families with multiple siblings or missing parents. Additionally, Pathway-PDT has a flexible and convenient user interface, which allows users to modify their analysis parameters as well as to apply various types of gene and pathway definitions. Conclusions The Pathway-PDT method is implemented in C++ with POSIX threads and is computationally feasible for pathway analysis with large scale family GWAS datasets. The Windows binary along with Makefile and source codes for the Linux are available at https://sourceforge.net/projects/pathway-pdt/. PMID:24006871
Palmer, R. |; Sessler, A.; Skrinsky, A.
The possibility of muon colliders was introduced by Skrinsky et al., Neuffer, and others. More recently, several workshops and collaboration meetings have greatly increased the level of discussion. In this paper we present scenarios for 4 TeV and 0.5 TeV colliders based on an optimally designed proton source, and for a lower luminosity 0.5 TeV demonstration based on an upgraded version of the AGS. It is assumed that a demonstration version based on upgrades of the FERMILAB machines would also be possible. 53 refs., 25 figs., 8 tabs.
PREFACE: Muon spin rotation, relaxation or resonance
NASA Astrophysics Data System (ADS)
Heffner, Robert H.; Nagamine, Kanetada
), is currently being built to replace the current Japanese muSR capability at KEK. These muSR institutions provide scientists a variety of sample environments, including a range of temperatures, magnetic fields and applied pressure. In addition, very low-energy muon beams (< 1 keV) have been developed for studies of thin films and nano-materials. In 2002 this world-wide community founded the International Society of muSR Spectroscopy (http://musr.org/~isms/) in order to promote the health of this growing field of research. The 20 papers presented in this volume are intended to highlight some of the current muSR research activities of interest to condensed matter physicists. It is not an exhaustive review. In particular, the active and exciting area of muonium chemistry is left to a future volume. The group of papers in section I addresses the physics of strongly correlated electrons in solids, one of the most active fields of condensed matter research today. Strong electron correlations arise from (Coulomb) interactions which render Landau's theory of electron transport for weakly interacting systems invalid. Included in this category are unconventional heavy-fermion superconductors, high-temperature copper-oxide superconductors, non-Fermi liquid (NFL) systems and systems with strong electron-lattice-spin coupling, such as the colossal magnetoresistance manganites. Two key properties often make the muon a unique probe of these materials: (1) the muon's large magnetic moment (~3 mup) renders it extremely sensitive to the tiny magnetic fields (~1 Gauss) found, for example, in many NFL systems and in superconductors possessing time-reversal-violating order parameters, and (2) the muon's spin 1/2 creates a simple muSR lineshape (no quadrupolar coupling), ideal for measuring spin-lattice-relaxation, local susceptibilities and magnetic-field distributions in ordered magnets and superconductors. Section II contains studies which exploit the unique sensitivities of muSR just
Noninvasive monitoring hemodynamic responses in RIF tumors during and after PDT
NASA Astrophysics Data System (ADS)
Yu, Guoqiang; Durduran, Turgut; Busch, Theresa M.; Wang, Hsing-Wen; Zhou, Chao; Saunders, H. Mark; Sehgal, Chandra M.; Yodh, Arjun G.
Changes in blood flow and oxygenation during and after PDT provide information about tumor vessel and cellular damage. The characterization of these changes may improve our understanding of PDT mechanisms and help predict treatment efficacy. We have designed a hybrid system that can non-invasively measure in vivo hemodynamic changes and provide independent information about tumor oxygenation and blood flow. Diffuse correlation spectroscopy (DCS) monitors blood flow by measuring the optical phase shifts caused by moving blood cells, while diffuse photon density wave (DPDW) spectroscopy measures tissue absorption and scattering. When mounted on a camera, our unique probe allows non-contact measurements that avoid compressing the tumor and altering blood flow. An optical filter mounted in front of the camera lens cut off light below 650nm, which allowed monitoring of blood flow during PDT. The utility of the hybrid system was demonstrated by monitoring the hemodynamic changes during and after PDT in mice bearing the experimental radiation-induced fibrosarcoma (RIF). For the first time, we non-invasively and continually monitored the in vivo flow changes during PDT. Relative oxygen consumption was calculated using flow values measured by DCS and oxygenation measured by a broadband absorption spectrometer. During PDT an initial rapid increase in blood flow was found, followed by a decrease and slow recovery. After PDT, substantial and continued reductions in blood saturation, blood flow and oxygen consumption were found after 3 hours, suggesting that permanent damage to tumor cells and blood vessels had occurred. The comparison of flow values after PDT as measured by DCS and by Power Doppler ultrasound (CWFA) demonstrated that both techniques non-invasively detected similar global changes in tumor blood flow or perfusion after PDT.
SU-D-16A-07: Photobleaching Predicts Necrosis in Interstitial PDT
Kim, M; Finlay, J; Liu, B; Zhu, T
Purpose: Dosimetry for PDT has proven to be a challenge thus far, and for prediction of PDT outcome, a singlet oxygen model based on fundamental photophysical parameters has been developed. Previously, the photobleaching effect of photosensitizers was taken into account in the singlet oxygen explicit dosimetry model; here we report of direct measurements of photobleaching in the same model to assess the conditions under which implicit dosimetry using photobleaching can serve as an intermediate surrogate for PDT damage. Methods: Fluorescence spectra were measured interstitially in sensitized mouse tumors prior to after irradiation via a cylindrical diffuser. Photobleaching was determined by the relative decrease in fluorescence amplitude from the initial pre-treatment measurement. Spectra were analyzed by singular value decomposition to determine the photosensitizer concentration. Different photosensitizers were used to see the effect of photobleaching on PDT outcome and the impact of fluence on photobleaching. The drugs used were BPD (at two drug-light intervals), HPPH, and Photofrin. PDT outcome was determined by tumor necrosis radii measured upon sectioning and staining of treated tumors. Results: Post-PDT photosentizer concentrations were compared to initial pre-PDT photosensitizer concentrations, and the decrease was greater with a higher fluence measured during treatment. Furthermore, photobleaching and necrosis radius were found to be positively correlated. The relationship between photobleaching and necrosis radius is sensitizer-dependent, however the differences among sensitizers can be understood in terms of their respective photophysical parameters. Conclusions: Photobleaching is predictive of PDT outcome, but a comprehensive singlet oxygen model, has the potential to further improve the prediction of PDT outcome and the understanding of implicit dosimetry.
The concept of a muon storage ring based Neutrino Source (Neutrino Factory) has sparked considerable interest in the High Energy Physics community. Besides providing a first phase of a muon collider facility, it would generate more intense and well collimated neutrino beams than currently available. The BNL-AGS or some other proton driver would provide an intense proton beam that hits a target, produces pions that decay into muons. The muons must be cooled, accelerated and injected into a storage ring with a long straight section where they decay. The decays occurring in the straight sections of the ring would generate neutrino beams that could be directed to detectors located thousands of kilometers away, allowing studies of neutrino oscillations with precisions not currently accessible. For example, with the neutrino source at BNL, detectors at Soudan, Minnesota (1,715 km), and Gran Sasso, Italy (6,527 km) become very interesting possibilities. The feasibility of constructing and operating such a muon-storage-ring based Neutrino-Factory, including geotechnical questions related to building non-planar storage rings (e.g. at 8{degree} angle for BNL-Soudan, and 3{degree} angle for BNL-Gran Sasso) along with the design of the muon capture, cooling, acceleration, and storage ring for such a facility is being explored by the growing Neutrino Factory and Muon Collider Collaboration (NFMCC). The authors present overview of Neutrino Factory concept based on a muon storage ring, its components, physics opportunities, possible upgrade to a full muon collider, latest simulations of front-end, and a new bowtie-muon storage ring design.
Monitoring PDT response of head and neck lesions with diffuse optical spectroscopies
NASA Astrophysics Data System (ADS)
Rohrbach, Daniel J.; Rigual, Nestor; Tracy, Erin; Keymel, Ken; Cooper, Michele T.; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas
Photodynamic therapy (PDT) has recently emerged as a potential treatment alternative for head and neck cancer. There is strong evidence that imprecise PDT dosimetry results in variations in clinical responses. Quantitative tools are likely to play an essential role in bringing PDT to a full realization of its potential benefits. They can provide standardization of site-specific individualized protocols that are used to monitor both light and photosensitizer (HPPH) dose, as well as the tissue response for individual patients. To accomplish this, we used a custom instrument and a hand-held probe that allowed quantification of blood flow, blood volume, blood oxygen saturation and drug concentration.
Differential susceptibility of primary cultured human skin cells to hypericin PDT in an in vitro model.
Popovic, A; Wiggins, T; Davids, L M
Skin cancer is the most common cancer worldwide, and its incidence rate in South Africa is increasing. Photodynamic therapy (PDT) has been shown to be an effective treatment modality, through topical administration, for treatment of non-melanoma skin cancers. Our group investigates hypericin-induced PDT (HYP-PDT) for the treatment of both non-melanoma and melanoma skin cancers. However, a prerequisite for effective cancer treatments is efficient and selective targeting of the tumoral cells with minimal collateral damage to the surrounding normal cells, as it is well established that cancer therapies have bystander effects on normal cells in the body, often causing undesirable side effects. The aim of this study was to investigate the cellular and molecular effects of HYP-PDT on normal primary human keratinocytes (Kc), melanocytes (Mc) and fibroblasts (Fb) in an in vitro tissue culture model which represented both the epidermal and dermal cellular compartments of human skin. Cell viability analysis revealed a differential cytotoxic response to a range of HYP-PDT doses in all the human skin cell types, showing that Fb (LD50=1.75μM) were the most susceptible to HYP-PDT, followed by Mc (LD50=3.5μM) and Kc (LD50>4μM HYP-PDT) These results correlated with the morphological analysis which displayed distinct morphological changes in Fb and Mc, 24h post treatment with non-lethal (1μM) and lethal (3μM) doses of HYP-PDT, but the highest HYP-PDT doses had no effect on Kc morphology. Fluorescent microscopy displayed cytoplasmic localization of HYP in all the 3 skin cell types and additionally, HYP was excluded from the nuclei in all the cell types. Intracellular ROS levels measured in Fb at 3μM HYP-PDT, displayed a significant 3.8 fold (p<0.05) increase in ROS, but no significant difference in ROS levels occurred in Mc or Kc. Furthermore, 64% (p<0.005) early apoptotic Fb and 20% (p<0.05) early apoptotic Mc were evident; using fluorescence activated cell sorting (FACS), 24
Search for excited and exotic muons at CDF
Gerberich, Heather; Hays, Christopher; Kotwal, Ashutosh; /Duke U.
The authors present a search for the production of excited or exotic muons ({mu}*) via the reaction {bar p} + p {yields} {mu}* + {mu} {yields} {mu}{gamma}+{mu} using 371 pb{sup -1} of data collected with the Run II CDF detector. In this signature-based search, we look for a resonance in the {mu}{gamma} mass spectrum. The data are compared to standard model and detector background expectations, and with predictions of excited muon production. We use these comparisons to set limits on the {mu}* mass and compositeness scale {Lambda} in contact interaction and gauge-mediated models.
NASA Astrophysics Data System (ADS)
Battistoni, G.; Campana, P.; Chiarella, V.; Denni, U.; Iarocci, E.
The design and performance of plastic streamer tubes for use in large underground particle-physics experiments such as the muon, astrophysics, and cosmic-ray observatory (MACRO) being developed for Gran Sasso Laboratory are reported. The large (1000 sq m or more) detector area required to achieve high-angular-resolution muon tracking in MACRO is covered by modules with eight 3 x 3-cm-cross section active streamer-tube cells each, similar to those used in the Mt. Blanc Laboratory detector. The MACRO modules have a maximum length of 12 m; and the cells have 60-micron-diameter wires, two conducting graphite sides, and two insulating sides (electrodeless electric-field shaping). The results of performance tests flowing 3:1 He:n-pentane through a tube module are presented graphically. Spatial resolution 1 cm and time resolution 100 ns are obtained, and the ability of the streamer tubes to detect large ionization losses with respect to the minimum is demonstrated.
Clinical studies of photodynamic therapy for malignant brain tumors: Karnofsky score and neurological score in patients with recurrent gloms treated with Photofrin PDT
NASA Astrophysics Data System (ADS)
Muller, Paul J.; Wilson, Brian C.; Lilge, Lothar D.; Yang, Victor X.; Varma, Abhay; Bogaards, Arjen; Hetzel, Fred W.; Chen, Qun; Fullagar, Tim; Fenstermaker, Robert; Selker, Robert; Abrams, Judith
In our previous phase II studies we treated 112 patients with malignant brain tumors with 2-mg/kg Photofrin i.v. and intra-operative cavitary PDT. We concluded that PDT was safe in patients with newly diagnosed or recurrent supratentorial malignant gliomas. Pathology, performance grade and light dose were significantly related to survival time. In selected patients when an adequate light dose was used survival time improved. The surgical mortality rate was less than 3%. [spie 2000] We have initiated two randomized prospective trials - the first, to determine if the addition of PDT to standard therapy [surgery, radiation and/or chemotherapy] prolongs the survival of patients with newly diagnosed malignant astrocytic tumors; and the second, to determine whether high light dose PDT [120 J/cm2] is superior to low light dose PDT [40 J/cm2] in patients with recurrent malignant astrocytic tumors. To date, 158 patients have been recruited - 72 to the newly diagnosed malignant glioma study and 86 to the recurrent glioma study. In the recurrent glioma study we compared the pre-operative KS and elements of the neurological examination [speech function, visual fields, cognitive function, sensory examination and gait] to the post-operative examinations at hospital discharge. The means were compared by paired student-t test. The KS in 86 of 88 patients with recurrent gliomas were assessable. The mean [s.d.] preoperative and post-operative KS were 82+/- 14 and 79+/- 17, respectively [p=0.003]. The mean decline in KS, although statistically significant, was small and of no clinical importance. The median Karnofsky score changed from 90 to 80. The KS improved in 8 patients; their post-operative average length of stay (alos) was =9.7 days. There was no change in 47 [alos=8.3], a decline of 10 points in 24 [aloc=13.4] and declined by more than 10 points in 7 [alos=23.3]. Three of these 7 patients who had a decline of >10 points improved in follow-up but did not reach their
Research and Development of Future Muon Collider
Yonehara, K.; /Fermilab
Muon collider is a considerable candidate of the next generation high-energy lepton collider machine. A novel accelerator technology must be developed to overcome several intrinsic issues of muon acceleration. Recent research and development of critical beam elements for a muon accelerator, especially muon beam phase space ionization cooling channel, are reviewed in this paper.
Adjuvant photodynamic therapy (PDT) of the superficial bladder cancer
NASA Astrophysics Data System (ADS)
Sokolov, V. V.; Russakov, I. G.; Teplov, A. A.; Filonenko, E. V.; Ul'yanov, R. V.; Bystrov, A. A.
Superficial transitional cell carcinoma represents 50 to 80% of newly diagnosed bladder cancer in various countries. Transurethral resection of the urinary bladder is the standard procedure for biopsy and treatment superficial bladder cancer. However recurrence tumors after transurethral resection alone is high enough (50-90%). Intravesical chemotherapy for prophylaxis after complete transurethral resection is reducing recurrence rate about 1 5%. Adjuvant intravesical Bacillus of Calmette and Guerin (BCG) is reducing recurrence rate about 30%, but frequency side effects of this therapy is very high. Purpose of this study is appreciate efficacy adjuvant PDT with photosensitizer Photogeme (Russia) of superficial bladder cancer for prophylaxis after complete transurethral resection. The follow up was from 3 to 63 months (27 months, on average). Sixty-five patients (75.6%) showed no recurrence. For the follow up period, the recurrence was revealed in 21 (24.4%) patient, in two of them it was progressing (one case of invasive growth and one case of remote metastases). Four cases of recurrence were revealed 4 months after the surgery. In other cases, the recurrence was diagnosed from 9 to 18 months.
Clinical experience of PDT in Brazil: a 300 patient overview
NASA Astrophysics Data System (ADS)
Kurachi, Cristina; Ferreira, Juliana; Marcassa, Luis G.; Cestari Filho, Guilherme A.; Souza, Cacilda S.; Bagnato, Vanderlei S.
Clinical application of Photodynamic Therapy (PDT) in Brazil is a result of a pioneering work in a collaborative program involving the Physics Institute and the Medical School of the University of Sao Paulo and the Amaral Carvalho Cancer Hospital in the city of Jau, Sao Paulo. This work began in 1997 with the first patient treated in 1999. Up to the end of 2003 this program has treated over 300 patients and the ones with correct follow up had their lesions included in this report. The majority of the lesions were of non-melanoma skin cancer located on the head and neck region, but the group has also treated Esophagus, Bladder, Gynecological, chest wall recurrence of breast cancer, among others. The results have shown to be compatible with internationally reported data, and we have modified some application procedures towards to a better benefit for the patient and an optimization of the results. We present the overall results observed after 5 year of experimental clinical treatment.
Biocompatible magnetic microspheres for Use in PDT and hyperthermia.
Vaccari, C B; Cerize, N N P; Morais, P C; Ré, M I; Tedesco, A C
Loaded microspheres with a silicon (IV) phthalocyanine derivative (NzPC) acting as a photosensitizer were prepared from polyhydroxybutyrate-co-valerate (PHBHV) and poly(ecaprolactone) (PCL) polymers using the emulsification solvent evaporation method (EE). The aim of our study was to prepare two systems of these biodegradable PHBHV/PCL microspheres. The first one containing only photosensitizer previously incorporated in the PHBHV and poly(ecaprolactone) (PCL) microspheres and the second one with the post magnetization of the DDS with magnetic nanoparticles. Magnetic fluid is successfully used for controlled incorporation of nanosized magnetic particles within the micron-sized template. This is the first time that we could get a successful pos incorporation of nanosized magnetic particles in a previously-prepared polymeric template. This procedure opens a great number of possibilities of post-functionalization of polymeric micro or nanoparticles with different bioactive materials. The NzPC release profile of the systems is ideal for PDT, the zeta potential and the size particle are stable upon aging in time. In vitro studies were evaluated using gingival fibroblastic cell line. The dark citotoxicity, the phototoxicity and the AC magnetic field assays of the as-prepared nanomagnetic composite were evaluated and the cellular viability analyzed by the classical test of MTT. PMID:22905587
Muon energy reconstruction in the Antarctic muon and neutrino detector array (AMANDA)
NASA Astrophysics Data System (ADS)
Miocinovic, Predrag
that the energy spectrum of detected atmospheric neutrinos is consistent with its prediction. The atmospheric-neutrino energy spectrum supports the neutrino-flavor oscillation hypothesis as put forward by the Super-Kamiokande group. Based on the assumption of complete mixing (sin2 2theta = 1) and using energy spectrum shape comparison, I find that the AMANDA preferred squared mass difference is 1.6 · 10-4 eV2 ≤ Delta m2 ≤ 3.46 · 10-3 eV 2. The measurement of the atmospheric-muon energy spectrum shows a disagreement with the prediction, possibly indicating an incomplete understanding of physics that is currently used to describe atmospheric muon flux. The method presented here makes it possible to estimate energy an order of magnitude greater than was previously possible by AMANDA and it improves the resolution and accuracy over the currently used technique. It naturally scales for use in larger detectors like AMANDA- II and IceCube, and it can be easily extended for use in energy reconstruction of electron- and muon-neutrino contained events.
Quasi-isochronous Muon Collection Channels
Yoshikawa, C.; Ankenbrandt, C.; Neuffer, D.; /Fermilab
Intense muon beams have many potential applications, including neutrino factories and muon colliders. However, muons are produced as tertiary beams, resulting in diffuse phase space distributions. To make useful beams, the muons must be rapidly cooled before they decay. An idea conceived recently for the collection and cooling of muon beams, namely, the use of a Quasi-Isochronous Helical Channel (QIHC) to facilitate capture of muons into RF buckets, has been developed further. The resulting distribution could be cooled quickly and coalesced into a single bunch to optimize the luminosity of a muon collider. After a brief elaboration of the QIHC concept, recent developments are described.
Probing beyond the Standard Model with Muons
Hisano, Junji
Muon's Properties are the most precisely studied among unstable particles. After discovery of muons in 40's, the studies of muons contributed to construction and establishment of the standard model in the particle physics. Now we are going to LHC era, however, precision frontier is still important in the particle physics. In this article, we review roles of muon physics in the particle physics. Muon g-2, lepton flavor violation (LFV) in muon decay, and electric dipole moment (EDM) of muon are mainly discussed.
Fernandez-Martinez, Enrique; Mahbubani, Rakhi E-mail: firstname.lastname@example.com
We carry out a time-series analysis of the combined data from three experiments measuring the cosmic muon flux at the Gran Sasso laboratory, at a depth of 3800 m.w.e. These data, taken by the MACRO, LVD and Borexino experiments, span a period of over 20 years, and correspond to muons with a threshold energy, at sea level, of around 1.3 TeV. We compare the best-fit period and phase of the full muon data set with the combined DAMA/NaI and DAMA/LIBRA data, which spans the same time period, as a test of the hypothesis that the cosmic ray muon flux is responsible for the annual modulation detected by DAMA. We find in the muon data a large-amplitude fluctuation with a period of around one year, and a phase that is incompatible with that of the DAMA modulation at 5.2σ. Aside from this annual variation, the muon data also contains a further significant modulation with a period between 10 and 11 years and a power well above the 99.9% C.L threshold for noise, whose phase corresponds well with the solar cycle: a surprising observation for such high energy muons. We do not see this same period in the stratospheric temperature data.
Muon Simulation at the Daya Bay SIte
Mengyun, Guan; Jun, Cao; Changgen, Yang; Yaxuan, Sun; Luk, Kam-Biu
With a pretty good-resolution mountain profile, we simulated the underground muon background at the Daya Bay site. To get the sea-level muon flux parameterization, a modification to the standard Gaisser's formula was introduced according to the world muon data. MUSIC code was used to transport muon through the mountain rock. To deploy the simulation, first we generate a statistic sample of sea-level muon events according to the sea-level muon flux distribution formula; then calculate the slant depth of muon passing through the mountain using an interpolation method based on the digitized data of the mountain; finally transport muons through rock to get underground muon sample, from which we can get results of muon flux, mean energy, energy distribution and angular distribution.
Muon Collider Task Force Report
Ankenbrandt, C.; Alexahin, Y.; Balbekov, V.; Barzi, E.; Bhat, C.; Broemmelsiek, D.; Bross, A.; Burov, A.; Drozhdin, A.; Finley, D.; Geer, S.; /Fermilab /Argonne /Brookhaven /Jefferson Lab /LBL, Berkeley /MUONS Inc., Batavia /UCLA /UC, Riverside /Mississippi U.
Muon Colliders offer a possible long term path to lepton-lepton collisions at center-of-mass energies {radical}s {ge} 1 TeV. In October 2006 the Muon Collider Task Force (MCTF) proposed a program of advanced accelerator R&D aimed at developing the Muon Collider concept. The proposed R&D program was motivated by progress on Muon Collider design in general, and in particular, by new ideas that have emerged on muon cooling channel design. The scope of the proposed MCTF R&D program includes muon collider design studies, helical cooling channel design and simulation, high temperature superconducting solenoid studies, an experimental program using beams to test cooling channel RF cavities and a 6D cooling demonstration channel. The first year of MCTF activities are summarized in this report together with a brief description of the anticipated FY08 R&D activities. In its first year the MCTF has made progress on (1) Muon Collider ring studies, (2) 6D cooling channel design and simulation studies with an emphasis on the HCC scheme, (3) beam preparations for the first HPRF cavity beam test, (4) preparations for an HCC four-coil test, (5) further development of the MANX experiment ideas and studies of the muon beam possibilities at Fermilab, (6) studies of how to integrate RF into an HCC in preparation for a component development program, and (7) HTS conductor and magnet studies to prepare for an evaluation of the prospects for of an HTS high-field solenoid build for a muon cooling channel.
Involvement of ASK1 activation in apoptosis induced by NPe6-PDT
NASA Astrophysics Data System (ADS)
Liu, Lei; Zhang, Zhen-zhen; Zhang, Zhigang
Photodynamic therapy (PDT) employing photosensiter N-aspartyl chlorin e6 (NPe6) can induce lysosome disruption and initiate apoptotic pathway. Apoptosis signal-regulating kinase (ASK1) is an important regulator of apoptosis in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide (LPS) and calcium influx. In this study, we investigated the molecular mechanisms of apoptosis induced by NPe6-PDT in ASTC-a-1 cells. The results showed that the activities of ASK1 increased in response to NPe6-PDT. Over-expression of wild-type or activated mutant of ASK1 could obviously decrease cell viability and increase cell death; while inhibition of ASK1 significantly decreased cell apoptosis. These results suggested that ASK1 plays an important role in apoptosis induced by NPe6-PDT.
Observations of the incidence of metastasis following laser hyperthermia in combination with chemotherapy, PDT, and excision
NASA Astrophysics Data System (ADS)
Wang, Mianjing; Gao, Menglin; Gao, Jin; Xue, Kexun; Xu, Zuyan; Zhang, Jingyuan; Li, Qongru; Geng, Zifan; Gong, Zhuo; Ye, Qing; Gu, Pei; Xao, Jing-Lian
Our early observations have confirmed that laser hyperthermia or PDT alone does not promote the tumor metastasis. In order to evaluate the combined effect of local tumor laser hyperthermia on the distant metastasis, transplantable forestomach carcinoma (Fc) in 615 line mice was treated by Nd:YAG laser hyperthermia (45 degree(s)C/20 min) combined with PDT (HpD 5 mg/kg, 480 J/cm2, 20 min), chemotherapy (Cyclophosphamide 28.8 mg/kg) and excision, respectively. The results show that (1) the tumor growth inhibition by various treatment was significant compared with a control group; (2) no statistics different in metastasis rate were observed in laser hyperthermia combined with PDT, chemotherapy, or scalpel excision separately. It is suggested that laser hyperthermia combined with PDT, chemotherapy, or excision does not increase the incidence of the tumor metastasis.
Preparation and Protonation of Fe2(pdt)(CNR)6, Electron-Rich Analogues of Fe2(pdt)(CO)6.
Zhou, Xiaoyuan; Barton, Bryan E; Chambers, Geoffrey M; Rauchfuss, Thomas B; Arrigoni, Federica; Zampella, Giuseppe
The complexes Fe2(pdt)(CNR)6 (pdt(2-) = CH2(CH2S(-))2) were prepared by thermal substitution of the hexacarbonyl complex with the isocyanides RNC for R = C6H4-4-OMe (1), C6H4-4-Cl (2), Me (3). These complexes represent electron-rich analogues of the parent Fe2(pdt)(CO)6. Unlike most substituted derivatives of Fe2(pdt)(CO)6, these isocyanide complexes are sterically unencumbered and have the same idealized symmetry as the parent hexacarbonyl derivatives. Like the hexacarbonyls, the stereodynamics of 1-3 involve both turnstile rotation of the Fe(CNR)3 as well as the inversion of the chair conformation of the pdt ligand. Structural studies indicate that the basal isocyanide has nonlinear CNC bonds and short Fe-C distances, indicating that they engage in stronger Fe-C π-backbonding than the apical ligands. Cyclic voltammetry reveals that these new complexes are far more reducing than the hexacarbonyls, although the redox behavior is complex. Estimated reduction potentials are E1/2 ≈ -0.6 ([2](+/0)), -0.7 ([1](+/0)), and -1.25 ([3](+/0)). According to DFT calculations, the rotated isomer of 3 is only 2.2 kcal/mol higher in energy than the crystallographically observed unrotated structure. The effects of rotated versus unrotated structure and of solvent coordination (THF, MeCN) on redox potentials were assessed computationally. These factors shift the redox couple by as much as 0.25 V, usually less. Compounds 1 and 2 protonate with strong acids to give the expected μ-hydrides [H1](+) and [H2](+). In contrast, 3 protonates with [HNEt3]BAr(F)4 (pKa(MeCN) = 18.7) to give the aminocarbyne [Fe2(pdt)(CNMe)5(μ-CN(H)Me)](+) ([3H](+)). According to NMR measurements and DFT calculations, this species adopts an unsymmetrical, rotated structure. DFT calculations further indicate that the previously described carbyne complex [Fe2(SMe)2(CO)3(PMe3)2(CCF3)](+) also adopts a rotated structure with a bridging carbyne ligand. Complex [3H](+) reversibly adds MeNC to give [Fe2(pdt
Investigation of photodynamic effect caused by MPPa-PDT on breast cancer Investigation of photodynamic effect caused by MPPa-PDT
NASA Astrophysics Data System (ADS)
Tian, Y. Y.; Hu, X. Y.; Leung, W. N.; Yuan, H. Q.; Zhang, L. Y.; Cui, F. A.; Tian, X.
Breast cancer is the common malignant tumor, the incidence increases with age. Photodynamic therapy (PDT) is a new technique applied in tumors, which involves the administration of a tumor localizing photosensitizer and it is followed by the activation of a specific wavelength. Pyropheophorbide-a methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. We are exploring the photodynamic effect caused by MPPa-PDT on breast cancer. The in vitro and in vivo experiments indicate that MPPa is a comparatively ideal photosensitizer which can induce apoptosis in breast cancer.
First-principles investigation of electronic structures and properties of impurities in molecular solids and semiconductors: I. Muon and muonium in organic ferromagnets. II. Erbium in silicon-optoelectronic system
NASA Astrophysics Data System (ADS)
Jeong, Junho
The first-principles Hartree-Fock theory is used to obtain the electronic structures and properties of three different systems. For the TEMPO system, the trapping sites were obtained near NO group site for muonium singlet and near chlorine and bridge nitrogen for muon. The calculated hyperfine interactions including relaxation and vibrational effect were used to compare the observed zero field muSR frequency 3.2 MHz. It has been concluded that the two trapping centers that can best explain the observed muSR frequency is trapped singlet muonium near the radical oxygen and a trapped muon site near the chlorine. The direction for the easy axis is determined to be the b-axis of the monoclinic lattice and also is obtained using the magnetic moment distributions in the ferromagnetic state in the absence of muon and muonium. The nuclear quadrupole coupling constants and asymmetry parameters (eta) have studied for the 35Cl, 17O, and 14N nuclei in the TEMPO system for the bare system and systems with trapped muon and muonium. Substantial influence of the muon and muonium on the coupling constants and eta for the nuclei close to the trapping sites have been observed for the systems with trapped muon and muonium. For the beta-NPNN, the observed muSR signal at zero field with frequency 2.1 MHz is assigned to the singlet muonium sites near the two oxygens of the two NO groups and the high frequency signal ascribed to an isotropic hyperfine constant of 400MHz is assigned to the trapped muon sites near the oxygen atoms of the NO groups. Er3+-Si material which emits 1.54 mum wavelength has led to interest in optoelectronic system. Using first-principles HF procedure, the locations of Er3+ in silicon cluster without codopant were determined. Since covalent radius of Er3+ is bigger than that of silicon, the first nearest and second nearest silicon of Er3+ for Hi (Er3+Si14H18), Ti (Er3+ Si10H16, Er3+Si26H 48), and Substitutional site (Er3+Si18H 36) applied relaxation effect. The
Liu Aihua; Li Shumin; Berakdar, Jamal
We show theoretically that the muon lifetime can be changed dramatically by embedding the decaying muon in a strong linearly polarized laser field. Evaluating the S-matrix elements taking all electronic multiphoton processes into account we find that a CO{sub 2} laser with an electric field amplitude of 10{sup 6} V cm{sup -1} results in an order of magnitude shorter lifetime of the muon. We also analyze the dependencies of the decay rate on the laser frequency and intensity.
Measurement of muon intensity by Cerenkov method
NASA Technical Reports Server (NTRS)
Liu, Z. H.; Li, G. J.; Bai, G. Z.; Liu, J. G.; Geng, Q. X.; Ling, J.
Optical detection is an important technique in studies and observations of air showers, muons and relevant phenomena. The muon intensity is measured in a proper energy range and to study some problems about Cerenkov radiation of cosmic rays are studied, by a muon-telescope operated with Cerenkov detector. It is found that the measured muon intensity agrees with the integral energy spectrum of cosmic ray muons.
Muon front end for the neutrino factory
NASA Astrophysics Data System (ADS)
Rogers, C. T.; Stratakis, D.; Prior, G.; Gilardoni, S.; Neuffer, D.; Snopok, P.; Alekou, A.; Pasternak, J.
In the neutrino factory, muons are produced by firing high-energy protons onto a target to produce pions. The pions decay to muons and pass through a capture channel known as the muon front end, before acceleration to 12.6 GeV. The muon front end comprises a variable frequency rf system for longitudinal capture and an ionization cooling channel. In this paper we detail recent improvements in the design of the muon front end.
Muon ID - taking care of lower momenta muons
Milstene, C.; Fisk, G.; Para, A.; /Fermilab
In the Muon package under study, the tracks are extrapolated using an algorithm which accounts for the magnetic field and the ionization (dE/dx). We improved the calculation of the field dependent term to increase the muon detection efficiency at lower momenta using a Runge-Kutta method. The muon identification and hadron separation in b-bbar jets is reported with the improved software. In the same framework, the utilization of the Kalman filter is introduced. The principle of the Kalman filter is described in some detail with the propagation matrix, with the Runge-Kutta term included, and the effect on low momenta for low momenta single muons particles is described.
Lifetime-resolved photoacoustic (LPA) spectroscopy for monitoring oxygen change and photodynamic therapy (PDT)
NASA Astrophysics Data System (ADS)
Jo, Janggun; Lee, Chang Heon; Kopelman, Raoul; Wang, Xueding
The Methylene Blue loaded Polyacrylamide Nanoparticles (MB-PAA NPs) are used for oxygen sensing and Photodynamic therapy (PDT), a promising therapeutic modality employed for various tumors, with distinct advantages of delivery of biomedical agents and protection from other bio-molecules overcoming inherent limitations of molecular dyes. Lifetime-resolved photoacoustic spectroscopy using quenched-phosphorescence method is applied with MB-PAA NPs so as to sense oxygen, while the same light source is used for PDT. The dye is excited by absorbing 650 nm wavelength light from a pump laser to reach triplet state. The probe laser at 810 nm wavelength is used to excite the first triplet state at certain delayed time to measure the dye lifetime which indicates oxygen concentration. The 9L cells (106 cells/ml) incubated with MB-PAA NP solution are used for monitoring oxygen level change during PDT in situ test. The oxygen level and PDT efficacy are confirmed with a commercial oximeter, and fluorescence microscope imaging and flow cytometry results. This technique with the MB-PAA NPs allowed us to demonstrate a potential non-invasive theragnostic operation, by monitoring oxygen depletion during PDT in situ, without the addition of secondary probes. Here, we demonstrate this theragnostic operation, in vitro, performing PDT while monitoring oxygen depletion. We also show the correlation between O2 depletion and cell death.
Soluble guanylyl cyclase is involved in PDT-induced injury of crayfish glial cells
NASA Astrophysics Data System (ADS)
Kovaleva, V. D.; Uzdensky, A. B.
Photodynamic therapy (PDT) is a potential tool for selective destruction of malignant brain tumors. However, not only malignant but also healthy neurons and glial cells may be damaged during PDT. Nitric oxide is an important modulator of cell viability and intercellular neuroglial communications. NO have been already shown to participate in PDT-induced injury of neurons and glial cells. As soluble guanylyl cyclase is the only known receptor for NO, we have studied the possible role of soluble guanylyl cyclase in the regulation of survival and death of neurons and surrounding glial cells under photo-oxidative stress induced by photodynamic treatment (PDT). The crayfish stretch receptor consisting of a single identified sensory neuron enveloped by glial cells is a simple but informative model object. It was photosensitized with alumophthalocyanine photosens (10 nM) and irradiated with a laser diode (670 nm, 0.4 W/cm2). Using inhibitory analysis we have shown that during PDT soluble guanylyl cyclase, probably, has proapoptotic and antinecrotic effect on the glial cells of the isolated crayfish stretch receptor. Proapoptotic effect of soluble guanylyl cyclase could be mediated by protein kinase G (PKG). Thus, the involvement of NO/sGC/cGMP/PKG signaling pathway in PDT-induced apoptosis of glial cells was indirectly demonstrated.
Next-generation light delivery system for multitreatment extended-duration photodynamic therapy (MED-PDT)
NASA Astrophysics Data System (ADS)
Chen, James C.
The primary focus of laser based oncologic PDT has been on the treatment of skin and hollow organ tumors. Extending PDT to other primary internal lesions and metastasis requires a different approach. Light Sciences has developed a series of semiconductor-based devices which will be completely implanted in the patient using established, minimally invasive surgical techniques. These devices are energized noninvasively utilizing inductive coupling. The light delivery system will allow the clinician to modulate the intensity, spatial distribution, and duration of light delivery in order to maximize the benefits derived from each PDT drug dose. Light Sciences' technology minimizes patient risk and discomfort, is cost competitive, and expands the treatment options available to the clinician. Avoidance of lengthy operations, bone marrow suppression, and an emphasis on organ preservation allow this next generation of PDT light delivery devices to be effectively integrated with other forms of cancer treatment, if desired. We have termed our technique 'Multi-treatment Extended Duration PDT'. In what follows, we shall describe Light Sciences' technology and development of minimally invasive oncologic PDT.
Photodynamic therapy (PDT) with endoscopic ultrasound for the treatment of esophageal cancer
NASA Astrophysics Data System (ADS)
Woodward, Timothy A.; Wolfsen, Herbert C.
In 1995, PDT was approved for palliative use in patients with esophageal cancer. We report our experience using PDT to treat esophageal cancer patients previously treated with combination chemotherapy and radiation therapy. In our series, nine patients referred for PDT with persistent esophageal cancer after chemo-radiation therapy. We found: (1) All patients were men with a mean age of 63 years and eight out of nine had adenocarcinoma with Barrett's esophagus; (2) All patients required endoscopic dilation after PDT; (3) At a mean follow up of 4 months, two T2N0 patients had no demonstrable tumor and all three T3N0 patients had greater than 50% tumor reduction (the partially responsive T3N0 patients will be offered repeat PDT); (4) Patients with metastatic disease (T3N1 or M1) had effective dysphagia palliation. Thus, PDT is safe and effective in ablating all or most tumor in patients with persistent esophageal cancer after chemotherapy and radiation therapy.
EGF targeted fluorescence molecular tomography as a predictor of PDT outcomes in pancreas cancer models
NASA Astrophysics Data System (ADS)
Samkoe, Kimberley S.; Davis, Scott C.; Srinivasan, Subhadra; Isabelle, Martin E.; O'Hara, Julia; Hasan, Tayyaba; Pogue, Brian W.
Verteporfin photodynamic therapy (PDT) is a promising adjuvant therapy for pancreas cancer and investigations for its use are currently underway in both orthotopic xenograft mouse models and in human clinical trials. The mouse models have been studied extensively using magnetic resonance (MR) imaging as a measure of surrogate response to verteporfin PDT and it was found that tumor lines with different levels of aggression respond with varying levels to PDT. MR imaging was successful in determining the necrotic volume caused by PDT but there was difficultly in distinguishing inflamed tissues and regions of surviving tumor. In order to understand the molecular changes within the tumor immediately post-PDT we propose the implementation of MR-guided fluorescence molecular tomography (FMT) in conjunction with an exogenously administered fluorescently labeled epidermal growth factor (EGF-IRDye800CW, LI-COR Biosciences). We have previously shown that MR-guided FMT is feasible in the mouse abdomen when multiple regions of fluorescence are considered from contributing internal organs. In this case the highly aggressive AsPC-1 (+EGFR) orthotopic tumor was implanted in SCID mice, interstitial verteporfin PDT (1mg/kg, 20J/cm) was performed when the tumor reached ~60mm3 and both tumor volume and EGF binding were followed with MR-guided FMT.
Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA
NASA Astrophysics Data System (ADS)
Marrero, Allison; Sunar, Ulas; Sands, Theresa; Oseroff, Allan; Bellnier, David
Photodynamic treatment of subcutaneously implanted Colon 26 tumors in BALB/c mice using the aminolevulinic acid (ALA)-induced photosensitizer protoporphyrin IX (PpIX) was shown to be enhanced by the addition of the vascular disrupting agent 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA; Novartis ASA404). DMXAA increases vascular permeability and decreases blood flow in both murine and human tumors. Sufficiently high parenteral DMXAA doses can lead to tumor collapse and necrosis. We have previously reported marked enhancement of antitumor activity when PDT, using either Photofrin or HPPH, is combined with low-dose intraperitoneal DMXAA. We now describe the first attempt to combine topically-applied DMXAA with PDT. For this, DMXAA was applied two hours before PpIX-activating light delivery. PDT with ALA-PDT alone (ALA 20%; 80 J/cm2 delivered at 75 mW/cm2) caused a 39% decrease in tumor volume compared to unirradiated controls. Addition of topical DMXAA to ALA-PDT resulted in a 74% reduction in tumor volume. Diffuse correlation spectroscopy (DCS), a non-invasive blood flow imaging method, is being used to understand the mechanism of this effect and to aid in the proper design of the therapy. For instance, our most recent DCS data suggests that the 2-hour interval between the DMXAA and light applications may not be optimum. This preliminary study suggests a potential role for topical DMXAA in combination with PDT for dermatologic tumors.
Slawomir Bogacz, Rolland Johnson
Future Muon Colliders (MC) and Neutrino Factories (NF) based on muon storage rings will require innovative linacs to: produce the muons, cool them, compress longi-tudinally and 'shape' them into a beam and finally to rap-idly accelerate them to multi-GeV (NF) and TeV (MC) energies. Each of these four linac applications has new requirements and opportunities that follow from the na-ture of the muon in that it has a short lifetime (τ = 2.2 μsec) in its own rest frame, it is produced in a tertiary process into a large emittance, and its electron, photon, and neutrino decay products can be more than an annoy-ance. As an example, for optimum performance, the linac repetition rates should scale inversely with the laboratory lifetime of the muon in its storage ring, something as high as 1 kHz for a 40 GeV Neutrino Factory or as low as 20 Hz for a 5 TeV Muon Collider. A superconducting 8 GeV Linac capable of CW operation is being studied as a ver-satile option for muon production [1] for colliders, facto-ries, and muon beams for diverse purposes. A linac filled with high pressure hydrogen gas and imbedded in strong magnetic fields has been proposed to rapidly cool muon beams [2]. Recirculating Linear Accelerators (RLA) are possible because muons do not generate significant syn-chrotron radiation even at extremely high energy and in strong magnetic fields. We will describe the present status of linacs for muon applications; in particular the longitu-dinal bunch compression in a single pass linac and multi-pass acceleration in the RLA, especially the optics and technical requirements for RLA designs, using supercon-ducting RF cavities capable of simultaneous acceleration of both μ+ and μ- species, with pulsed linac quadrupoles to allow the maximum number of passes. The design will include the optics for the multi-pass linac and droplet-shaped return arcs.
NASA Technical Reports Server (NTRS)
Stronach, C. E.
The muon spin rotation (MuSR) technique is used to probe the microscopic electron density in materials. High temperature MuSR and magnetization measurements in nickel are in progress to allow an unambiguous determination of the muon impurity interaction and the impurity induced change in local spin density. The first results on uniaxial stress induced frequency shifts in an Fe single crystal are also reported.
Muon Colliders: The Next Frontier
Tourun, Yagmur [Illinois Institute of Technology, Chicago, Illinois, United States
Muon Colliders provide a path to the energy frontier in particle physics but have been regarded to be "at least 20 years away" for 20 years. I will review recent progress in design studies and hardware R&D and show that a Muon Collider can be established as a real option for the post-LHC era if the current vigorous R&D effort revitalized by the Muon Collider Task Force at Fermilab can be supported to its conclusion. All critical technologies are being addressed and no show-stoppers have emerged. Detector backgrounds have been studied in detail and appear to be manageable and the physics can be done with existing detector technology. A muon facility can be built through a staged scenario starting from a low-energy muon source with unprecedented intensity for exquisite reach for rare processes, followed by a Neutrino Factory with ultrapure neutrino beams with unparalleled sensitivity for disentangling neutrino mixing, leading to an energy frontier Muon Collider with excellent energy resolution.
Muon Colliders: The Next Frontier
Tourun, Yagmur
Muon Colliders provide a path to the energy frontier in particle physics but have been regarded to be 'at least 20 years away' for 20 years. I will review recent progress in design studies and hardware R&D and show that a Muon Collider can be established as a real option for the post-LHC era if the current vigorous R&D effort revitalized by the Muon Collider Task Force at Fermilab can be supported to its conclusion. All critical technologies are being addressed and no show-stoppers have emerged. Detector backgrounds have been studied in detail and appear to be manageable and the physics can be done with existing detector technology. A muon facility can be built through a staged scenario starting from a low-energy muon source with unprecedented intensity for exquisite reach for rare processes, followed by a Neutrino Factory with ultrapure neutrino beams with unparalleled sensitivity for disentangling neutrino mixing, leading to an energy frontier Muon Collider with excellent energy resolution.
Muon Colliders: The Next Frontier
Tourun, Yagmur
Muon Colliders provide a path to the energy frontier in particle physics but have been regarded to be "at least 20 years away" for 20 years. I will review recent progress in design studies and hardware R&D and show that a Muon Collider can be established as a real option for the post-LHC era if the current vigorous R&D effort revitalized by the Muon Collider Task Force at Fermilab can be supported to its conclusion. All critical technologies are being addressed and no show-stoppers have emerged. Detector backgrounds have been studied in detail and appear to be manageable and the physics can be done with existing detector technology. A muon facility can be built through a staged scenario starting from a low-energy muon source with unprecedented intensity for exquisite reach for rare processes, followed by a Neutrino Factory with ultrapure neutrino beams with unparalleled sensitivity for disentangling neutrino mixing, leading to an energy frontier Muon Collider with excellent energy resolution.
Effects of TOOKAD-PDT on canine prostates pre-treated with ionizing radiation
NASA Astrophysics Data System (ADS)
Chen, Qun; Huang, Zheng; Luck, David L.; Beckers, Jill; Trncic, Nadira; LaRue, Susan M.; Brun, Pierre-Herve; Wilson, Brian C.; Hetzel, Fred W.
PDT in prostate cancer will likely be implemented clinically with patients who have failed prior ionizing radiation therapy (RT). The current study is to develop an in vivo model to evaluate the effects of PDT on prostatic tissue after RT. To produce a physiological and anatomical environment in prostate similar to that in patients who have failed RT, canine prostates (n=4) were subjected to a definitive course of ionizing radiation therapy (2.7 Gy x 20 fractions) 5 to 6 months prior to PDT. A laparotomy was performed to expose the prostate for PDT. Second generation photosensitizer Tookad (Palladium-Bacteriopheophorbide, Steba Biotech, The Netherlands) acts primarily on tissue vasculature and is very effective in destroying normal prostatic tissue, as shown by our prior studies. Due to the extremely fast clearance of the photosensitizer, interstitial light irradiation (760 nm, 50-200 J/cm, 150 mW/cm from a 1 cm diffuser fiber) was delivered 4 minutes after the onset of Tookad infusion (i.v. 2.5 mg/ml, 2 mg/kg, total infusion time 10 min). The prostates were harvested for histopathology one week after PDT. At one week, the lesions were characterized by acute hemorrhagic necrosis with patchy sub-capsular hyperemia and edema. The maximum lesion diameter for 50, 100 and 200 J/cm PDT was approximately 15, 20 and 28 mm, respectively. The lesion size is well correlated with light fluence and comparable to that in prostates treated with identical PDT doses but without prior-RT. Under light-microscopy, the PDT induced necrosis is clearly distinguishable from the radiation induced fibrosis. No urethral lesions were observed. Dyer"s Verhoeff stain showed the loss of stromal connective tissue and the acinar collagen in the PDT treated area. There was no noticeable damage on the bladder or underlying colon section. In conclusion, Tookad-PDT can effectively destroy prostate tissue with prior-RT induced fibrosis, thus, may provide an alternative modality for those prostate
Quasi-isochronous muon collection channels
Ankenbrandt, Charles M.; Neuffer, David; Johnson, Rolland P.
Intense muon beams have many potential commercial and scientific applications, ranging from low-energy investigations of the basic properties of matter using spin resonance to large energy-frontier muon colliders. However, muons originate from a tertiary process that produces a diffuse swarm. To make useful beams, the swarm must be rapidly captured and cooled before the muons decay. In this STTR project a promising new concept for the collection and cooling of muon beams to increase their intensity and reduce their emittances was investigated, namely, the use of a nearly isochronous helical cooling channel (HCC) to facilitate capture of the muons into RF bunches. The muon beam can then be cooled quickly and coalesced efficiently to optimize the luminosity of a muon collider, or could provide compressed muon beams for other applications. Optimal ways to integrate such a subsystem into the rest of a muon collection and cooling system, for collider and other applications, were developed by analysis and simulation. The application of quasi-isochronous helical cooling channels (QIHCC) for RF capture of muon beams was developed. Innovative design concepts for a channel incorporating straight solenoids, a matching section, and an HCC, including RF and absorber, were developed, and its subsystems were simulated. Additionally, a procedure that uses an HCC to combine bunches for a muon collider was invented and simulated. Difficult design aspects such as matching sections between subsystems and intensity-dependent effects were addressed. The bunch recombination procedure was developed into a complete design with 3-D simulations. Bright muon beams are needed for many commercial and scientific reasons. Potential commercial applications include low-dose radiography, muon catalyzed fusion, and the use of muon beams to screen cargo containers for homeland security. Scientific uses include low energy beams for rare process searches, muon spin resonance applications, muon beams for
Explanation for the low flux of high-energy astrophysical muon neutrinos.
Pakvasa, Sandip; Joshipura, Anjan; Mohanty, Subhendra
There has been some concern about the unexpected paucity of cosmic high-energy muon neutrinos in detectors probing the energy region beyond 1 PeV. As a possible solution we consider the possibility that some exotic neutrino property is responsible for reducing the muon neutrino flux at high energies from distant sources; specifically, we consider (i) neutrino decay and (ii) neutrinos being pseudo-Dirac-particles. This would provide a mechanism for the reduction of high-energy muon events in the IceCube detector, for example. PMID:23679707
ALA-PDT of glioma cell micro-clusters in BD-IX rat brain
NASA Astrophysics Data System (ADS)
Madsen, Steen J.; Angell-Petersen, Even; Spetalen, Signe; Carper, Stephen W.; Ziegler, Sarah A.; Hirschberg, Henry
A significant contributory factor to the poor prognosis of patients with glioblastoma multiforme is the inability of conventional treatments to eradicate infiltrating glioma cells. A syngeneic rat brain tumor model is used to investigate the effects of aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on small clusters of tumor cells sequestered in normal brain. The intrinsic sensitivity of rat glioma cells to PDT was investigated by exposing ALA-incubated cells to a range of radiant exposures and irradiances using 635 nm light. Biodistribution studies were undertaken on tumor-bearing animals in order to determine the tumor selectivity of the photosensitizer following systemic administration (i.p.) of ALA. Effects of ALA-PDT on normal brain and gross tumor were evaluated using histopathology. Effects of PDT on isolated glioma cells in normal brain were investigated by treating animals 48 h after tumor cell implantation: a time when the micro-clusters of cells are protected by an intact blood-brain-barrier (BBB). Rat glioma cells in monolayer are susceptible to ALA-PDT - lower irradiances are more effective than higher ones. Fluorescence microscopy of frozen tissue sections showed that photosensitizer is produced with better than 200:1 tumor-to-normal tissue selectivity following i.p. ALA administration. ALA-PDT resulted in significant damage to both gross tumor and normal brain, however, the treatment failed to prolong survival of animals with newly implanted glioma cells compared to non-treated controls if the drug was delivered either i.p. or directly into the brain. In contrast, animals inoculated with tumor cells pre-incubated in vitro with ALA showed a significant survival advantage in response to PDT.
A clinical trial testing the efficacy of PDT in preventing amputation in diabetic patients.
Tardivo, João Paulo; Adami, Fernando; Correa, João Antonio; Pinhal, Maria Aparecida S; Baptista, Mauricio S
The feet of diabetic patients continue to be an unsolved problem in medicine. Uncontrolled neuropathy, ulceration and infection usually lead to amputation and presently there is no effective and reliable method that can be used to provide an efficient cure. Overall improvement in the salvage strategies, based on comprehensive pre-clinical evaluation, debridement, antibiotic therapy and follow up, has shown improvements in certain hospital settings, but the general picture for patients with diabetic foot is to have some sort of amputation, especially in underserved populations. It is clearly necessary to develop novel treatment strategies for this worldwide health problem. Photodynamic therapy (PDT) is a treatment modality that uses light to generate in situ reactive oxygen species, which can cause cell death. PDT can be used to treat several diseases, including foot infections that do not respond well to antibiotic therapy. There are several characteristics of PDT that make it potentially ideal to treat diabetic feet: the photosensitizer is non-toxic in the dark, but after illumination it becomes a very efficient antimicrobial agent with topical use, and it can regenerate small bones, such as the phalanges. However, PDT is still not used in clinical practice to treat diabetic feet. Therefore, we decided to perform a clinical study to prove that PDT is an effective method to avoid amputation of infected diabetic feet. An inexpensive PDT protocol was developed and applied to 18 patients with osteomyelitis, classified as Grade 3 on the Wagner scale. Only one of these patients suffered amputation. At least two of them were cured from resistant bacteria strains without intravenous antibiotic therapy. In the control group of 16 patients, all of them ended up suffering amputation. The rate of amputation in the PDT group was 0.029 times the rate in the control group and the difference is clearly statistically significant (p=0.002). PMID:24814697
Effect of hematoporphyrin monomethyl ether-mediated PDT on the mitochondria of canine breast cancer cells.
Li, H T; Song, X Y; Yang, C; Li, Q; Tang, Damu; Tian, W R; Liu, Y
Hematoporphyrin monomethyl ether (HMME) is a promising porphyrin-related photosensitize for photodynamic therapy (PDT). There still remains unknown changes regarding the mitochondrial in canine breast cancer cells treated with HMME-PDT. The aim of this study is to investigate the effect of HMME-PDT on structure and dysfunction of mitochondrial in cancer cells. The experimental approach included an initial study on the uptake of HMME using microscopic observation of the HMME-treated cells, optimization of the PDT-induced cell death by the MTT assay. These cells were then treated with HMME and a He-Ne laser at the wavelength of 632.8 nm following our optimized condition. Examination of mitochondrial changes by observing the stained cells under light microscope, mitochjondrial membrane potential flow cytometry, measuring the Ca(2+), SOD/GSH activity, ATPase and MDA contents for the mitochondria functions. The kinetics of HMME uptake in CHMm cells was determined and its cytocolic instead of nuclear distribution was demonstrated. The dose of 16mM HMME-PDT combined with 2.8 J/cm(2) laser irradiation was had the maximal impact on cell viability. This treatment resulted in structural changes in mitochondria that were accompanied with the loss of mitochjondrial membrane potential. As a result, HMME-PDT increased mitochondrial ROS, inhibited the enzymatic activities of mitochondrial SOD and GSH-Px, abolished mitochondrial ability in the uptake and release of calcium, and decreased mitochondrial ATPase activity. The combination of these abnormalities led to accumulation of ROS in mitochondrial to high levels, which in turn contributed to HMME-PDT-induced damages of mitochondrial structure and mitochondrial dysfunction. PMID:24284094
In vitro therapeutic effect of PDT combined with VEGF-A gene therapy
NASA Astrophysics Data System (ADS)
Lecaros, Rumwald Leo G.; Huang, Leaf; Hsu, Yih-Chih
Vascular endothelial growth factor A (VEGF-A), commonly known as VEGF, is one of the primary factors that affect tumor angiogenesis. It was found to be expressed in cancer cell lines including oral squamous cell carcinoma. Photodynamic therapy (PDT) is a novel therapeutic modality to treat cancer by using a photosensitizer which is activated by a light source to produce reactive oxygen species and mediates oxygen-independent hypoxic conditions to tumor. Another emerging treatment to cure cancer is the use of interference RNA (e.g. siRNA) to silence a specific mRNA sequence. VEGF-A was found to be expressed in oral squamous cell carcinoma and overexpressed after 24 hour post-PDT by Western blot analysis. Cell viability was found to decrease at 25 nM of transfected VEGF-A siRNA. In vitro combined therapy of PDT and VEGF-A siRNA showed better response as compared with PDT and gene therapy alone. The results suggest that PDT combined with targeted gene therapy has a potential mean to achieve better therapeutic outcome.
Interleukin-12 reverses the inhibitory impact of photodynamic therapy (PDT) on the murine contact hypersensitivity response
NASA Astrophysics Data System (ADS)
Simkin, Guillermo O.; Levy, Julia G.; Hunt, David W. C.
Treatment of mice with certain photosensitizers combined with exposure to visible light limits the development of the immunologically-mediated contact hypersensitivity (CHS) response against topically-applied chemical haptens. Understanding of the inhibitory action of photosensitizers upon the CHS response is incomplete. Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin), a photosensitizer with immunomodulatory activity, strongly depressed CHS responses to the hapten dinitrofluorobenzene (DNFB). However, if mice were administered 1 (mu) g of a recombinant preparation of the pro- inflammatory cytokine interleukin-12 (rIL-12), full-fledged CHS responses to DNFB ensued in animals treated with BPD-MA and light. In contrast, when rIL-12 was given in combination with an anti-IL-12 antibody the restorative effect of rIL-12 on the CHS response of PDT-treated mice was blocked. Evaluation of the cytokine status of spleen and draining lymph node cells showed for DNFB painted animals, that the release of the immunosuppressive cytokine IL-10 was increased by PDT and rIL-12 counter-acted the increase in IL-10 liberation associated with PDT. These studies indicate that IL-10 formation is upregulated and the availability of IL-12 may be limited in mice treated with PDT. These features may contribute to deficient CHS responses observed with PDT.
Double-targeting Using A TrkC-Ligand Conjugated To BODIPY-based PDT Agent
Kamkaew, Anyanee; Burgess, Kevin
A molecule 1 (IY-IY-PDT) was designed to contain a fragment (IY-IY) that targets the TrkC receptor, and a photosensitizer that acts as an agent for photodynamic therapy (PDT). Molecule 1 had sub-micromolar photocytotoxicities to cells that were either engineered to stably express TrkC (NIH3T3-TrkC) or that naturally express high levels of TrkC (SY5Y neuroblastoma lines). Control experiments showed 1 is not cytotoxic in the dark, and has significantly less photocytotoxicity towards cells that do not express TrkC (NIH3T3-WT). Other controls featuring a similar agent 2 (YI-YI-PDT) which is identical and isomeric with 1 except that the targeting region is scrambled (a YI-YI motif, see text) showed 1 is considerably more photocytotoxic than 2 on TrkC+ cells. Imaging live TrkC+ cells after treatment with a fluorescent agent 1 (IY-IY-PDT) proved that 1 permeates into TrkC+ cells and localizes in the lysosomes. This observation indirectly indicates agent 1 enters the cells via the TrkC receptor. Consistent with this, the dose-dependent PDT effects of 1 can be competitively reduced by the natural TrkC ligand, neurotrophin NT3. PMID:24063347
Our experience of PDT of cancer with two Russian-produced photosensitizers
NASA Astrophysics Data System (ADS)
Stranadko, Eugeny P.; Skobelkin, Oleg K.
Analysis of the results of photodynamic therapy (PDT) for treating malignant neoplasms of the skin, mammary glands, tongue, oral mucous, lower lip, larynx, lungs, urinary bladder, rectum,and other locations has been made. During 1992-1994 432 tumoral foci in 108 patients have been treated with PDT. All patients were previously treated with conventional techniques without effect or they were not treated due to contraindications either because of sever accompanying diseases or because of old age. A number of the patients had PDT because of recurrences or intradermal metastases within one to two years after surgical, radial, or combined treatment. Two homemade preparations were used as photosensitizers: Photohem (hematoporphyrin derivative) and Photosense (aluminum sulfonated phthalocyanine). Light sources were an American dye laser with argon laser pumping and homemade laser devices including a copper vapor laser-pumped dye laser, gas discharge unit, gold vapor laser for the Photohem sessions, wile for the Photosense sessions were used solid state lasers on yttrium aluminate. Up to now we have follow-up control data within 2 months and 3 years. Positive effect of PDT was seen in 90.7% of patients including complete regression of tumors in 52% and partial in 38.7%. Currently this new technique of treating malignant neoplasms is successfully being used in Russia; new photosensitizers and light sources for PDT and fluorescent tumor diagnostics are being developed as well.
Muon-muon and other high energy colliders
Palmer, R.B.; Gallardo, J.C.
The first section looks at the high energy physics advantages, disadvantages and luminosity requirements of hadron, of lepton and photon-photon colliders for comparison. The second section discusses the physics considerations for the muon collider. The third section covers muon collider components. The fourth section is about the intersection region and detectors. In the fifth section, the authors discuss modifications to enhance the muon polarization`s operating parameters with very small momentum spreads, operations at energies other than the maximum for which the machine is designed, and designs of machines for different maximum energies. The final section discusses a Research and Development plan aimed at the operation of a 0.5 TeV demonstration machine by the year 2010, and of the 4 TeV machine by the year 2020.
Muon motion in titanium hydride
NASA Technical Reports Server (NTRS)
Kempton, J. R.; Petzinger, K. G.; Kossler, W. J.; Schone, H. E.; Hitti, B. S.; Stronach, C. E.; Adu, N.; Lankford, W. F.; Reilly, J. J.; Seymour, E. F. W.
Motional narrowing of the transverse-field muon spin rotation signal was observed in gamma-TiH(x) for x = 1.83, 1.97, and 1.99. An analysis of the data for TiH1.99 near room temperature indicates that the mechanism responsible for the motion of the muon out of the octahedral site is thermally activated diffusion with an attempt frequency comparable to the optical vibrations of the lattice. Monte Carlo calculations to simulate the effect of muon and proton motion upon the muon field-correlation time were used to interpret the motional narrowing in TiH1.97 near 500 K. The interpretation is dependent upon whether the Bloembergen, Purcell, and Pound (BPP) theory or an independent spin-pair relaxation model is used to obtain the vacancy jump rate from proton NMR T1 measurements. Use of BPP theory shows that the field-correction time can be obtained if the rate of motion of the muon with respect to the rate of the motion for the protons is decreased. An independent spin-pair relaxation model indicates that the field-correlation time can be obtained if the rate of motion for the nearest-neighbor protons is decreased.
Muon-Pair Production by Atmospheric Muons in CosmoALEPH
Maciuc, F.; Grupen, C.; Hashim, N.O.; Luitz, S.; Mailov, A.; Muller, A.S.; Putzer, A.; Sander, H.G.; Schmeling, S.; Schmelling, M.; Tcaciuc, R.; Wachsmuth, H.; Ziegler, T.; Zuber, K.; /Heidelberg, Max Planck Inst. /Siegen U. /SLAC /Karlsruhe, Forschungszentrum /Heidelberg U. /Mainz U., Inst. Phys. /CERN /Princeton U. /Oxford U.
Data from a dedicated cosmic ray run of the ALEPH detector were used in a study of muon trident production, i.e., muon pairs produced by muons. Here the overburden and the calorimeters are the target materials while the ALEPH time projection chamber provides the momentum measurements. A theoretical estimate of the muon trident cross section is obtained by developing a Monte Carlo simulation for muon propagation in the overburden and the detector. Two muon trident candidates were found to match the expected theoretical pattern. The observed production rate implies that the nuclear form factor cannot be neglected for muon tridents.
Muon collider interaction region design
Alexahin, Y.I.; Gianfelice-Wendt, E.; Kashikhin, V.V.; Mokhov, N.V.; Zlobin, A.V.; Alexakhin, V.Y.; /Dubna, JINR
Design of a muon collider interaction region (IR) presents a number of challenges arising from low {beta}* < 1 cm, correspondingly large beta-function values and beam sizes at IR magnets, as well as the necessity to protect superconducting magnets and collider detectors from muon decay products. As a consequence, the designs of the IR optics, magnets and machine-detector interface are strongly interlaced and iterative. A consistent solution for the 1.5 TeV c.o.m. muon collider IR is presented. It can provide an average luminosity of 10{sup 34} cm{sup -2}s{sup -1} with an adequate protection of magnet and detector components.
DOE R&D Accomplishments Database
Feinberg, G.; Weinberg, S.
A multiplicative selection rule for mu meson-electron transitions is proposed. A "muon parity" = -1 is considered for the muon and its neutrino, while the "muon parity" for all other particles is +1. The selection rule then states that (-1) exp(no. of initial (-1) parity particles) = (-1) exp(no. of final (-1) parity particles). Several reactions that are forbidden by an additive law but allowed by the multiplicative law are suggested; these reactions include mu{sup +} .> e{sup +} + nu{sub mu} + {ovr nu}{sub e}, e{sup -} + e{sup -} .> mu{sup -} + mu{sup -}, and muonium .> antimuonium (mu{sup +} + e{sup -} .> mu{sup -} + e{sup +}). An intermediate-boson hypothesis is suggested. (T.F.H.)
Apollonio, Marco
In the Muon Ionization Cooling Experiment (MICE) at RAL, muons are produced and transported in a dedicated beam line connecting the production point (target) to the cooling channel. We discuss the main features of the beamline, meant to provide muons with momenta between 140 MeV/c and 240 MeV/c and emittances up to 10 mm rad, which is accomplished by means of a diffuser. Matching procedures to the MICE cooling channel are also described. In summer 2010 we performed an intense data taking campaign to finalize the calibration of the MICE Particle Identification (PID) detectors and the understanding of the beam line, which completes the STEPI phase of MICE. We highlight the main results from these data.
Cell cycle arrest induced by MPPa-PDT in MDA-MB-231 cells
NASA Astrophysics Data System (ADS)
Liang, Liming; Bi, Wenxiang; Tian, Yuanyuan
Photodynamic therapy (PDT) is a medical treatment using a photosensitizing agent and light source to treat cancers. Pyropheophorbidea methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. To learn more about this photosensitizer, we examined the cell cycle arrest in MDA-MB-231. Cell cycle and apoptosis were measured by flow cytometer. Checkpoints of the cell cycle were measured by western blot. In this study, we found that the expression of Cyclin D1 was obviously decreased, while the expression of Chk2 and P21 was increased after PDT treatment. This study showed that MPPa-PDT affected the checkpoints of the cell cycle and led the cells to apoptosis.
Advances in the understanding of host response associated with tumor PDT
NASA Astrophysics Data System (ADS)
Korbelik, Mladen
Photodynamic therapy (PDT) is clinically established modality used for treatment of solid cancers and other conditions, which destroys lesions by localized generation of cytotoxic oxygen species mediated by administered drugs (photosensitizers) that are activated at targeted sites by exposure to light. Since over 20 years ago it has become increasingly clear that important contribution to the antitumor effect of PDT is secured by host reaction induced by this therapy and manifested as inflammatory and immune response. Presented is an overview of advances in the understanding of this host response associated with tumor PDT by tracing its evolution from initial breakthroughs and discoveries in the early 1980s, followed by advances preceding recent developments, and concluding with recently acquired knowledge and directions for clinical exploitation. Tribute is given to researchers making important contributions to this field during the last three decades including Drs. Gianfranco Canti, Julia Levy, and Barbara Henderson.
Glucose-functionalized amino-OPEs as biocompatible photosensitizers in PDT.
Deni, Elisa; Zamarrón, Alicia; Bonaccorsi, Paola; Carmen Carreño, M; Juarranz, Ángeles; Puntoriero, Fausto; Sciortino, Maria Teresa; Ribagorda, María; Barattucci, Anna
Photodynamic therapy (PDT) is a minimally invasive procedure that can provide a selective eradication of neoplastic diseases by the combined effect of a photosensitizer, light and oxygen. New amino oligo(phenylene-ethynylene)s (OPEs), bearing hydrophilic glucoside terminations, have been prepared, characterized and tested as photosensitizers in PDT. The effectiveness of these compounds in combination with UVA light has been checked on two tumor cell lines (HEp-2 and HeLa cells, derived from a larynx carcinoma and a cervical carcinoma, respectively). The compounds triggered a mitotic blockage that led to the cell death, being the effect active up to 3 μm concentration. The photophysical properties of OPEs, such as high quantum yield, stability, singlet oxygen production, biocompatibility, easy cell-internalization and very good response even at low concentration, make them promising photosensitizers in the application of PDT. PMID:26854378
MICE: The International Muon Ionization Cooling Experiment
Kaplan, Daniel M.
Ionization cooling of a muon beam is a key technique for a Neutrino Factory or Muon Collider. An international collaboration is mounting an experiment to demonstrate muon ionization cooling at the Rutherford Appleton Laboratory. We aim to complete the experiment by 2010.
A Highly intense DC muon source, MuSIC and muon CLFV search
NASA Astrophysics Data System (ADS)
Hino, Y.; Kuno, Y.; Sato, A.; Sakamoto, H.; Matsumoto, Y.; Tran, N. H.; Hashim, I. H.; Fukuda, M.; Hayashida, Y.; Ogitsu, T.; Yamamoto, A.; Yoshida, M.
MuSIC is a new muon facility, which provides the world's highest intense muon beam with continuous time structure at Research Center of Nuclear Physics (RCNP), Osaka University. It's intensity is designed to be 108 muons per second with only 0.4 kW proton beam. Such a high intense muon beam is very important for searches of rare decay processes, for example search for the muon to electron conversion.
Photofrin-PDT for gastric cancer in the era of endoscopic submucosal dissection
NASA Astrophysics Data System (ADS)
Nishiwaki, Yoshiro; Ikematsu, Yoshito; Tokunaga, Yuuji; Kanai, Toshikazu
Background: Endoscopic mucosal resection (EMR) was originated to treat early gastric cancer (EGC). EMR was suitable for small, mucosal and well-differentiated adenocarcinoma without ulceration. It was difficult to resect larger tumors en bloc by this method. In recent years, a more useful method, endoscopic submuscosal dissection (ESD) has been developed, which enables en bloc resection of large mucosal lesions. On the contrary, photodynamic therapy (PDT) is applicable to submucosal, poorly differentiated, or carcinoma with ulceration. In the era of ESD, we evaluated the value of Photofrin-PDT. Patients & Methods: We applied PDT to 36 patients including three advanced cancers, who had been excluded from EMR (ESD) and were at high risks for surgery or refused surgery. Four EGC patients who had not been cured by EMR (ESD) were included. Our PDT procedure consisted of polyhematoporphyrin ether/ester administration (Photofrin, 2 mg/Kg) and pulsed excimer dye laser irradiation at 630 nm 48 hours (and 96 hours) after sensitization. Results: Complete response (CR) at three months was obtained in 84% (21/25) of mucosal cancer and in 50% (4/8) of submucosal cancer. Although three patients with an advanced cancer improved but were not cured, quality of their life was maintained. There were no serious side effects except skin photosensitivity. Conclusion: Photofrin-PDT should be applied not only EGC patients who are excluded from ESD and have not been cured by ESD with poor risk for surgery, and have high possibilitiy to be cured by PDT, but also advanced cancer patients for local improvement of lesions.
ALA PDT for high grade dysplasia in Barrett's oesophagus: review of a decade's experience
NASA Astrophysics Data System (ADS)
Bown, Stephen G.; Mackenzie, Gary D.; Dunn, Jason M.; Thorpe, Sally M.; Lovat, Laurence B.
We have been investigating PDT with 5 aminolaevulinic acid (ALA) for the treatment of high grade dysplasia (HGD) in Barrett's oesophagus (BO) for over a decade. This drug has inherent advantages over porfimer sodium (Photofrin), the current approved photosensitiser in the UK and USA, which causes strictures in 18-50% and light sensitivity for up to three months. ALA has a lower rate of oesophageal strictures due to its preferential activity in the mucosa, sparing the underlying muscle, and patients are only light sensitive for 1-2 days. Within a randomised controlled trial, we demonstrated that an ALA dose of 60mg/kg activated by 1000J/cm red laser light is the most effective. Using these values we achieved complete reversal of HGD at 1 year in 89% of 27 patients. A randomised controlled trial of ALA vs porfimer sodium PDT for HGD is currently under way with end points of efficacy and safety. 50 of 66 patients have been recruited. Preliminary data suggest ALA PDT is safer with a trend to higher efficacy. Late relapse can occur in 20% of patients. New prognostic markers, in particular aneuploidy, are helping us to identify and target patients at risk of late relapse. Furthermore optical biopsy techniques such as elastic scattering spectroscopy (ESS) may allow detection of nuclear abnormalities in vivo and enable us to target areas of interest whilst reducing sampling error. PDT faces new challenges for the treatment of HGD in BO, with the recent introduction of balloon based radiofrequency ablation. This technique appears simpler and as effective as PDT, but follow up is currently short and long term safety data is lacking. In our experience ALA PDT is currently the most effective minimally invasive treatment for HGD in BO. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.
Contribution of the nos-pdt operon to virulence phenotypes in methicillin-sensitive Staphylococcus aureus.
Sapp, April M; Mogen, Austin B; Almand, Erin A; Rivera, Frances E; Shaw, Lindsey N; Richardson, Anthony R; Rice, Kelly C
Nitric oxide (NO) is emerging as an important regulator of bacterial stress resistance, biofilm development, and virulence. One potential source of endogenous NO production in the pathogen Staphylococcus aureus is its NO-synthase (saNOS) enzyme, encoded by the nos gene. Although a role for saNOS in oxidative stress resistance, antibiotic resistance, and virulence has been recently-described, insights into the regulation of nos expression and saNOS enzyme activity remain elusive. To this end, transcriptional analysis of the nos gene in S. aureus strain UAMS-1 was performed, which revealed that nos expression increases during low-oxygen growth and is growth-phase dependent. Furthermore, nos is co-transcribed with a downstream gene, designated pdt, which encodes a prephenate dehydratase (PDT) enzyme involved in phenylalanine biosynthesis. Deletion of pdt significantly impaired the ability of UAMS-1 to grow in chemically-defined media lacking phenylalanine, confirming the function of this enzyme. Bioinformatics analysis revealed that the operon organization of nos-pdt appears to be unique to the staphylococci. As described for other S. aureus nos mutants, inactivation of nos in UAMS-1 conferred sensitivity to oxidative stress, while deletion of pdt did not affect this phenotype. The nos mutant also displayed reduced virulence in a murine sepsis infection model, and increased carotenoid pigmentation when cultured on agar plates, both previously-undescribed nos mutant phenotypes. Utilizing the fluorescent stain 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate, decreased levels of intracellular NO/reactive nitrogen species (RNS) were detected in the nos mutant on agar plates. These results reinforce the important role of saNOS in S. aureus physiology and virulence, and have identified an in vitro growth condition under which saNOS activity appears to be upregulated. However, the significance of the operon organization of nos-pdt and potential
Contribution of the nos-pdt Operon to Virulence Phenotypes in Methicillin-Sensitive Staphylococcus aureus
Almand, Erin A.; Rivera, Frances E.; Shaw, Lindsey N.; Richardson, Anthony R.; Rice, Kelly C.
Nitric oxide (NO) is emerging as an important regulator of bacterial stress resistance, biofilm development, and virulence. One potential source of endogenous NO production in the pathogen Staphylococcus aureus is its NO-synthase (saNOS) enzyme, encoded by the nos gene. Although a role for saNOS in oxidative stress resistance, antibiotic resistance, and virulence has been recently-described, insights into the regulation of nos expression and saNOS enzyme activity remain elusive. To this end, transcriptional analysis of the nos gene in S. aureus strain UAMS-1 was performed, which revealed that nos expression increases during low-oxygen growth and is growth-phase dependent. Furthermore, nos is co-transcribed with a downstream gene, designated pdt, which encodes a prephenate dehydratase (PDT) enzyme involved in phenylalanine biosynthesis. Deletion of pdt significantly impaired the ability of UAMS-1 to grow in chemically-defined media lacking phenylalanine, confirming the function of this enzyme. Bioinformatics analysis revealed that the operon organization of nos-pdt appears to be unique to the staphylococci. As described for other S. aureus nos mutants, inactivation of nos in UAMS-1 conferred sensitivity to oxidative stress, while deletion of pdt did not affect this phenotype. The nos mutant also displayed reduced virulence in a murine sepsis infection model, and increased carotenoid pigmentation when cultured on agar plates, both previously-undescribed nos mutant phenotypes. Utilizing the fluorescent stain 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate, decreased levels of intracellular NO/reactive nitrogen species (RNS) were detected in the nos mutant on agar plates. These results reinforce the important role of saNOS in S. aureus physiology and virulence, and have identified an in vitro growth condition under which saNOS activity appears to be upregulated. However, the significance of the operon organization of nos-pdt and potential
Feasibility of repeated sequential treatments of RIF-1 tumors with photodynamic therapy (PDT) using lutetium texaphyrin (PCI-0123)
NASA Astrophysics Data System (ADS)
Miles, Dale R.; Parker, Lynn M.; Thiemann, Patricia A.; Woodburn, Kathryn W.; Young, Stuart W.
Lutetium texaphyrin (PCI-0123) is currently in clinical trials as a PDT agent for the treatment of cancer patients. The drug is cleared rapidly from the plasma, and photoirradiation can be performed shortly after drug administration.T He photosensitizer as yet does not appear to elicit any significant skin photosensitivity. These characteristics favor frequent multiple PDT treatments with PCI-0123. In order to support repeated PDT treatments in the clinic, the safety of multiple drug dosing was studied in rats and mice. In rats, each group received 5 consecutive daily intravenous administrations of 5, 15, 30, or 60 mg/kg/day of PCI-0123. There were no deaths in any of the groups, and no drug-related effects were detected in the 5 mg/kg/day group. In mice, there were no observable signs of toxicity after consecutive daily administration of 10 micrometers ol/kg/day of PCI-0123 for 13 days. The feasibility and efficacy of repeated PDT treatments were assessed in C3H mice bearing RIF-1 tumors. Repeated PDT proved to be superior to a single PDT treatment. Repeated PDT treatments were well tolerated. Seven PDT treatments were administered over a nine day period without significant toxicity while achieving good therapeutic responses. All six groups receiving repeated PDT treatments showed an improved response compared to groups receiving a single PDT cycle, and the improvement was statistically significant for five of these groups. Sixty-two percent of mice receiving four sequential daily treatments were cured, and daily treatments were superior to regimens with longer intervals between PDT cycles.
Light fractionation increases the efficacy of ALA-PDT but not of MAL-PDT: What is the role of (vascular) endothelial cells?
NASA Astrophysics Data System (ADS)
de Bruijn, H. S.; de Vijlder, H. C.; de Haas, E. R. M.; van der Ploeg-van den Heuvel, A.; Kruijt, B.; Poel-Dirks, D.; Sterenborg, H. J. C. M.; ten Hagen, T. L. M.; Robinson, D. J.
Photodynamic therapy (PDT) using protoporpyrin IX (PpIX) precursors like 5-aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL) has shown to be effective in the treatment of various skin diseases. Using ALA we have shown in numerous studies a significantly improved efficacy by applying light fractionation with a long dark interval. In contrast, in the hairless mouse model, the PDT efficacy using MAL is unaffected by adopting this approach. More acute edema is found after ALA-PDT suggesting a difference in response of endothelial cells to PDT. To investigate the role of endothelial cells, cryo-sections of hairless mouse skin after 4 hours of topical MAL or ALA application were stained with a fluorescent endothelial cell marker (CD31). Co-localization of this marker with the PpIX fluorescence was performed using the spectral imaging function of the confocal microscope. We have also used intra-vital confocal microscopy to image the PpIX fluorescence distribution in correlation with the vasculature of live mouse skin. Our results show PpIX fluorescence at depth in cryo-sections of mouse skin after 4 hours of topical application. Co-localization has shown to be difficult due to the changes in tissue organization caused by the staining procedure. As expected we found high PpIX fluorescence levels in the epidermis after both MAL and ALA application using intra-vital microscopy. After ALA application more PpIX fluorescence was found deep in the dermal layer of the skin than after MAL. Furthermore we detected localized fluorescence in unidentified structures that could not be correlated to blood vessels or nerves.
A method for video-assisted thoracoscopic photodynamic therapy (VAT-PDT).
Moghissi, Keyvan; Dixon, Kate; Thorpe, J Andrew C
A technique is described for application of photodynamic therapy (PDT) to peripheral pulmonary and other intrathoracic malignant tumours. For video-assisted thoracoscopic-PDT we advocate the use of the flexible fibreoptic bronchoscope through an appropriately placed port. This, together with the standard thoracoscope and attached monitor can provide three-dimensional visualisation of the intrathoracic lesion and more importantly allow the accurate delivery of laser light to the tumour. At the present time we have successfully used this method without complication in three patients with advanced inoperable disease. PMID:17670074
Endoscopic treatment of early bronchial cancer: our experience with photodynamic therapy (PDT)
NASA Astrophysics Data System (ADS)
Corti, Luigi; Toniolo, Lamberto; Boso, Caterina; Colaut, Flavio; Fiore, Davide; Muzzio, Pier-Carlo; Loreggian, Lucio; Sotti, Guido
The role of photodynamic therapy (PDT) in the treatment of small cancers has been established in several clinical studies. Here, we report on the efficacy of PDT for early inoperable or recurrent non-small-cell lung cancer (NSCLC). Methods and Materials: From June 1989 to November 2004, 40 patients with 50 NSCLC were treated with PDT. Twelve cases were inoperable for medical reasons and were staged as T1N0M0, and 28 had recurrent in situ carcinoma. Patients with residual disease after PDT received definitive radiotherapy and/or brachytherapy. Follow-up ranged from 6 to 167 months (median 43.59). Twenty of the 40 patients received i.v. injections of hematoporphyrin derivative (5 mg/kg), the other 20 had injections of porfimer sodium (Photofrin, 2 mg/kg). An argon dye laser (630 nm wavelength, 200-300 J/cm2) was used for light irradiation in 24 of the 40 patients, a diode laser (Diomed, 630 nm wavelength, 100- 200 J/cm2) in the other 16. Results: PDT obtained a 72% complete response (CR) rate (36/50 treated lesions), that is 27 CR among the 37 Tis carcinomas and 9 among the 13 T1 cases. Kaplan-Meier curves showed a mean overall survival (OS) of 75.59 months (median 91.4 months). Two- and 5- year OS rates were 72.78% and 59.55%. The mean and median survival rates for patients with Tis stage were 86.5 and 120.4 months, respectively (standard error 9.50) and for patients with T1 disease they were 45.78 and 35.71 months, respectively; the difference was statistically significant (P< 0.03). No severe early or late PDT-related adverse events were recorded. Conclusions: PDT is effective in early primary or recurrent NSCLC, resulting in a CR rate of 72%. The incorporation of PDT in standard clinical practice, in combination with radiotherapy, warrants further investigation.
Synthesis, characterization and preclinical studies of two-photon-activated targeted PDT therapeutic triads
NASA Astrophysics Data System (ADS)
Spangler, C. W.; Starkey, J. R.; Rebane, A.; Meng, F.; Gong, A.; Drobizhev, M.
Photodynamic therapy (PDT) continues to evolve into a mature clinical treatment of a variety of cancer types as well as age-related macular degeneration of the eye. However, there are still aspects of PDT that need to be improved in order for greater clinical acceptance. While a number of new PDT photo-sensitizers, sometimes referred to as second- or third- generation therapeutic agents, are currently under clinical investigation, the direct treatment through the skin of subcutaneous tumors deeper than 5 mm remains problematic. Currently approved PDT porphyrin photo-sensitizers, as well as several modified porphyrins (e.g. chlorins, bacteriochlorins, etc.) that are under clinical investigation can be activated at 630-730 nm, but none above 800 nm. It would be highly desirable if new PDT paradigms could be developed that would allow photo-activation deep in the tissue transparency window in the Near-infrared (NIR) above 800 nm to reduce scattering and absorption phenomena that reduce deep tissue PDT efficacy. Rasiris and MPA Technologies have developed new porphyrins that have greatly enhanced two-photon absorption ( P A ) cross-sections and can be activated deep in the NIR (ca. 780-850 nm). These porphyrins can be incorporated into a therapeutic triad that also employs an small molecule targeting agent that directs the triad to over-expressed tumor receptor sites, and a NIR onephoton imaging agent that allows tracking the delivery of the triad to the tumor site, as well as clearance of excess triad from healthy tissue prior to the start of PDT treatment. We are currently using these new triads in efficacy studies with a breast cancer cell line that has been transfected with luciferase genes that allow implanted tumor growth and post- PDT treatment efficacy studies in SCID mouse models by following the rise and decay of the bioluminescence signal. We have also designed highly absorbing and scattering collagen breast cancer phantoms in which we have demonstrated
Superconducting magnet system for muon beam cooling
Andreev, N.; Johnson, R.P.; Kashikhin, V.S.; Kashikhin, V.V.; Novitski, I.; Yonehara, K.; Zlobin, A.; /Fermilab
A helical cooling channel has been proposed to quickly reduce the six-dimensional phase space of muon beams for muon colliders, neutrino factories, and intense muon sources. A novel superconducting magnet system for a muon beam cooling experiment is being designed at Fermilab. The inner volume of the cooling channel is filled with liquid helium where passing muon beam can be decelerated and cooled in a process of ionization energy loss. The magnet parameters are optimized to match the momentum of the beam as it slows down. The results of 3D magnetic analysis for two designs of magnet system, mechanical and quench protection considerations are discussed.
Physics with a millimole of muons
Quigg, C.
The eventual prospect of muon colliders reaching several TeV encourages us to consider the experimental opportunities presented by very copious stores of muons, approaching 10{sup 21} per year. I summarize and comment upon some highlights of the Fermilab Workshop on Physics at the First Muon Collider and at the Front End of a Muon Collider. Topics include various varieties of {mu}{mu} colliders, {mu}p colliders, and applications of the intense neutrino beams that can be generated in muon storage rings.
Combination of PI3K/Akt/mTOR inhibitors and PDT in endothelial and tumor cells
NASA Astrophysics Data System (ADS)
Fateye, Babasola; Chen, Bin
The PI3/Akt/mTOR kinase signaling pathway is a major signaling pathway in eukaryotic cells, and dysregulation of this signaling pathway has been implicated in tumorigenesis and malignancy in several cancers including prostate cancer. We assessed the effects of combination PI3K pathway inhibition on the efficacy of PDT in human prostate tumor cell line (PC3) and SV40-transformed mouse endothelial cell line (SVEC-40). Combination of PDT and BEZ 235 (BEZ), a pan-PI3/ mTOR kinase inhibitor additively enhanced efficacy of sub-lethal PDT in both cell lines. The combination of the pan-PI3/ mTOR kinase inhibitor LY294002 (LY) with PDT also enhanced efficacy of PDT in PC3 in an additive manner but synergistically in SVEC. In order to determine the mechanism of enhancement of efficacy, we assessed apoptosis and autophagy following PDT. PDT-mediated apoptosis was enhanced in endothelial cells, by both BEZ and LY rapidly after treatment. Compared to SVEC, PC3 cells are apoptosis-deficient and apoptosis was not significantly enhanced by either LY or BEZ. However, lethal PDT of PC3 cells induced a delayed autophagic response which may be enhanced by combination, depending on PI3K inhibitor and dose.
Structures of Open (R) and Close (T) States of Prephenate Dehydratase (PDT) - Implication of Allosteric Regulation by L-Phenylalanine
Tan, Kemin; Li, Hui; Zhang, Rongguang; Gu, Minyi; Clancy, Shonda T.; Joachimiak, Andrzej
The enzyme prephenate dehydratase (PDT) converts prephenate to phenylpyruvate in L-phenylalanine biosynthesis. PDT is allosterically regulated by L-Phe and other amino acids. We report the first crystal structures of PDT from Staphylococcus aureus in a relaxed (R) state and PDT from Chlorobium tepidum in a tense (T) state. The two enzymes show low sequence identity (27.3%) but the same prototypic architecture and domain organization. Both enzymes are tetramers (dimer of dimers) in crystal and solution while a PDT dimer can be regarded as a basic catalytic unit. The N-terminal PDT domain consists of two similar subdomains with a cleft in between, which hosts the highly conserved active site. In one PDT dimer two clefts are aligned to form an extended active site across the dimer interface. Similarly at the interface two ACT regulatory domains create two highly conserved pockets. Upon binding of the L-Phe inside the pockets, PDT transits from an open to a closed conformation. PMID:18171624
Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) of photodynamic therapy (PDT) outcome and associated changes in the blood-brain barrier following Pc 4-PDT of glioma in an athymic nude rat model
NASA Astrophysics Data System (ADS)
Belle, Vaijayantee; Anka, Ali; Cross, Nathan; Thompson, Paul; Mott, Eric; Sharma, Rahul; Gray, Kayla; Zhang, Ruozhen; Xu, Yueshuo; Sun, Jiayang; Flask, Chris A.; Oleinick, Nancy L.; Dean, David
Introduction: Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) appears to provide an unambiguous means of tracking the outcome of photodynamic therapy (PDT) of brain tumors with the photosensitizer Pc 4. The increase in Gd enhancement observed after Pc 4-PDT may be due to a temporary opening of the blood-brain-barrier which, as noted by others, may offer a therapeutic window. Methods: We injected 2.5 x 105 U87 cells into the brains of 9 athymic nude rats. After 8-9 days peri-tumor DCE-MRI images were acquired on a 7.0 T microMRI scanner before and after the administration of 150 μL Gd. DCE-MRI scans were repeated three times following Pc 4-PDT. Results: The average, normalized peak enhancement in the tumor region, approximately 30-90 seconds after Gd administration, was 1.31 times greater than baseline (0.03 Standard Error [SE]) prior to PDT and was 1.44 (0.02 SE) times baseline in the first Post-PDT scans (Day 11), a statistically significant (p ~ 0.014, N=8) increase over the Pre- PDT scans, and was 1.38 (0.02 SE) times baseline in the second scans (Day 12), also a statistically significant (p ~ 0.008, N=7) increase. Observations were mixed in the third Post-PDT scans (Day 13), averaging 1.29 (0.03 SE) times baseline (p ~ 0.66, N=7). Overall a downward trend in enhancement was observed from the first to the third Post-PDT scans. Discussion: DCE-MRI may provide an unambiguous indication of brain tumor PDT outcome. The initial increase in DCE-MRI signal may correlate with a temporary, PDT-induced opening of the blood-brain-barrier, creating a potential therapeutic window.
Design Concepts for Muon-Based Accelerators
Ryne, R. D.; Berg, J. S.; Kirk, H. G.; Palmer, R. B.; Stratkis, D.; Alexahin, Y.; Bross, A.; Gollwitzer, K.; Mokhov, N. V.; Neuffer, D.; Palmer, M. A.; Yonehara, K.; Snopok, P.; Bogacz, A.; Roberts, T. J.; Delahaye, J. -P.
Muon-based accelerators have the potential to enable facilities at both the Intensity and the Energy Frontiers. Muon storage rings can serve as high precision neutrino sources, and a muon collider is an ideal technology for a TeV or multi-TeV collider. Progress in muon accelerator designs has advanced steadily in recent years. In regard to 6D muon cooling, detailed and realistic designs now exist that provide more than 5 order-of-magnitude emittance reduction. Furthermore, detector performance studies indicate that with suitable pixelation and timing resolution, backgrounds in the collider detectors can be significantly reduced, thus enabling high-quality physics results. Thanks to these and other advances in design & simulation of muon systems, technology development, and systems demonstrations, muon storage-ring-based neutrino sources and a muon collider appear more feasible than ever before. A muon collider is now arguably among the most compelling approaches to a multi-TeV lepton collider. This paper summarizes the current status of design concepts for muon-based accelerators for neutrino factories and a muon collider.
Neutrino Factory and Muon Collider Fellow
Hanson, Gail G.; Snopak, Pavel; Bao, Yu
Muons are fundamental particles like electrons but much more massive. Muon accelerators can provide physics opportunities similar to those of electron accelerators, but because of the larger mass muons lose less energy to radiation, allowing more compact facilities with lower operating costs. The way muon beams are produced makes them too large to fit into the vacuum chamber of a cost-effective accelerator, and the short muon lifetime means that the beams must be reduced in size rather quickly, without losing too many of the muons. This reduction in size is called "cooling." Ionization cooling is a new technique that can accomplish such cooling. Intense muon beams can then be accelerated and injected into a storage ring, where they can be used to produce neutrino beams through their decays or collided with muons of the opposite charge to produce a muon collider, similar to an electron-positron collider. We report on the research carried out at the University of California, Riverside, towards producing such muon accelerators, as part of the Muon Accelerator Program based at Fermilab. Since this research was carried out in a university environment, we were able to involve both undergraduate and graduate students.
Kiburg, Brendan
The Muon g-2 experiment at Fermilab will use as its primary instrument a 52-foot-wide electromagnet that creates a precise magnetic field. In this video, Fermilab's Brendan Kiburg explains the lengthy process of finely "shimming" that magnetic field into shape.
Cosmic muons, as messengers from the Universe
NASA Astrophysics Data System (ADS)
Brancus, I. M.; Rebel, H.
Penetrating from the outer space into the Earth atmosphere, primary cosmic rays are producing secondary radiation by the collisions with the air target subsequently decaying in hadrons, pions, muons, electrons and photons, phenomenon called Extensive air Shower (EAS). The muons, considered as the "penetrating" component, survive the propagation to the Earth and even they are no direct messenger of the Universe, they reflect the features of the primary particles. The talk gives a description of the development of the extensive air showers generating the secondary particles, especially the muon component. Results of the muon flux and of the muon charge ratio, (the ratio between the positive and the negative muons), obtained in different laboratories and in WILLI experiment, are shown. At the end, the contribution of the muons measured in EAS to the investigation of the nature of the primary cosmic rays is emphasized in KASCADE and WILLI-EAS experiments.
Cosmic muons, as messengers from the Universe
Brancus, I. M.; Rebel, H.
Penetrating from the outer space into the Earth atmosphere, primary cosmic rays are producing secondary radiation by the collisions with the air target subsequently decaying in hadrons, pions, muons, electrons and photons, phenomenon called Extensive air Shower (EAS). The muons, considered as the "penetrating" component, survive the propagation to the Earth and even they are no direct messenger of the Universe, they reflect the features of the primary particles. The talk gives a description of the development of the extensive air showers generating the secondary particles, especially the muon component. Results of the muon flux and of the muon charge ratio, (the ratio between the positive and the negative muons), obtained in different laboratories and in WILLI experiment, are shown. At the end, the contribution of the muons measured in EAS to the investigation of the nature of the primary cosmic rays is emphasized in KASCADE and WILLI-EAS experiments.
Pion contamination in the MICE muon beam
NASA Astrophysics Data System (ADS)
Adams, D.; Alekou, A.; Apollonio, M.; Asfandiyarov, R.; Barber, G.; Barclay, P.; de Bari, A.; Bayes, R.; Bayliss, V.; Bertoni, R.; Blackmore, V. J.; Blondel, A.; Blot, S.; Bogomilov, M.; Bonesini, M.; Booth, C. N.; Bowring, D.; Boyd, S.; Brashaw, T. W.; Bravar, U.; Bross, A. D.; Capponi, M.; Carlisle, T.; Cecchet, G.; Charnley, C.; Chignoli, F.; Cline, D.; Cobb, J. H.; Colling, G.; Collomb, N.; Coney, L.; Cooke, P.; Courthold, M.; Cremaldi, L. M.; DeMello, A.; Dick, A.; Dobbs, A.; Dornan, P.; Drews, M.; Drielsma, F.; Filthaut, F.; Fitzpatrick, T.; Franchini, P.; Francis, V.; Fry, L.; Gallagher, A.; Gamet, R.; Gardener, R.; Gourlay, S.; Grant, A.; Greis, J. R.; Griffiths, S.; Hanlet, P.; Hansen, O. M.; Hanson, G. G.; Hart, T. L.; Hartnett, T.; Hayler, T.; Heidt, C.; Hills, M.; Hodgson, P.; Hunt, C.; Iaciofano, A.; Ishimoto, S.; Kafka, G.; Kaplan, D. M.; Karadzhov, Y.; Kim, Y. K.; Kuno, Y.; Kyberd, P.; Lagrange, J.-B.; Langlands, J.; Lau, W.; Leonova, M.; Li, D.; Lintern, A.; Littlefield, M.; Long, K.; Luo, T.; Macwaters, C.; Martlew, B.; Martyniak, J.; Mazza, R.; Middleton, S.; Moretti, A.; Moss, A.; Muir, A.; Mullacrane, I.; Nebrensky, J. J.; Neuffer, D.; Nichols, A.; Nicholson, R.; Nugent, J. C.; Oates, A.; Onel, Y.; Orestano, D.; Overton, E.; Owens, P.; Palladino, V.; Pasternak, J.; Pastore, F.; Pidcott, C.; Popovic, M.; Preece, R.; Prestemon, S.; Rajaram, D.; Ramberger, S.; Rayner, M. A.; Ricciardi, S.; Roberts, T. J.; Robinson, M.; Rogers, C.; Ronald, K.; Rubinov, P.; Rucinski, P.; Sakamato, H.; Sanders, D. A.; Santos, E.; Savidge, T.; Smith, P. J.; Snopok, P.; Soler, F. J. P.; Speirs, D.; Stanley, T.; Stokes, G.; Summers, D. J.; Tarrant, J.; Taylor, I.; Tortora, L.; Torun, Y.; Tsenov, R.; Tunnell, C. D.; Uchida, M. A.; Vankova-Kirilova, G.; Virostek, S.; Vretenar, M.; Warburton, P.; Watson, S.; White, C.; Whyte, C. G.; Wilson, A.; Winter, M.; Yang, X.; Young, A.; Zisman, M.
The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240 MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than ~1% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is fπ < 1.4% at 90% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.
Intense muon sources for the purpose of providing intense high energy neutrino beams ({nu} factory) represents very interesting possibilities. If successful, such efforts would significantly advance the state of muon technology and provides intermediate steps in technologies required for a future high energy muon collider complex. High intensity muon: production, capture, cooling, acceleration and multi-turn muon storage rings are some of the key technology issues that needs more studies and developments, and will briefly be discussed here. A muon collider requires basically the same number of muons as for the muon storage ring neutrino factory, but would require more cooling, and simultaneous capture of both {+-} {mu}. We present some physics possibilities, muon storage ring based neutrino facility concept, site specific examples including collaboration feasibility studies, and upgrades to a full collider.
In vivo study of ALA PLGA nanoparticles-mediated PDT for treating cutaneous squamous cell carcinoma
NASA Astrophysics Data System (ADS)
Wang, Xiaojie; Shi, Lei; Huang, Zheng; Wang, Xiuli
Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still a challenge. Although topical photodynamic therapy (PDT) is effective for treating in situ and superficial SCC, the effectiveness of topical ALA delivery to thick SCC can be limited by its bioavailability. Polylactic-co-glycolic acid nanopartieles (PLGA NPs) might provide a promising ALA delivery strategy. The aim of this study was to evaluate the efficacy of ALA PLGA NPs PDT for the treatment of cutaneous SCC in a mouse model. Methods: ALA loaded PLGA NPs were prepared and characterized. The therapeutic efficacy of ALA PLGA NP mediated PDT in treating UV-induced cutaneous SCC in the mice model were examined. Results: In vivo study showed that ALA PLGA NPs PDT were more effective than free ALA of the same concentration in treating mouse cutaneous SCC. Conclusion: ALA PLGA NPs provides a promising strategy for delivering ALA and treating cutaneous SCC.
Biochemical changes in cutaneous squamous cell carcinoma submitted to PDT using ATR-FTIR spectroscopy
NASA Astrophysics Data System (ADS)
Lima, Cassio A.; Goulart, Viviane P.; de Castro, Pedro A. A.; Correa, Luciana; Benetti, Carolina; Zezell, Denise M.
Nonmelanoma skin cancers are the most common form of malignancy in humans. Between the traditional treatment ways, the photodynamic therapy (PDT) is a promising alternative which is minimally invasive and do not requires surgical intervention or exposure to ionizing radiation. The understanding of the cascade of effects playing role in PDT is not fully understood, so that define and understand the biochemical events caused by photodynamic effect will hopefully result in designing better PDT protocols. In this study we investigated the potential of the FTIR spectroscopy to assess the biochemical changes caused by photodynamic therapy after 10 and 20 days of treatment using 5-aminolevulinic acid (ALA) as precursor of the photosensitizer photoporphyrin IX (PpIX). The amplitude values of second derivative from vibrational modes obtained with FTIR spectroscopy showed similar behavior with the morphological features observed in histopathological analysis, which showed active lesions even 20 days after PDT. Thus, the technique has the potential to be used to complement the investigation of the main biochemical changes that photodynamic therapy promotes in tissue.
In vivo outcome study of BPD-mediated PDT using a macroscopic singlet oxygen model
NASA Astrophysics Data System (ADS)
Kim, Michele M.; Penjweini, Rozhin; Zhu, Timothy C.
Macroscopic modeling of the apparent reacted singlet oxygen concentration ([1O2]rx) for use with photodynamic therapy (PDT) has been developed and studied for benzoporphryin derivative monoacid ring A (BPD), a common photosensitizer. The four photophysical parameters (ξ, σ, β, δ) and threshold singlet oxygen dose ([1O2]rx, sh) have been investigated and determined using the RIF model of murine fibrosarcomas and interstitial treatment delivery. These parameters are examined and verified further by monitoring tumor growth post-PDT. BPD was administered at 1 mg/kg, and mice were treated 3 hours later with fluence rates ranging between 75 - 150 mW/cm2 and total fluences of 100 - 350 J/cm2. Treatment was delivered superficially using a collimated beam. Changes in tumor volume were tracked following treatment. The tumor growth rate was fitted for each treatment condition group and compared using dose metrics including total light dose, PDT dose, and reacted singlet oxygen. Initial data showing the correlation between outcomes and various dose metrics indicate that reacted singlet oxygen serves as a good dosimetric quantity for predicting PDT outcome.
Photodynamic Therapy (PDT) with Chemotherapy for Advanced Lung Cancer with Airway Stenosis
Kimura, Masakazu; Miyajima, Kuniharu; Kojika, Masakazu; Kono, Takafumi; Kato, Harubumi
Intractable advanced lung cancer can be treated palliatively with photodynamic therapy (PDT) combined with chemotherapy to remove central and peripheral (lobar or segmental bronchi) bronchial stenosis and obstruction. We present data for 12 (eight men, four women) consecutive patients with 13 advanced non-small cell lung carcinomas in whom curative operations were contraindicated, who underwent PDT combined with chemotherapy for local control of the intraluminal lesions. The mean age was 73.3 years (range, 58–80 years), and the stages of cancer were IIA–IV. The median stenosis rates before treatment, one week post-treatment, and one month post-treatment were 60% (range, 30%–100%), 15% (range, 15%–99%), and 15% (range 15%–60%), respectively. The mean and median survival times were 9.3 and 5.9 months, respectively. The overall 1-year survival rate was 30.0%. No PDT-related morbidity or mortality occurred. In this single-institution study, all patients experienced improved symptoms and quality of life at one week after treatment; furthermore, an objective response was evidenced by the substantial increase in the openings of the bronchial lumen and prevention of obstructive pneumonia. Therefore, PDT with chemotherapy was useful and safe for the treatment of bronchial obstruction. PMID:26512656
Topical application of ALA PDT for the treatment of moderate to severe acne vulgaris
NASA Astrophysics Data System (ADS)
Wang, Xiu-Li; Wang, Hong-Wei; Zhang, Ling-Lin; Su, Lina; Guo, Ming-Xia; Huang, Zheng
Objectives: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)- medicated photodynamic therapy (ALA PDT) for the treatment of moderate to severe acne vulgaris. Methods: Sixteen Chinese patients with moderate to severe facial acne were treated with 1-3 courses of ALA PDT. ALA cream (3%) was freshly prepared and applied to acne lesions for 3-4 h. The lesions were irradiated by a 635 nm diode laser at dose levels of 60 - 80 J/cm2 at 100 mW/cm2. Clinical assessments were conducted before and after treatment up to 3 months. Results: All patents showed response to ALA PDT. Complete clearance was seen in 10 patients (62.5%) and partial clearance in 6 patients (37.5%). One case showed recurrence after complete clearance at 2 months and another two showed recurrence after complete clearance at 3 months. However, the number of new lesions were significantly reduced. Adverse effects were minimal. Conclusions: The results of this preliminary clinical study is encouraging. ALA PDT is a simple, safe and useful therapeutic option for the treatment of moderate to severe acne. Further studies to evaluate the treatment with a larger number of patients and for a longer period of follow-up are needed.
Label-Free, Longitudinal Visualization of PDT Response In Vitro with Optical Coherence Tomography.
Jung, Yookyung; Nichols, Alexander J; Klein, Oliver J; Roussakis, Emmanuel; Evans, Conor L
A major challenge in creating and optimizing therapeutics in the fight against cancer is visualizing and understanding the microscale spatiotemporal treatment response dynamics that occur in patients. This is especially true for photodynamic therapy (PDT), where therapeutic optimization relies on understanding the interplay between factors such as photosensitizer localization and uptake, in addition to light dose and delivery rate. In vitro 3D culture systems that recapitulate many of the biological features of human disease are powerful platforms for carrying out detailed studies on PDT response and resistance. Current techniques for visualizing these models, however, often lack accuracy due to the perturbative nature of the sample preparation, with light attenuation complicating the study of intact models. Optical coherence tomography (OCT) is an ideal method for the long-term, non-perturbative study of in vitro models and their response to PDT. Monitoring the response of 3D models to PDT by time-lapse OCT methods promises to provide new perspectives and open the way to cancer treatment methodologies that can be translated towards the clinic. PMID:23316088
Label-Free, Longitudinal Visualization of PDT Response In Vitro with Optical Coherence Tomography
Jung, Yookyung; Nichols, Alexander J.; Klein, Oliver J.; Roussakis, Emmanuel; Evans, Conor L.
A major challenge in creating and optimizing therapeutics in the fight against cancer is visualizing and understanding the microscale spatiotemporal treatment response dynamics that occur in patients. This is especially true for photodynamic therapy (PDT), where therapeutic optimization relies on understanding the interplay between factors such as photosensitizer localization and uptake, in addition to light dose and delivery rate. In vitro 3D culture systems that recapitulate many of the biological features of human disease are powerful platforms for carrying out detailed studies on PDT response and resistance. Current techniques for visualizing these models, however, often lack accuracy due to the perturbative nature of the sample preparation, with light attenuation complicating the study of intact models. Optical coherence tomography (OCT) is an ideal method for the long-term, non-perturbative study of in vitro models and their response to PDT. Monitoring the response of 3D models to PDT by time-lapse OCT methods promises to provide new perspectives and open the way to cancer treatment methodologies that can be translated towards the clinic. PMID:23316088
Establishment of treatment parameters for ALA-PDT of plaque psoriasis
NASA Astrophysics Data System (ADS)
Stringer, Mark R.; Robinson, Dominic J.; Collins, P.
We report an investigation into the use of photodynamic therapy (PDT), following topically applied 5-aminolaevulinic acid (ALA), as a treatment for plaque psoriasis. Treatment was performed 4 hours post-ALA, using white light doses of 2 - 16 J cm-2 delivered at 10 - 40 mW cm-2. The fluorescence emission of protoporphyrin IX was used as an indicator of the relative concentration of photosensitizer within each plaque before, during, and after therapy. Results show that the rate of sensitizer photo- oxidation is proportional to both pre-treatment fluorescence intensity and surface irradiance, consistent with a rate- equation analysis. A correlation of fluorescence measurements with clinical response of plaques indicates that the effectiveness of PDT is dominated by the level of PpIX at the onset of treatment, and is much less dependent upon light dose. Using these findings we have established a PDT treatment protocol that involves the delivery of 8 J cm-2 of white light, at a rate of 15 mW cm-2. The possibility of ALA-PDT being established as the therapy of choice is discussed.
Identifying initial molecular targets of PDT: protein and lipid oxidation products
NASA Astrophysics Data System (ADS)
Oleinick, Nancy L.; Kim, Junhwan; Rodriguez, Myriam E.; Xue, Liang-yan; Kenney, Malcolm E.; Anderson, Vernon E.
Photodynamic Therapy (PDT) generates singlet oxygen (1O2) which oxidizes biomolecules in the immediate vicinity of its formation. The phthalocyanine photosensitizer Pc 4 localizes to mitochondria and endoplasmic reticulum, and the primary targets of Pc 4-PDT are expected to be lipids and proteins of those membranes. The initial damage then causes apoptosis in cancer cells via the release of cytochrome c (Cyt-c) from mitochondria into the cytosol, followed by the activation of caspases. That damage also triggers the induction of autophagy, an attempt by the cells to eliminate damaged organelles, or when damage is too extensive, to promote cell death. Cyt-c is bound to the cytosolic side of the mitochondrial inner membrane through association with cardiolipin (CL), a phospholipid containing four unsaturated fatty acids and thus easily oxidized by 1O2 or by other oxidizing agents. Increasing evidence suggests that oxidation of CL loosens its association with Cyt-c, and that the peroxidase activity of Cyt-c can oxidize CL. In earlier studies of Cyt-c in homogeneous medium by MALDI-TOF-MS and LC-ESI-MS, we showed that 1O2 generated by Pc 4-PDT oxidized histidine, methionine, tryptophan, and unexpectedly phenylalanine but not tyrosine. Most of the oxidation products were known to be formed by other oxidizing agents, such as hydroxyl radical, superoxide radical anion, and peroxynitrite. However, two products of histidine were unique to 1O2 and may be useful for reporting the action of 1O2 in cells and tissues. These products, as well as CL oxidation products, have now been identified in liposomes and mitochondria after Pc 4-PDT. In mitochondria, the PDT dose-dependent oxidations can be related to specific changes in mitochondrial function, Bcl-2 photodamage, and Cyt-c release. Thus, the role of PDT-generated 1O2 in oxidizing Cyt-c and CL and the interplay between protein and lipid targets may be highly relevant to understanding one mechanism for cell killing by PDT.
Assessment of biophysical tumor response to PDT in pancreatic cancer using localized reflectance spectroscopy
NASA Astrophysics Data System (ADS)
Isabelle, Martin; Klubben, William; He, Ting; Laughney, Ashley M.; Glaser, Adam; Krishnaswamy, Venkataramanan; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.
Biophysical changes such as inflammation and necrosis occur immediately following PDT and may be used to assess the treatment response to PDT treatment in-vivo. This study uses localized reflectance measurements to quantify the scatter changes in tumor tissue occurring in response to verteporfin-based PDT treatment in xenograft pancreas tumors. Nude mice were implanted with subcutaneous AsPC-1 pancreatic tumors cells in matrigel, and allowed to establish solid tumors near 100mm3 volume. The mice were sensitized with 1mg/kg of the active component of verteporfin (benzoporphryin derivative, BPD), one hour before light delivery. The optical irradiation was performed using a 1 cm cylindrical interstitial diffusing tip fiber with 20J of red light (690nm). Tumor tissue was excised progressively and imaged, from 1 day to 4 weeks, after PDT treatment. The tissue sections were stained and analyzed by an expert veterinary pathologist, who provided information on tissue regions of interest. This information was correlated with variations in scattering and absorption parameters elucidated from the spectral images and the degree of necrosis and inflammation involvement was identified. Areas of necrosis and dead cells exhibited the lowest average scatter irradiance signature (3.78 and 4.07 respectively) compared to areas of viable pancreatic tumor cells and areas of inflammation (5.81 and 7.19 respectively). Bilirubin absorbance parameters also showed a lower absorbance value in necrotic tissue and areas of dead cells (0.05 and 0.1 respectively) compared to tissue areas for viable pancreatic tumor cells and areas of inflammation (0.28 and 0.35). These results demonstrate that localized reflectance spectroscopy is an imaging modality that can be used to identify tissue features associated with PDT treatment (e.g. necrosis and inflammation) that can be correlated with histopathologically-reviewed H&E stained slides. Further study of this technique may provide means for automated
Open-Midplane Dipoles for a Muon Collider
Weggel, R.; Gupta, R.; Kolonko, J., Scanlan, R., Cline, D., Ding, X., Anerella, M., Kirk, H., Palmer, B., Schmalzle, J.
For a muon collider with copious decay particles in the plane of the storage ring, open-midplane dipoles (OMD) may be preferable to tungsten-shielded cosine-theta dipoles of large aperture. The OMD should have its midplane completely free of material, so as to dodge the radiation from decaying muons. Analysis funded by a Phase I SBIR suggests that a field of 10-20 T should be feasible, with homogeneity of 1 x 10{sup -4} and energy deposition low enough for conduction cooling to 4.2 K helium. If funded, a Phase II SBIR would refine the analysis and build and test a proof-of-principle magnet. A Phase I SBIR has advanced the feasibility of open-midplane dipoles for the storage ring of a muon collider. A proposed Phase II SBIR would refine these predictions of stresses, deformations, field quality and energy deposition. Design optimizations would continue, leading to the fabrication and test, for the first time, of a proof-of-principle dipole of truly open-midplane design.
Efficacy of low-dose mTHPC-PDT for the treatment of basal cell carcinomas
NASA Astrophysics Data System (ADS)
Betz, Christian S.; Rauschning, Winrich; Stranadko, Evgueni P.; Riabov, Mikhail V.; Albrecht, Volker; Nifantiev, Nikolay E.; Hopper, Colin
Objectives: Basal cell carcinomas (BCCs) are the most common skin cancers, and incidence rates are still rising. Photodynamic Therapy (PDT) with mTHPC (Foscan®) has shown to be a promising alternative to other treatments with good cosmetic results. This study was performed to determine optimal treatment parameters for this indication. Methods: 117 patients with a total of 460 BCCs received mTHPC-PDT. The treatment parameters were varied as follows: Foscan® dose 0.03 - 0.15 mg/kg, drug-light interval (DLI) 1 - 96 hours, total energy density 20 - 120 J/cm2. The clinical outcomes were assessed 8 weeks after PDT following WHO guidelines. Results: The rate of complete remissions (CR) was 96.7% and the general cosmetic outcome rated very good. In the largest subgroup (n=80) with low-dose mTHPC (0.05 mg/kg mTHPC; 48 hours DLI; 50 J/cm2 total energy density), a CR rate of 100% was accomplished. Minor changes of the parameters (0.04 mg/kg mTHPC or 24 hours DLI) yielded similar results. Side effects were encountered in 52 out of 133 PDT sessions. They were more common in patients who had received high drug doses (0.06 - 0.15 mg/kg) and comprised pain and phototoxic reactions. 3 patients developed severe sunburns with subsequent scarring at the injection site following sunlight exposure 2-3 weeks after mTHPC administration. Conclusions: The data suggests that low-dose mTHPC-PDT is an effective treatment option for BCCs. If sensibly applied, it is well tolerated and provides mostly excellent cosmetic results. The evaluation of long term results is still to be undertaken.
Optimization of targeted two-photon PDT triads for the treatment of head and neck cancers
NASA Astrophysics Data System (ADS)
Spangler, Charles W.; Starkey, Jean R.; Dubinina, Galyna; Fahlstrom, Carl; Shepard, Joyce
Synthesis of new PDT triads that incorporate a tumor-killing porphyrin with large two-photon cross-section for 150 fs laser pulses (2000 GM) in the Near-infrared (NIR) at 840 nm, a NIR imaging agent, and a small peptide that targets over-expressed EGF receptors on the tumor surface. This triad formulation has been optimized over the past year to treat FADU Head and Neck SCC xenograft tumors in SCID mice. Effective PDT triad dose (1-10 mg/Kg) and laser operating parameters (840 nm, 15-45 min, 900 mW) have been established. Light, dark and PDT treatment toxicities were determined, showing no adverse effects. Previous experiments in phantom and mouse models indicate that tumors can be treated directly through the skin to effective depths between 2 and 5 cm. Treated mice demonstrated rapid tumor regression with some complete cures in as little as 15-20 days. No adverse effects were observed in any healthy tissue through which the focused laser beam passed before reaching the tumor site, and excellent healing occurred post treatment including rapid hair re-growth. Not all irradiation protocols lead to complete cures. Since two-photon PDT is carried out by rastering focused irradiation throughout the tumor, there is the possibility that as the treatment depth increases, some parts of the tumor may escape irradiation due to increased scattering, thus raising the possibility that tumor re-growth could be triggered by small islands of untreated cells, especially at the rapidly growing tumor margins, a problem we hope to alleviate by using image-guided two-photon PDT.
Metronomic photodynamic therapy (mPDT) for intracranial neoplasm: physiological, biological, and dosimetry considerations
NASA Astrophysics Data System (ADS)
Bisland, Stuart L.; Lilge, Lothar; Lin, Annie; Wilson, Brian C.
Metronomic photodynamic therapy (mPDT), a procedure in which both the photosensitizer and light are delivered continuously so that the individual doses overlap pharmacologically is introduced. The fundamental hypothesis in mPDT is that by providing therapy at low fluence over extended periods of time, there is potential for improved selectivity in tumor cell kill through non necrotic pathways. This is especially important in the treatment of malignant brain tumors, in which selectivity between damage to tumor cells versus normal brain tissue is critical. Previous studies have shown that low-dose PDT using aminolevulinic acid (ALA)-induced protoporphyrin IX (PiIX) can induce apoptosis in tumor cells without causing necrosis in either tumor or normal brain tissue nor apoptosis in the latter. However, in order to achieve tumor control, multiple PDT treatments, such as hyper fractionation or metronomic delivery, are required, where the frequency and duration of the treatment are determined by the levels of apoptosis achieved in relationship to tumor cell doubling times, mPDT poses two substantial technical challenges: extended delivery of ALA and implantation of interstitial devices for extended light delivery at a sufficiently high enough density to achieve low fluence exposure to the brain adjacent to tumor or the entire hemisphere. In a rat model we evaluated the feasibility of delivering sustained ALA administration via the drinking water for up to 10 days without loss of PPIX selectivity. Post mortem quantitative spectrofluorimetry of tumor, normal brain and other tissues demonstrates a 4 times higher PPIX concentration in the 9L gliosarcoma model without noticeable toxicity. Light sources and delivery devices based either on laser diode or light emitting diode (LED) coupled to an implanted optical fiber were shown to be feasible. The maximum permissible spacing of cylindrical isotropic emitters is determined using known apoptotic indices and the necrosis
Simulation of large acceptance LINAC for muons
Miyadera, H; Kurennoy, S; Jason, A J
There has been a recent need for muon accelerators not only for future Neutrino Factories and Muon Colliders but also for other applications in industry and medical use. We carried out simulations on a large-acceptance muon linac with a new concept 'mixed buncher/acceleration'. The linac can accept pions/muons from a production target with large acceptance and accelerate muon without any beam cooling which makes the initial section of muon-linac system very compact. The linac has a high impact on Neutrino Factory and Muon Collider (NF/MC) scenario since the 300-m injector section can be replaced by the muon linac of only 10-m length. The current design of the linac consists of the following components: independent 805-MHz cavity structure with 6- or 8-cm-radius aperture window; injection of a broad range of pion/muon energies, 10-100 MeV, and acceleration to 150 - 200 MeV. Further acceleration of the muon beam are relatively easy since the beam is already bunched.
Histopathological and expression profiling studies of early tumor responses to near-infrared PDT treatment in SCID mice
NASA Astrophysics Data System (ADS)
Starkey, Jean R.; Rebane, Aleksander; Drobizhev, Mikhail A.; Meng, Fanqin; Gong, Aijun; Elliott, Aleisha; McInnerney, Kate; Pascucci, Elizabeth; Spangler, Charles W.
A novel class of porphyrin-based near-infrared photodynamic therapy (PDT) sensitizers is studied. We achieve regressions of human small cell lung cancer (NCI-H69), non-small cell lung cancer (A 459) and breast cancer (MDAMB- 231) xenografts in SCID mice at significant tissue depth by irradiation with an amplified femtosecond pulsed laser at 800 nm wavelength. Significant tumor regressions were observed during the first 10-14 days post treatment. Tumor histopathology was consistent with known PDT effects, while no significant changes were noted in irradiated normal tissues. In vivo imaging studies using intravenous injections of fluorescent dextran demonstrated an early loss of tumor blood flow. RNA was isolated from NCI-H69 PDT treated SCID mouse xenografts and paired untreated xenografts at 4 hours post laser irradiation. Similarly RNA was isolated from PDT treated and untreated Lewis lung carcinomas growing in C57/Bl6 mice. Expression profiling was carried out using Affymetrix TM human and mouse GeneChips®. Cluster analysis of microarray expression profiling results demonstrated reproducible increases in transcripts associated with apoptosis, stress, oxygen transport and gene regulation in the PDT treated NCI-H69 samples. In addition, PDT treated Lewis lung carcinomas showed reproducible increases in transcripts associated with immune response and lipid biosynthesis. PDT treated C57/Bl6 mice developed cytotoxic T cell activity towards this tumor, while untreated tumor bearing mice failed to do so.
The first muon beam from a new highly-intense DC muon source, MuSIC
NASA Astrophysics Data System (ADS)
Tran, Nam Hoai; MuSIC Collaboration
A new DC muon source, MuSIC, is now under construction at Research Center for Nuclear Physics (RCNP), Osaka University, Japan. The MuSIC adopts a new pion/muon collection system and a curved transport solenoid. These techniques are important in realization of future muon programs such as the muon to electron conversion experiments (COMET/Mu2e), neutrino factories, and muon colliders. The pion capture magnet and a part of the transport solenoid have been built and beam tests were carried out to assess the MuSIC's performance. Muon lifetime measurements and muonic X-ray measurements have been used for estimation of muon yield of the MuSIC. The result indicates that the MuSIC would be one of the most intense DC muon beams in the world.
Directivity function of muon detector
NASA Astrophysics Data System (ADS)
Karapetyan, G. G.
We introduce a new concept of directivity function (DF) to describe directional sensitivity of a particle detector. DF is a 3D function, describing the sensitivity of a detector to asymptotic directions of primary protons. It defines the contribution of primary protons, arriving from different asymptotic directions to the count rate of the detector. We develop the approach for computing the DF and derive it in particular case of SEVAN muon detector, located at mount Aragats, Armenia. Obtained data enable one to outline the region of solid angles, inside of which the arriving protons contribute a given percentage of count rate. In general, the DF can have the multi peak shape. It provides the most detailed and accurate description of directional sensitivity of a particle detector and we suggest that it is used in space research based on neutron and muon detectors.
Muon data analysis program RUMDA
NASA Astrophysics Data System (ADS)
Kilcoyne, S. H.
There are currently two data analysis programs available for muon users at ISIS. Both programs can be used for analyzing MuSR and EMU data and can be run on (MUSR01), (EMU01) or set-up to run on a user's account. RUMDA - 'Reading University Muon Data Analysis' was originally from Reading University and is now controlled at ISIS. At present (mid 1994) this suite of programs is run using VAX/VMS and the ISIS plotting package 'GENIE'. It is possible to fit data to any function with a maximum of 10 variables. UDA - 'mu Data Analysis' is a dashboard driven program which allows the user to plot and fit data files on the screen or as hard copies. It is possible to fit data to a combination of Gaussian and/or Lorentzian line shapes. A manual describing this program can be found in the back of the MuSR User Guide.
Milstene, C.; Fisk, G.; Para, A.; /Fermilab
This paper describes a new way to reconstruct and identify muons with high efficiency and high pion rejection. Since muons at the ILC are often produced with or in jets, for many of the physics channels of interest [1], an efficient algorithm to deal with the identification and separation of particles within jets is important. The algorithm at the core of the method accounts for the effects of the magnetic field and for the loss of energy by charged particles due to ionization in the detector. We have chosen to develop the analysis within the setup of one of the Linear Collider Concept Detectors adopted by the US. Within b-pair production jets, particles cover a wide range in momenta; however {approx}80% of the particles have a momentum below 30 GeV[2]. Our study, focused on bbar-b jets, is preceded by a careful analysis of single energy particles between 2 and 50 GeV. As medium energy particles are a substantial component of the jets, many of the particles lose part of their energy in the calorimeters and the solenoid coil before reaching the muon detector where they may have energy below 2 GeV. To deal with this problem we have implemented a Runge-Kutta correction of the calculated trajectory to better handle these lower energy particles. The multiple scattering and other stochastic processes, more important at lower energy, is addressed by a Kalman-filter integrated into the reconstruction algorithm. The algorithm provides a unique and powerful separation of muons from pions. The 5 Tesla magnetic field from a solenoid surrounds the hadron calorimeter and allows the reconstruction and precision.
Neutron densities from muon capture
NASA Astrophysics Data System (ADS)
Huan Ching, Chiang; Oset, Eulogio
We show that, because of Pauli blocking and renormalization of the weak currents in nuclei, the muon capture rates are rather sensitive to the neutron distributions. We also show that, because of intrinsic theoretical uncertainties, neutron radia cannot be determined with precision but some reasonable limits can be given. However, the ratio of capture rates in different isotopes serves to determine the neutron radii of the isotopes provided the neutron density distribution for one of them is known.
Introduction to Mini Muon Tracker
Borozdin, Konstantin N.
Using a mini muon tracker developed at the Los Alamos National Laboratory we performed experiments of simple landscapes of various materials, including TNT, 9501, lead, tungsten, aluminium, and water. Most common scenes are four two inches thick step wedges of different dimensions: 12-inch x 12-inch, 12-inch x 9-inch, 12-inch x 6-inch, and 12-inch x 3-inch; and a one three inches thick hemisphere of lead with spherical hollow, and a similar full lead sphere.
Information extraction from muon radiography data
Borozdin, K. N.; Asaki, T. J.; Chartrand, R.; Hengartner, N. W.; Hogan, G. E.; Morris, C. L.; Priedhorsky, W. C.; Schirato, R.C.; Schultz, L. J.; Sottile, M. J.; Vixie, K. R.; Wohlberg, B. E.; Blanpied, G.
Scattering muon radiography was proposed recently as a technique of detection and 3-d imaging for dense high-Z objects. High-energy cosmic ray muons are deflected in matter in the process of multiple Coulomb scattering. By measuring the deflection angles we are able to reconstruct the configuration of high-Z material in the object. We discuss the methods for information extraction from muon radiography data. Tomographic methods widely used in medical images have been applied to a specific muon radiography information source. Alternative simple technique based on the counting of high-scattered muons in the voxels seems to be efficient in many simulated scenes. SVM-based classifiers and clustering algorithms may allow detection of compact high-Z object without full image reconstruction. The efficiency of muon radiography can be increased using additional informational sources, such as momentum estimation, stopping power measurement, and detection of muonic atom emission.
In vivo suppression of solid Ehrlich cancer via chlorophyllin derivative mediated PDT: an albino mouse tumour model
NASA Astrophysics Data System (ADS)
Gomaa, Iman; Saraya, Hend; Zekri, Maha; Abdel-Kader, Mahmoud
In this study, copper chlorophyllin was used as a photosensitizer for photodynamic therapy (PDT) in Ehrlich tumour mouse model. Six groups of animals comprising 5 animals per group were subcutaneously transplanted with 1x106 Ehrlich tumour cells. A single dose of 200 μg/gm body weight chlorophylin derivative was administered by intravenous (IV) or intratumoral (IT) routes. Mice were exposed to monochromatic red laser of 630 nm for 1 h, and tumour regression was followed up for three consecutive months post treatment. Several Biochemical, histological and molecular tests were performed in order to evaluate the efficacy and safety of the applied treatment. An interest has been also directed towards investigating the molecular mechanisms underlying chlorophyllin derivative mediated PDT. PDT-treated animals via either the IV or IT routes showed significant decrease in tumour size 72 h post-treatment. Tumours at the IV-PDT group disappeared totally within a week with no recurrence over three months follow up. In the IT-PDT, the decrease in tumour size at the first week was interrupted by a slight increase; however never reached the original size. Histological examination of tumour tissues of the IV-PDT group at 24 h post treatment demonstrated restoring the normal muscle tissue architecture, and the biochemical assays indicated normal liver functions. The immunohistochemical analysis of caspase-3, and the quantitative PCR results of caspases-8 and 9 proved the presence of extrinsic apoptotic pathway after cholorphyllin derivative-mediated PDT. In conclusion IV-PDT strategy proved better cure rate than the IT-PDT, with no recurrence over three months of follow up.
Anticancer effect and cell cycle regulation of photodynamic therapy (PDT) using 9-hydroxypheophorbide-a and 660-nm diode laser
NASA Astrophysics Data System (ADS)
Chung, Phil-Sang; Rhee, Chung-Ku; Oh, Chung-Hun; Kim, Han-Gyun; Jung, Sang-Oun; Ahn, Jin-Chul
Tumor hypoxia, either pre-existing or as a result of oxygen bleaching during Photodynamic Therapy (PDT) light irradiation, can significantly reduce the effectiveness of PDT induced cell killing. To overcome the effect of tumor hypoxia and improve tumor cell killing, we propose using supplemental hyperoxygenation during Photofrin PDT. Our previous study has demonstrated that, in an in vivo model, tumor control can be improved by normobaric or hyperbaric 100% oxygen supply. The mechanism for the tumor cure enhancement of the hyperoxygenation-PDT combined therapy is investigated in this study by using an in vivo/in vitro technique. A hypoxic tumor model was established by implanting mammary adenocarcinoma (MCA) in hind legs of C3H mice. Light irradiation (200 J/cm2 at either 75 or 150 mW/cm2), under various oxygen supplemental conditions (room air or carbogen or 100% normobaric or hyperbaric 100% oxygen), was delivered through an optical fiber with a microlens to animals who received 12.5 mg/kg Photofrin 24 hours prior to light irradiation. Tumors treated with PDT were harvested and grown in vitro for colony formation analysis. Treated tumors were also analyzed histologically. The results show that, when combined with hyperoxygenation, the cell killing rate immediately after a PDT treatment is significantly improved over that treated without hyperoxygenation, suggesting an enhanced direct cell killing. This study further confirms our earlier observation that when a PDT treatment is combined with hyperoxygenation, it can be more effective in controlling hypoxic tumors. H&E stain revealed that PDT induced tumor necrosis and hemorrhage. In conclusion, by using an in vivo/in vitro assay, we have shown that PDT combined with hyper-oxygenation can enhance direct cell killing and improve tumor cure.
Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells.
Qiao, Li; Xu, Chengshan; Li, Qiang; Mei, Zhusong; Li, Xinji; Cai, Hong; Liu, Wei
5-Aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been used for part of squamous cell carcinoma (premalignant conditions or in situ cutaneous SCC-Bowen disease). However, mechanism of ALA-PDT is not fully understood yet on the cell apoptosis pathway. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on human squamous carcinoma A431cells. Apoptosis and cell viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit and MTT assay. The mRNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Our data showed that 5-ALA-PDT significantly inhibited cell proliferation (p<0.05), but there was no significant difference when the photosensitizer reached to 4.8mM. The inhibition in cell proliferation after 5-ALA-PDT treatment was correlated to more cells being arrested in the G0/G1 phase of the cell cycle (p<0.01). Immunocytochemical observations using anti-active caspase-3 antibodies showed active caspase-3 was translocated from cytoplasm to nuclear during apoptosis. STAT3 and its downstream gene Bax and BCL-2 were changed after 5-ALA-PDT treatment for the mRNA and protein expression. Our studies confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment. PMID:26607555
Muon cooling in a quadrupole magnet channel
Neuffer, David; Poklonskiy, A.; /Michigan State U.
As discussed before,[1] a cooling channel using quadrupole magnets in a FODO transport channel can be used for initial cooling of muons. In the present note we discuss this possibility of a FODO focusing channel for cooling, and we present ICOOL simulations of muon cooling within a FODO channel. We explore a 1.5m cell-length cooling channel that could be used for the initial transverse cooling stage of a muon collider or neutrino factory.
Status of the MANX muon cooling experiment
Yonehara, K.; Broemmelsiek, D.; Hu, M.; Jansson, A.; Kashikhin, V.S.; Kashikhin, V.V.; Lamm, M.; Lopes, M.; Shiltsev, V.; Yarba, V.; Yu, M.; /Fermilab /Muons Inc., Batavia
A demonstration experiment of six-dimensional (6D) phase space muon beam cooling is a key milestone on the roadmap toward to a real muon collider. In order to achieve this goal, they have designed the Muon Collider and Neutrino Factory Experiment (MANX) channel, which consists of the Helical Cooling Channel (HCC). They discuss the status of the simulation study of the MANX in this document.
The US Muon Accelerator Program (MAP)
Bross, Alan D.; /Fermilab
The US Department of Energy Office of High Energy Physics has recently approved a Muon Accelerator Program (MAP). The primary goal of this effort is to deliver a Design Feasibility Study for a Muon Collider after a 7 year R&D program. This paper presents a brief physics motivation for, and the description of, a Muon Collider facility and then gives an overview of the program. I will then describe in some detail the primary components of the effort.
Materials science with muon spin rotation
NASA Technical Reports Server (NTRS)
During this reporting period, the focus of activity in the Materials Science with Muon Spin Rotation (MSMSR) program was muon spin rotation studies of superconducting materials, in particular the high critical temperature and heavy-fermion materials. Apart from these studies, work was continued on the analysis of muon motion in metal hydrides. Results of these experiments are described in six papers included as appendices.
Combination of verteporfin-PDT and PI3K inhibitors enhances cell growth inhibition and apoptosis in endothelial cells
NASA Astrophysics Data System (ADS)
Kraus, Daniel; Chen, Bin
Vascular targeted photodynamic therapy is a promising cancer treatment modality by ablating tumor vasculature. The effectiveness of this treatment is often compromised by regrowth of endothelial cells, which causes tumor recurrence. In this preliminary report, we showed that activated PI3K signaling was involved in endothelial cell regrowth after PDT with verteporfin and combination between verteporfin-PDT and PI3K pathway inhibitor BEZ235 induced more cell apoptosis and greater inhibition in cell proliferation. These results suggest that rational combination of verteporfin-PDT and PI3K inhibitors result in enhanced treatment outcomes.
Neutrino induced muons in Soudan 2.
DeMuth, D. M.; Soudan 2 Collaboration
The neutrino-induced muon rate underground has been measured at Soudan 2. To discriminate from the intense background of atmospheric muons we consider only the through-going muons which originate from horizontal direction ({minus}0.14 < cos{theta} < 0.14). We calculate the horizontal, neutrino-induced muon rate at Soudan 2 from an exposure of 1.23 x 10{sup 8} s as {Phi}{sub {nu}{mu}} = (3.45 {+-} 0.52 {+-} 0.61) x 10{sup {minus}13} (cm{sup 2} sr s){sup {minus}1}.
Question of Lorentz violation in muon decay
NASA Astrophysics Data System (ADS)
Noordmans, J. P.; Onderwater, C. J. G.; Wilschut, H. W.; Timmermans, R. G. E.
Possibilities to test the Lorentz invariance of the weak interaction in muon decay are considered. We derive the direction-dependent muon-decay rate with a general Lorentz-violating addition to the W -boson propagator. We discuss measurements of the directional and boost dependence of the Michel parameters and of the muon lifetime as a function of absolute velocity. The total muon-decay rate in the Lorentz-violating standard model extension is addressed. Suggestions are made for dedicated (re)analyses of the pertinent data and for future experiments.
Magnets for Muon 6D Cooling Channels
Johnson, Rolland; Flanagan, Gene
The Helical Cooling Channel (HCC), an innovative technique for six-dimensional (6D) cooling of muon beams using a continuous absorber inside superconducting magnets, has shown considerable promise based on analytic and simulation studies. The implementation of this revolutionary method of muon cooling requires high field superconducting magnets that provide superimposed solenoid, helical dipole, and helical quadrupole fields. Novel magnet design concepts are required to provide HCC magnet systems with the desired fields for 6D muon beam cooling. New designs feature simple coil configurations that produce these complex fields with the required characteristics, where new high field conductor materials are particularly advantageous. The object of the program was to develop designs and construction methods for HCC magnets and design a magnet system for a 6D muon beam cooling channel. If successful the program would develop the magnet technologies needed to create bright muon beams for many applications ranging from scientific accelerators and storage rings to beams to study material properties and new sources of energy. Examples of these applications include energy frontier muon colliders, Higgs and neutrino factories, stopping muon beams for studies of rare fundamental interactions and muon catalyzed fusion, and muon sources for cargo screening for homeland security.
The MANX Muon Cooling Experiment Detection System
Kahn, S. A.; Abrams, R. J.; Ankenbrandt, C.; Cummings, M. A. C.; Johnson, R. P.; Robertsa, T. J.; Yoneharab, K.
The MANX experiment is being proposed to demonstrate the reduction of 6D muon phase space emittance, using a continuous liquid absorber to provide ionization cooling in a helical solenoid magnetic channel. The experiment involves the construction of a two-period-long helical cooling channel (HCC) to reduce the muon invariant emittance by a factor of two. The HCC would replace the current cooling section of the MICE experiment now being set up at the Rutherford Appleton Laboratory. The MANX experiment would use the existing MICE spectrometers and muon beam line. We discuss the placement of detection planes to optimize the muon track resolution.
Synthesis of decacationic [60]fullerene decaiodides giving photoinduced production of superoxide radicals and effective PDT-mediation on antimicrobial photoinactivation
Wang, Min; Maragani, Satyanarayana; Huang, Liyi; Jeon, Seaho; Canteenwala, Taizoon; Hamblin, Michael R.; Chiang, Long Y.
We report a novel class of highly water-soluble decacationic methano[60]fullerene decaiodides C60[>M(C3N6+C3)2]-(I−)10[1-(I−)10] capable of co-producing singlet oxygen (Type-II) and highly reactive hydroxyl radicals, formed from superoxide radicals in Type-I photosensitizing reactions, upon illumination at both UVA and white light wavelengths. The O2-·-production efficiency of 1-(I−)10 was confirmed by using an O2-·-reactive bis(2,4-dinitrobenzenesulfonyl)tetrafluorofluorescein probe and correlated to the photoinduced electron-transfer event going from iodide anions to C360∗[>M(C3N6+C3)2] leading to C60-·[>M(C3N6+C3)2]. Incorporation of a defined number (ten) of quaternary ammonium cationic charges per C60 in 1 was aimed to enhance its ability to target pathogenic Gram-positive and Gram-negative bacterial cells. We used the well-characterized malonato[60]fullerene diester mono-adduct C60[>M(t-Bu)2] as the starting fullerene derivative to provide a better synthetic route to C60[>M(C3N6+C3)2] via transesterification reaction under trifluoroacetic acid catalyzed conditions. These compounds may be used as effective photosensitizers and nano-PDT drugs for photoinactivation of pathogens. PMID:23474903
Absolute calibration of optical power for PDT: report of AAPM TG140.
Zhu, Timothy C; Bonnerup, Chris; Colussi, Valdir C; Dowell, Marla L; Finlay, Jarod C; Lilge, Lothar; Slowey, Thomas W; Sibata, Claudio
This report is primarily concerned with methods for optical calibration of laser power for continuous wave (CW) light sources, predominantly used in photodynamic therapy (PDT). Light power calibration is very important for PDT, however, no clear standard has been established for the calibration procedure nor the requirements of power meters suitable for optical power calibration. The purposes of the report are to provide guidance for establishing calibration procedures for thermopile type power meters and establish calibration uncertainties for most commercially available detectors and readout assemblies. The authors have also provided a review of the use of various power meters for CW and pulsed optical sources, and provided recommended temporal frequencies for optical power meter calibrations and guidance for routine quality assurance procedure. PMID:23927297
Photodynamic therapy (ALA-PDT) in the treatment of pathological states of the cornea
NASA Astrophysics Data System (ADS)
Switka-Wieclawska, Iwona; Kecik, Tadeusz; Kwasny, Miroslaw; Graczyk, Alfreda
Each year an increasing amount of research is published on the use of photodynamic therapy in medicine. The most recent research has focused mostly on the use of photosensitizer called vertoporphyrin (Visudyne) is the treatment of subretinal neovascularization in age-related macular degeneration (AMD) or myopia, following a substantial amount of ophthalmology research mostly experimental on the application of the method in diagnosis and treatment of some eye tumors. In the Department of Ophthalmology of Polish Medical University in Warsaw, PDT was used as supplementary method in a selected group of patients with chronic virus ulcer of the cornea and keratopathies. During the treatment 5-aminolevulinic acid (5-ALA) was applied in ointment form as a photosensitizer activated with light wave of 633 nm. It appears, on the basis of the results obtained, that photodynamic therapy (ALA-PDT) may become in the future a valuable supplement to the methods being used at the present treating pathological states of the cornea.
Spatial and temporal changes in Bax subcellular localization during NPe6-PDT-induced apoptosis
NASA Astrophysics Data System (ADS)
Liu, Lei; Xing, Da; Chen, Wei R.; Wan, Qingling; Zhou, Feifan
Photodynamic therapy (PDT) employing photosensiter N-aspartyl chlorin e6 (NPe6) can induce lysosome disruption and initiate the intrinsic apoptotic pathway. Bax, a member of the Bcl-2 family of proteins, is an essential regulator of apoptosis. Bax is normally found in the cytosol of healthy cells, and translocates to mitochondria in response to many apoptotic stimuli. In this study, using real-time single-cell analysis, we have investigated the kinetics of Bax distribution during NPe6-induced apoptosis in ASTC-a-1 cells. In order to monitor Bax subcellular distribution, cells were stained with GFP-Bax and Mito Tracker Red. The results show that Bax redistribution occurred at about 170 min after treated with NPe6-PDT, and then sequestered into clusters associated with the mitochondira within 30 min. Our data clearly showed the spatial and temporal changes in Bax distribution in living cells during NPe6-induced apoptosis.
Real-time treatment light dose guidance of Pleural PDT: an update
NASA Astrophysics Data System (ADS)
Zhu, Timothy C.; Kim, Michele M.; Jacques, Steven L.; Penjweini, Rozhin; Dimofte, Andreea; Finlay, Jarod C.; Simone, Charles B.; Cengel, Keith A.; Friedberg, Joseph
The goal of this study was to develop and improve an infrared (IR) navigation system to deliver light dose uniformly during intracavitory PDT by tracking the movement of the light source and providing real-time feedback on the light fluence rate on the entire cavity surface area. In the current intrapleural PDT protocol, several detectors placed in selected locations in the pleural cavity monitor the light doses. To improve the delivery of light dose uniformity, an IR camera system is used to track the motion of the light source as well as the surface contour of the pleural cavity. Monte- Carlo simulation is used to improve the calculation algorithm for the effect of light that undergoes multiple scattering along the surface in addition to an improvement of the direct light calculation using an improved model that accounts for the anisotropy of the light from the light source.
Application of laser and PDT to treatment of recurrent cancer in the paranasal sinuses
NASA Astrophysics Data System (ADS)
Xin, Jiang
Forty-one cases of recurrent cancer in the maxillary sinus and ethmoid sinus were treated by Nd:YAG laser, CO2 laser, PDT, and operation. The partial skull fundus invaded by the advanced carcinoma in the maxillary sinus and ethmoid sinus was resected with laser through the cranial facial section. The cancer in the maxillary sinus is the most common in primary paranasal carcinoma, accounting for 80 percent. The malignant tumors in the ethmoid sinus are minor. Radiation and operation are usually performed in them, but it is easy for the cancer to recur after treatment. To save and continue life, 41 cases of recurrent carcinoma in the paranasal sinuses were cured by laser and PDT from 1979 to 1991.
Monitoring PDT effects in murine tumors by spectroscopic and imaging techniques
NASA Astrophysics Data System (ADS)
Ramaprasad, Subbaraya; Rzepka, Elzbieta; Pi, Jiaxiong; Joshi, Shantaram S.; Dobhal, Mahabeer; Missert, Joseph; Pandey, Ravindra K.
The changes in the tumor that occur following photodynamic therapy (PDT) were studied using a small animal MR imager operating at 7Tesla. The animal model used in these studies was mice bearing radiation induced fibrosarcoma (RIF) tumor on the foot dorsum. The mice were injected with 10μM/kg of one of the photosensitizers: (1) Photofrin, (2) Non-fluorinated porphyrin photosensitizer (DOD-1), (3) Fluorinated porphyrin photosensitizer (DOD-2) and, (4) Fluorinated chlorin photosensitizer (DOD-6). Laser light at 630 or 650 nm (150 mW/cm2, 270 joules/cm2) was delivered to the tumor at 2-24 hours of photosensitizer administration. The MR spectroscopic and imaging examination of the tumors involved both the 1H and 31P nuclei. The tumor bioenergetics was measured by 31P spectroscopy. The water proton relaxivity and diffusion measurements were used to obtain local changes in different regions of the tumor. Changes in 31P MR spectra were observed following PDT using Photofrin and fluorinated chlorin sensitizer (DOD-6). However, no significant changes were observed when the fluorinated porphyrin and its nonfluorinated analog were used. The PDT induced changes in tumor volumes showed significant tumor regression with Photofrin, fluorinated porphyrin and chlorin sensitizers. No tumor regression was observed with the non labeled porphyrin sensitizer and the growth profile followed the general pattern of unperturbed tumors. Serial noninvasive measurements of tumor response to PDT are measurable by both MRI and MRS. The MR derived parameters that are characteristic of the tumor status before and after the therapy are discussed here.
The tools of PDT: light sources and devices. Can they help in getting better therapeutic results?
NASA Astrophysics Data System (ADS)
Boucher, Didier
PDT is a drug and device therapy using photosensitizing drugs activated by laser light, for tissue ablation. PDT light sources must deliver wavelengths matching the absorption of photosensitizers' compound without any side thermal effect. According to applications, these sources need to be: - pled to relatively small optical fibres so as to bring the light energy, of specific wavelength, inside of the body (gastroenterology, head & neck, urology, pneumology), - coupled to a slit lamp adapter to transmit the light to the eye (AMD) - or allow a direct illumination of tissues when large areas must be treated (dermatology). But they also need to be user-friendly with limited investment and installation costs. So as to achieve the required effects, several light sources are available and will be used but practical and economical reasons have limited the number and types of these sources. For PDT oncology applications, besides dermatology, it has also been necessary to develop specific light delivery systems based on optical fibres. These devices allow the treatment: - of circular lumens such as oesophagus, bile ducts, lungs - of solid volumes such as prostate, pancreas - of surfaces such as in head and neck - of empty volumes such as bladder, uterus, cervix. Due to the variety of these treatments, a full family of sources has been developed from original sophisticated costly lasers to more recent easy-to-use diode laser systems. The aim of this presentation is to present the actual state of the art of actual available PDT tools, analyze their qualities and weaknesses, analyze the consequences of a good and/or bad choice or good and/or bad utilization on the quality of the therapeutic results and resulting side effects. It will also evaluate the short and medium term developments of new tools and their effect on the development of the therapy including economical aspects.
Comparison between mALA- and ALA-PDT in the treatment of basal cell carcinomas
NASA Astrophysics Data System (ADS)
Schleier, Peter; Zenk, Witold; Hyckel, Peter; Berndt, Alexander
Introduction: The external application of aminoleavulinic acid (ALA), which is a substrate of physiologic cell metabolism, represents a possible treatment option in superficial basal cell carcinomas (BCC). The development of new ALA-esters (mALA) with potential for higher penetration depths promises higher therapeutic success. This research aimed to prove the following hypothesis: The cytotoxic effect of the mALA- photodynamic therapy (mALA-PDT), when compared to the ALA-PDT, leads to a higher clinical success rate. Material and Methods: 24 patients with multiple facial tumors, after having received several local surgical excisions with known histology, were treated with either ALA- or mALA-PDT, during the past two years. In total, 89 basal cell carcinoma, 45 actinic keratoses, 6 keratoacanthoma, and 2 squamous cell carcinomas were treated. ALA-PDT: A thermo gel with 40 % mALA or ALA was applied from a cooled syringe. Three to five hours after gel application the skin was cleaned from any gel residues. Irradiation was done with a diode laser and was performed in two sessions, each 10 min long. After intervals of 2, 4 and 12 weeks, the patients were recalled to assess therapeutic efficacy. This was followed by photographic documentation. Results: More than 80% of the tumors treated primarily were resolved successfully. A recurrence rate of approximately 15% was observed. Three per cent of the tumors showed no reaction to therapy. There were no statistically significant differences between the two therapeutic groups. Discussion: The advantage of the use of ALA lies foremost in the fast metabolic use of the body's own photosensitizer PpIX. There are no known side effects of this therapy. Moreover, external application is superior to systemic application with regard to patient management. The method can be combined with other therapies. Although the mALA should have a better penetration in tumor tissue, the therapeutic outcome is similar to the use of ALA.
Technical Challenges and Scientific Payoffs of Muon BeamAccelerators for Particle Physics
Zisman, Michael S.
Historically, progress in particle physics has largely beendetermined by development of more capable particle accelerators. Thistrend continues today with the recent advent of high-luminosityelectron-positron colliders at KEK and SLAC operating as "B factories,"the imminent commissioning of the Large Hadron Collider at CERN, and theworldwide development effort toward the International Linear Collider.Looking to the future, one of the most promising approaches is thedevelopment of muon-beam accelerators. Such machines have very highscientific potential, and would substantially advance thestate-of-the-art in accelerator design. A 20-50 GeV muon storage ringcould serve as a copious source of well-characterized electron neutrinosor antineutrinos (a Neutrino Factory), providing beams aimed at detectorslocated 3000-7500 km from the ring. Such long baseline experiments areexpected to be able to observe and characterize the phenomenon ofcharge-conjugation-parity (CP) violation in the lepton sector, and thusprovide an answer to one of the most fundamental questions in science,namely, why the matter-dominated universe in which we reside exists atall. By accelerating muons to even higher energies of several TeV, we canenvision a Muon Collider. In contrast with composite particles likeprotons, muons are point particles. This means that the full collisionenergy is available to create new particles. A Muon Collider has roughlyten times the energy reach of a proton collider at the same collisionenergy, and has a much smaller footprint. Indeed, an energy frontier MuonCollider could fit on the site of an existing laboratory, such asFermilab or BNL. The challenges of muon-beam accelerators are related tothe facts that i) muons are produced as a tertiary beam, with very large6D phase space, and ii) muons are unstable, with a lifetime at rest ofonly 2 microseconds. How these challenges are accommodated in theaccelerator design will be described. Both a Neutrino Factory and a Muon
First results of the cosmic ray muon variation study by means of the scintillation muon hodoscope
NASA Astrophysics Data System (ADS)
Ampilogov, N. V.; Astapov, I. I.; Barbashina, N. S.; Borog, V. V.; Dmitrieva, A. N.; Kovylyaeva, A. A.; Kompaniets, K. G.; Petrukhin, A. A.; Shutenko, V. V.; Yashin, I. I.
The new scintillation muon hodoscope to study cosmic ray muon flux variations was created in MEPhI. The basic characteristics of the hodoscope (sensitivity area, precision of the muon track reconstruction, 'live' time etc.) are comparable with other hodoscopes (TEMP and URAGAN) of MEPhI. Modular design is a distinctive feature of the detector, supplying relativity easy transportability, and low maintenance requirements give a possibility of a long-term autonomic operation. First results of the cosmic ray muon variation study by means of the scintillation muon hodoscope are presented and discussed.
Hadronic interactions and EAS muon pseudorapidities investigated with the Muon Tracking Detector in KASCADE-Grande
NASA Astrophysics Data System (ADS)
Zabierowski, J.; Apel, W. D.; Arteaga, J. C.; Badea, F.; Bekk, K.; Bertaina, M.; Blümer, H.; Bozdog, H.; Brancus, I. M.; Brüggemann, M.; Buchholz, P.; Cantoni, E.; Chiavassa, A.; Cossavella, F.; Daumiller, K.; de Souza, V.; di Pierro, F.; Doll, P.; Engel, R.; Engler, J.; Finger, M.; Fuhrmann, D.; Ghia, P. L.; Gils, H. J.; Glasstetter, R.; Grupen, C.; Haungs, A.; Heck, D.; Hörandel, J. R.; Huege, T.; Isar, P. G.; Kampert, K.-H.; Kang, D.; Kickelbick, D.; Klages, H. O.; Kolotaev, Y.; Łuczak, P.; Mathes, H. J.; Mayer, H. J.; Milke, J.; Mitrica, B.; Morello, C.; Navarra, G.; Nehls, S.; Oehlschläger, J.; Ostapchenko, S.; Petcu, M.; Pierog, T.; Rebel, H.; Roth, M.; Schieler, H.; Schröder, F.; Sima, O.; Stümpert, M.; Toma, G.; Trinchero, G. C.; Ulrich, H.; van Buren, J.; Walkowiak, W.; Weindl, A.; Wochele, J.; Wommer, M.; KASCADE-Grande Collaboration
The Muon Tracking Detector in the KASCADE-Grande EAS experiment allows the precise measurement of shower muon directions up to 700 m distance from the shower center. This directional information is used to study the pseudorapidity of muons in EAS, closely related to the pseudorapidity of their parent mesons. Moreover, the mean value of muon pseudorapidity in a registered shower reflects the longitudinal development of its hadronic component. All of this makes it a good tool for testing hadronic interaction models. The possibilities of such tests given by the KASCADE-Grande experimental setup are discussed and an example of the obtained muon pseudorapidity spectrum is shown.
Imaging the Subsurface with Upgoing Muons
NASA Astrophysics Data System (ADS)
Bonal, N.; Preston, L. A.; Schwellenbach, D.; Dreesen, W.; Green, A.
We assess the feasibility of imaging the subsurface using upgoing muons. Traditional muon imaging focuses on more-prevalent downgoing muons. Muons are subatomic particles capable of penetrating the earth's crust several kilometers. Downgoing muons have been used to image the Pyramid of Khafre of Giza, various volcanoes, and smaller targets like cargo. Unfortunately, utilizing downgoing muons requires below-target detectors. For aboveground objects like a volcano, the detector is placed at the volcano's base and the top portion of the volcano is imaged. For underground targets like tunnels, the detector would have to be placed below the tunnel in a deeper tunnel or adjacent borehole, which can be costly and impractical for some locations. Additionally, detecting and characterizing subsurface features like voids from tunnels can be difficult. Typical characterization methods like sonar, seismic, and ground penetrating radar have shown mixed success. Voids have a marked density contrast with surrounding materials, so using methods sensitive to density variations would be ideal. High-energy cosmic ray muons are more sensitive to density variation than other phenomena, including gravity. Their absorption rate depends on the density of the materials through which they pass. Measurements of muon flux rate at differing directions provide density variations of the materials between the muon source (cosmic rays and neutrino interactions) and detector, much like a CAT scan. Currently, tomography using downgoing muons can resolve features to the sub-meter scale. We present results of exploratory work, which demonstrates that upgoing muon fluxes appear sufficient to achieve target detection within a few months. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.
PDT in non-surgical treatment of periodontitis in kidney transplanted patients: a split-mouth, randomized clinical trial
NASA Astrophysics Data System (ADS)
Marinho, Kelly C. T.; Giovani, Elcio M.
This study was to evaluate clinical and microbiological effectiveness of photodynamic therapy (PDT) in the treatment of periodontal disease in kidney-transplanted patients. Eight kidney transplanted patients treated at Paulista University were arranged in two groups: SRP performed scaling and root planning by ultrasound; SRP+PDT- in the same patient, which was held to PDT in the opposite quadrant, with 0.01% methylene blue and red laser gallium aluminum arsenide, wavelength 660 nm, power 100 mW. There was reduction in probing pocket depth after 45 days and 3 months regardless the group examined; plaque and bleeding index showed improvement over time, regardless the technique used, and bleeding index in the SRP+PDT group was lower when compared with the baseline the other times. There was no difference in the frequency of pathogens. Photodynamic therapy may be an option for treatment of periodontal disease in renal-transplanted patients and its effectiveness is similar to conventional therapy.
Squaraine PDT induces oxidative stress in skin tumor of swiss albino mice
NASA Astrophysics Data System (ADS)
Cibin, T. R.; Gayathri, Devi D.; Ramaiah, D.; Abraham, Annie
Photodynamic Therapy (PDT) using a sensitizing drug is recognized as a promising medical technique for cancer treatment. It is a two step process that requires the administration of a photosensitizer followed by light exposure to treat a disease. Following light exposure the photosensitizer is excited to a higher energy state which generates free radicals and singlet oxygen. The present study was carried out to assess the oxidative damage induced by bis (3, 5-diiodo-2, 4, 6- trihydroxyphenyl) squaraine in skin tumor tissues of mice with/ without light treatment. Skin tumor was induced using 7, 12-Dimethyl Benz(a)anthracene and croton oil. The tumor bearing mice were given an intraperitoneal injection with the squaraine dye. After 24h, the tumor area of a few animals injected with the dye, were exposed to visible light from a 1000 W halogen lamp and others kept away from light. All the mice were sacrificed one week after the PDT treatment and the oxidative profile was analyzed (TBARS, SOD, catalase, GSH, GPx and GR) in tumor/ skin tissues. The dye induces oxidative stress in the tumor site only on illumination and the oxidative status of the tumor tissue was found to be unaltered in the absence of light. The results of the study clearly shows that the tumor destruction mediated by PDT using bis (3, 5-diiodo-2, 4, 6-trihydroxyphenyl) squaraine as a photosensitizer is due to the generation of reactive oxygen species, produced by the light induced changes in the dye.
EtNBS and EtNBS-COOH PDT efficacy in ovarian cancer cells
NASA Astrophysics Data System (ADS)
Park, Yong Jin; Klein, Oliver J.; Bahayana, Brijesh; Evans, Conor L.
The effective treatment of metastatic cancer continues to be a challenge due to the highly invasive nature of metastatic lesions and their propensity to develop therapeutic resistance. Optimal therapeutic regimens for peritoneal metastases should have both rapid uptake and penetrate throughout cancerous lesions. Using in vitro models of ovarian cancer, we have found that the cores of tumor nodules are both hypoxic and acidic, rendering most chemotherapeutic agents ineffective, and considerably reducing the therapeutic efficacy of the majority of photodynamic therapy (PDT) and radiation therapy regimens. PDT using EtNBS, a cationic photosensitizer, is a promising approach for treating these hypoxic and acidic nodule cores as it rapidly accumulates into the hypoxic cores of tumor nodules, and is effective even in completely anoxic environments. To improve the uptake rate of EtNBS into cells, we utilized a carboxylic acid terminated derivative of EtNBS that is zwitterionic at biological pH levels. In this study, we investigated the effect of this structural change on PDT efficacy in ovarian cancer cells.
Photodynamic therapy (PDT) to treat a chronic skin wound in a dog
NASA Astrophysics Data System (ADS)
Hage, Raduan; Plapler, Hélio; Bitar, Renata A.
Photodynamic Therapy (PDT) is an emerging and promising therapeutic modality for treatment of a wide variety of malignant and nononcologic tumors, as well as in the treatment of infected skin ulcers. This study evaluated the effectiveness of the PDT to treat a chronic skin wound that had been already subjected to several clinical and surgical type treatments in a dog. The animal with an infected chronic skin wound with 8 cm diameter in the left leg received an injection of an aqueous solution of 1% methylene blue (MB) with 2% lidocaine into the lesion. After MB injection the wound was irradiated using a LED (LED-VET MMOptics(r)) with a wavelength between 600 and 700 nm, 2 cm diameter circular light beam, of 150 mW of power, light dose of 50 J/cm2. After 3 and 6 weeks PDT was repeated and the wound was re-evaluated. Complete healing was achieved 10 weeks after the first procedure.
The role of NO synthase isoforms in PDT-induced injury of neurons and glial cells
NASA Astrophysics Data System (ADS)
Kovaleva, V. D.; Berezhnaya, E. V.; Uzdensky, A. B.
Nitric oxide (NO) is an important second messenger, involved in the implementation of various cell functions. It regulates various physiological and pathological processes such as neurotransmission, cell responses to stress, and neurodegeneration. NO synthase is a family of enzymes that synthesize NO from L-arginine. The activity of different NOS isoforms depends both on endogenous and exogenous factors. In particular, it is modulated by oxidative stress, induced by photodynamic therapy (PDT). We have studied the possible role of NOS in the regulation of survival and death of neurons and surrounding glial cells under photo-oxidative stress induced by photodynamic treatment (PDT). The crayfish stretch receptor consisting of a single identified sensory neuron enveloped by glial cells is a simple but informative model object. It was photosensitized with alumophthalocyanine photosens (10 nM) and irradiated with a laser diode (670 nm, 0.4 W/cm2). Antinecrotic and proapoptotic effects of NO on the glial cells were found using inhibitory analysis. We have shown the role of inducible NO synthase in photoinduced apoptosis and involvement of neuronal NO synthase in photoinduced necrosis of glial cells in the isolated crayfish stretch receptor. The activation of NO synthase was evaluated using NADPH-diaphorase histochemistry, a marker of neurons expressing the enzyme. The activation of NO synthase in the isolated crayfish stretch receptor was evaluated as a function of time after PDT. Photodynamic treatment induced transient increase in NO synthase activity and then slowly inhibited this enzyme.
Designing PDT-based combinations to overcome chemoresistance in heterocellular 3D tumor models (Conference Presentation)
NASA Astrophysics Data System (ADS)
Rizvi, Imran; Briars, Emma A.; Bulin, Anne-Laure; Anbil, Sriram; Vecchio, Daniela; Alkhateeb, Ahmed; Hanna, William R.; Celli, Jonathan P.; Hasan, Tayyaba
A major barrier to treating advanced-stage cancers is heterogeneity in the responsiveness of metastatic disease to conventional therapies leading to resistance and treatment failure. Photodynamic therapy (PDT) has been shown to synergize with conventional agents and to overcome the evasion pathways that cause resistance. Developing PDT-based combinations that target resistant tumor populations and cooperate mechanistically with conventional agents is an increasingly promising approach to improve therapeutic efficacy while minimizing toxicity, particularly in complex disease sites. Identifying the molecular, cellular, and microenvironmental cues that lead to heterogeneity and treatment resistance is critical to developing strategies to target unresponsive regions of stubborn disease. Cell-based research platforms that integrate key microenvironmental cues are emerging as increasingly important tools to improve the translational efficiency of new agents, and to design combination regimens. Among the challenges associated with developing and scaling complex cell-based screening platforms is the need to integrate, and balance, biological relevance with appropriate, high-content imaging routines that provide meaningful quantitative readouts of therapeutic response. The benefits and challenges associated with deriving meaningful insights from complex cell-based models will be presented, with a particular emphasis on overcoming chemoresistance mediated by physical stress and communication with stromal partners (e.g. tumor endothelial cells, which are emerging as dynamic regulators of treatment resistance) using PDT-based combinations.
PDT-induced apoptosis in brain tissue in vivo: a retrospective study
NASA Astrophysics Data System (ADS)
Lilge, Lothar D.; Portnoy, Michelle; Wilson, Brian C.
The apoptotic response of normal brain and intracranial VX2 tumor following photodynamic therapy mediated by five different photodynamic drugs, Photofrin, ALA, AlClPc, SnET2 and mTHPC, was evaluated in a preliminary retrospective analysis. Rabbit brain, with or without tumor, was treated by PDT with interstitial light delivery. Histological sections at 24 h post PDT were assessed by the TUNEL assay. Confocal fluorescence microscopy was used to determine the total apoptotic cell count and the spatial distribution of apoptotic bodies within the tissue. The data were confirmed qualitatively by light microscopy on adjacent H&E-stained sections. Light-only and drug-only controls produced background levels. The highest apoptotic count was seen with Photofrin. The counts in AlClPc-treated animals were not above the background level, while the other 3 photosensitizers gave intermediate levels. With some, but not all, drugs the spatial distribution of apoptotic bodies correlated well with the light fluence distribution. Apoptosis was seen outside the zone of frank coagulative necrosis. There was not apparent drug-dose dependency at the relatively high doses used here. The retrospective nature of this study did not allow optimization of the treatment parameters. Nevertheless, the findings have potentially significant implications, both for understanding the mechanisms of apoptosis in brain tissue and for improving the clinical use of PDT for treatment of patients with malignant brain tumors.
An IR navigation system for real-time treatment guidance of pleural PDT
NASA Astrophysics Data System (ADS)
Zhu, Timothy C.; Liang, Xing; Chang, Chang; Sandell, Julia; Finlay, Jarod C.; Dimofte, Andreea; Rodriguez, Carmen; Cengel, Keith; Friedberg, Joseph; Glatstein, Eli; Hahn, Stephen M.
Uniform light fluence distribution for patients undergoing photodynamic therapy (PDT) is critical to ensure predictable PDT outcome. However, common practice uses a point source to deliver light to the pleural cavity with the light uniformity monitored by 7 detectors placed within the pleural cavity. To improve the uniformity of light fluence rate distribution, we have used a real-time infrared (IR) tracking camera to track the movement of the light point source. The same tracking device is used to determine the surface contour of the treatment area. This study examines the light fluence (rate) delivered between the measurement and calculation in phantom studies. Isotropic detectors were used for in-vivo light dosimetry. Light fluence rate in the pleural cavity is calculated and compared with the in-vivo calculation. Phantom studies show that the surface contour can be determined with an accuracy of 2 mm, with maximum deviation of 5 mm. We can successfully match the calculated light fluence rates with the in-vivo measurements. Preliminary results indicate that the light fluence rate can have up to 50% deviation compared to the prescription in phantom experiments. The IR camera has been used successfully in pleural PDT patient treatment to track the motion of light source in realtime. We concluded that it is feasible to develop an IR camera based system to guide the motion of the light source to improve the uniformity of light distribution.
Photodynamic therapy (PDT) of malignant tumors by photosensitzer photosens: results of 45 clinical cases
NASA Astrophysics Data System (ADS)
Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Aristarkhova, E. I.; Filonenko, E. V.; Belous, T. A.; Vorozhtsov, Georgy N.; Zharkova, Natalia N.; Smirnov, V. V.; Zhitkova, Margarita B.
Photosensitizer Photosens is a mixture of sulphonated Al-phthalocyanines with a different number of substituents per phthalocyanine molecule. In the beginning of 1994, this photosensitizer was approved for clinical trials. Since that time till May 1995, 45 patients with 120 tumors were treated by PDT-Photosens. The main tumor localizations were lung (5/6), head and neck (4/4), esophagus (8/8), stomach (2/2), vulva (2/2), bladder (1/1), breast cancer (3/3), skin (basalioma, melanoma, sarcoma Kaposi, mts breast cancer) (20 patients/94 tumors). The lesions were photoirradiated 48-72 h after intravenous injection of Photosens in doses from 0.5 to 2.0 mg/kg b.w. (1.0 mg/kg b.w., on average). PDT was performed by laser power density from 20 to 1400 mW/sq cm (300 mW/sq.cm, on average), energy density varying from 15 to 200 J/sq cm (100 J/sq.cm, on average). The therapeutical effect of PDT was evaluated histologically, endoscopically, roentgenologically and sonographically 3 - 4 weeks after the treatment. Complete regression of tumors was reached in 56%, significant remission was reached in 34%, and partial remission was observed in 10% of cases. The follow-up of patients with complete tumor regression was to 15 months.
The difference of the PDT's effects between interstitial lighting and continuous lighting in low oxygen density
NASA Astrophysics Data System (ADS)
Yang, Jiumin; Li, Yingxin; Liu, Tiegen; Xu, Tao
Tumor oxygen depletion plays an important role in the process of Photodynamic Therapy (PDT). The paper focuses on the improvement of the lighting mode to carry out this cancer therapy more effectively in low oxygen content. The effect of interstitial lighting was compared with that of continuous lighting in different oxygen density measured with a homemade device in PDT. 90 mice were divided into 3 groups: the contrast group, the continuous lighting group and the interstitial lighting group. The initial oxygen content was measured with a homemade device before the treatment. To examine the different effects, both the interstitial lighting and the continuous lighting have the same fluent rates (30mW/cm2, 32.4J/ cm2). The continuous lighting lasted 18 minutes while the interstitial lighting lasted 36 minutes with 1 second's idle time and 1 second's effective time of each pulse. The result shows that the volume of tumor doubling duration in interstitial lighting group is longer in the condition of low initial oxygen content. Thus with low initial oxygen content, the interstitial lighting is more effective than the continuous lighting during PDT.
Evaluation with mTHPC of early squamous cell carcinomas of the cheek pouch mucosa of Golden Syrian hamsters as a model for clinical PDT of early cancers in the upper aerodigestive tract, the esophag
NASA Astrophysics Data System (ADS)
Glanzmann, Thomas M.; Theumann, Jean-Francois; Forrer, Martin; Braichotte, Daniel; Wagnieres, Georges A.; van den Bergh, Hubert; Andrejevic-Blant, Snezana; Savary, Jean-Francois; Monnier, Philippe
Golden Syrian hamsters are evaluated as an animal model for light induced fluorescence (LIF) photodetection and phototherapy of early squamous cell carcinomas of the upper aerodigestive tract, the esophagus, and the traecheo-bronchial tree. Carcinomas of this type are induced on the hamster cheek pouch mucosa by the application of the carcinogen 7,12-DMBA. For phototherapeutic experiments on the animals we utilized meso-(tetrahydoxyphenyl) chlorin (mTHPC). This drug is currently in phase I and II clinical trials for ENT patients presenting superficial `early' squamous cell carcinomas. By means of LIF we measured in vivo the kinetics of the uptake and removal of mTHPC in the normal and tumoral cheek mucosa and in the skin. The photodynamic therapy (PDT) reaction of the tissue after excitation of the photosensitizer with laser light at 652 nm was studied. Both pharmacokinetics and PDT efficacy are compared between animal model and clinical results with special emphasis on selectivity between normal and tumoral mucosa. These first experiments show that this tumor model in the hamster cheek pouch seems to be suitable for testing new photosensitizers preceding their clinical application as well as for optimization of the multiple parameters of clinical PDT.
A plastic scintillator-based muon tomography system with an integrated muon spectrometer
NASA Astrophysics Data System (ADS)
Anghel, V.; Armitage, J.; Baig, F.; Boniface, K.; Boudjemline, K.; Bueno, J.; Charles, E.; Drouin, P.-L.; Erlandson, A.; Gallant, G.; Gazit, R.; Godin, D.; Golovko, V. V.; Howard, C.; Hydomako, R.; Jewett, C.; Jonkmans, G.; Liu, Z.; Robichaud, A.; Stocki, T. J.; Thompson, M.; Waller, D.
A muon scattering tomography system which uses extruded plastic scintillator bars for muon tracking and a dedicated muon spectrometer that measures scattering through steel slabs has been constructed and successfully tested. The atmospheric muon detection efficiency is measured to be 97% per plane on average and the average intrinsic hit resolution is 2.5 mm. In addition to creating a variety of three-dimensional images of objects of interest, a quantitative study has been carried out to investigate the impact of including muon momentum measurements when attempting to detect high-density, high-Z material. As expected, the addition of momentum information improves the performance of the system. For a fixed data-taking time of 60 s and a fixed false positive fraction, the probability to detect a target increases when momentum information is used. This is the first demonstration of the use of muon momentum information from dedicated spectrometer measurements in muon scattering tomography.
Design, fabrication, and analysis of miniature reflective oxygen monitoring system for use in PDT of esophageal carcinoma
NASA Astrophysics Data System (ADS)
Premasiri, Amaranath; Happawana, Gemunu
Photodynamic therapy (PDT) is an effective and minimally invasive treatment modality with relatively less side effects, which is approved by FDA for the treatment of esophageal cancer. Maximum therapeutic outcome of the PDT protocol for each individual patient requires optimization of the components of PDT operating at their highest efficacy. Tumor necrosis, the method of malignant tissue destruction by PDT, is carried out by the toxic singlet oxygen molecules that are being formed from the molecular oxygen in the tumor. The availability of molecular oxygen, hence being the rate limiting step for PDT plays a key role in the treatment protocol. Currently the PDT of esophageal carcinoma is rather a blind process since there is no method to monitor the tumor oxygen level during the treatment. In this paper we present an optical technique to monitor molecular oxygen level in the PDT milieu. The technique described herein is a reflection oximetry technique designed with small semiconductor lasers and a silicon photodiode. The light used for monitoring system comes from two semiconductor diode lasers of 650 nm and 940 nm wavelengths. The two lasers and the photodiode are mounted onto a small package which is to be imprinted onto a balloon catheter containing the PDT light delivery system. Lasers and the photodiode are powered and controlled by a control box that is connected via a cable. Light sources and the respective photodiode output are controlled by the LabVIEW virtual instrumentation. The sequential on and off light source and the respective reflective signal are processed with MATLAB. The latter code integrates with LabVIEW to make an automatic calculation of the corresponding light absorption by each chromophore and to calculate the change in oxygen level as well as the amount of blood and oxygen present in the treatment area. The designed system is capable of monitoring the change in oxygen level and the blood flow in any part of the human body where the
Fluorescent-spectroscopic and imaging methods of investigations for diagnostics of head and neck tumors and control of PDT
NASA Astrophysics Data System (ADS)
Edinak, N. E.; Chental, Victor V.; Komov, D.; Vaculovskaya, E.; Tabolinovskaya, T. D.; Abdullin, N. A.; Pustynsky, I.; Chatikhin, V.; Loschenov, Victor B.; Meerovich, Gennady A.; Stratonnikov, A. A.; Linkov, Kirill G.; Agafonov, Vladimir I.; Zuravleva, V.; Lukjanets, E.
Methodics of PDT control and fluorescent-spectroscopic diagnostic of head and neck tumors and mammary gland cancer (nodular) with the use of Kr, He-Ne and semiconductor lasers and photosensitizer (PS) -- Al phtalocyanin (Photosense) are discussed. The results show that applied diagnostic methods permit us not only to identify the topology and malignancy of a tumor but also to correct PDT process directly during irradiation.
Study of multi-muon events produced in p anti-p interactions at s**(1/2) = 1.96-TeV
Aaltonen, T.; Adelman, J.; Alvarez Gonzalez, B.; Amerio, S.; Amidei, D.; Anastassov, A.; Antos, J.; Apollinari, G.; Apresyan, A.; Arisawa, T.; Artikov, A.; /Dubna, JINR /Fermilab
We report the results of a study of multi-muon events produced at the Fermilab Tevatron collider and acquired with the CDF II detector using a dedicated dimuon trigger. The production cross section and kinematics of events in which both muon candidates are produced inside the beam pipe of radius 1.5 cm are successfully modeled by known processes which include heavy flavor production. In contrast, we are presently unable to fully account for the number and properties of the remaining events, in which at least one muon candidate is produced outside of the beam pipe, in terms of the same understanding of the CDF II detector, trigger, and event reconstruction.
In this paper, high energy physics possibilities and future colliders are discussed. The {mu}{sup +} {mu}{sup {minus}} collider and experiments with high intensity muon beams as the stepping phase towards building Higher Energy Muon Colliders (HEMC) are briefly reviewed and encouraged.
Muon radiography for exploration of Mars geology
NASA Astrophysics Data System (ADS)
Kedar, S.; Tanaka, H. K. M.; Naudet, C. J.; Jones, C. E.; Plaut, J. P.; Webb, F. H.
Muon radiography is a technique that uses naturally occurring showers of muons (penetrating particles generated by cosmic rays) to image the interior of large-scale geological structures in much the same way as standard X-ray radiography is used to image the interior of smaller objects. Recent developments and application of the technique to terrestrial volcanoes have demonstrated that a low-power, passive muon detector can peer deep into geological structures up to several kilometers in size, and provide crisp density profile images of their interior at ten meter scale resolution. Preliminary estimates of muon production on Mars indicate that the near horizontal Martian muon flux, which could be used for muon radiography, is as strong or stronger than that on Earth, making the technique suitable for exploration of numerous high priority geological targets on Mars. The high spatial resolution of muon radiography also makes the technique particularly suited for the discovery and delineation of Martian caverns, the most likely planetary environment for biological activity. As a passive imaging technique, muon radiography uses the perpetually present background cosmic ray radiation as the energy source for probing the interior of structures from the surface of the planet. The passive nature of the measurements provides an opportunity for a low power and low data rate instrument for planetary exploration that could operate as a scientifically valuable primary or secondary instrument in a variety of settings, with minimal impact on the mission's other instruments and operation.
The authors describe a method for designing the acceleration systems for a muon collider, with particular application and examples for a high energy muon collider. This paper primarily concentrates on design considerations coming from longitudinal motion, but some transverse issues are briefly discussed.
Polarization Effects at a Muon Collider
Parsa, Z.
For Muon Colliders, Polarization will be a useful tool if high polarization is achievable with little luminosity loss. Formulation and effects of beam polarization and luminosity including polarization effects in Higgs resonance studies are discussed for improving precision measurements and Higgs resonance ''discovery'' capability e.g. at the First Muon Collider (FMC).
Neutrino physics at a muon collider
King, B.J.
This paper gives an overview of the neutrino physics possibilities at a future muon storage ring, which can be either a muon collider ring or a ring dedicated to neutrino physics that uses muon collider technology to store large muon currents. After a general characterization of the neutrino beam and its interactions, some crude quantitative estimates are given for the physics performance of a muon ring neutrino experiment (MURINE) consisting of a high rate, high performance neutrino detector at a 250 GeV muon collider storage ring. The paper is organized as follows. The next section describes neutrino production from a muon storage rings and gives expressions for event rates in general purpose and long baseline detectors. This is followed by a section outlining a serious design constraint for muon storage rings: the need to limit the radiation levels produced by the neutrino beam. The following two sections describe a general purpose detector and the experimental reconstruction of interactions in the neutrino target then, finally, the physics capabilities of a MURINE are surveyed.
Extracellular matrix composition and rigidity regulate invasive behavior and response to PDT in 3D pancreatic tumor models
NASA Astrophysics Data System (ADS)
Cramer, Gwendolyn; El-Hamidi, Hamid; Jafari, Seyedehrojin; Jones, Dustin P.; Celli, Jonathan P.
The composition and mechanical compliance of the extracellular matrix (ECM) have been shown to serve as regulators of tumor growth and invasive behavior. These effects may be particularly relevant in tumors of the pancreas, noted for a profound desmoplastic reaction and an abundance of stroma rich in ECM. In view of recent progress in the clinical implementation of photodynamic therapy (PDT) for pancreatic tumors, in this report we examine how ECM composition and rheological properties impact upon invasive behavior and response to PDT in 3D multicellular pancreatic tumor spheroids in ECM environments with characterized rheological properties. Tumor spheroids were cultured initially in attachment-free conditions to form millimeter-sized spheroids that were transplanted into reconstituted ECM microenvironments (Matrigel and Type I Collagen) that were characterized using bulk oscillatory shear rheology. Analysis of growth behavior shows that the soft collagen ECM promoted growth and extensive invasion and this microenvironment was used in subsequent assessment of PDT and chemotherapy response. Evaluation of treatment response revealed that primary tumor nodule growth is inhibited more effectively with PDT, while verteporfin PDT response is significantly enhanced in the ECM-infiltrating populations that are non-responsive to oxaliplatin chemotherapy. This finding is potentially significant, suggesting the potential for PDT to target these clinically problematic invasive populations that are associated with aggressive metastatic progression and chemoresistance. Experiments to further validate and identify the mechanistic basis of this observation are ongoing.
Photodynamic therapy combined with terbinafine against chromoblastomycosis and the effect of PDT on Fonsecaea monophora in vitro.
Hu, Yongxuan; Huang, Xiaowen; Lu, Sha; Hamblin, Michael R; Mylonakis, Eleftherios; Zhang, Junmin; Xi, Liyan
Chromoblastomycosis, a chronic fungal infection of skin and subcutaneous tissue caused by dematiaceous fungi, is associated with low cure and high relapse rates. Among all factors affecting clinical outcome, etiological agents have an important position. In southern China, Fonsecaea pedrosoi and Fonsecaea monophora are main causative agents causing Chromoblastomycosis. We treated one case of chromoblastomycosis by photodynamic therapy (PDT) of 5-aminolevulinic acid (ALA) irradiation combined with terbinafine 250 mg a day. The lesions were improved after two sessions of ALA-PDT treatment, each including nine times, at an interval of 1 week, combined with terbinafine 250 mg/day oral, and clinical improvement could be observed. In the following study, based on the clinical treatment, the effect of PDT and antifungal drugs on this isolate was detected in vitro. It showed sensitivity to terbinafine, itraconazole or voriconazole, and PDT inhibited the growth. Both the clinic and experiments in vitro confirm the good outcome of ALA-PDT applied in the inhibition of F. monophora. It demonstrated that combination of antifungal drugs with ALA-PDT arises as a promising alternative method for the treatment of these refractory cases of chromoblastomycosis. PMID:25366276
Photodynamic Therapy Combined with Terbinafine Against Chromoblastomycosis and the Effect of PDT on Fonsecaea monophora In Vitro
Hu, Yongxuan; Huang, Xiaowen; Lu, Sha; Hamblin, Michael R.; Mylonakis, Eleftherios; Zhang, Junmin
Chromoblastomycosis, a chronic fungal infection of skin and subcutaneous tissue caused by dematiaceous fungi, is associated with low cure and high relapse rates. Among all factors affecting clinical outcome, etiological agents have an important position. In southern China, Fonsecaea pedrosoi and Fonsecaea monophora are main causative agents causing Chromoblastomycosis. We treated one case of chromoblastomycosis by photodynamic therapy (PDT) of 5-aminolevulinic acid (ALA) irradiation combined with terbinafine 250 mg a day. The lesions were improved after two sessions of ALA-PDT treatment, each including nine times, at an interval of 1 week, combined with terbinafine 250 mg/day oral, and clinical improvement could be observed. In the following study, based on the clinical treatment, the effect of PDT and antifungal drugs on this isolate was detected in vitro. It showed sensitivity to terbinafine, itraconazole or voriconazole, and PDT inhibited the growth. Both the clinic and experiments in vitro confirm the good outcome of ALA-PDT applied in the inhibition of F. monophora. It demonstrated that combination of antifungal drugs with ALA-PDT arises as a promising alternative method for the treatment of these refractory cases of chromoblastomycosis. PMID:25366276
NASA Astrophysics Data System (ADS)
Akers, R. J.; Allison, J.; Ashton, P.; Bahan, G. A.; Baines, J. T. M.; Banks, J. N.; Barlow, R. J.; Barnett, S.; Beeston, C.; Chrin, J. T. M.; Clowes, S. G.; Davies, O. W.; Duerdoth, I. P.; Hinde, P. S.; Hughes-Jones, R. E.; Lafferty, G. D.; Loebinger, F. K.; Macbeth, A. A.; McGowan, R. F.; Moss, M. W.; Murphy, P. G.; Nijjhar, B.; O'Dowd, A. J. P.; Pawley, S. J.; Phillips, P. D.; Richards, G. E.; Skillman, A.; Stephens, K.; Tresillian, N. J.; Wood, N. C.; Wyatt, T. R.
The barrel part of the OPAL muon detector consists of 110 drift chambers forming four layers outside the hadron absorber. Each chamber covers an area of 1.2 m by up to 10.4 m and has two cells with wires parallel to the beam and a drift distance of 297 mm. A detailed description of the design, construction, operation and performance of the sub-detector is given. The system has been operating successfully since the start of LEP in 1989.
Detector Background at Muon Colliders
Mokhov, N.V.; Striganov, S.I.; /Fermilab
Physics goals of a Muon Collider (MC) can only be reached with appropriate design of the ring, interaction region (IR), high-field superconducting magnets, machine-detector interface (MDI) and detector. Results of the most recent realistic simulation studies are presented for a 1.5-TeV MC. It is shown that appropriately designed IR and MDI with sophisticated shielding in the detector have a potential to substantially suppress the background rates in the MC detector. The main characteristics of backgrounds are studied.
PDT in the thoracic cavity: Spectroscopic methods and fluence modeling for treatment planning
NASA Astrophysics Data System (ADS)
Meo, Julia Lauren
PDT for the thoracic cavity provides a promising cancer treatment modality, but improvements in treatment planning, particularly in PDT dosimetry, can be made to improve uniformity of light delivery. When a cavity of arbitrary geometry is illuminated, the fluence increases due to multiple-scattered photons, referred to as the Integrating Sphere Effect (ISE). Current pleural PDT treatment protocol at the University of Pennsylvania monitors light fluence (hereafter simply fluence, measured in W/cm2) via seven isotropic detectors sutured at different locations in thoracic cavity of a patient. This protocol monitors light at discrete locations, but does not provide a measurement of fluence for the thoracic cavity as a whole. Current calculation of light fluence includes direct light only and thus does not account for the unique optical properties of each tissue type present, which in turn affects the accuracy of the calculated light distribution in the surrounding tissue and, in turn, the overall cell death and treatment efficacy. Treatment planning for pleural PDT can be improved, in part, by considering the contribution of scattered light, which is affected by the two factors of geometry and in vivo optical properties. We expanded the work by Willem Star in regards to the ISE in a spherical cavity. A series of Monte Carlo (MC) simulations were run for semi-infinite planar, spherical, and ellipsoidal geometries for a range of optical properties. The results of these simulations are compared to theory and numerical solutions for fluence in the cavity and at the cavity-medium boundary. The development via MC simulations offers a general method of calculating the required light fluence specialized to each patient, based on the treatment surface area. The scattered fluence calculation is dependent on in vivo optical properties (μa and μs') of the tissues treated. Diffuse reflectance and fluorescence spectroscopy methods are used to determine the optical properties and
Recirculating Linac Accelerators For Future Muon Facilities
Yves Roblin, Alex Bogacz, Vasiliy Morozov, Kevin Beard
Neutrino Factories (NF) and Muon Colliders (MC) require rapid acceleration of shortlived muons to multi-GeV and TeV energies. A Recirculating Linear Accelerator (RLA) that uses superconducting RF structures can provide exceptionally fast and economical acceleration to the extent that the focusing range of the RLA quadrupoles allows each muon to pass several times through each high-gradient cavity. A new concept of rapidly changing the strength of the RLA focusing quadrupoles as the muons gain energy is being developed to increase the number of passes that each muon will make in the RF cavities, leading to greater cost effectiveness. We discuss the optics and technical requirements for RLA designs, using RF cavities capable of simultaneous acceleration of both m+ and m- species. The design will include the optics for the multi-pass linac and droplet-shaped return arcs.
Can 250 fusions per muon be achieved
Jones, S.E.
Nuclear fusion of hydrogen isotopes can be induced by negative muons ( ) in reactions such as: + d + t + n + . This reaction is analagous to the nuclear fusion reaction achieved in stars in which hydrogen isotopes (such as deuterium, d, and tritium, t) at very high temperatures first penetrate the Coulomb repulsive barrier and then fuse together to produce an alpha particle ( ) and a neutron (n), releasing energy. The muon in general reappears after inducing fusion so that the reaction can be repeated many (N) times. Thus, the muon may serve as an effective catalyst for nuclear fusion. Muon-catalozed fusion is unique in that it proceeds rapidly in deuterium-tritium mixtures at relatively cold temperatures, e.g., room temperature. The need for plasma temperatures to initiate fusion is overcome by the presence of the muon.
Reverse Emittance Exchange for Muon Colliders
V. Ivanov, A. Afanasev, C.M. Ankenbrandt, R.P. Johnson, G.M. Wang, S.A. Bogacz, Y.S. Derbenev
Muon collider luminosity depends on the number of muons in the storage ring and on the transverse size of the beams in collision. Ionization cooling as it is currently envisioned will not cool the beam sizes sufficiently well to provide adequate luminosity without large muon intensities. Six-dimensional cooling schemes will reduce the longitudinal emittance of a muon beam so that smaller high frequency RF cavities can be used for later stages of cooling and for acceleration. However, the bunch length at collision energy is then shorter than needed to match the interaction region beta function. New ideas to shrink transverse beam dimensions by lengthening each bunch will help achieve high luminosity in muon colliders. Analytic expressions for the reverse emittance exchange mechanism were derived, including a new resonant method of beam focusing.
Cold fusion catalyzed by muons and electrons
Kulsrud, R.M.
Two alternative methods have been suggested to produce fusion power at low temperature. The first, muon catalyzed fusion or MCF, uses muons to spontaneously catalyze fusion through the muon mesomolecule formation. Unfortunately, this method fails to generate enough fusion energy to supply the muons, by a factor of about ten. The physics of MCF is discussed, and a possible approach to increasing the number of MCF fusions generated by each muon is mentioned. The second method, which has become known as Cold Fusion,'' involves catalysis by electrons in electrolytic cells. The physics of this process, if it exists, is more mysterious than MCF. However, it now appears to be an artifact, the claims for its reality resting largely on experimental errors occurring in rather delicate experiments. However, a very low level of such fusion claimed by Jones may be real. Experiments in cold fusion will also be discussed.
We present a new racetrack coil magnet design, with an open midplane gap, that keeps decay particles in a neutrino factory muon storage ring from directly hitting superconducting coils. The structure is very compact because coil ends overlap middle sections top and bottom for skew focusing optics. A large racetrack coil bend radius allows ''react and wind'' magnet technology to be used for brittle Nb{sub 3}Sn superconductors. We describe two versions: Design-A, a magnet presently under construction and Design-B, a further iterated concept that achieves the higher magnetic field quality specified in the neutrino factory feasibility Study-II report. For Design-B reverse polarity and identical end design of consecutive long and short coils offers theoretically perfect magnet end field error cancellation. These designs avoid the dead space penalty from coil ends and interconnect regions (a large fraction in machines with short length but large aperture magnets) and provide continuous bending or focusing without interruption. The coil support structure and cryostat are carefully optimized.
Muon spin rotation research program
NASA Technical Reports Server (NTRS)
Stronach, C. E.
Data from cyclotron experiments and room temperature studies of dilute iron alloys and iron crystals under strain were analyzed. The Fe(Mo) data indicate that the effect upon the contact hyperfine field in Fe due to the introduction of Mo is considerably less than that expected from pure dilution, and the muon (+) are attracted to the Mo impurity sites. There is a significant change in the interstitial magnetic field with Nb concentration. The Fe(Ti) data, for which precession could clearly be observed early only at 468K and above, show that the Ti impurities are attractive to muon (+), and the magnitude of B(hf) is reduced far beyond the amount expected from pure dilution. Changes in the intersitital magnetic field with the introduction of Cr, W, Ge, and Si are also discussed. When strained to the elastic limit, the interstitial magnetic field in Fe crystals is reduced by 33 gauss, and the relaxation rate of the precession signal increases by 47%.
The muon collider (Sandro's snake)
Ruggiero, A.G.
This paper describes a feasibility study for the design of a muon collider. Recognized the fact that the particle lifetime increases linearly with the energy, we have adopted a scheme where steps of cooling and acceleration are entwined. We have indeed found convenient to accelerate the beam as fast as possible to increase its chances of survival, and necessary to dilute the action of cooling throughout the entire accelerating process to make it more effective and affordable. All acceleration and cooling steps are executed in a single pass essentially along a curvilinear and open path. We do not believe it is possible to handle the beam otherwise in circular and closed rings, as it has been proposed in the past. The example shown in this paper describes a muon collider at the energy of 250 GeV per beam and a luminosity of 4 [times] 10[sup 28] cm[sup [minus]2]s[sup [minus]1]. We have adopted an extrapolation of the stochastic cooling method for the reduction of the beam emittance.
Measurement of the muon beam direction and muon flux for the T2K neutrino experiment
NASA Astrophysics Data System (ADS)
Suzuki, K.; Aoki, S.; Ariga, A.; Ariga, T.; Bay, F.; Bronner, C.; Ereditato, A.; Friend, M.; Hartz, M.; Hiraki, T.; Ichikawa, A. K.; Ishida, T.; Ishii, T.; Juget, F.; Kikawa, T.; Kobayashi, T.; Kubo, H.; Matsuoka, K.; Maruyama, T.; Minamino, A.; Murakami, A.; Nakadaira, T.; Nakaya, T.; Nakayoshi, K.; Otani, M.; Oyama, Y.; Patel, N.; Pistillo, C.; Sakashita, K.; Sekiguchi, T.; Suzuki, S. Y.; Tada, S.; Yamada, Y.; Yamamoto, K.; Yokoyama, M.
The Tokai-to-Kamioka (T2K) neutrino experiment measures neutrino oscillations by using an almost pure muon neutrino beam produced at the J-PARC accelerator facility. The T2K muon monitor was installed to measure the direction and stability of the muon beam which is produced in conjunction with the muon neutrino beam. The systematic error in the muon beam direction measurement was estimated, using data and MC simulation, to be 0.28 mrad. During beam operation, the proton beam has been controlled using measurements from the muon monitor and the direction of the neutrino beam has been tuned to within 0.3 mrad with respect to the designed beam-axis. In order to understand the muon beam properties, measurement of the absolute muon yield at the muon monitor was conducted with an emulsion detector. The number of muon tracks was measured to be (4.06± 0.05± 0.10)× 10^4cm^{-2} normalized with 4× 10^{11} protons on target with 250 kA horn operation. The result is in agreement with the prediction, which is corrected based on hadron production data.
The program in muon and neutrino physics: Superbeams, cold muon beams, neutrino factory and the muon collider
R. Raja et al.
The concept of a Muon Collider was first proposed by Budker [10] and by Skrinsky [11] in the 60s and early 70s. However, there was little substance to the concept until the idea of ionization cooling was developed by Skrinsky and Parkhomchuk [12]. The ionization cooling approach was expanded by Neufer [13] and then by Palmer [14], whose work led to the formation of the Neutrino Factory and Muon Collider Collaboration (MC) [3] in 1995. The concept of a neutrino source based on a pion storage ring was originally considered by Koshkarev [18]. However, the intensity of the muons created within the ring from pion decay was too low to provide a useful neutrino source. The Muon Collider concept provided a way to produce a very intense muon source. The physics potential of neutrino beams produced by muon storage rings was investigated by Geer in 1997 at a Fermilab workshop [19, 20] where it became evident that the neutrino beams produced by muon storage rings needed for the muon collider were exciting on their own merit. The neutrino factory concept quickly captured the imagination of the particle physics community, driven in large part by the exciting atmospheric neutrino deficit results from the SuperKamiokande experiment. As a result, the MC realized that a Neutrino Factory could be an important first step toward a Muon Collider and the physics that could be addressed by a Neutrino Factory was interesting in its own right. With this in mind, the MC has shifted its primary emphasis toward the issues relevant to a Neutrino Factory. There is also considerable international activity on Neutrino Factories, with international conferences held at Lyon in 1999, Monterey in 2000 [21], Tsukuba in 2001 [22], and another planned for London in 2002.
Muons in minimum bias events from the first CMS data
Barbone, Lucia
Muon signatures are extremely important in the challenging environment of collisions at the LHC. Understanding the observed muon yield from Standard Model processes is the first task for all analyses involving muons. Basic muon kinematical observables are presented for the first CMS data at {radical}(s) = 7 TeV and compared with Monte Carlo expectations. The muon sample composition is studied by using the MC truth in terms of muons from heavy flavours, muons from light hadron decays and hadron punch-through is studied from MC truth.
Pion contamination in the MICE muon beam
Adams, D.; Alekou, A.; Apollonio, M.; Asfandiyarov, R.; Barber, G.; Barclay, P.; de Bari, A.; Bayes, R.; Bayliss, V.; Bertoni, R.; et al
Here, the international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240\\,MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less thanmore » $$\\sim$$1% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is $$f_\\pi < 1.4\\%$$ at 90% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.« less
Photodynamic therapy (PDT) in early central lung cancer: a treatment option for patients ineligible for surgical resection
Moghissi, Keyvan; Dixon, Kate; Thorpe, James Andrew Charles; Stringer, Mark; Oxtoby, Christopher
Objectives To review the Yorkshire Laser Centre experience with bronchoscopic photodynamic therapy (PDT) in early central lung cancer in subjects not eligible for surgery and to discuss diagnostic problems and the indications for PDT in such cases. Methods Of 200 patients undergoing bronchoscopic PDT, 21 had early central lung cancer and were entered into a prospective study. Patients underwent standard investigations including white light bronchoscopy in all and autofluorescence bronchoscopy in 12 of the most recent cases. Indications for bronchoscopic PDT were recurrence/metachronous endobronchial lesions following previous treatment with curative intent in 10 patients (11 lesions), ineligibility for surgery because of poor cardiorespiratory function in 8 patients (9 lesions) and declined consent to operation in 3 patients. PDT consisted of intravenous administration of Photofrin 2 mg/kg followed by bronchoscopic illumination 24–48 h later. Results 29 treatments were performed in 21 patients (23 lesions). There was no procedure‐related or 30 day mortality. One patient developed mild skin photosensitivity. All patients expressed satisfaction with the treatment and had a complete response of variable duration. Six patients died at 3–103 months (mean 39.3), three of which were not as a result of cancer. Fifteen patients were alive at 12–82 months. Conclusion Bronchoscopic PDT in early central lung cancer can achieve long disease‐free survival and should be considered as a treatment option in those ineligible for resection. Autofluorescence bronchoscopy is a valuable complementary investigation for identification of synchronous lesions and accurate illumination in bronchoscopic PDT. PMID:17090572
Low dose Photofrin PDT for recurrent in-situ squamous cell tumors of the head and neck
NASA Astrophysics Data System (ADS)
Allison, R. R.; Austerlitz, C.; Sheng, C.; Mota, H.; Brodish, B.; Camnitz, P.; Sibata, C. H.
Multifocal recurrence of in-situ squamous cell cancer of the oral cavity, pharynx and vocal cord following surgical failure can be a therapeutic dilemma. Salvage surgery or radiation may be an option but morbidity can be significant. We evaluated the potential role of low dose Photofrin (1.2mg/Kg) Photodynamic Therapy for this cohort of patients. A total of 25 patients with multifocal recurrent in-situ squamous cell cancer of the oral cavity, pharynx and vocal cord who had failed local resection, and where additional surgery or radiation therapy would likely result in permanent morbidity, were offered Photodynamic Therapy. PDT consisted of off label infusion of Photofrin (1.2mg/kg) followed 48 hours later by illumination at 630nm employing a light diffuser (300J) and/or microlens (150Jcm2). All patients completed their prescribed PDT and no patient has been lost to follow up (minimum 1 year). No photosensitivity reactions were noted. No significant morbidity was seen. All patients were able to maintain oral nutrition. Procedure related pain was well controlled by one week of oral narcotics. At one month post PDT all patients were biopsy negative in the treatment region and no failures within the treatment region have been noted. No fibrosis or permanent PDT morbidity has been seen with follow up to three years. Vocal cord and voice function were excellent. Three patients developed new regions of in-situ disease outside the PDT fields, two underwent additional PDT and one had laser resection. Low dose Photofrin PDT offers excellent palliation and durable local control of recurrent in-situ squamous cell cancers of the oral cavity, pharynx and true cords. This is a well tolerated therapy. Low dose Photofrin appears to improve selectivity and minimize normal tissue injury. It should be tested in a larger patient population.
SNM detection by active muon interrogation
Jason, Andrew J; Miyadera, Haruo; Turchi, Peter J
Muons are charged particles with mass between the electron and proton and can be produced indirectly through pion decay by interaction of a charged-particle beam with a target. There are several distinct features of the muon interaction with matter attractive as a probe for detection of SNM at moderate ranges. These include muon penetration of virtually any amount of material without significant nuclear interaction until stopped by ionization loss in a short distance. When stopped, high-energy penetrating x-rays (in the range of 6 MeV for uranium,) unique to isotopic composition are emitted in the capture process. The subsequent interaction with the nucleus produces additional radiation useful in assessing SNM presence. A focused muon beam can be transported through the atmosphere, at a range limited mainly by beam-size growth through scattering. A muonbeam intensity of > 10{sup 9} /second is required for efficient interrogation and, as in any other technique, dose limits are to be respected. To produce sufficient muons a high-energy (threshold {approx}140 MeV) high-intensity (<1 mA) proton or electron beam is needed implying the use of a linear accelerator to bombard a refractory target. The muon yield is fractionally small, with large angle and energy dispersion, so that efficient collection is necessary in all dimensions of phase space. To accomplish this Los Alamos has proposed a magnetic collection system followed by a unique linear accelerator that provides the requisite phase-space bunching and allows an energy sweep to successively stop muons throughout a large structure such as a sea-going vessel. A possible maritime application would entail fitting the high-gradient accelerators on a large ship with a helicopter-borne detection system. We will describe our experimental results for muon effects and particle collection along with our current design and program for a muon detection system.
Cosmic muon detector using proportional chambers
NASA Astrophysics Data System (ADS)
Varga, Dezső; Gál, Zoltán; Hamar, Gergő; Sára Molnár, Janka; Oláh, Éva; Pázmándi, Péter
A set of classical multi-wire proportional chambers was designed and constructed with the main purpose of efficient cosmic muon detection. These detectors are relatively simple to construct, and at the same time are low cost, making them ideal for educational purposes. The detector layers have efficiencies above 99% for minimum ionizing cosmic muons, and their position resolution is about 1 cm, that is, particle trajectories are clearly observable. Visualization of straight tracks is possible using an LED array, with the discriminated and latched signal driving the display. Due to the exceptional operating stability of the chambers, the design can also be used for cosmic muon telescopes.
Imaging Fukushima Daiichi reactors with muons
NASA Astrophysics Data System (ADS)
Miyadera, Haruo; Borozdin, Konstantin N.; Greene, Steve J.; Lukić, Zarija; Masuda, Koji; Milner, Edward C.; Morris, Christopher L.; Perry, John O.
A study of imaging the Fukushima Daiichi reactors with cosmic-ray muons to assess the damage to the reactors is presented. Muon scattering imaging has high sensitivity for detecting uranium fuel and debris even through thick concrete walls and a reactor pressure vessel. Technical demonstrations using a reactor mockup, detector radiation test at Fukushima Daiichi, and simulation studies have been carried out. These studies establish feasibility for the reactor imaging. A few months of measurement will reveal the spatial distribution of the reactor fuel. The muon scattering technique would be the best and probably the only way for Fukushima Daiichi to make this determination in the near future.
Imaging Fukushima Daiichi reactors with muons
Miyadera, Haruo; Borozdin, Konstantin N.; Greene, Steve J.; Milner, Edward C.; Morris, Christopher L.; Lukic, Zarija; Masuda, Koji; Perry, John O.
A study of imaging the Fukushima Daiichi reactors with cosmic-ray muons to assess the damage to the reactors is presented. Muon scattering imaging has high sensitivity for detecting uranium fuel and debris even through thick concrete walls and a reactor pressure vessel. Technical demonstrations using a reactor mockup, detector radiation test at Fukushima Daiichi, and simulation studies have been carried out. These studies establish feasibility for the reactor imaging. A few months of measurement will reveal the spatial distribution of the reactor fuel. The muon scattering technique would be the best and probably the only way for Fukushima Daiichi to make this determination in the near future.
Systematic muon capture rates in PQRPA
Samana, A. R.; Sande, D.; Krmpotić, F.
In this work we performed a systematic study of the inclusive muon capture rates for several nuclei with A < 60 using the Projected Random Quasi-particle Phase Approximation (PQRPA) as nuclear model, because it is the only RPA model that treats the Pauli Principle correctly. We reckon that the comparison between theory and data for the inclusive muon capture is not a fully satisfactory test on the nuclear model that is used. The exclusive muon transitions are more robust for such a purpose.
Measurement and modelling of protoporphyrin IX photo-oxidation during superficial PDT
NASA Astrophysics Data System (ADS)
Robinson, Dominic J.; Stringer, Mark R.; Crum, William R.; Collins, P.
The oxidation of photosensitizers during photodynamic therapy (PDT) has important implications for their therapeutic and diagnostic potential. The reduction in sensitizer concentration during illumination progressively reduces the effectiveness of therapy and, ultimately, limits the destruction of the host tissue. In the course of our studies of the effects of PDT upon superficial skin disorders, following topical application of 5- aminolaevulinic acid (ALA), we routinely record the surface fluorescence emission of protoporphyrin IX (PpIX) before, during, and after therapy, in order to monitor the sensitizer photo-oxidation. It is important, therefore, to establish that measurements made in this way are representative of the variation in sensitizer concentration throughout the illuminated volume. We have developed a time- dependent Monte-Carlo model to simulate PpIX photo-oxidation during either low intensity laser (488 nm) or white light irradiation of plaque psoriasis. We have assessed the effect of differences in the optical properties of tissue at sites on different patients prior to treatment, and the effect of these variations on the surface fluorescence signal detected during treatment, at sites within the same plaque. The results show that the PpIX fluorescence intensity recorded from plaque psoriasis is an accurate indicator of the relative concentration of the sensitizer and can be used as a direct comparison between different sites and different patients. Also, the reduction in fluorescence emission during PDT is an effective measure of the depletion in sensitizer concentration throughout the illuminated volume. These results illustrate that the light dose required to achieve significant PpIX photo-oxidation is significantly lower than that often adopted for the treatment of superficial skin conditions.
An additional study of multi-muon events produced in $p\\bar{p}$ collisions at $\\sqrt{s}=1.96$ TeV
Aaltonen, T.; Alvarez Gonzalez, B.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Apresyan, A.; Arisawa, T.; Artikov, A.; /Dubna, JINR /Fermilab
We present one additional study of multi-muon events produced at the Fermilab Tevatron collider and recorded by the CDF II detector. We use a data set acquired with a dedicated dimuon trigger and corresponding to an integrated luminosity of 3.9 fb{sup -1}. We investigate the distribution of the azimuthal angle between the two trigger muons in events containing at least four additional muon candidates to test the compatibility of these events with originating from known QCD processes. We find that this distribution is markedly different from what is expected from such QCD processes and this observation strongly disfavours the possibility that multi-muon events result from an underestimate of the rate of misidentified muons in ordinary QCD events.
Mechanism of cell destruction and cell protection during methylene-blue-induced PDT
NASA Astrophysics Data System (ADS)
Rueck, Angelika C.; Beck, G.; Heckelsmiller, K.; Knoedlsdorfer, U.; Genze, Felicitas; Orth, K.
Methylene Blue (MB+) is a well-known dye in medicine and has been discussed as an easily applicable drug for the topical treatment in photodynamic therapy (PDT). MB+ can potentially be used as a redox indicator to detect the important redox reactions that are induced during PDT. MB+ induced PDT was successful in the intraluminal treatment of inoperable esophageal tumors and in the topical treatment of psoriasis. In order to improve the therapy, the reaction mechanism of MB+ was investigated in vivo by local injection of MB+ in a xenotransplanted subcutaneous tumor (adeno-carcinoma, G-3) in female nude mice. The MB+ preparation 'MB+1%' was applied both undiluted and diluted to 0.1% and 0.01% with isotonic sodium chloride. After an incubation period of 1 h, the tumors were irradiated at 662 nm. Treatment with 1% MB+ and subsequent irradiation with 100 J/cm2 led to complete tumor destruction in 79% of the treated animals. A decrease of the fluence rate from 100 mW/cm2 to 50 mW/cm2 significantly increased the phototoxic response, which was attributed to oxygen depletion but also to nonlinear redox reactions. In addition, fractionated light application with 15 s interruption intervals enhanced the effect. When 0.1% MB+ was used, complete tumor destruction was observed only in 10% of the treated animals. Below a relatively high threshold dose the therapeutic response was not significant. The efficiency of the therapy was correlated with nonlinear dynamics of MB+ on a subcellular level, using laser scanning microscopy. During MB+-PDT nonlinear redox- reactions were induced. This could be deduced from local fast changes of the MB+-fluorescence as well as the pH-value during irradiation of single cells. The light induced reaction of MB+ seems to be correlated with the nonlinear production of reactive oxygen species (ROS). As a consequence below a threshold dose the reducing ability of MB+ prevents tissue from oxidative damage. However, above this dose, as a point of no
Radiative muon capture in nuclei
Doebeli, M.; Doser, M.; van Elmbt, L.; Schaad, M.W.; Truoel, P.; Bay, A.; Perroud, J.P.; Imazato, J.; Ishikawa, T.
The energy spectra of photons following negative muon absorption in /sup 12/C, /sup 16/O, /sup 27/Al, /sup 40/Ca, /sup nat/Fe, /sup 165/Ho, and /sup 209/Bi have been measured with two NaI spectrometers. The branching ratios for the emission of high energy photons give information on the induced pseudoscalar coupling constant g/sub P/ in nuclear matter. The data for light nuclei are in agreement with the theoretical calculations using the nucleonic value of g/sub P/approx. =7g/sub A/ predicted by the partially conserved axial vector current hypothesis, while significantly lower values of g/sub P/ are required to fit the data of the heavier elements with presently existing theoretical predictions. Disregarding the remaining theoretical uncertainties, these results can be interpreted as a further indication of the renormalization of the nucleonic form factors inside the nucleus.
Atmospheric muons and neutrinos, and the neutrino-induced muon flux underground
NASA Technical Reports Server (NTRS)
Liland, A.
The diffusion equation for neutrino-induced cosmic ray muons underground was solved. The neutrino-induced muon flux and charge ratio underground have been calculated. The calculated horizontal neutrino-induced muon flux in the energy range 0.1 - 10000 GeV is in agreement with the measured horizontal flux. The calculated vertical flux above 2 GeV is in agreement with the measured vertical flux. The average charge ratio of neutrino-induced muons underground was found to be mu+/mu- = 0.40.
Multi-course PDT of malignant tumors: the influence on primary tumor, metastatic spreading and homeostasis of cancer patients
NASA Astrophysics Data System (ADS)
Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Filonenko, E. V.; Sukhin, Garry M.; Nemtsova, E. R.; Belous, T. A.; Zharkova, Natalia N.
The first clinical trials of photodynamic therapy (PDT) of cancer with two photosensitizers, PHOTOHEME and PHOTOSENS, were started in P.A. Hertzen Research Oncological Institute (Moscow, Russia) in 1992 and 1994. Up to now, 208 patients with primary, recurrent and metastatic malignant tumors (469) of skin (34 patients/185 tumors), breast cancer (24/101), head and neck (30/31), trachea and bronchus (31/42), esophagus (35/35), stomach (31/32), rectum (4/4), vagina and uterine cervix (7/8) and bladder (12/31) have been treated by PDT. One-hundred-thirty patients were injected with PHOTOHEME, 64 patients were injected with PHOTOSENS, 14 patients were injected with PHOTOHEME and PHOTOSENS. Totally, 302 courses of treatment were performed: 155 patients had one course and 53 patients were subjected to two to nine PDT sources with intervals from 1 to 18 months. A therapeutic effect of a one-course and multi- course PDT of malignant tumors (respiratory, digestive and urogenital systems) was evaluated clinically, histologically, roentgenologically, sonographically and endoscopically. The biochemical, hematological and immunological investigations were performed for all the patients in dynamics. Results of our study showed that a multi-course PDT method seems to be perspective in treatment of malignant tumors of basic localizations.
Effect of HMME-PDT with different parameters in rabbit ear model: a possible way for hypertrophic scarring
NASA Astrophysics Data System (ADS)
Cai, Hong; Gu, Ying; Zeng, Jing; Li, Shao-ran; Sun, Qiang; Wang, Ying; Shi, Dong-wen; Zhang, Lu-yong
Background and Objective: Hypertrophic scar is a pathological scar that grows aberrantly by excessive deposition of collagens in the dermis. It is known that photodynamic therapy (PDT) contributes to a variety of diseases, however, the use of inhibiting scar formation has not been fully explored. The purpose of this study is to investigate the effect of HMME-PDT (Photodynamic therapy induced by Hematoporphyrin Monomethyl Ether) with different parameters on hypertrophic scar in rabbit ear. Materials and Methods: After the placement of 7-mm diameter dermal wounds on each ear, the acute model of dermal hypertrophic scar in the New Zealand white rabbits was established. Scar wounds were randomly separated into 2 groups: the experimental group received HMME-PDT with different parameters, and the control group received no special treatment. Specimens were harvested from scar wounds on postoperative day 28. Scar and hypertrophic index (HI) were observed by haematoxylin-eosin staining. Results: Compared with the control group, scar formation was inhibited by HMME-PDT in the experimental group with parameters as follows: photosensitizer dose 10mg/kg, power density 20mw/cm2, fluence 5J/cm2, meanwhile, HI was decreased significantly. Conclusion: HMME-PDT may play a role in inhibiting hypertrophic scarring in rabbit ear. The biological effect is determined by the dose of photosensitizer, interval between the injection of photosensitizer and irradiation, power density and energy fluence.
Three-year results of a modified photodynamic therapy procedure (Ironing PDT) for age-related macular degeneration patients with large lesions
Otsuji, Tsuyoshi; Sho, Kenichiro; Tsumura, Akiko; Koike, Naoko; Nishimura, Tetsuya; Takahashi, Kanji
Background To evaluate the effect of photodynamic therapy (PDT) using a modified procedure on exudative age-related macular degeneration having been conventionally difficult to treat. Methods The medical records of eight consecutive patients (eight eyes) with age-related macular degeneration treated with modified PDT were reviewed retrospectively. Modified PDT was used for the lesions that could not be covered by conventional use of PDT, either because the lesion was too large or too close to the optic disc. A moving PDT laser spot at constant speed, for 83 seconds, was used to cover the entire lesion, and was named "Ironing PDT." This retrospective study was performed with informed patient consent. It was approved by the Institutional Review Board of Kansai Medical University. Results No exudation could be found 36 months after treatment in five eyes (62.5%). There was no significant difference between the best-corrected visual acuity before PDT (0.95 logMAR) and after PDT (1.09 logMAR). The logMAR best-corrected visual acuity was improved in one eye, maintained in five eyes, and deteriorated in two eyes. Conclusion Ironing PDT decreased subfoveal fluid and preserved visual acuity in some patients with age-related macular degeneration difficult to treat with conventional therapy. PMID:27041985
Epigenetically Enhanced Photodynamic Therapy (ePDT) is Superior to Conventional Photodynamic Therapy for Inducing Apoptosis in Cutaneous T-Cell Lymphoma.
Salva, Katrin Agnes; Wood, Gary S
Conventional photodynamic therapy with aminolevulinate (ALA-PDT) selectively induces apoptosis in diseased cells and is highly effective for treating actinic keratoses. However, similar results are achieved only in a subset of patients with cutaneous T-cell lymphoma (CTCL). Our previous work shows that the apoptotic resistance of CTCL correlates with low expression of death receptors like Fas cell surface death receptor (FAS), and that methotrexate upregulates FAS by inhibiting the methylation of its promoter, acting as an epigenetic derepressor that restores the susceptibility of FAS-low CTCL to caspase-8-mediated apoptosis. Here, we demonstrate that methotrexate increases the response of CTCL to ALA-PDT, a concept we refer to as epigenetically enhanced PDT (ePDT). Multiple CTCL cell lines were subjected to conventional PDT versus ePDT. Apoptotic biomarkers were analyzed in situ with multispectral imaging analysis of immunostained cells, a method that is quantitative and 5× more sensitive than standard immunohistology for antigen detection. Compared to conventional PDT or methotrexate alone, ePDT led to significantly greater cell death in all CTCL cell lines tested by inducing greater activation of caspase-8-mediated extrinsic apoptosis. Upregulation of FAS and/or tumor necrosis factor-related apoptosis-inducing ligand pathway components was observed in different CTCL cell lines. These findings provide a rationale for clinical trials of ePDT for CTCL. PMID:26302991
Muon calculations for the polarized proton beamline
Cossairt, J.D.
Monte Carlo calculations of the muon intensities due to the new polarized proton beam using the program CASIM are reported. Results are reported in terms of tissue absorbed dose per incident proton. (LEW)
Intense muon beams and neutrino factories
Parsa, Z.
High intensity muon sources are needed in exploring neutrino factories, lepton flavor violating muon processes, and lower energy experiments as the stepping phase towards building higher energy {mu}{sup +}{mu}{sup {minus}} colliders. We present a brief overview, sketch of a neutrino source, and an example of a muon storage ring at BNL with detector(s) at Fermilab, Sudan, etc. Physics with low energy neutrino beams based on muon storage rings ({mu}SR) and conventional Horn Facilities are described and compared. CP violation Asymmetries and a new Statistical Figure of Merit to be used for comparison is given. Improvements in the sensitivity of low energy experiments to study Flavor changing neutral currents are also included.
Mapping Overburden and Cave Networks with Muons
NASA Astrophysics Data System (ADS)
Prettyman, T. H.; Titus, T. N.; Boston, P. J.; Koontz, S. L.; Miller, R. S.
We describe the use of highly-penetrating muons produced by cosmic ray showers to measure overburden and image the rock formation around terrestrial/extraterrestrial caves, and implications for cave science, exploration, and habitation.
Muon acceleration for muon collider or neutrino factory is still in a stage where further improvements are likely as a result of further study. This report presents a design of the racetrack non-scaling Fixed Field Alternating Gradient (NS-FFAG) accelerator to allow fast muon acceleration in small number of turns. The racetrack design is made of four arcs: two arcs at opposite sides have a smaller radius and are made of closely packed combined function magnets, while two additional arcs, with a very large radii, are used for muon extraction, injection, and RF accelerating cavities. The ends of the large radii arcs are geometrically matched at the connections to the arcs with smaller radii. The dispersion and both horizontal and vertical amplitude fictions are matched at the central energy.
Topcolor and the First Muon Collider
Hill, C.T.
We describe a class of models of electroweak symmetry breaking that involve strong dynamics and top quark condensation. A new scheme based upon a seesaw mechanism appears particularly promising. Various implications for the first-stage muon collider are discussed.
Development of a Portable Muon Witness System
Aguayo Navarrete, Estanislao; Kouzes, Richard T.; Orrell, John L.
Since understanding and quantifying cosmic ray induced radioactive backgrounds in copper and germanium are important to the MAJORANA DEMONSTRATOR, methods are needed for monitoring the levels of such backgrounds produced in materials being transported and processed for the experiment. This report focuses on work conducted at Pacific Northwest National Laboratory to develop a muon witness system as a one way of monitoring induced activities. The operational goal of this apparatus is to characterize cosmic ray exposure of materials. The cosmic ray flux at the Earth's surface is composed of several types of particles, including neutrons, muons, gamma rays and protons. These particles induce nuclear reactions, generating isotopes that contribute to the radiological background. Underground, the main mechanism of activation is by muon produced spallation neutrons since the hadron component of cosmic rays is removed at depths greater than a few tens of meters. This is a sub-dominant contributor above ground, but muons become predominant in underground experiments. For low-background experiments cosmogenic production of certain isotopes, such as 68Ge and 60Co, must be accounted for in the background budgets. Muons act as minimum ionizing particles, depositing a fixed amount of energy per unit length in a material, and have a very high penetrating power. Using muon flux measurements as a "witness" for the hadron flux, the cosmogenic induced activity can be quantified by correlating the measured muon flux and known hadronic production rates. A publicly available coincident muon cosmic ray detector design, the Berkeley Lab Cosmic Ray Detector (BLCRD), assembled by Juniata College, is evaluated in this work. The performance of the prototype is characterized by assessing its muon flux measurements. This evaluation is done by comparing data taken in identical scenarios with other cosmic ray telescopes. The prototype is made of two plastic scintillator paddles with
Muon dynamics in a toroidal sector magnet
Gallardo, J.C.; Fernow, R.; Palmer, R.B.
The present scenario for the cooling channel in a high brightness muon collider calls for a quasi-continuous solenoidal focusing channel. The beam line consists of a periodic array of rf cavities and approximately 2 cm long LiH absorbers immersed in a solenoid with alternating focusing field (FOFO). The authors present a Hamiltonian formulation of muon dynamics in toroidal sector solenoids (bent solenoid).
Targeted two-photon PDT photo-sensitizers for the treatment of subcutaneous tumors
NASA Astrophysics Data System (ADS)
Spangler, C. W.; Rebane, A.; Starkey, J.; Drobizhev, M.
New porphyrin-based photo-sensitizers have been designed, synthesized and characterized that exhibit greatly enhanced intrinsic two-photon absorption. These new photo-sensitizers have been incorporated into triad formulations that also incorporate Near-infrared (NIR) imaging agents, and small-molecule targeting agents that direct the triads to cancerous tumors' over-expressed receptor sites. PDT can be initiated deep into the tissue transparency window at 780-800 nm utilizing a regeneratively amplified Ti:sapphire laser using 100-150 fs pulses of 600-800 mW. Human tumor xenografts of human breast cancer (MDA-MB-231) and both small SCLC (NCI-H69) and NSCLC (A-459) have been successfully treated using octreotate targeting of over-expressed SST2 receptors. In particular, the lung cancer xenografts can be successfully treated by irradiating from the side of the mouse opposite the implanted tumor, thereby passing through ca. 2 cm of mouse skin, tissue and organs with no discernible damage to healthy tissue while causing regression in the tumors. These results suggest a new PDT paradigm for the noninvasive treatment of subcutaneous tumors, including the possibility that the targeting moiety could be matched to individual patient genetic profiles (patient-specific therapeutics).
Can Antimicrobial Photodynamic Therapy (aPDT) Enhance the Endodontic Treatment?
Chiniforush, Nasim; Pourhajibagher, Maryam; Shahabi, Sima; Kosarieh, Emad; Bahador, Abbas
In order to achieve a long-lasting effect, one of the main goals in root canal treatment is to eliminate the endodontic bacteria. Conventional chemomechanical debridement is considered as the basic treatment in root canal therapy, but adjunctive techniques such as antimicrobial photodynamic therapy (aPDT) can also be helpful. The aim of this study was to evaluate reports in the scientific literature that used different photosensitizers (PSs) for bacterial reduction. The literature search was conducted using databases including PubMed, Scopus, and Google Scholar with the keywords "photodynamic therapy," "antimicrobial photodynamic therapy," or "photoactivated disinfection" and "endodontic," "Enterococcus faecalis," or "root canal treatment," from 2000 to 2015. By evaluating different studies, it was concluded that aPDT should be applied in combination with conventional mechanical debridement and irrigants. However, it is also important to note that the success rate is critically dependent on the type of the PS, output power of the laser used, irradiation time, pre-irradiation time, and type of tips used. PMID:27330702
Comparative analysis of different phthalocyanine photosensitizers for experimental PDT of cancer
NASA Astrophysics Data System (ADS)
Galpern, Maria G.; Novozhilova, Irina; Sokolova, Galina; Vorozhtsov, Georgy N.; Zharkova, Natalia N.; Kozlov, Dmitrij N.; Sokolov, Victor V.; Sukhin, Garry M.
Preliminary biological screening has resulted in data about the considerable difference in photodynamic activity of sulfuric acids of aluminum phthalocyanine and their different salts have been obtained. The photosensitizers have been introduced intravenously in laboratory male mice 24 hours before direct laser irradiation of the liver area through the front abdominal side. Seven-day Erlich carcinomas with a diameter of 0.5 cm transplanted hypodermically to the mice have been used as an experimental tumor model. Obtained data of preliminary biological screening on photodynamic activity and tumor selectivity of different photosensitizers has been confirmed by direct experiments on the PDT experimental tumor in mice with the use of a laser system on the basis of yttrium aluminate with the wavelength 670 nm. Preparations have been introduced as a solution 2 mg/ml intravenous with a dose 10 mg/kg 48 hours before irradiation with the laser. Irradiation dose was 90 J with a spot diameter of 1 cm. Efficiency of anti-tumor PDT has been estimated by sight and with morphological study of the material.
Muon Emittance Exchange with a Potato Slicer
Summers, D. J.; Hart, T. L.; Acosta, J. G.; Cremaldi, L. M.; Oliveros, S. J.; Perera, L. P.; Neuffer, D. V.
We propose a novel scheme for final muon ionization cooling with quadrupole doublets followed by emittance exchange in vacuum to achieve the small beam sizes needed by a muon collider. A flat muon beam with a series of quadrupole doublet half cells appears to provide the strong focusing required for final cooling. Each quadrupole doublet has a low beta region occupied by a dense, low Z absorber. After final cooling, normalized transverse, longitudinal, and angular momentum emittances of 0.100, 2.5, and 0.200 mm-rad are exchanged into 0.025, 70, and 0.0 mm-rad. A skew quadrupole triplet transforms a round muon bunch with modest angular momentum into a flat bunch with no angular momentum. Thin electrostatic septa efficiently slice the flat bunch into 17 parts. The 17 bunches are interleaved into a 3.7 meter long train with RF deflector cavities. Snap bunch coalescence combines the muon bunch train longitudinally in a 21 GeV ring in 55 µs, one quarter of a synchrotron oscillation period. A linear long wavelength RF bucket gives each bunch a different energy causing the bunches to drift in the ring until they merge into one bunch and can be captured in a short wavelength RF bucket with a 13% muon decay loss and a packing fraction as high as 87 %.
High intensity muon beam source for neutrino beam experiments
NASA Astrophysics Data System (ADS)
Kamal Sayed, Hisham
High intensity muon beams are essential for Muon accelerators like Neutrino Factories and Muon Colliders. In this study we report on a global optimization of the muon beam production and capture based on end-to-end simulations of the Muon Front End. The study includes the pion beam production target geometry, capture field profile, and forming muon beam into microbunches for further acceleration. The interplay between the transverse and longitudinal beam dynamics during the capture and transport of muon beam is evaluated and discussed. The goal of the optimization is to provide a set of design parameters that delivers high intensity muon beam that could be fit within the acceptance of a muon beam accelerator.
Post-acute response of 9L gliosarcoma to Photofrin-mediated PDT in athymic nude mice.
Zhang, Xuepeng; Jiang, Feng; Kalkanis, Steven N; Zhang, ZhengGang; Hong, Xin; Yang, Hongyan; Chopp, Michael
The objective of this study is to measure the chronic responses of 9L glioma and normal brain to photodynamic therapy (PDT). Tumor size, proliferation activity of glioma cells, and vascular endothelial growth factor (VEGF) expression in both the tumor area and the brain adjacent to tumor (BAT) were observed 7 days after clinically relevant doses of PDT treatment. 9L Gliosarcoma cells were implanted into the brain of 20 athymic nude mice. Fifteen mice were injected intraperitoneally with Photofrin at a dose of 2 mg/kg on day 6 after tumor implantation and were treated with laser at different optical doses of 40 J/cm(2) (n = 5), 80 J/cm(2) (n = 5), and 120 J/cm(2) (n = 5) at 24 h after Photofrin injection, respectively. The remaining five tumor-bearing mice served as a tumor-only control. All animals were killed 14 days after tumor implantation. Hematoxylin and eosin and immunostaining were performed to assess tumor volume, VEGF expression in the tumor and the BAT, as well as Ki67 expression in the tumor area. The tumor volume of the mice receiving 80 or 120 J/cm(2) group was significantly smaller than the control group (p < 0.01). VEGF immunoreactivity in the BAT was significantly increased in the 120 J/cm(2) PDT-treated mice (p < 0.001), compared with the immunoreactivity seen in untreated mice and those receiving Photofrin and lower optical doses. No significant differences were detected in the proliferation of glioma cells and VEGF expression in the tumor area between these groups. These data indicate that PDT can shrink tumor, especially at the high light dose, and that PDT induces expression of VEGF in the BAT, which is associated with tumor recurrence. Therefore, PDT combined with anti-angiogenic agents may be an effective treatment strategy for glioma. PMID:17505777
Combination of PDT and a DNA demethylating agent produces anti-tumor immune response in a mouse tumor model
NASA Astrophysics Data System (ADS)
Mroz, Pawel; Hamblin, Michael R.
Epigenetic mechanisms, which involve DNA methylation and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. However, these changes must be actively maintained after each cell division rendering them a promising target for pharmacologic inhibition. DNA methyltransferase inhibitors like 5-aza-deoxycytidine (5-aza-dC) induce and/or up-regulate the expression of MAGE-type antigens in human and mice cancer cells. Photodynamic therapy (PDT) has been shown to be an effective locally ablative anti-cancer treatment that has the additional advantage of stimulating tumor-directed immune response. We studied the effects of a new therapy that combined the demethylating agent 5-aza-dC with PDT in the breast cancer model 4T1 syngenic to immunocompetent BALB/c mice. PDT was used as a locally ablating tumor treatment that is capable of eliciting strong and tumor directed immune response while 5-aza-dC pretreatment was used promote de novo induction of the expression of P1A.protein. This is the mouse homolog of human MAGE family antigens and is reported to function as a tumor rejection antigen in certain mouse tumors. This strategy led to an increase in PDT-mediated immune response and better treatment outcome. These results strongly suggest that the MAGE family antigens are important target for PDT mediated immune response but that their expression can be silenced by epigenetic mechanisms. Therefore the possibility that PDT can be combined with epigenetic strategies to elicit anti-tumor immunity in MAGE-positive tumor models is highly clinically significant and should be studied in detail.
Novel PDD-PDT system based on spectrophotometric real-time fluorescence monitoring and MALDI-TOF-MS analysis of tumors
NASA Astrophysics Data System (ADS)
Yoshida, Takato O.; Kohno, Eiji; Dodeller, Marc; Sakurai, Takashi; Yamamoto, Seiji; Terakawa, Susumu
In the PDT practice for tumor patients, the dose and irradiation time for the treatment are chosen by experience and not by real need. To establish advanced PDD-PDT model system for patients, we developed a method for monitoring the cell-death based on a spectrophotometric real-time change in fluorescence in HeLa-tumors during Photofrin®-PDT and ALA-PDT. Here, we describe the results of application of the new PDD-PDT system to human tumors. The fluorescence spectra obtained from human tumors were analyzed by the differential spectral analysis. The mass-spectral changes of tumor tissues during PDD-PDT were also examined by MALDI-TOF-MS/MS. The first author's seborrheic keratosis was monitored with this system during the PDD-PDT with a topically applied ALA-ointment. The changes in fluorescence spectrum were successfully detected, and the tumor regressed completely within 5 months. The differential spectral analysis of PDD-PDT-fluorescence monitoring spectra of tumors and isolated mitochondria showed a marked decrease of three peaks in the red region indicative of the PDD (600 - 720 nm), and a transient rise followed by a decline of peaks in the green region indicative of the PDT (450 - 580 nm). The MALDI-TOF-MS analysis of PDD-PDT HeLa-tumors showed a consumption of Photofrin-deuteroporphyrin and ALA-PpIX, and decreases in protein mass in the range of 4,000 - 16,000 Da, m/z 4929, 8564, 10089, 15000, and an increase in m/z 7002 in a Photofrin® PDD-PDT monitoring tumor.
Modular detector for deep underwater registration of muons and muon groups
NASA Technical Reports Server (NTRS)
Demianov, A. I.; Sarycheva, L. I.; Sinyov, N. B.; Varadanyan, I. N.; Yershov, A. A.
Registration and identification of muons and muon groups penetrating into the ocean depth, can be performed using a modular multilayer detector with high resolution bidimensional readout - deep underwater calorimeter (project NADIR). Laboratory testing of a prototype sensor cell with liquid scintillator in light-tight casing, testifies to the practicability of the full-scale experiment within reasonable expences.
Successful treatment of recalcitrant dissecting cellulitis of the scalp with ALA-PDT: case report and literature review.
Liu, Ye; Ma, Ying; Xiang, Lei-Hong
A case of refractory dissecting cellulitis of the scalp (DCS) in a forty-one-year-old Chinese female patient was treated with a total of 6 sessions of topical ALA-PDT at one week intervals. The patient tolerated and responded well to this new approach without any adverse events. This suggested that topical ALA-PDT could be an effective and safe alternative for DCS patients who were refractory to other conventional therapies. We also reviewed etiology, pathophysiology, natural history and treatment options for DCS. PMID:24284093
Proceedings of the International Workshop on Low Energy Muon Science: LEMS`93
Leon, M.
This report contains papers on research with low energy muons. Topics cover fundamental electroweak physics; muonic atoms and molecules, and muon catalyzed fusion; muon spin research; and muon facilities. These papers have been indexed and cataloged separately.
Testing model energy spectra of charged particles produced in hadron interactions on the basis of atmospheric muons
Dedenko, L. G.; Roganova, T. M.; Fedorova, G. F.
An original method for calculating the spectrum of atmospheric muons with the aid of the CORSIKA 7.4 code package and numerical integration is proposed. The first step consists in calculating the energy distribution of muons for various fixed energies of primary-cosmic-ray particles and within several chosen hadron-interaction models included in the CORSIKA 7.4 code package. After that, the spectrum of atmospheric muons is calculated via integrating the resulting distribution densities with the chosen spectrum of primary-cosmic-ray particles. The atmospheric-muon fluxes that were calculated on the basis of the SIBYLL 2.1, QGSJET01, and QGSJET II-04 models exceed the predictions of the wellknown Gaisser approximation of this spectrum by a factor of 1.5 to 1.8 in the range of muon energies between about 10{sup 3} and 10{sup 4} GeV.Under the assumption that, in the region of extremely highmuon energies, a dominant contribution to the muon flux comes from one to two generations of charged π{sup ±} and K{sup ±} mesons, the production rate calculated for these mesons is overestimated by a factor of 1.3 to 1.5. This conclusion is confirmed by the results of the LHCf and TOTEM experiments.
Testing model energy spectra of charged particles produced in hadron interactions on the basis of atmospheric muons
NASA Astrophysics Data System (ADS)
Dedenko, L. G.; Roganova, T. M.; Fedorova, G. F.
An original method for calculating the spectrum of atmospheric muons with the aid of the CORSIKA 7.4 code package and numerical integration is proposed. The first step consists in calculating the energy distribution of muons for various fixed energies of primary-cosmic-ray particles and within several chosen hadron-interaction models included in the CORSIKA 7.4 code package. After that, the spectrum of atmospheric muons is calculated via integrating the resulting distribution densities with the chosen spectrum of primary-cosmic-ray particles. The atmospheric-muon fluxes that were calculated on the basis of the SIBYLL 2.1, QGSJET01, and QGSJET II-04 models exceed the predictions of the wellknown Gaisser approximation of this spectrum by a factor of 1.5 to 1.8 in the range of muon energies between about 103 and 104 GeV.Under the assumption that, in the region of extremely highmuon energies, a dominant contribution to the muon flux comes from one to two generations of charged π± and K ± mesons, the production rate calculated for these mesons is overestimated by a factor of 1.3 to 1.5. This conclusion is confirmed by the results of the LHCf and TOTEM experiments.
R&D Toward a Neutrino Factory and Muon Collider
Zisman, Michael S
Significant progress has been made in recent years in R&D towards a neutrino factory and muon collider. The U.S. Muon Accelerator Program (MAP) has been formed recently to expedite the R&D efforts. This paper will review the U.S. MAP R&D programs for a neutrino factory and muon collider. Muon ionization cooling research is the key element of the program. The first muon ionization cooling demonstration experiment, MICE (Muon Ionization Cooling Experiment), is under construction now at RAL (Rutherford Appleton Laboratory) in the UK. The current status of MICE will be described.
Study of muon-induced neutron production using accelerator muon beam at CERN
Nakajima, Y.; Lin, C. J.; Ochoa-Ricoux, J. P.; Draeger, E.; White, C. G.; Luk, K. B.; Steiner, H.
Cosmogenic muon-induced neutrons are one of the most problematic backgrounds for various underground experiments for rare event searches. In order to accurately understand such backgrounds, experimental data with high-statistics and well-controlled systematics is essential. We performed a test experiment to measure muon-induced neutron production yield and energy spectrum using a high-energy accelerator muon beam at CERN. We successfully observed neutrons from 160 GeV/c muon interaction on lead, and measured kinetic energy distributions for various production angles. Works towards evaluation of absolute neutron production yield is underway. This work also demonstrates that the setup is feasible for a future large-scale experiment for more comprehensive study of muon-induced neutron production.
Muon Acceleration - RLA and FFAG
Bogacz, Alex
Various acceleration schemes for muons are presented. The overall goal of the acceleration systems: large acceptance acceleration to 25 GeV and 'beam shaping' can be accomplished by various fixed field accelerators at different stages. They involve three superconducting linacs: a single pass linear Pre-accelerator followed by a pair of multi-pass Recirculating Linear Accelerators (RLA) and finally a non-scaling FFAG ring. The present baseline acceleration scenario has been optimized to take maximum advantage of appropriate acceleration scheme at a given stage. The solenoid based Pre-accelerator offers very large acceptance and facilitates correction of energy gain across the bunch and significant longitudinal compression trough induced synchrotron motion. However, far off-crest acceleration reduces the effective acceleration gradient and adds complexity through the requirement of individual RF phase control for each cavity. The RLAs offer very efficient usage of high gradient superconducting RF and ability to adjust path-length after each linac pass through individual return arcs with uniformly periodic FODO optics suitable for chromatic compensation of emittance dilution with sextupoles. However, they require spreaders/recombiners switchyards at both linac ends and significant total length of the arcs. The non-scaling Fixed Field Alternating Gradient (FFAG) ring combines compactness with very large chromatic acceptance (twice the injection energy) and it allows for large number of passes through the RF (at least eight, possibly as high as 15).
First Run II results from ALICE
NASA Astrophysics Data System (ADS)
Toia, Alberica
The ALICE Collaboration is collecting data with both Minimum Bias and Muon triggers with pp collisions at √s = 13 TeV in the ongoing LHC Run II. An excellent performance of tracking and PID in the central barrel and in the muon spectrometer has been obtained. First results on the charged-particle pseudorapidity density and on identified particle transverse momentum spectra at √s = 13 TeV is presented.
Zisman, Michael S.
An international experiment to demonstrate muon ionization cooling is scheduled for beam at Rutherford Appleton Laboratory (RAL) in 2007. The experiment comprises one cell of the Study II cooling channel [1], along with upstream and downstream detectors to identify individual muons and measure their initial and final 6D phase-space parameters to a precision of 0.1%. Magnetic design of the beam line and cooling channel are complete and portions are under construction. The experiment will be described, including cooling channel hardware designs, fabrication status, and running plans. Phase 1 of the experiment will prepare the beam line and provide detector systems, including time-of-flight, Cherenkov, scintillating-fiber trackers and their spectrometer solenoids, and an electromagnetic calorimeter. The Phase 2 system will add the cooling channel components, including liquid-hydrogen absorbers embedded in superconducting Focus Coil solenoids, 201-MHz normal-conducting RF cavities, and their surrounding Coupling Coil solenoids. The MICE Collaboration goal is to complete the experiment by 2010; progress toward this is discussed.
The < ln A > study with the Muon tracking detector in the KASCADE-Grande experiment - comparison of hadronic interaction models
NASA Astrophysics Data System (ADS)
Łuczak, P.; Apel, W. D.; Arteaga-Velázquez, J. C.; Bekk, K.; Bertaina, M.; Blümer, J.; Bozdog, H.; Brancus, I. M.; Cantoni, E.; Chiavassa, A.; Cossavella, F.; Curcio, C.; Daumiller, K.; de Souza, V.; Di Pierro, F.; Doll, P.; Engel, R.; Engler, J.; Fuchs, B.; Fuhrmann, D.; Gils, H. J.; Glasstetter, R.; Grupen, C.; Haungs, A.; Heck, D.; Hörandel, J. R.; Huber, D.; Huege, T.; Kampert, K.-H.; Kang, D.; Klages, H. O.; Link, K.; Ludwig, M.; Mathes, H. J.; Mayer, H. J.; Melissas, M.; Milke, J.; Mitrica, B.; Morello, C.; Oehlschläger, J.; Ostapchenko, S.; Palmieri, N.; Petcu, M.; Pierog, T.; Rebel, H.; Roth, M.; Schieler, H.; Schoo, S.; Schröder, F. G.; Sima, O.; Toma, G.; Trinchero, G. C.; Ulrich, H.; Weindl, A.; Wochele, J.; Zabierowski, J.
With the KASCADE-Grande Muon Tracking Detector it was possible to measure with high accuracy directions of EAS muons with energy above 0.8 GeV and up to 700 m distance from the shower centre. Reconstructed muon tracks allow investigation of muon pseudorapidity (η) distributions. These distributions are nearly identical to the pseudorapidity distributions of their parent mesons produced in hadronic interactions. Comparison of the η distributions from measured and simulated showers can be used to test the quality of the high energy hadronic interaction models. The pseudorapidity distributions reflect the longitudinal development of EAS and, as such, are sensitive to the mass of the cosmic ray primary particles. With various parameters of the η distribution, obtained from the Muon Tracking Detector data, it is possible to calculate the average logarithm of mass of the primary cosmic ray particles. The results of the < ln A > analysis in the primary energy range 1016 eV-1017 eV with the 1st quartile and the mean value of the distributions will be presented for the QGSJet-II-2, QGSJet-II-4, EPOS 1.99 and EPOS LHC models in combination with the FLUKA model.
X-ray Production By Cosmic Muons
NASA Astrophysics Data System (ADS)
Mrdja, D.; Bikit, I.; Aničin, I.; Vesković, M.; Forkapić, S.
Muons have a small cross section for interactions and high energy, so they are very penetrating and give the significant contribution to the gamma spectra of Ge detectors, even in deep underground laboratories. One of the muon interaction effects with material is X-rays production. Having in mind that gold is often used as a detectors component, in this paper the production of X-rays in gold sample is analyzed by using an coincidence system based on plastic scintillation detector and Ge detector. The Au disc-shaped sample with mass of 40.6 g, radius 3.34 cm and 0.06 cm thickness was inside 12 cm thick lead shield of extended range HPGe detector. The plastic detector of 0.5 × 0.5 × 0.05 m dimensions was placed above the lead shield at the distance of 32 cm from detector endcap. The producing rate of Kα rays per Au mass unit from coincidence gamma spectrum is determined as R ~7.1 × 10-4 g-1s-1. Taking in account the measured muon flux of Φ=54 s-1m-2, the muon cross section σKα~ 43 Barn, for Au Kα X-rays production is calculated. Also, the cross sections of X-ray production by cosmic muons in lead and tungsten are measured. Unexpectedly, the results obtained did not reveal Z dependence in the Z= 74-82 region.
Determination of the low concentration correction in the macroscopic singlet oxygen model for PDT
NASA Astrophysics Data System (ADS)
Kim, Michele M.; Penjweini, Rozhin; Finlay, Jarod C.; Zhu, Timothy C.
The macroscopic singlet oxygen model has been used for singlet oxygen explicit dosimetry in photodynamic therapy (PDT). The photophysical parameters for commonly used sensitizers, HPPH and BPD, have been investigated in pre-clinical studies using mouse models. So far, studies have involved optimizing fitting algorithms to obtain the some of the photophysical parameters (ξ, σ, g) and the threshold singlet oxygen dose ([1O2]rx,sh), while other parameters such as the low concentration correction, δ, has been kept as a constant. In this study, using photobleaching measurements of mice in vivo, the value of δ was also optimized and fit to better describe experimental data. Furthermore, the value of the specific photobleaching ratio (σ) was also fine-tuned using the photobleaching results. Based on literature values of δ, σ for photosensitizers can be uniquely determined using the additional photobleaching measurements. This routine will further improve the macroscopic model of singlet oxygen production for use in explicit dosimetry.
Effective treatment of d-penicillamine induced elastosis perforans serpiginosa with ALA-PDT.
Wang, Duoqin; Liang, Jun; Xu, Jinhua; Chen, Lianjun
A case of D-penicillamine(DPA) induced elastosis perforans serpiginosa(EPS) in a 32-year-old Chinese man was reported. The presentation lasted two years and was refractory to traditional medical treatment. He was then commenced on 7.6% 5-aminolevulinic acid (ALA) induced photodynamic therapy(PDT) by a LED light of 633 nm at dose levels of 130J/ cm2 for each session with total 3 sessions at one week interval. The patient was tolerated and responded well to this new approach for DPA-induced EPS without any adverse events. The etiology, pathophysiology, natural history, and treatment options for DPA-induced EPS are reviewed, and the authors suggest this method of treatment to be effective and safe for patients of DPA-induced EPS refractory to conventional therapy. PMID:25463318
Efficiency of autofluorescence diagnosis and photodynamic therapy (PDT) of bladder tumors: our own experience
NASA Astrophysics Data System (ADS)
Szygula, Michal; Wojciechowski, Boguslaw; Sieron, Aleksander; Adamek, Mariusz; Cebula, Wojciech; Biniszkiewicz, Tomasz; Zieleznik, Witold; Kawczyk-Krupka, Aleksandra
The efficiency of autofluorescence diagnosis within urinary bladder was analyzed in the study. We examined two groups of patients: the first one consisting of 22 patients suspected to have bladder cancer and the second one consisting of 45 patients who have undergone transurethral electro resection due to urinary bladder neoplasms. Our goal was to detect cancerous tissue invisible in white-light examination. In the first group sensitivity was 100 percent and specificity was 69.23 percent. In the second group sensitivity was 96 percent and specificity was 80 percent. We also report in the study treatment efficiency of PDT in 12 patients with superficial bladder cancer. In our procedure two hours after the instillation of bladder with ALA solution, the lesion was irradiated by laser light. In 9 out of 12 treated patients regression of bladder tumor was obtained, while in 3 cases a progression of neoplasmatic process was observed.
Strongest Pulsed Muon Source at J-PARC MUSE
Miyake, Y.; Shimomura, K.; Kawamura, N.; Strasser, P.; Koda, A.; Fujimori, H.; Makimura, S.; Nakahara, K.; Kato, M.; Takeshita, S.; Nishiyama, K.; Kobayashi, Y.; Kojima, K.; Kadono, R.; Higemoto, W.; Ito, T.; Ninomiya, K.; Hiraishi, M.; Miyazaki, M.; Kubo, K.
The muon science facility (MUSE, abbreviation of MUon Science Establishment), along with the neutron, hadron, and neutrino facilities, is located in the Materials and Life Science Facility (MLF), which is a building integrated to include both neutron and muon science programs. On the November, 2009 beam cycle, we achieved extraction of the world's strongest pulsed muon beam at J-PARC MUSE by beam tuning at the Decay-Surface muon beam line (D-line). Surface muons ({mu}{sup +}) as much as 1.8x10{sup 6}/s were extracted with the use of 120 kW of protons from the Rapid Cycle Synchrotron (RCS), which corresponds to 1.5x10{sup 7}/s surface muons when a future proton beam reached at the intensity of 1MW. These intensities, at the future 1 MW operation, will correspond to more than ten times those at the RIKEN-RAL Muon facility.
Showering cosmogenic muons in a large liquid scintillator
NASA Astrophysics Data System (ADS)
Grassi, Marco; Evslin, Jarah; Ciuffoli, Emilio; Zhang, Xinmin
We present the results of FLUKA simulations of the propagation of cosmogenic muons in a 20 kton spherical liquid scintillator detector underneath 700 to 900 meters of rock. A showering muon is one which deposits at least 3 GeV in the detector in addition to ionization energy. We find that 20 percent of muons are showering and a further 11 percent of muon events are muon bundles, of which more than one muon enters the detector. In this range the showering and bundle fractions are robust against changes in the depth and topography, thus the total shower and bundle rate for a given experiment can be obtained by combining our results with an estimate for the total muon flux. One consequence is that a straightforward adaptation of the full detector showering muon cuts used by KamLAND to JUNO or RENO 50 would yield a nearly vanishing detector efficiency.
Pion production for neutrino factories and muon colliders
Mokhov, N.V.; Guidman, K.K.; Strait, J.B.; Striganov, S.I.; /Fermilab
Optimization of pion and muon production/collection for neutrino factories and muon colliders is described along with recent developments of the MARS15 code event generators and effects influencing the choice of the optimal beam energy.
Glycodendrimeric phenylporphyrins as new candidates for retinoblastoma PDT: blood carriers and photodynamic activity in cells.
Wang, Ze-Jian; Chauvin, Benoît; Maillard, Philippe; Hammerer, Fabien; Carez, Danièle; Croisy, Alain; Sandré, Catherine; Chollet-Martin, Sylvie; Prognon, Patrice; Paul, Jean-Louis; Blais, Jocelyne; Kasselouri, Athena
Photodynamic therapy (PDT) has recently been proposed as a possible indication in the conservative treatment of hereditary retinoblastoma. In order to create photosensitizers with enhanced targeting ability toward retinoblastoma cells, meso-tetraphenylporphyrins bearing one glycodendrimeric moiety have been synthesized. The binding properties to plasma proteins and photodynamic activity of two monodendrimeric porphyrins bearing three mannose units via monoethylene glycol (1) or diethylene glycol (2) linkers have been compared to that of the non-dendrimeric tri-substituted derivative [TPP(p-Deg-O-α-ManOH)(3)]. The dendrimeric structure was found to highly increase the binding affinity to plasma proteins and to modify to some extent plasma distribution. HDL and to a lesser extent LDL have been shown to be the main carriers of dendrimeric and non-dendrimeric compounds. The phototoxicity observed for the two glycodendrimers (1) and (2) (LD(50)=0.5 μM) in Y79 cells is of the same order of magnitude that for TPP(p-Deg-O-α-ManOH)(3) (LD(50)=0.7 μM), with a similar cellular uptake level for (1) and a lower for (2). A serum content increase from 2% to 20% (v/v) in the incubation medium was found to inhibit both cellular uptake and photoactivity of dendrimeric derivatives, whereas those of TPP(p-Deg-O-α-ManOH)(3) remained little affected. Specificities of glycodendrimeric porphyrins, combining a lower cellular uptake together with a higher affinity toward plasma proteins, make these derivatives possible candidates for a vascular targeting PDT. PMID:22796430
The mechanism of PDT-induced electrical blockade: the dependence of time-lapse localization of talaporfin sodium on the cell death phenotypes in rat cardiac myocytes
NASA Astrophysics Data System (ADS)
Ito, A.; Matsuo, H.; Suenari, T.; Miyoshi, S.; Takatsuki, S.; Ogawa, S.; Arai, T.
We have proposed a new type of atrial fibrillation treatment with the early state photodynamic therapy (PDT), in which the interval time between the photosensitizer injection and irradiation is shorter than that in conventional way. We had demonstrated the acute electrical blockade by the PDT with talaporfin sodium and a red (670 nm) diode laser in ex vivo and in vivo experiment using rat normal myocardial tissue. The previous study of intracellular Ca2+ concentration measurement in rat cardiac myocytes during the PDT indicated that Ca2+ influx induced by the plasma membrane damage might be the main cause of the acute reaction of myocardial tissue. We found that the cell damage of cardiac myocytes triggered by the PDT was mainly influenced by the site where the photosensitizer exists. In this study, we examined the relationship between the sites of talaporfin sodium existing and cell death phenotypes in response to the PDT, in order to clarify the mechanism of the acute electrical blockade induced by the PDT in myocardial tissue. The talaporfin sodium fluorescence was observed after the various incubation times to visualize the time-lapse intracellular photosensitizer localization. The distribution of the photosensitizer was dependent on the incubation time. The change in intracellular Ca2+ concentration during the PDT was examined with a fluorescent Ca2+ indicator by a high-speed Nipkow confocal laser microscope (CSU-X1, Yokogawa Electric Company). We obtained the Ca2+ dynamics during the PDT which can explain the PDT-induced cell death pathways. We concluded that the Ca2+ influx induced by plasma membrane damage is the possible mechanism of the electrical blockade by the early state PDT.
The involvement of NF-κB in PDT-induced death of crayfish glial and nerve cells
NASA Astrophysics Data System (ADS)
Berezhnaya, E. V.; Neginskaya, M. A.; Kovaleva, V. D.; Rudkovskii, M. V.; Uzdensky, A. B.
Photodynamic therapy (PDT) is used for selective destruction of cells, in particular, for treatment of brain tumors. However, photodynamic treatment damages not only tumor cells, but also healthy neurons and glial cells. To study the possible role of NF-κB in photodynamic injury of neurons and glial cells, we investigated the combined effect of photodynamic treatment and NF-κB modulators: activator betulinic acid, or inhibitors parthenolide and CAPE on an isolated crayfish stretch receptor consisting of a single neuron surrounded by glial cells. A laser diode (670 nm, 0.4 W/cm2) was used as a light source. The inhibition of NF-κB during PDT increased the duration of neuron firing and glial necrosis and decreased neuron necrosis and glial apoptosis. The activation of NF-κB during PDT increased neuron necrosis and glial apoptosis and decreased glial necrosis. The difference between the effects of NF-κB modulators on photosensitized neurons and glial cells indicates the difference in NF-κB-mediated signaling pathways in these cell types. Thus, NF-κB is involved in PDT-induced shortening of neuron firing, neuronal and glial necrosis, and apoptosis of glial cells.
Self-assembled IR780-loaded transferrin nanoparticles as an imaging, targeting and PDT/PTT agent for cancer therapy.
Wang, Kaikai; Zhang, Yifan; Wang, Juan; Yuan, Ahu; Sun, Minjie; Wu, Jinhui; Hu, Yiqiao
Combination of photothermal and photodynamic therapy (PTT/PDT) offer unique advantages over PDT alone. However, to achieve synergetic PDT/PTT effect, one generally needs two lasers with different wavelengths. Near-infrared dye IR-780 could be used as photosensitizer both for PTT and PDT, but its lipophilicity limits its practical use and in vivo efficiency. Herein, a simple multifunctional IR780-loaded nanoplatform based on transferrin was developed for targeted imaging and phototherapy of cancer compatible with a single-NIR-laser irradiation. The self-assembled transferrin-IR780 nanoparticles (Tf-IR780 NPs) exhibited narrow size distribution, good photo-stability, and encouraging photothermal performance with enhanced generation of ROS under laser irradiation. Following intravenous injection, Tf-IR780 NPs had a high tumor-to-background ratio in CT26 tumor-bearing mice. Treatment with Tf-IR780 NPs resulted in significant tumor suppression. Overall, the Tf-IR780 NPs show notable targeting and theranostic potential in cancer therapy. PMID:27263444
Self-assembled IR780-loaded transferrin nanoparticles as an imaging, targeting and PDT/PTT agent for cancer therapy
Wang, Kaikai; Zhang, Yifan; Wang, Juan; Yuan, Ahu; Sun, Minjie; Wu, Jinhui; Hu, Yiqiao
Combination of photothermal and photodynamic therapy (PTT/PDT) offer unique advantages over PDT alone. However, to achieve synergetic PDT/PTT effect, one generally needs two lasers with different wavelengths. Near-infrared dye IR-780 could be used as photosensitizer both for PTT and PDT, but its lipophilicity limits its practical use and in vivo efficiency. Herein, a simple multifunctional IR780-loaded nanoplatform based on transferrin was developed for targeted imaging and phototherapy of cancer compatible with a single-NIR-laser irradiation. The self-assembled transferrin-IR780 nanoparticles (Tf-IR780 NPs) exhibited narrow size distribution, good photo-stability, and encouraging photothermal performance with enhanced generation of ROS under laser irradiation. Following intravenous injection, Tf-IR780 NPs had a high tumor-to-background ratio in CT26 tumor-bearing mice. Treatment with Tf-IR780 NPs resulted in significant tumor suppression. Overall, the Tf-IR780 NPs show notable targeting and theranostic potential in cancer therapy. PMID:27263444
Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status
NASA Astrophysics Data System (ADS)
Marcus, Stuart L.; Sobel, Russel S.; Golub, Allyn L.; Carroll, Ronald L.; Lundahl, Scott L.; Shulman, D. Geoffrey
Exogenous provision of ALA to many tissues results in the accumulation of sufficient quantities of the endogenous photosensitizer protoporphyrin IX, (PpIX), to produce a photodynamic effect. Therefore, ALA may be considered the only current PDT agent in clinical development which is a biochemical precursor of a photosensitizer. Topical ALA application, followed by exposure to activating light (ALA PDT), has been reported effective for the treatment of a variety of dermatologic diseases including cutaneous T-cell lymphoma, superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses, and is also being examined for treatment of acne and hirsutism. PpIX induced by ALA application also may serve as a fluorescence detection marker for photodiagnosis (PD) of malignant and pre- malignant conditions of the urinary bladder and other organs. Local internal application of ALA has also been used for selective endometrial ablation in animal model systems and is beginning to be examined in human clinical studies. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer, various gastrointestinal cancers, and the condition known as Barrett's esophagus. This brief paper reviews the current clinical and development status of ALA PDT.
The effect of ALA/PpIX PDT on putative cancer stem cells in tumor side populations
NASA Astrophysics Data System (ADS)
Morgan, Janet; Petrucci, Cara M.
Protoporphyrin IX (PpIX) synthesized endogenously from 5-aminolevulinic acid (ALA), is effluxed from cells expressing the ATP-dependent transporter ABCG2. Side population (SP) cells (named for their low red/blue fluorescence distribution in flow cytometry plots with ABCG2 substrates such as Hoechst) are postulated to contain cancer stem cells (CSC). The SP in U87 (human gliblastoma cell line) were more resistant to ALA-PDT than NON-SP cells. Inhibiting ABCG2 activity with the tyrosine kinase inhibitor imatinib mesylate (IM, Gleevec) during incubation with ALA increased PpIX in the SP by preventing its efflux and decreased the SP after subsequent PDT, enhancing phototoxicity. Evasion of SP cells from ALA-PDT could cause tumor recurrence from CSC. Manipulation of ABCG2 levels on the SP with small molecule modulators may be a potential strategy for enhancing PDT by decreasing the amount of substrate photosensitizer extruded from cells and lowering the threshold for phototoxicity.
Regulation of miRNA Expression by Low-Level Laser Therapy (LLLT) and Photodynamic Therapy (PDT)
Kushibiki, Toshihiro; Hirasawa, Takeshi; Okawa, Shinpei; Ishihara, Miya
Applications of laser therapy, including low-level laser therapy (LLLT), phototherapy and photodynamic therapy (PDT), have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will aid in the development of laser therapies. In order to understand in detail the molecular mechanisms of LLLT and PDT-related responses, it will be useful to characterize the specific expression of miRNAs and proteins. Such analyses will provide an important source for new applications of laser therapy, as well as for the development of individualized treatments. Although several miRNAs should be up- or down-regulated upon stimulation by LLLT, phototherapy and PDT, very few published studies address the effect of laser therapy on miRNA expression. In this review, we focus on LLLT, phototherapy and PDT as representative laser therapies and discuss the effects of these therapies on miRNA expression. PMID:23807510
Studies of muon-induced radioactivity at NuMI
Boehnlein, David j.; Leveling, A.F.; Mokhov, N.V.; Vaziri, K.; Iwamoto, Y.; Kasugai, Y.; Matsuda, N.; Nakashima, H.; Sakamoto, Y.; Hagiwara, M.; Iwase, Hiroshi; /KEK, Tsukuba /Kyoto U., KURRI /Pohang Accelerator Lab. /Shimizu, Tokyo /Tohoku U.
The JASMIN Collaboration has studied the production of radionuclides by muons in the muon alcoves of the NuMI beamline at Fermilab. Samples of aluminum and copper are exposed to the muon field and counted on HpGe detectors when removed to determine their content of radioactive isotopes. We compare the results to MARS simulations and discuss the radiological implications for neutrino factories and muon colliders.
Tissue photosensitizer dosimetry using spectrally-resolved fluorescence for pre-clinical and clinical verteporfin-PDT of pancreatic cancer
NASA Astrophysics Data System (ADS)
Isabelle, Martin; Davis, Scott; Li, Zan; Gunn, Jason; Hoopes, P. J.; Pereira, S.; Mosse, C. A.; Hasan, T.; Pogue, B. W.
Photodynamic therapy (PDT) mediated with verteporfin is currently being investigated to treat pancreatic cancer in patients who are not surgical candidates. Clinically, interstitial light delivery is administered through a fiber, via percutaneous needle implantation guided by ultrasound and/or verified by CT. Tumor response to PDT is based on photosensitizer (PS) dose, light dose, light dose rate and the timing of light application following PS injection. However, studies have shown that even when matching administered PDT treatment parameters such as drug dose and light level, there can be significant inter-patient variation in tissue damage post-PDT, and this has been primarily attributed to imprecise PS concentration at the target tissue site. In order to achieve optimal tumor response from PDT without causing major damage to surrounding tissue, it would be advantageous to measure the PS concentration in the target tissue just prior to light application. From these measurements, the clinician can adapt the light application dose to the measured target tissue PS concentration (i.e. insufficient target tissue PS concentrations compensated by higher light doses and vice versa.) in order to provide an optimal light dose for each patient. In animal studies, a spectrometer-based in-vivo fluorescence dosimetry system has been used to assess accumulated PS levels (verteporfin) in situ. Measurements are taken from skin, leg muscle, buccal mucosa and tumor tissue locations one hour after injection of the photosensitizer. Real-time spectral fitting, subtraction of background autofluorescence and ratiometric analysis is performed on the raw data to extract out only the photosensitizer fluorescence and therefore concentration. Using a pre-measured calibration data set of varying concentrations for verteporfin in tissue phantoms composed of intralipid and whole blood, it was possible detect concentrations of the photosensitizer below 0.5nM. In the clinical studies being
Highly Charged Ruthenium(II) Polypyridyl Complexes as Lysosome-Localized Photosensitizers for Two-Photon Photodynamic Therapy.
Huang, Huaiyi; Yu, Bole; Zhang, Pingyu; Huang, Juanjuan; Chen, Yu; Gasser, Gilles; Ji, Liangnian; Chao, Hui
Photodynamic therapy (PDT) is a noninvasive medical technique that has received increasing attention over the last years and been applied for the treatment of certain types of cancer. However, the currently clinically used PDT agents have several limitations, such as low water solubility, poor photostability, and limited selectivity towards cancer cells, aside from having very low two-photon cross-sections around 800 nm, which limits their potential use in TP-PDT. To tackle these drawbacks, three highly positively charged ruthenium(II) polypyridyl complexes were synthesized. These complexes selectively localize in the lysosomes, an ideal localization for PDT purposes. One of these complexes showed an impressive phototoxicity index upon irradiation at 800 nm in 3D HeLa multicellular tumor spheroids and thus holds great promise for applications in two-photon photodynamic therapy. PMID:26447888
Conceptual design studies are underway for both muon colliders and high-current non-colliding muon storage rings that have the potential to become the first true neutrino factories. Muon decays in long straight sections of the storage rings would produce uniquely intense and precisely characterized two-component neutrino beams--muon neutrinos plus electron antineutrinos from negative muon decays and electron neutrinos plus muon antineutrinos from positive muons. This article presents a long-term overview of the prospects for these facilities to greatly extend the capabilities for accelerator-based neutrino physics studies for both high rate and long baseline neutrino experiments. As the first major physics topic, recent experimental results involving neutrino oscillations have motivated a vigorous design effort towards dedicated neutrino factories that would store muon beams of energies 50 GeV or below. These facilities hold the promise of neutrino oscillation experiments with baselines up to intercontinental distances and utilizing well understood beams that contain, for the first time, a substantial component of multi-GeV electron-flavored neutrinos. In deference to the active and fast-moving nature of neutrino oscillation studies, the discussion of long baseline physics at neutrino factories has been limited to a concise general overview of the relevant theory, detector technologies, beam properties, experimental goals and potential physics capabilities. The remainder of the article is devoted to the complementary high rate neutrino experiments that would study neutrino-nucleon and neutrino-electron scattering and would be performed at high performance detectors placed as close as is practical to the neutrino production straight section of muon storage rings in order to exploit beams with transverse dimensions as small as a few tens of centimeters.
Muon (g-2) Technical Design Report
Grange, J.
The Muon (g-2) Experiment, E989 at Fermilab, will measure the muon anomalous magnetic moment a factor-of-four more precisely than was done in E821 at the Brookhaven National Laboratory AGS. The E821 result appears to be greater than the Standard-Model prediction by more than three standard deviations. When combined with expected improvement in the Standard-Model hadronic contributions, E989 should be able to determine definitively whether or not the E821 result is evidence for physics beyond the Standard Model. After a review of the physics motivation and the basic technique, which will use the muon storage ring built at BNL and now relocated to Fermilab, the design of the new experiment is presented. This document was created in partial fulfillment of the requirements necessary to obtain DOE CD-2/3 approval.
Muon Fluence Measurements for Homeland Security Applications
Ankney, Austin S.; Berguson, Timothy J.; Borgardt, James D.; Kouzes, Richard T.
This report focuses on work conducted at Pacific Northwest National Laboratory to better characterize aspects of backgrounds in RPMs deployed for homeland security purposes. Two polyvinyl toluene scintillators were utilized with supporting NIM electronics to measure the muon coincidence rate. Muon spallation is one mechanism by which background neutrons are produced. The measurements performed concentrated on a broad investigation of the dependence of the muon flux on a) variations in solid angle subtended by the detector; b) the detector inclination with the horizontal; c) depth underground; and d) diurnal effects. These tests were conducted inside at Building 318/133, outdoors at Building 331G, and underground at Building 3425 at Pacific Northwest National Laboratory.
Muon Tracking to Detect Special Nuclear Materials
Schwellenbach, D.; Dreesen, W.; Green, J. A.; Tibbitts, A.; Schotik, G.; Borozdin, K.; Bacon, J.; Midera, H.; Milner, C.; Morris, C.; Perry, J.; Barrett, S.; Perry, K.; Scott, A.; Wright, C.; Aberle, D.
Previous experiments have proven that nuclear assemblies can be imaged and identified inside of shipping containers using vertical trajectory cosmic-ray muons with two-sided imaging. These experiments have further demonstrated that nuclear assemblies can be identified by detecting fission products in coincidence with tracked muons. By developing these technologies, advanced sensors can be designed for a variety of warhead monitoring and detection applications. The focus of this project is to develop tomographic-mode imaging using near-horizontal trajectory muons in conjunction with secondary particle detectors. This will allow imaging in-situ without the need to relocate the objects and will enable differentiation of special nuclear material (SNM) from other high-Z materials.
Zisman, Michael S.
Both a Neutrino Factory and a Muon Collider place stringent demands on the proton beam used to generate the desired beam of muons. Here we discuss the advantages and challenges of muon accelerators and the rationale behind the requirements on proton beam energy, intensity, bunch length, and repetition rate. Example proton driver configurations that have been considered in recent years are also briefly indicated.
Noninvasive Reactor Imaging Using Cosmic-Ray Muons
NASA Astrophysics Data System (ADS)
Miyadera, H.; Fujita, K.; Karino, Y.; Kume, N.; Nakayama, K.; Sano, Y.; Sugita, T.; Yoshioka, K.; Morris, C. L.; Bacon, J. D.; Borozdin, K. N.; Perry, J. O.; Mizokami, S.; Otsuka, Y.; Yamada, D.
Cosmic-ray-muon imaging is proposed to assess the damages to the Fukushima Daiichi reactors. Simulation studies showed capability of muon imaging to reveal the core conditions.The muon-imaging technique was demonstrated at Toshiba Nuclear Critical Assembly, where the uranium-dioxide fuel assembly was imaged with 3-cm spatial resolution after 1 month of measurement.
Higgs boson and Z physics at the first muon collider
Demarteau, M.; Han, T.
The potential for the Higgs boson and Z-pole physics at the first muon collider is summarized, based on the discussions at the ``Workshop on the Physics at the First Muon Collider and at the Front End of a Muon Collider``.
Characterisation of the muon beams for the Muon Ionisation Cooling Experiment
Adams, D.; et al.,
A novel single-particle technique to measure emittance has been developed and used to characterise seventeen different muon beams for the Muon Ionisation Cooling Experiment (MICE). The muon beams, whose mean momenta vary from 171 to 281 MeV/c, have emittances of approximately 1.5--2.3 \\pi mm-rad horizontally and 0.6--1.0 \\pi mm-rad vertically, a horizontal dispersion of 90--190 mm and momentum spreads of about 25 MeV/c. There is reasonable agreement between the measured parameters of the beams and the results of simulations. The beams are found to meet the requirements of MICE.
Jet production in muon-proton and muon-nuclei scattering at Fermilab-E665
Salgado, C.W.; E665 Collaboration
Measurements of multi-jet production rates from Muon-Proton Muon- Nuclei scattering at Fermilab-E665 are presented. Jet rates are defined by the JADE clustering algorithm. Rates in Muon-Proton deep-inelastic scattering are compared to perturbative Quantum Chromodynamics (PQCD) and Monte Carlo model predictions. We observe hadronic (2+1)-jet rates which are a factor of two higher than PQCD predictions at the partonic level. Preliminary results from jet production on heavy targets, in the shadowing region, show a suppression of the jet rates as compared to deuterium. The two- forward jet sample present higher suppression as compared to the one-forward jet sample.
Constraints on muon-specific dark forces
NASA Astrophysics Data System (ADS)
Karshenboim, Savely G.; McKeen, David; Pospelov, Maxim
The recent measurement of the Lamb shift in muonic hydrogen allows for the most precise extraction of the charge radius of the proton which is currently in conflict with other determinations based on e-p scattering and hydrogen spectroscopy. This discrepancy could be the result of some new muon-specific force with O(1-100) MeV force carrier—in this paper we concentrate on vector mediators. Such an explanation faces challenges from the constraints imposed by the g-2 of the muon and electron as well as precision spectroscopy of muonic atoms. In this work we complement the family of constraints by calculating the contribution of hypothetical forces to the muonium hyperfine structure. We also compute the two-loop contribution to the electron parity-violating amplitude due to a muon loop, which is sensitive to the muon axial-vector coupling. Overall, we find that the combination of low-energy constraints favors the mass of the mediator to be below 10 MeV and that a certain degree of tuning is required between vector and axial-vector couplings of new vector particles to muons in order to satisfy constraints from muon g-2. However, we also observe that in the absence of a consistent standard model embedding high-energy weak-charged processes accompanied by the emission of new vector particles are strongly enhanced by (E/mV)2, with E a characteristic energy scale and mV the mass of the mediator. In particular, leptonic W decays impose the strongest constraints on such models completely disfavoring the remainder of the parameter space.
Differences of response of human bladder cancer cells to photodynamic therapy (PDT) with Hypericum perforantum L extract and Photofrin
NASA Astrophysics Data System (ADS)
Nseyo, Unyime; Kim, Albert; Stavropoulos, Nikos E.; Skalkos, Dimitris; Nseyo, Unwana U.; Chung, Theodore D.
Refractory carcinoma in situ and resistant multifocal transitional cell carcinoma (TCC) of the human urinary bladder respond modestly to PHOTOFRIN (PII) PDT. Hypericum perforatum L., (St. John"s wort /Epirus" Vasalmo, Greece), a medicinal plant used for many human ailments, is under investigation as a new photosensitizer. We have reported on the antiproliferative activity of the lipophilic extract of the Hypericum perforatum L. (HP) against cultured T-24, and NBT-11 bladder cancer cells. We investigated response of the polar methanolic fraction (PMF) of the HP extract versus PHOTOFRIN in photodynamic therapy (PDT) of human bladder cancer cells, RT-4 and T-24.The PMF was extracted from the dry herb with methanol, followed by liquid extraction with petroleum ether. RT-4/T-24, were plated (105 cells/well) and placed in the incubator (370 C, 5%CO) for 24 hours prior to addition of drugs. PII 2ug/ml, or PMF 60ug /ml was added and incubation continued. After 24 hours, the cells were treated with laser light (630nm) with 0,1,2,4 and 8 Joules. The cells were then washed and reincubated for another 24 hours. After this incubation cell survival was assessed by the MTT assay. PMF-PDT induced percent cell kill of 0%, 0%, 0%, 29% and 75%, in RT-4 cells (primary noninvasive urinary bladder TCC) versus 5%, 9%, 13%, 69% and 86%, in T-24 cells(metastatic TTC) at 0,1,2,4 and 8 Joules respectively. PII-PDT induced cell kill of 0 %, 0% ,0%,0% and 9 %, in RT-4 cells versus 0%,10%,0%,21% and 77%, in T-24 cells at 0,1,2,4 and 8 Joules respectively.RT-24 cells were relatively more resistant than T-24 cells to PMF and PII-PDT. Understanding mechanisms of such differential responses might prove useful
Z' models for the LHCb and g -2 muon anomalies
NASA Astrophysics Data System (ADS)
Allanach, Ben; Queiroz, Farinaldo S.; Strumia, Alessandro; Sun, Sichun
We revisit a class of Z' explanations of the anomalies found by the LHCb collaboration in B decays, and show that the scenario is tightly constrained by a combination of constraints: (i) LHC searches for dimuon resonances, (ii) perturbativity of the Z' couplings; (iii) the Bs mass difference, and (iv) electroweak precision data. Solutions are found by suppressing the Z' coupling to electrons and to light quarks and/or by allowing for a Z' decay width into dark matter. We also present a simplified framework where a TeV-scale Z' gauge boson that couples to standard leptons as well as to new heavy vectorlike leptons, can simultaneously accommodate the LHCb anomalies and the muon g -2 anomaly.
Muon production in extended air shower simulations.
Pierog, T; Werner, K
Whereas air shower simulations are very valuable tools for interpreting cosmic ray data, there is a long-standing problem: it is difficult to accommodate at the same time the longitudinal development of air showers and the number of muons measured on the ground. Using a new hadronic interaction model (EPOS) in air shower simulations produces much more muons, in agreement with results from the HiRes-MIA experiment. We find that this is mainly due to a better description of (anti) baryon production in hadronic interactions. This is an aspect of air shower physics which has been neglected so far. PMID:18999734
Stochastic cooling requirements for a muon collider
Ruggiero, A.G.
The most severe limitation to the muon production for a large-energy muon collider is the short time allowed for cooling the beam to dimensions small enough to provide reasonably high luminosity. The limitation is caused by the short lifetime of the particles. It appears to be desirable to accelerate the beam quickly in very short bunches. This paper describes the requirements of single-pass, fast stochastic cooling for very short bunches. Bandwidth, amplifier gain and Schottky power do not seem to be of major concern. Problems do arise with the ultimate low emittance that can be achieved, the value of which is seriously affected by the front-end noise.
Rare kaon, muon, and pion decay
Littenberg, L.
The author discusses the status of and prospects for the study of rare decays of kaons, muons, and pions. Studies of rare kaon decays are entering an interesting new phase wherein they can deliver important short-distance information. It should be possible to construct an alternative unitarity triangle to that determined in the B sector, and thus perform a critical check of the Standard Model by comparing the two. Rare muon decays are beginning to constrain supersymmetric models in a significant way, and future experiments should reach sensitivities which this kind of model must show effects, or become far less appealing.
A complete scheme for production, cooling, acceleration, and ring for a 1.5 TeV center of mass muon collider is presented, together with parameters for two higher energy machines. The schemes starts with the front end of a proposed neutrino factory that yields bunch trains of both muon signs. Six dimensional cooling in long-period helical lattices reduces the longitudinal emittance until it becomes possible to merge the trains into single bunches, one of each sign. Further cooling in all dimensions is applied to the single bunches in further helical lattices. Final transverse cooling to the required parameters is achieved in 50 T solenoids.
Energy loss measurement of cosmic ray muons
NASA Astrophysics Data System (ADS)
Unger, Joseph
Measurements of energy losses of high energy cosmic ray muons in an ionization chamber are presented. The chamber consists of 16 single gap layers, and the liquid tetra methyl silane (TMS) was used as active medium. The absolute energy loss and the relativistic rise were measured and compared with theoretical calculations. The importance of the measurements within the framework of the cosmic ray experiment KASCADE (German acronym for Karlsruhe Shower Core and Array Detector) are discussed, especially with respect to energy calibration of hadrons and high energy muons above 1 TeV.
Large muon electric dipole moment from flavor?
Hiller, Gudrun; Huitu, Katri; Rueppell, Timo; Laamanen, Jari
We study the prospects and opportunities of a large muon electric dipole moment (EDM) of the order (10{sup -24}-10{sup -22}) ecm. We investigate how natural such a value is within the general minimal supersymmetric extension of the standard model with CP violation from lepton flavor violation in view of the experimental constraints. In models with hybrid gauge-gravity-mediated supersymmetry breaking, a large muon EDM is indicative for the structure of flavor breaking at the Planck scale, and points towards a high messenger scale.
FFAG Designs for Muon Collider Acceleration
Berg, J. Scott
I estimate FFAG parameters for a muon collider with a 70mm longitudinal emittance. I do not discuss the lower emittance beam for a Higgs factory. I produce some example designs, giving only parameters relevant to estimating cost and performance. The designs would not track well, but the parameters of a good design will be close to those described. I compare these cost estimates to those for a fast-ramping synchrotron and a recirculating linear accelerator. I conclude that FFAGs do not appear to be cost-effective for the large longitudinal emittance in a high-energy muon collider.
Feasibility Study of Compact Gas-Filled Storage Ring for 6D Cooling of Muon Beams
A. Garren, J. Kolonlo
The future of elementary particle physics in the USA depends in part on the development of new machines such as the International Linear Collider, Muon Collider and Neutrino Factories which can produce particle beams of higher energy, intensity, or particle type than now exists. These beams will enable the continued exploration of the world of elementary particles and interactions. In addition, the associated development of new technologies and machines such as a Muon Ring Cooler is essential. This project was to undertake a feasibility study of a compact gas-filled storage ring for 6D cooling of muon beams. The ultimate goal, in Phase III, was to build, test, and operate a demonstration storage ring. The preferred lattice for the storage ring was determined and dynamic simulations of particles through the lattice were performed. A conceptual design and drawing of the magnets were made and a study of the RF cavity and possible injection/ejection scheme made. Commercial applications for the device were investigated and the writing of the Phase II proposal completed. The research findings conclude that a compact gas-filled storage ring for 6D cooling of muon beams is possible with further research and development.
Photodynamic therapy with photofrin II derivative in the treatment of carcinosarcoma of rats with diabetes mellitus
NASA Astrophysics Data System (ADS)
Dima, Vasile F.; Vasiliu, Virgil V.; Ionescu, Mircea D.; Laky, Dezideriu
Four batches of Wistar rats with Walker-256 carcinosarcoma were used to test the effects of PDT upon `in vivo' tumor growth. Ten days after tumor transplantation, rats from batch I(DM) were exposed to Photofrin II (20 mg/kg), given i.p. 24 h before exposure to laser (632.8 nm; 10 mw; He-Ne laser), five doses given at 4 days intervals; batch II and batch III received sole treatment (DM or PDT). The control batch IV included animals with untreated Walker-256 tumors. The animals were followed up 42 days.
Performance of the ALICE muon trigger system in pp and Pb-Pb collisions at the LHC
NASA Astrophysics Data System (ADS)
Fronzé, G. G.
The ALICE muon spectrometer studies the production of quarkonia and open heavy-flavour particles. It is equipped with a trigger system composed of Resistive Plate Chambers which, by applying a transverse-momentum-based muon selection, minimises the background from light-hadron decays. The system has been continuously taking data throughout the LHC Run I; it has undergone maintenance and consolidation operations during the LHC shutdown period 1. In the first year of the LHC Run II, the system, fully recommissioned, has participated in data taking in pp and Pb-Pb collisions. The performance of the system throughout the last data-taking period is presented.
Thiessen, H.A.
The present conception of LAMPF II is a high-intensity 16-GeV synchrotron injected by the LAMPF 800-MeV H/sup -/ beam. The proton beam will be used to make secondary beams of neutrinos, muons, pions, kaons, antiprotons, and hyperons more intense than those of any existing or proposed accelerator. For example, by taking maximum advantage of a thick target, modern beam optics, and the LAMPF II proton beam, it will be possible to make a negative muon beam with nearly 100% duty factor and nearly 100 times the flux of the existing Stopped Muon Channel (SMC). Because the unique features of the proposed machine are most applicable to beams of the same momentum as LAMPF (that is, < 2 GeV/c), it may be possible to use most of the experimental areas and some of the auxiliary equipment, including spectrometers, with the new accelerator. The complete facility will provide improved technology for many areas of physics already available at LAMPF and will allow expansion of medium-energy physics to include kaons, antiprotons, and hyperons. When LAMPF II comes on line in 1990 LAMPF will have been operational for 18 years and a major upgrade such as this proposal will be reasonable and prudent.
Search for muon EDM with ultra-cold muon beam at J-PARC
NASA Astrophysics Data System (ADS)
Mibe, Tsutomu; J-PARC muon g-2/EDM Collaboration
The J-PARC experiment E34 aims to measure the anomalous magnetic moment (g-2) and electric dipole moment (EDM) of the positive muon with a novel technique utilizing an ultra-cold muons accelerated to 300 MeV/ c and a 66 cm-diameter compact muon storage ring without focusing-electric field. This measurement will be complementary to the previous BNL E821 experiment and upcoming FNAL E989 experiment with the muon beam at the magic momentum 3.1 GeV/ c in a 14 m-diameter storage ring. The experiment aims to achieve the sensitivity down to 0.1 ppm for g-2, and 10-21 e . cm for EDM. In this presentation, I'd like to discuss the technical achievements and prospects for realization of the experiment.
The International Muon Ionization Cooling Experiment: MICE and Neutrino Factories
NASA Astrophysics Data System (ADS)
Freemire, Ben
The Muon Ionization Cooling Experiment (MICE) is an accelerator and particle physics experiment aimed at demonstrating the technique of ionization cooling on a beam of muons. Ionization cooling is the process by which muons are sent through an absorbing material, thereby losing energy and decreasing their normalized emittance. The muons are then reaccelerated in the appropriate direction with radio frequency (RF) cavities. This produces an overall reduction in transverse emittance of the muon beam. Ionization cooling could be a key technique in the design of a high intensity Neutrino Factory.
Low-energy negative muon interaction with matter
NASA Astrophysics Data System (ADS)
Danev, Petar; Adamczak, Andrzej; Bakalov, Dimitar; Mocchiutti, Emiliano; Stoilov, Mihail; Vacchi, Andrea
Using simulated data, obtained with the FLUKA code, we derive empirical regularities about the propagation and stopping of low-energy negative muons in hydrogen and selected solid materials. The results are intended to help the preliminary stages of the set-up design for experimental studies of muon capture and muonic atom spectroscopy. Provided are approximate expressions for the parameters of the the momentum, spatial and angular distribution of the propagating muons. In comparison with the available data on the stopping power and range of muons (with which they agree in the considered energy range) these results have the advantage to also describe the statistical spread of the muon characteristics of interest.
Apoptosis of HeLa cells induced by a new targeting photosensitizer-based PDT via a mitochondrial pathway and ER stress
Li, Donghong; Li, Lei; Li, Pengxi; Li, Yi; Chen, Xiangyun
Photodynamic therapy (PDT) is emerging as a viable treatment for many cancers. To decrease the cutaneous photosensitivity induced by PDT, many attempts have been made to search for a targeting photosensitizer; however, few reports describe the molecular mechanism of PDT mediated by this type of targeting photosensitizer. The present study aimed to investigate the molecular mechanism of PDT induced by a new targeting photosensitizer (PS I), reported previously by us, on HeLa cells. Apoptosis is the primary mode of HeLa cell death in our system, and apoptosis occurs in a manner dependent on concentration, irradiation dose, and drug–light intervals. After endocytosis mediated by the folate receptor, PS I was primarily localized to the mitochondria and the endoplasmic reticulum (ER) of HeLa cells. PS I PDT resulted in rapid increases in intracellular reactive oxygen species (ROS) production and Ca2+ concentration, both of which reached a peak nearly simultaneously at 15 minutes, followed by the loss of mitochondrial membrane potential at 30 minutes, release of cytochrome c from mitochondria into the cytoplasm, downregulation of Bcl-2 expression, and upregulation of Bax expression. Meanwhile, activation of caspase-3, -9, and -12, as well as induction of C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP78), in HeLa cells after PS I PDT was also detected. These results suggest that apoptosis of HeLa cells induced by PS I PDT is not only triggered by ROS but is also regulated by Ca2+ overload. Mitochondria and the ER serve as the subcellular targets of PS I PDT, the effective activation of which is responsible for PS I PDT-induced apoptosis in HeLa cells. PMID:25897245
Muon Collider Machine-Detector Interface
Mokhov, Nikolai V.; /Fermilab
In order to realize the high physics potential of a Muon Collider (MC) a high luminosity of {mu}{sup +}{mu}{sup -}-collisions at the Interaction Point (IP) in the TeV range must be achieved ({approx}10{sup 34} cm{sup -2}s{sup -1}). To reach this goal, a number of demanding requirements on the collider optics and the IR hardware - arising from the short muon lifetime and from relatively large values of the transverse emittance and momentum spread in muon beams that can realistically be obtained with ionization cooling should be satisfied. These requirements are aggravated by limitations on the quadrupole gradients as well as by the necessity to protect superconducting magnets and collider detectors from muon decay products. The overall detector performance in this domain is strongly dependent on the background particle rates in various sub-detectors. The deleterious effects of the background and radiation environment produced by the beam in the ring are very important issues in the Interaction Region (IR), detector and Machine-Detector Interface (MDI) designs. This report is based on studies presented very recently.
Current ideas for designing neutrino factories [ 1,2] and muon colliders [3] require unique configurations of fields and materials to prepare the muon beam for acceleration. This so-called front end system must accomplish the goals of phase rotation, bunching and cooling. We have continued the development of a 3-D tracking code, ICOOL [4], for examining possible muon collider front end configurations. A system is described in terms of a series of longitudinal regions with associated material and field properties. The tracking takes place in a coordinate system that follows a reference orbit through the system. The code takes into account decays and interactions of {approx}50-500 MeV/c muons in matter. Material geometry regions include cylinders and wedges. A number of analytic models are provided for describing the field configurations. Simple diagnostics are built into the code, including calculation of emittances and correlations, longitudinal traces, histograms and scatter plots. A number of auxiliary codes can be used for pre-processing, post-processing and optimization.
Neutrino masses, Majorons, and muon decay
Santamaria, A.; Bernabeu, J.; Pich, A.
The contributions to the parameters xi, delta, rho, and eta in muon decay coming from double Majoron emission, Majorana neutrino masses, and effects of charged scalars are evaluated in the scalar-triplet model. The relevance of these effects for planned experiments is discussed.
Target studies for surface muon production
NASA Astrophysics Data System (ADS)
Berg, F.; Desorgher, L.; Fuchs, A.; Hajdas, W.; Hodge, Z.; Kettle, P.-R.; Knecht, A.; Lüscher, R.; Papa, A.; Rutar, G.; Wohlmuther, M.
Meson factories are powerful drivers of diverse physics programs. With beam powers already in the MW-regime attention has to be turned to target and beam line design to further significantly increase surface muon rates available for experiments. For this reason we have explored the possibility of using a neutron spallation target as a source of surface muons by performing detailed Geant4 simulations with pion production cross sections based on a parametrization of existing data. While the spallation target outperforms standard targets in the backward direction by more than a factor 7 it is not more efficient than standard targets viewed under 90°. Not surprisingly, the geometry of the target plays a large role in the generation of surface muons. Through careful optimization, a gain in surface muon rate of between 30% and 60% over the standard "box-like" target used at the Paul Scherrer Institute could be achieved by employing a rotated slab target. An additional 10% gain could also be possible by utilizing novel target materials such as, e.g., boron carbide.
Commissioning of CMS Endcap Muon System
NASA Astrophysics Data System (ADS)
Brownell, Elizabeth
This talk is as an overview of the evolution and current state of commissioning work on the CMS endcap muon system. I intend to highlight the progress in operating the detector, some problems encountered and solutions developed, lessons learned in the process, points which still require action to be taken, and data taking results.
Gamma rays from muons from WIMPs: Implementation of radiative muon decays for dark matter analyses
NASA Astrophysics Data System (ADS)
Scaffidi, Andre; Freese, Katherine; Li, Jinmian; Savage, Christopher; White, Martin; Williams, Anthony G.
Dark matter searches in gamma ray final states often make use of the fact that photons can be produced from final state muons. Modern Monte Carlo generators and dark matter codes include the effects of final state radiation from muons produced in the dark matter annihilation process itself, but neglect the O (1 %) radiative correction that arises from the subsequent muon decay. After implementing this correction we demonstrate the effect that it can have on dark matter phenomenology by considering the case of dark matter annihilation to four muons via scalar mediator production. We first show that the AMS-02 positron excess can no longer easily be made consistent with this final state once the Fermi-LAT dwarf limits are calculated with the inclusion of radiative muon decays, and we next show that the Fermi-LAT galactic center gamma excess can be improved with this final state after inclusion of the same effect. We provide code and tables for the implementation of this effect in the popular dark matter code micrOMEGAs, providing a solution for any model producing final state muons.
Novel approach to imaging by cosmic-ray muons
NASA Astrophysics Data System (ADS)
Bikit, Istvan; Mrdja, Dusan; Bikit, Kristina; Slivka, Jaroslav; Jovancevic, Nikola; Oláh, László; Hamar, Gergő; Varga, Dezső
Cosmic-ray muons can be used for imaging of large structures, or high-density objects with high atomic number. The first task can be performed by measurement of muon absorption within very thick material layers, while the second approach is based on muon multiple scattering. However, the muon imaging of small structures with low atomic number and density was not yet solved appropriately. Here we show the first results of cosmic-ray muon imaging of small objects made of elements of low atomic number. This novel approach includes detection of secondary particles produced by muons, which were not used at all in previous muon imaging methods. Thus, the list of elements, as well as the range of dimensions of objects which can be imaged are significantly expanded.
Identification of Low PT Muon with the Atlas Tile Calorimeter
NASA Astrophysics Data System (ADS)
Usai, G.
A method for the identification of muons with the ATLAS Tile Calorimeter is presented and its efficiency and mis-tagging fraction are discussed. It is demonstrated that the Tile Calorimeter can identify muons with good efficiency down to 2 GeV/c transverse momentum, where the stand-alone Muon Spectrometer has zero efficiency. This kinematic region is important for study of B meson physics and in the particular for the CP violating decay channels. The effectiveness of this method is tested, in particular, in the case of bbar {b} events at low LHC luminosity (1033cm-1s-2) with full simulation of experimental conditions. The muon identification with the Tile Calorimeter is fast and can be used for muon selection at the trigger level. A method of exploiting the information available in other ATLAS sub-detectors in order to reduce spurious muon-tag and measure the candidate muon momentum is discussed.
Corrections for temperature effect for ground-based muon hodoscopes
NASA Astrophysics Data System (ADS)
Dmitrieva, A. N.; Kokoulin, R. P.; Petrukhin, A. A.; Timashkov, D. A.
Influence of atmospheric temperature on muon flux at sea level is considered. Results of calculations of muon spectrum for normal atmospheric conditions, differential temperature coefficients (DTC) for muons at different zenith angles and threshold energies are presented. In calculations, a six-layer stationary spherical model of atmosphere is used, contributions of both pions and kaons as well as dependence of muon energy loss on muon energy are taken into account. Comparison of muon spectrum calculations and experimental data in a wide range of zenith angles and momentums shows a good agreement. Comparison of results of DTC calculations with results of earlier works exhibits only qualitative agreement; possible sources of differences are analyzed. Some practical questions of the use of DTC for muon hodoscope data analysis are discussed.
Design and commissioning of a high magnetic field muon spin relaxation spectrometer at the ISIS pulsed neutron and muon source.
Lord, J S; McKenzie, I; Baker, P J; Blundell, S J; Cottrell, S P; Giblin, S R; Good, J; Hillier, A D; Holsman, B H; King, P J C; Lancaster, T; Mitchell, R; Nightingale, J B; Owczarkowski, M; Poli, S; Pratt, F L; Rhodes, N J; Scheuermann, R; Salman, Z
The high magnetic field (HiFi) muon instrument at the ISIS pulsed neutron and muon source is a state-of-the-art spectrometer designed to provide applied magnetic fields up to 5 T for muon studies of condensed matter and molecular systems. The spectrometer is optimised for time-differential muon spin relaxation studies at a pulsed muon source. We describe the challenges involved in its design and construction, detailing, in particular, the magnet and detector performance. Commissioning experiments have been conducted and the results are presented to demonstrate the scientific capabilities of the new instrument. PMID:21806196
Design and commissioning of a high magnetic field muon spin relaxation spectrometer at the ISIS pulsed neutron and muon source
Lord, J. S.; McKenzie, I.; Baker, P. J.; Cottrell, S. P.; Giblin, S. R.; Hillier, A. D.; Holsman, B. H.; King, P. J. C.; Nightingale, J. B.; Pratt, F. L.; Rhodes, N. J.; Blundell, S. J.; Lancaster, T.; Good, J.; Mitchell, R.; Owczarkowski, M.; Poli, S.; Scheuermann, R.; Salman, Z.
The high magnetic field (HiFi) muon instrument at the ISIS pulsed neutron and muon source is a state-of-the-art spectrometer designed to provide applied magnetic fields up to 5 T for muon studies of condensed matter and molecular systems. The spectrometer is optimised for time-differential muon spin relaxation studies at a pulsed muon source. We describe the challenges involved in its design and construction, detailing, in particular, the magnet and detector performance. Commissioning experiments have been conducted and the results are presented to demonstrate the scientific capabilities of the new instrument.
Volcanoes muon imaging using Cherenkov telescopes
NASA Astrophysics Data System (ADS)
Catalano, O.; Del Santo, M.; Mineo, T.; Cusumano, G.; Maccarone, M. C.; Pareschi, G.
A detailed understanding of a volcano inner structure is one of the key-points for the volcanic hazards evaluation. To this aim, in the last decade, geophysical radiography techniques using cosmic muon particles have been proposed. By measuring the differential attenuation of the muon flux as a function of the amount of rock crossed along different directions, it is possible to determine the density distribution of the interior of a volcano. Up to now, a number of experiments have been based on the detection of the muon tracks crossing hodoscopes, made up of scintillators or nuclear emulsion planes. Using telescopes based on the atmospheric Cherenkov imaging technique, we propose a new approach to study the interior of volcanoes detecting of the Cherenkov light produced by relativistic cosmic-ray muons that survive after crossing the volcano. The Cherenkov light produced along the muon path is imaged as a typical annular pattern containing all the essential information to reconstruct particle direction and energy. Our new approach offers the advantage of a negligible background and an improved spatial resolution. To test the feasibility of our new method, we have carried out simulations with a toy-model based on the geometrical parameters of ASTRI SST-2M, i.e. the imaging atmospheric Cherenkov telescope currently under installation onto the Etna volcano. Comparing the results of our simulations with previous experiments based on particle detectors, we gain at least a factor of 10 in sensitivity. The result of this study shows that we resolve an empty cylinder with a radius of about 100 m located inside a volcano in less than 4 days, which implies a limit on the magma velocity of 5 m/h.
Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 12. New heteropentanuclear complexes carrying four exocyclic cis-platin-like functionalities as potential bimodal (PDT/cis-platin) anticancer agents.
Donzello, Maria Pia; Viola, Elisa; Ercolani, Claudio; Fu, Zhen; Futur, David; Kadish, Karl M
Heteropentanuclear porphyrazines having the formula [(PtCl2)4LM] where L = tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazinato dianion and M = Zn(II), Mg(II)(H2O), Pd(II), Cu(II) or Co(II) were characterized by elemental analyses, IR-UV-visible spectroscopy and electrochemistry and the data compared to new and previously published results for the corresponding homopentanuclear compound [(PtCl2)4LPt]. This latter species has four external N2(py)PtCl2 coordination sites which closely resemble cis-platin, (NH3)2PtCl2, the potent chemotherapeutic anticancer drug, and is able to act as a photosensitizer for the generation of (1)O2, the cytotoxic agent in photodynamic therapy (PDT). UV-visible spectra and half wave potentials for reduction of [(PtCl2)4LM], [(PtCl2)4LPt], the parallel series of mononuclear [LM] compounds and the pentanuclear [(PdCl2)4LM] compounds were examined in the nonaqueous solvents dimethyl sulfoxide, pyridine, and dimethylformamide. The complete set of available data indicate that external coordination of the PtCl2 and PdCl2 units significantly increases the level of the electron-deficiency of the entire molecular framework despite the fact that these groups are far away from the central porphyrazine π-ring system and have coordination sites nearly orthogonal to the plane of the macrocycle. The pentanuclear species [(M'Cl2)4LM] (M' = Pt(II), Pd(II)) undergo multiple one-electron transfers and exhibit an easier reducibility as compared to related electrode reactions of the parent compounds [LM] having the same central metal. Aggregation phenomena and reducibility of the porphyrazines to their monoanionic form (prevalently in DMF) are observed for some of the examined compounds and were analyzed and accurately taken into account. Quantum yields of (1)O2 (ΦΔ), of interest in PDT, were measured for [(PtCl2)4LM] with M = Zn(II), Mg(II)(H2O), or Pd(II) and the related macrocycles [(PdCl2)4LM] and [LM] in dimethylformamide (DMF) and/or DMF
Frontiers of muon spectroscopy—25 years of muon science at ISIS
NASA Astrophysics Data System (ADS)
Cottrell, Stephen
The ISIS muon source developed with support from the European Community (EC) and groups at Grenoble, Parma, Uppsala and Munich in the late 1980s, with a single instrument providing many scientists with their first opportunity to explore the unique capabilities of muon spectroscopy. The timing was opportune, as the muon technique was making an important contribution to the study of the then recently discovered cuprate high T c superconductors. The ISIS user community developed rapidly over subsequent years, with the technique finding a broad range of applications in condensed matter physics, materials science and chemistry. The single instrument was hugely oversubscribed, and the importance of the technique was recognized in 1993 with a further grant from the EC to develop the triple beamline facility that is currently available at ISIS. During 2009 the suite of spectrometers available at the facility received a major upgrade, with the Science and Technology Facilities Council funding the development of a 5 T high field instrument that has enabled entirely new applications of muon spectroscopy to be explored. The facility continues to flourish, with a strong user community exploiting the technique to support research across an increasingly broad range of subject areas. Condensed matter science continues to be a major area of interest, with applications including semiconductors and dielectrics, superconductors, magnetism, interstitial diffusion and charge transport. Recently, however, molecular science and radical chemistry have become prominent in the ISIS programme, applications where the availability of high magnetic fields is frequently vital to the success of the experiments. For ISIS, 23 March 2012 marked a significant milestone, it being 25 years since muons were first produced at the facility for research in condensed matter and molecular science. To celebrate, the ISIS muon group organized a science symposium with the theme 'Frontiers of Muon Spectroscopy
Noninvasive imaging of absolute PpIX concentration distribution in nonmelanoma skin tumors at pre-PDT
NASA Astrophysics Data System (ADS)
Sunar, Ulas; Rohrbach, Daniel; Morgan, Janet; Zeitouni, Natalie
Photodynamic Therapy (PDT) has proven to be an effective treatment option for nonmelanoma skin cancers. The ability to quantify the concentration of drug in the treated area is crucial for effective treatment planning as well as predicting outcomes. We utilized spatial frequency domain imaging for quantifying the accurate concentration of protoporphyrin IX (PpIX) in phantoms and in vivo. We correct fluorescence against the effects of native tissue absorption and scattering parameters. First we quantified the absorption and scattering of the tissue non-invasively. Then, we corrected raw fluorescence signal by compensating for optical properties to get the absolute drug concentration. After phantom experiments, we used basal cell carcinoma (BCC) model in Gli mice to determine optical properties and drug concentration in vivo at pre-PDT.
Calculation of singlet oxygen formation from one photon absorbing photosensitizers used in PDT
NASA Astrophysics Data System (ADS)
Potasek, M.; Parilov, Evgueni; Beeson, K.
Advances in biophotonic medicine require new information on photodynamic mechanisms. In photodynamic therapy (PDT), a photosensitizer (PS) is injected into the body and accumulates at higher concentrations in diseased tissue compared to normal tissue. The PS absorbs light from a light source and generates excited-state triplet states of the PS. The excited triplet states of the PS can then react with ground state molecular oxygen to form excited singlet - state oxygen or form other highly reactive species. The reactive species react with living cells, resulting in cel l death. This treatment is used in many forms of cancer including those in the prostrate, head and neck, lungs, bladder, esophagus and certain skin cancers. We developed a novel numerical method to model the photophysical and photochemical processes in the PS and the subsequent energy transfer to O2, improving the understanding of these processes at a molecular level. Our numerical method simulates light propagation and photo-physics in PS using methods that build on techniques previously developed for optical communications and nonlinear optics applications.
Photodynamic therapy (PDT) of endometrium primary cultures serving as an in-vitro model for endometriosis
NASA Astrophysics Data System (ADS)
Herter, Wiebke; Viereck, Volker; Keckstein, J.; Steiner, Rudolf W.; Rueck, Angelika C.
As a new treatment model for endometriosis, photodynamic therapy (PDT) was applied to endometrium cultures. Endometriosis is a benign disease. Therefore primary cultures were used instead of cell lines. Endometrium is composed of epithelial and stromal cells which can also be found in primary culture. While stromal cells take a polygonal shape in culture, epithelial cells form cell colonies. PSIII (Photasan III), which is similar to hematorporphyrin derivate (HpD), meso-tetra (4-sulfonatophenyl) porphyrin (TPPS4), which posses a high fluorescence quantum yield and may be useful in fluorescence diagnosis of subtle endometriotic spots, and methylene blue (MB), a vital dye with phototoxic properties, were used as photosensitizers. Different sensitizer concentrations and incubation times were applied. The highest phototoxicity was observed for PSIII; TPPS4 and MB were less phototoxic. We compared our results with the sensitivity of cell lines described in the literature. The necessary irradiation to destroy stromal cells was relatively high but still in the same dimension as for cell lines. However they were even more sensitive than epithelial cells. This was true for all sensitizers used.
Photodynamic treatment (PDT) of endometrium primary cultures serving as an in-vitro-model for endometriosis
NASA Astrophysics Data System (ADS)
Werter, Wiebke; Viereck, Volker; Keckstein, J.; Steiner, Rudolf W.; Rueck, Angelika C.
As a new treatment model for endometriosis, photodynamic therapy (PDT) was applied to endometrium cultures. Endometriosis is a benign disease. Therefore primary cultures were used instead of cell lines. Endometrium is composed of epithelial and stromal cells which can also be found in primary culture. While stromal cells take a polygonal shape in culture, epithelial cells form cell colonies. PSIII (Photasan III), which is similar to hematorporphyrin derivate (HpD), meso-tetra (4-sulfonatophenyl) porphyrin (TPPS4), which posses a high fluorescence quantum yield and may be useful in fluorescence diagnosis of subtle endometriotic spots, and methylene blue (MB), a vital dye with phototoxic properties, were used as photosensitizers. Different sensitizer concentrations and incubation times were applied. The highest phototoxicity was observed for PSIII; TPPS4 and MB were less phototoxic. We compared our results with the sensitivity of cell lines described in the literature. The necessary irradiation to destroy stromal cells was relatively high but still in the same dimension as for cell lines. However they were even more sensitive than epithelial cells. This was true for all sensitizers used.
Chlorins with six-membered imide ring as prospective sensitizers for cancer PDT
NASA Astrophysics Data System (ADS)
Mironov, Andrei F.; Lebedeva, Victoria S.; Yakubovskaya, Raisa I.; Kazachkina, Natalia I.; Fomina, Galina I.
A series of promising PDT sensitizers having intensive absorption maximum at 710 - 750 nm has been synthesized from the readily available purpurin 18. Modification of an anhydride ring is purpurin 18 afforded two series of cyclic imides. The first group comprises the N-substituted derivatives containing residues of aliphatic alcohols (C2- C4) and carboxylic acids (C1, C5). The second series is represented by the cyclic N-hydroxyimides containing the -N-OR group, where R is either alkyl or acyl residue. Cyclic imides possess increased resistance to alkali treatment, which enhances their water solubility. They absorb in the region of 706 - 718 nm. Further development of the spectral characteristics was achieved by the oxidation of a 3- vinyl group into the formyl one. The obtained compounds have the absorption maximum in the region of 750 nm, which makes them comparable to those of bacteriochlorophyll derivatives. The presence of a spacer group in the molecule of compounds synthesized affords their attachment to the carriers for the directed transport of a sensitizer into tumor.
Development of image-guided targeted two-photon PDT for the treatment of head and neck cancers
NASA Astrophysics Data System (ADS)
Spangler, Charles W.; Starkey, Jean R.; Liang, Bo; Fedorka, Sara; Yang, Hao; Jiang, Huabei
There has been significant effort over the past two decades in the treatment of malignancies of epithelial origin, including some of the most devastating of cancers, such as colorectal cancer (CRC), squamous call carcinoma of the head and neck (HNSCC), and carcinomas of the pancreas, lungs, (both Small Cell and Non-Small Cell), renal cell, prostate, bladder and breast. Recurring, refractory HNSCC is a particularly difficult cancer to treat once the tumors recur due to mutations that are resistant to repeat chemotherapy and radiation. In addition, repeat surgery is often difficult due to the requirement of significant surgical margins that may not be possible due to the attending potential functional deficits (e.g., salivary glands, nerves and major blood vessels in confined areas). In this study FaDu HNSCC xenograft tumors in SCID mice were imaged, and "optical", as opposed to "surgical" margins defined for the tumor being treated. The subsequent two-photon treatment irradiation was computer-controlled to carry out the tumor treatment by rastering the laser beam throughout the tumor volume plus the defined optical margins simultaneously. In our initial studies, up to 85% regression in tumor volume was observed in 5 days post PDT, with complete tumor regression in 18 days. No re-growth was observed up to 41 days post-PDT, with little or no scarring and complete hair re-growth. However, competition between imaging and PDT moieties was also observed in some mouse models, possibly favoring tumor re-growth. Strategies to selectively optimize the PDT effect will be discussed.
A study of MRI-guided diffuse fluorescence molecular tomography for monitoring PDT effects in pancreas cancer
NASA Astrophysics Data System (ADS)
Samkoe, Kimberley S.; Davis, Scott C.; Srinivasan, Subhadra; O'Hara, Julia A.; Hasan, Tayyaba; Pogue, Brian W.
Over the last several decades little progress has been made in the therapy and treatment monitoring of pancreas adenocarcinoma, a devastating and aggressive form of cancer that has a 5-year patient survival rate of 3%. Currently, investigations for the use of interstitial Verteporfin photodynamic therapy (PDT) are being undertaken in both orthotopic xenograft mouse models and in human clinical trials. In the mouse models, magnetic resonance (MR) imaging has been used as a measure of surrogate response to Verteporfin PDT; however, MR imaging alone lacks the molecular information required to assess the metabolic function and growth rates of the tumor immediately after treatment. We propose the implementation of MR-guided fluorescence tomography in conjunction with a fluorescently labeled (IR-Dye 800 CW, LI-COR) epidermal growth factor (EGF) as a molecular measure of surrogate response. To demonstrate the effectiveness of MR-guided diffuse fluorescence tomography for molecular imaging, we have used the AsPC-1 (+EGFR) human pancreatic adenocarcinoma in an orthotopic mouse model. EGF IRDye 800CW was injected 48 hours prior to imaging. MR image sequences were collected simultaneously with the fluorescence data using a MR-coupled diffuse optical tomography system. Image reconstruction was performed multiple times with varying abdominal organ segmentation in order to obtain a optimal tomographic image. It is shown that diffuse fluorescence tomography of the orthotopic pancreas model is feasible, with consideration of confounding fluorescence signals from the multiple organs and tissues surrounding the pancreas. MR-guided diffuse fluorescence tomography will be used to monitor EGF response after photodynamic therapy. Additionally, it provide the opportunity to individualize subsequent therapies based on response to PDT as well as to evaluate the success of combination therapies, such as PDT with chemotherapy, antibody therapy or even radiation.
Imaging a vertical shaft from a tunnel using muons
NASA Astrophysics Data System (ADS)
Bonal, N.; Preston, L. A.; Dorsey, D. J.; Schwellenbach, D.; Green, A.; Smalley, D.
We use muon technology to image a vertical shaft from a tunnel. The density of the materials through which cosmic ray muons pass influences the flux of muons because muons are more attenuated by higher density material. Additionally, muons can travel several kilometers allowing measurements through deep rock. Density maps are generated from muon flux measurements to locate subsurface features like tunnel structures and ore bodies. Additionally, muon data can be jointly inverted with other data such as gravity and seismic to produce higher quality earth models than produced from a single method. We collected several weeks of data in a tunnel to image a vertical shaft. The minimum length of rock between the vertical shaft and the detector is 120 meters and the diameter of the vertical shaft is 4.6 meters. The rock the muons traveled through consists of Tertiary age volcanic tuff and steeply dipping, small-displacement faults. Results will be presented for muon flux in the tunnel and Monte-Carlo simulations of this experiment. Simulations from both GEANT4 (Geometry And Tracking version 4) and MCNP6 (Monte-Carlo N-Particle version 6) models will be compared. The tunnel overburden from muon measurements is also estimated and compared with actual the overburden. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.
Studies on muon tomography for archaeological internal structures scanning
NASA Astrophysics Data System (ADS)
Gómez, H.; Carloganu, C.; Gibert, D.; Jacquemier, J.; Karyotakis, Y.; Marteau, J.; Niess, V.; Katsanevas, S.; Tonazzo, A.
Muon tomography is a potential non-invasive technique for internal structure scanning. It has already interesting applications in geophysics and can be used for archaeological purposes. Muon tomography is based on the measurement of the muon flux after crossing the structure studied. Differences on the mean density of these structures imply differences on the detected muon rate for a given direction. Based on this principle, Monte Carlo simulations represent a useful tool to provide a model of the expected muon rate and angular distribution depending on the composition of the studied object, being useful to estimate the expected detected muons and to better understand the experimental results. These simulations are mainly dependent on the geometry and composition of the studied object and on the modelling of the initial muon flux at surface. In this work, the potential of muon tomography in archaeology is presented and evaluated with Monte Carlo simulations by estimating the differences on the muon rate due to the presence of internal structures and its composition. The influence of the chosen muon model at surface in terms of energy and angular distributions in the final result has been also studied.
Hydrokolloid occlusive dressings for photodynamic therapy (PDT) of cutaneous lesions with endogenous porphyrins induced by 5-aminolevulinic acid
NASA Astrophysics Data System (ADS)
Gahlen, Johannes; Stern, Josef; Herfarth, Christian
Protoporphyrin (Pp IX) is the final intermediate product before haem and can be stimulated to a phototoxic reaction with light. The presence of 5-aminolevulinic acid can increase the intracellular biosynthesis of Pp IX in certain types of tumor cells. The photosensitizing concentrations of Pp IX make laser light induced fluorescence diagnostics (LIFD) and photodynamic therapy possible. A topical application of a 5-aminolevulinic acid solution requires a waterproof occlusive dressing for several hours. We developed a simple technique for a practical preparation for PDT using a hydrocolloid dressing. The normal surrounding skin can be spared. We present our first therapeutic experience with a case of cutaneous breast cancer in a 65-year-old female patient. Six hours after topical application of 10% isotonic 5- aminolevulinic acid under the hydrocolloid dressing PDT was performed (Ar-Dye Laser, 630 nm wavelength). Twenty four hours after PDT a superficial tumor necrosis could be observed with a maximum depth of tumor necrosis of 2 - 3 mm. The surrounding normal skin was without any inflammation.
The utilization of a non-invasive fluorescence imaging system to follow clinical dermatological MAL-PDT
NASA Astrophysics Data System (ADS)
Tyrrell, Jessica; Campbell, Sandra; Curnow, Alison
This study employed a commercially available, non-invasive, fluorescence imaging system (Dyaderm, Biocam, Germany), to measure protoporphyrin IX (PpIX) concentration at several different stages during clinical dermatological methyl aminolevulinate photodynamic therapy (MAL-PDT). We validated the system prior to use to ensure that the PpIX changes witnessed were accurate and not due to environmental or user induced artifacts. The system was then employed to acquire color (morphological) and fluorescent (physiological) images simultaneously during dermatological PDT. Clinical data was collected from a range of licensed dermatological conditions (actinic keratosis, Bowen's disease and superficial basal cell carcinoma) during initial and subsequent PDT treatment cycles. The initial clinical data indicated that each type of licensed lesion considered responded in a similar manner following the application of Metvix (Galderma, U.K.) and the subsequent light irradiation (Aktilite, Galderma, U.K.). Images acquired three hours after Metvix application showed a significant increase in PpIX concentration within the lesion (P < 0.05), whilst PpIX levels in the surrounding normal tissue remained unaltered. After irradiation, the PpIX concentration was significantly decreased and returned to a level similar to the initial concentration originally observed. Lesions that received subsequent treatment cycles accumulated significantly less PpIX (P < 0.05) prior to irradiation.
Combination of PDT and topical angiogenic inhibitor for treatment of port wine stain (PWS) birthmarks: a novel approach
NASA Astrophysics Data System (ADS)
Yuan, Kaihua; Huang, Qiaobing; Huang, Zheng
Port wine stain (PWS) birthmarks are a congenital cutaneous vascular malformation involving ecstatic post-capillary venules. Current standard treatment for PWS is the pulsed dye laser (PDL). Vascular-targeted photodynamic therapy (PDT) has been used for the treatment of PWS in China since the early 1990's. Both can achieve a certain degree of color blanching in various types of PWS lesions. However, the majority of PWS lesions require multiple treatments. Some PWS lesions can recur or become darker after successful treatment. Recently, it has been proposed that this phenomenon might be initiated by neoangiogenesis that can be caused by treatment via wound healing response. The combined use of photothermolysis and a topical application of an angiogenic inhibitor such as Imiquimod and Rapamycin, were evaluated in several pilot studies. It is well-known that PDT can induce various host immune responses VEGF overexpression. Recent clinical data also show that improved clinical outcomes are obtained through the combination of ocular PDT and anti-VEGF therapy. This article will discuss rationales and implications of using such a combination modality and highlight recent progress based on our clinical experience and published data.
Tissue oxygen monitoring by photoacoustic lifetime imaging (PALI) and its application to image-guided photodynamic therapy (PDT)
NASA Astrophysics Data System (ADS)
Shao, Qi; Morgounova, Ekaterina; Ashkenazi, Shai
The oxygen partial pressure (pO2), which results from the balance between oxygen delivery and its consumption, is a key component of the physiological state of a tissue. Images of oxygen distribution can provide essential information for identifying hypoxic tissue and optimizing cancer treatment. Previously, we have reported a noninvasive in vivo imaging modality based on photoacoustic lifetime. The technique maps the excited triplet state of oxygen-sensitive dye, thus reflects the spatial and temporal distribution of tissue oxygen. We have applied PALI on tumor on small animals to identify hypoxia area. We also showed that PALI is able monitor changes of tissue oxygen, in an acute ischemia and breathing modulation model. Here we present our work on developing a treatment/imaging modality (PDT-PALI) that integrates PDT and a combined ultrasound/photoacoustic imaging system. The system provides real-time feedback of three essential parameters namely: tissue oxygen, light penetration in tumor location, and distribution of photosensitizer. Tissue oxygen imaging is performed by applying PALI, which relies on photoacoustic probing of oxygen-dependent, excitation lifetime of Methylene Blue (MB) photosensitizer. Lifetime information can also be used to generate image showing the distribution of photosensitizer. The level and penetration depth of PDT illumination can be deduced from photoacoustic imaging at the same wavelength. All images will be combined with ultrasound B-mode images for anatomical reference.
Application of Titanium Dioxide (TiO2) Nanoparticles in Photodynamic Therapy (PDT) of an Experimental Tumor
NASA Astrophysics Data System (ADS)
Miyoshi, Norio; Kume, Kyo; Tsutumi, Kotaro; Fukunaga, Yukihiro; Ito, Shinnji; Imamura, Yoshiaki; Bibin, Andriana B.
Nano-sized particles has been used for the photodynamic and sonodynamic treatments of pre-clinical cancer study in previous studies [1-7]. In this study, the 5-aminolevulinic acid (5-ALA) solution mixed with TiO2 nanoparticles was oral-administrated into the nude mouse transplanted under the skin with a human prostate cancer cell line. The experimental tumor model tissue (7×7×7 mm3) was measured of the size at different times after the photodynamic therapy (PDT) by laser to take a growth curve of the tumor. The treatment efficacy was jugged from the growth curves comparing different conditions. In the presence of the nanoparticle, the PDT treatment effect was enhanced those in the absence of the particles. Furthermore, the sonodynamic therapy (SDT) effect also enhanced with the nanoparticle to produce more OH radicals by ultrasound irradiation. These combination therapy of PDT and SDT with nanoparticles was very effectively resulted to be useful as a clinical use in future.
Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain
NASA Astrophysics Data System (ADS)
Rendon, Cesar A.; Lilge, Lothar
In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.
A Compact and High Performance Muon Capture Channel for Muon Accelerators
Stratakis, D.; Gallardo, J.; Palmer, R.B.
It is widely believed that a neutrino factory would deliver unparallel performance in studying neutrino mixing and would provide tremendous sensitivity to new physics in the neutrino sector. Here we will describe and simulate the front-end of the neutrino factory system, which plays critical role in determining the number of muons that can be accepted by the downstream accelerators. In this system, a proton bunch on a target creates secondaries that drift into a capture transport channel. A sequence of rf cavities forms the resulting muon beams into strings of bunches of differing energies, aligns the bunches to nearly equal central energies, and initiates ionization cooling. For this, the muon beams are transported through sections containing high-gradient cavities and strong focusing solenoids. In this paper we present results of optimization and variation studies toward obtaining the maximum number of muons for a neutrino factory by using a compact transport channel. It has been suggested computationally and experimentally that the maximum achievable gradient is enhanced by introducing an external magnetic field at right angles to the rf electric field since it suppresses field-emission processes. Here, we have discussed a possible scheme for extending the concept of magnetic insulation to capture, transport, and cool muons in a neutrino factory. We incorporated this idea into a new lattice design where the rf cavities are shaped so that their walls were tangential to the magnetic-field lines. We showed that, with magnetic insulation, the field-emitted electrons impact the cavity surface with energies four orders-of-magnitude less than in conventional pillbox cavities; consequently, damage from field-emission is suppressed significantly. While demanding in terms of power requirements, this neutrino factory lattice showed satisfactory performance in both cooling and collecting the accepted muons within the requirements for the IDSNF. Optimizations were also made
SuperB Muon Detector Prototype
Not Available
The test objective is to optimize the muon identification in an experiment at a Super B Factory. To accomplish this, experimenters will study the muon identification capability of a detector with different iron configurations at different beam energies. The detector is a full scale prototype, composed of a stack of iron tiles. The segmentation of the iron allows the study of different configurations. Between the tiles, one or two extruded scintillator slabs can be inserted to test two different readout options; a Binary Readout and a Time Readout. In the Binary Readout option the two coordinates are given by the two orthogonal scintillator bars, and the spatial resolution is driven by the bar width. In the Time Readout option one coordinate is determined by the scintillator position and the other by the arrival time of the signal read with a TDC.
Muon acceleration in cosmic-ray sources
Klein, Spencer R.; Mikkelsen, Rune E.; Becker Tjus, Julia
Many models of ultra-high energy cosmic-ray production involve acceleration in linear accelerators located in gamma-ray bursts, magnetars, or other sources. These transient sources have short lifetimes, which necessitate very high accelerating gradients, up to 10{sup 13} keV cm{sup –1}. At gradients above 1.6 keV cm{sup –1}, muons produced by hadronic interactions undergo significant acceleration before they decay. This muon acceleration hardens the neutrino energy spectrum and greatly increases the high-energy neutrino flux. Using the IceCube high-energy diffuse neutrino flux limits, we set two-dimensional limits on the source opacity and matter density, as a function of accelerating gradient. These limits put strong constraints on different models of particle acceleration, particularly those based on plasma wake-field acceleration, and limit models for sources like gamma-ray bursts and magnetars.
High luminosity muon scattering at FNAL
Bazizi, K. ); Conrad, J.; Fang, G. ); Erdmann, M. ); Geesaman, D.; Jackson, H. ); Guyot, C.; Virchaux, M. ); Holmgren, H. ); Malensek, A.; Melanson, H.; Morfin
The charge of this group was to evaluate the physics that can be done with a high luminosity {mu} scattering experiment at FNAL using the upgraded Tevatron muon beam, and consider the apparatus required. In this report, the physics that can be accomplished with a high luminosity {mu} scattering experiment is evaluated. The CERN and FNAL {mu} beams are compared in the context of such an experiment. The expected muon flux with the upgraded machine is estimated. Two possible detectors are compared: the air-core toroid experiment proposed by Guyot et al., and an upgraded version of the E665 double-diode apparatus now in place at FNAL. The relative costs of the detectors are considered. A list of detailed questions that need to be answered regarding the double-diode experiment has be compiled. 2 refs., 10 figs., 2 tabs.
Lithium lenses based muon cooling channel
Valeri I. Balbekov
A linear ionization cooling channel for neutrino factory or muon collider is considered. It includes short Li lenses, matching solenoids, and 201 MHz RF cavities. The basic challenge is a suppression of chromatic effects in a wide energy range typical for muon beams. A special lattice is proposed to reach this, and methodic of an optimization is developed to minimize the chromatic aberrations by suppression of several betatron resonances. The most engineering constraint is a high field of matching solenoids. A channel with less of 10 T field is considered in detail. It is capable to cool transverse emittance of a beam from 2-3 mm to 0.5 mm at the channel length of about 130 m. Because there is no emittance exchange, longitudinal emittance increases in the process from 10 to 20 mm at transmission of about 90%.
Muon RLA - design status and simulations
NASA Astrophysics Data System (ADS)
Beard, K. B.; Bogacz, S. A.; Morozov, V. S.; Roblin, Y. R.
The Neutrino Factory baseline design involves a complex chain of accelerators beginning with a linac. This first pre-linac follows the capture and bunching section and accelerates the muons from about 244 to 900 MeV and must accept a high emittance beam about 30 cm wide with a 10% energy spread. It uses counterwound, shielded superconducting solenoids and 201 MHz superconducting cavities, and currently consists of 24 3 m and 24 5 m long cryomodules. The next stage is a 1st dogbone-shaped RLA that takes the total energy from 900 MeV to 3.6 GeV in 4.5 passes, followed by a 2nd RLA that takes the energy from 3.6 to 12.6 GeV in 4.5 passes. Simulations are in progress to optimize the optics and determine the radiation loads from beam loss and muon decay.
The muon g - 2 and degenerate supersymmetry
NASA Astrophysics Data System (ADS)
Chowdhury, Debtosh; Patel, Ketan M.; Tata, Xerxes; Vempati, Sudhir K.
A degenerate supersymmetric particle spectrum can escape constraints from flavor physics and at the same time evade limits from the direct searches. If such a spectrum is light enough, it can also account for the observed value of the anomalous magnetic moment of the muon. Inspired by this, we consider a scenario where all the soft terms have approximately a common mass scale while allowing for small splittings. We study this scenario considering the constraints from Higgs mass, various B meson decays and the dark matter relic density. We find that, with superpartners ~ 800 - 1000 GeV, it is still possible to escape the present limits from the first run of LHC and flavor physics and can account for muon g - 2 within 2σ.
Helical Muon Beam Cooling Channel Engineering Design
Kashikhin, V.S.; Lopes, M.L.; Romanov, G.V.; Tartaglia, M.A.; Yonehara, K.; Yu, M.; Zlobin, A.V.; Flanagan, G.; Johnson, R.P.; Kazakevich, G.M.; Marhauser, F.; /MUONS Inc., Batavia
The Helical Cooling Channel (HCC), a novel technique for six-dimensional (6D) ionization cooling of muon beams, has shown considerable promise based on analytic and simulation studies. However, the implementation of this revolutionary method of muon cooling requires new techniques for the integration of hydrogen-pressurized, high-power RF cavities into the low-temperature superconducting magnets of the HCC. We present the progress toward a conceptual design for the integration of 805 MHz RF cavities into a 10 T Nb{sub 3}Sn based HCC test section. We include discussions on the pressure and thermal barriers needed within the cryostat to maintain operation of the magnet at 4.2 K while operating the RF and energy absorber at a higher temperature. Additionally, we include progress on the Nb{sub 3}Sn helical solenoid design.
Underground muons from Cygnus X-3
Price, L.E.
Underground detectors, intended for searches for nucleon decay and other rare processes, have recently begun searching for evidence of astrophysical sources, particularly Cygnus X-3, in the cosmic ray muons they record. Some evidence for signals from Cygnus X-3 has been reported. The underground observations are reported here in the context of previous (surface) observations of the source at high energies. 25 refs., 8 figs.
Recent results from COMPASS muon scattering measurements
Capozza, Luigi [Irfu Collaboration: COMPASS Collaboration
A sample of recent results in muon scattering measurements from the COMPASS experiment at CERN will be reviewed. These include high energy processes with longitudinally polarised proton and deuteron targets. High energy polarised measurements provide important constraints for studying the nucleon spin structure and thus permit to test the applicability of the theoretical framework of factorisation theorems and perturbative QCD. Specifically, latest results on longitudinal quark polarisation, quark helicity densities and gluon polarisation will be reviewed.
Analytical calculation of muon intensities under deep sea-water
NASA Technical Reports Server (NTRS)
Inazawa, H.; Kobayakawa, K.
The study of the energy loss of high energy muons through different materials, such as rock and sea-water can cast light on characteristics of lepton interactions. There are less ambiguities for the values of atomic number (Z) and mass number (A) in sea-water than in rock. Muon intensities should be measured as fundamental data and as background data for searching the fluxes of neutrino. The average range energy relation in sea-water is derived. The correction factors due to the range fluctuation is also computed. By applying these results, the intensities deep under sea are converted from a given muon energy spectra at sea-level. The spectra of conventional muons from eta, K decays have sec theta enhancement. The spectrum of prompt muons from charmed particles is almost isotropic. The effect of prompt muons is examined.
Seasonal modulations of the underground cosmic-ray muon energy
Malgin, A. S.
The parameters of the seasonal modulations in the intensity of muons and cosmogenic neutrons generated by them at a mean muon energy of 280 GeV have been determined in the LVD (Large Volume Detector) experiment. The modulations of muons and neutrons are caused by a temperature effect, the seasonal temperature and density variations of the upper atmospheric layers. The analysis performed here leads to the conclusion that the variations in the mean energy of the muon flux are the main source of underground cosmogenic neutron variations, because the energy of muons is more sensitive to the temperature effect than their intensity. The parameters of the seasonal modulations in the mean energy of muons and the flux of cosmogenic neutrons at the LVD depth have been determined from the data obtained over seven years of LVD operation.
SSC detector muon sub-system beam tests
Downing, R.; Errede, S.; Gauthier, A.; Haney, M.; Karliner, I.; Liss, T.; O`Halloran, T.; Sheldon, P.; Simiatis, V.; Thaler, J.; Wiss, J.; Green, D.; Martin, P.; Morfin, J.; Kunori, S.; Skuja, A.; Okusawa, T.; Takahashi, T.; Teramoto, Y.; Yoshida, T.; Asano, Y.; Mann, T.; Davisson, R.; Liang, G.; Lubatti, H.; Wilkes, R.; Zhao, T.; Carlsmith, D.
We propose to start a test-beam experiment at Fermilab studying the problems associated with tracking extremely high energy muons through absorbers. We anticipate that in this energy range the observation of the muons will be complicated by associated electromagnetic radiation Monte Carlo simulations of this background need to be tuned by direct observations. These beam tests are essential to determine important design parameters of a SSC muon detector, such as the choice of the tracking, geometry, hardware triggering schemes, the number of measuring stations, the amount of iron between measuring stations, etc. We intend to begin the first phase of this program in November of 1990 utilizing the Tevatron muon beam. We plan to measure the multiplicity, direction, and separation of secondary particles associated with the primary muon track as it emerges from an absorber. The second phase of beam test in 1992 or later will be a full scale test for the final design chosen in our muon subsystem proposal.
Muon g-2 Experiment at Fermilab
Gray, Frederick
A new experiment at Fermilab will measure the anomalous magnetic moment of the muon with a precision of 140 parts per billion (ppb). This measurement is motivated by the results of the Brookhaven E821 experiment that were first released more than a decade ago, which reached a precision of 540 ppb. As the corresponding Standard Model predictions have been refined, the experimental and theoretical values have persistently differed by about 3 standard deviations. If the Brookhaven result is confirmed at Fermilab with this improved precision, it will constitute definitive evidence for physics beyond the Standard Model. The experiment observes the muon spin precession frequency in flight in a well-calibrated magnetic fi eld; the improvement in precision will require both 20 times as many recorded muon decay events as in E821 and a reduction by a factor of 3 in the systematic uncertainties. This paper describes the current experimental status as well as the plans for the upgraded magnet, detector and storage ring systems that are being prepared for the start of beam data collection in 2017.
Next Generation Muon g-2 Experiments
Hertzog, David W.
I report on the progress of two new muon anomalous magnetic moment experiments, which are in advanced design and construction phases. The goal of Fermilab E989 is to reduce the experimental uncertainty of $a_\\mu$ from Brookhaven E821 by a factor of 4; that is, $\\delta a_\\mu \\sim 16 \\times 10^{-11}$, a relative uncertainty of 140~ppb. The method follows the same magic-momentum storage ring concept used at BNL, and pioneered previously at CERN, but muon beam preparation, storage ring internal hardware, field measuring equipment, and detector and electronics systems are all new or upgraded significantly. In contrast, J-PARC E34 will employ a novel approach based on injection of an ultra-cold, low-energy, muon beam injected into a small, but highly uniform magnet. Only a small magnetic focusing field is needed to maintain storage, which distinguishes it from CERN, BNL and Fermilab. E34 aims to roughly match the previous BNL precision in their Phase~1 installation.
Muon Beam Helical Cooling Channel Design
Johnson, Rolland; Ankenbrandt, Charles; Flanagan, G; Kazakevich, G M; Marhauser, Frank; Neubauer, Michael; Roberts, T; Yoshikawa, C; Derbenev, Yaroslav; Morozov, Vasiliy; Kashikhin, V S; Lopes, Mattlock; Tollestrup, A; Yonehara, Katsuya; Zloblin, A
The Helical Cooling Channel (HCC) achieves effective ionization cooling of the six-dimensional (6d) phase space of a muon beam by means of a series of 21st century inventions. In the HCC, hydrogen-pressurized RF cavities enable high RF gradients in strong external magnetic fields. The theory of the HCC, which requires a magnetic field with solenoid, helical dipole, and helical quadrupole components, demonstrates that dispersion in the gaseous hydrogen energy absorber provides effective emittance exchange to enable longitudinal ionization cooling. The 10-year development of a practical implementation of a muon-beam cooling device has involved a series of technical innovations and experiments that imply that an HCC of less than 300 m length can cool the 6d emittance of a muon beam by six orders of magnitude. We describe the design and construction plans for a prototype HCC module based on oxygen-doped hydrogen-pressurized RF cavities that are loaded with dielectric, fed by magnetrons, and operate in a superconducting helical solenoid magnet.
Recent Innovations in Muon Beam Cooling
Johnson, Rolland P.; Alsharo'a, Mohammad; Hanlet, Pierrick M.; Hartline, Robert; Kuchnir, Moyses; Paul, Kevin; Roberts, Thomas J.; Ankenbrandt, Charles; Barzi, Emanuela; Del Frate, Licia; Gonin, Ivan; Moretti, Alfred; Neuffer, David; Popovic, Milorad; Romanov, Gennady; Turrioni, Daniele; Yarba, Victor; Beard, Kevin; Bogacz, S. Alex; Derbenev, Yaroslav
Eight new ideas are being developed under SBIR/STTR grants to cool muon beams for colliders, neutrino factories, and muon experiments. Analytical and simulation studies have confirmed that a six-dimensional (6D) cooling channel based on helical magnets surrounding RF cavities filled with dense hydrogen gas can provide effective beam cooling. This helical cooling channel (HCC) has solenoidal, helical dipole, helical quadrupole, and helical sextupole magnetic fields to generate emittance exchange and achieve 6D emittance reduction of over 3 orders of magnitude in a 100 m segment. Four such sequential HCC segments, where the RF frequencies are increased and transverse physical dimensions reduced as the beams become cooler, implies a 6D emittance reduction of almost five orders of magnitude. Two new cooling ideas, Parametric-resonance Ionization Cooling and Reverse Emittance Exchange, then can be employed to reduce transverse emittances to a few mm-mr, which allows high luminosity with fewer muons than previously imagined. We describe these new ideas as well as a new precooling idea based on a HCC with z dependent fields that can be used as MANX, an exceptional 6D cooling demonstration experiment.
Next Generation Muon g - 2 Experiments
NASA Astrophysics Data System (ADS)
Hertzog, David W.
I report on the progress of two new muon anomalous magnetic moment experiments, which are in advanced design and construction phases. The goal of Fermilab E989 is to reduce the experimental uncertainty of aμ from Brookhaven E821 by a factor of 4; that is, δaμ ˜ 16 × 10-11, a relative uncertainty of 140 ppb. The method follows the same magic-momentum storage ring concept used at BNL, and pioneered previously at CERN, but muon beam preparation, storage ring internal hardware, field measuring equipment, and detector and electronics systems are all new or upgraded significantly. In contrast, J-PARC E34 will employ a novel approach based on injection of an ultra-cold, low-energy, muon beam injected into a small, but highly uniform magnet. Only a small magnetic focusing field is needed to maintain storage, which distinguishes it from CERN, BNL and Fermilab. E34 aims to roughly match the previous BNL precision in their Phase 1 installation.
Recent Innovations in Muon Beam Cooling
Rolland P. Johnson; Mohammad Alsharo'a; Charles Ankenbrandt; Emanuela Barzi; Kevin Beard; S. Alex Bogacz; Yaroslav Derbenev; Licia Del Frate; Ivan Gonin; Pierrick M. Hanlet; Robert Hartline; Daniel M. Kaplan; Moyses Kuchnir; Alfred Moretti; David Neuffer; Kevin Paul; Milorad Popovic; Thomas J. Roberts; Gennady Romanov; Daniele Turrioni; Victor Yarba; and Katsuya Yonehara
Eight new ideas are being developed under SBIR/STTR grants to cool muon beams for colliders, neutrino factories, and muon experiments. Analytical and simulation studies have confirmed that a six-dimensional (6D) cooling channel based on helical magnets surrounding RF cavities filled with dense hydrogen gas can provide effective beam cooling. This helical cooling channel (HCC) has solenoidal, helical dipole, helical quadrupole, and helical sextupole magnetic fields to generate emittance exchange and achieve 6D emittance reduction of over 3 orders of magnitude in a 100 m segment. Four such sequential HCC segments, where the RF frequencies are increased and transverse physical dimensions reduced as the beams become cooler, implies a 6D emittance reduction of almost five orders of magnitude. Two new cooling ideas, Parametric-resonance Ionization Cooling and Reverse Emittance Exchange, then can be employed to reduce transverse emittances to a few mm-mr, which allows high luminosity with fewer muons than previously imagined. We describe these new ideas as well as a new precooling idea based on a HCC with z dependent fields that can be used as MANX, an exceptional 6D cooling demonstration experiment.
Advances in Beam Cooling for Muon Colliders
R.P. Johnson, Y.S. Derbenev
A six-dimensional (6D) ionization cooling channel based on helical magnets surrounding RF cavities filled with dense hydrogen gas is the basis for the latest plans for muon colliders. This helical cooling channel (HCC) has solenoidal, helical dipole, and helical quadrupole magnetic fields, where emittance exchange is achieved by using a continuous homogeneous absorber. Momentum-dependent path length differences in the dense hydrogen energy absorber provide the required correlation between momentum and ionization loss to accomplish longitudinal cooling. Recent studies of an 800 MHz RF cavity pressurized with hydrogen, as would be used in this application, show that the maximum gradient is not limited by a large external magnetic field, unlike vacuum cavities. Two new cooling ideas, Parametric-resonance Ionization Cooling and Reverse Emittance Exchange, will be employed to further reduce transverse emittances to a few mm-mr, which allows high luminosity with fewer muons than previously imagined. We describe these new ideas as well as a new precooling idea based on a HCC with z dependent fields that is being developed for an exceptional 6D cooling demonstration experiment. The status of the designs, simulations, and tests of the cooling components for a high luminosity, low emittance muon collider will be reviewed.
Applications of Cosmic Ray Muon Radiography
NASA Astrophysics Data System (ADS)
Guardincerri, E.; Durham, J. M.; Morris, C. L.; Rowe, C. A.; Poulson, D. C.; Bacon, J. D.; Plaud-Ramos, K.; Morley, D. J.
The Dome of Santa Maria del Fiore, Florence Cathedral, was built between 1420 and 1436 by architect Filippo Brunelleschi and it is now cracking under its own weight. Engineering efforts are underway to model the dome's structure and reinforce it against further deterioration. According to some scholars, Brunelleschi might have built reinforcement structures into the dome itself; however, the only confirmed known subsurface reinforcement is a chain of iron and stone around the dome's base. Tomography with cosmic ray muons is a non-destructive imaging method that can be used to image the interior of the wall and therefore ascertain the layout and status of any iron substructure in the dome. We will show the results from a muon tomography measurement of iron hidden in a mockup of the dome's wall performed at Los Alamos National Lab in 2015. The sensitivity of this technique, and the status of this project will be also discussed. At last, we will show results on muon attenuation radiography of larger shallow targets.
The Muon Detector at the HERA-B experiment
NASA Astrophysics Data System (ADS)
Eiges, V.; Fominykh, B.; Khasanov, F.; Kvaratscheliia, T.; Laptin, L.; Tchoudakov, V.; Tichomirov, I.; Titov, M.; Zaitsev, Yu.; Buchler, M.; Harr, R. F.; Karchin, P. E.; Nam, S.; Shiu, J. G.; Gilitsky, Yu.; Takach, S. F.
The HERA-B experiment is designed to study beauty particle production and decay using the HERA 920 GeV proton beam interactions with an internal target. The Muon detector provides identification for muons having momenta greater than 5 GeV/c and triggering on the muon pair from J/ ψ decay. Three different chamber types are employed for operation in a high-rate environment. The overall design, performance and current status are discussed.
Superconducting magnets for muon capture and phase rotation
Green, M.A.; Weggel, R.J.
There are two key systems that must operate efficiently, in order for a muon collider to be a viable option for high energy physics. These systems are the muon production and collection system and the muon cooling system. Both systems require the use of high field superconducting solenoid magnets. This paper describes the supcrconducting solenoid system used for the capture and phase rotation of the pions that are produced on a target in a high intensity proton beam.
Muons in Air Showers at the Pierre Auger Observatory
NASA Astrophysics Data System (ADS)
Unger, M.
We present measurements of muons in air showers at ultra-high energies with the Pierre Auger Observatory. The number of muons at the ground in air showers detected at large zenith angles is determined as a function of energy and the results are compared to air shower simulations. Furthermore, using data collected at zenith angles smaller than 60°, rescaling factors are derived that quantify the deficit of muon production in air shower simulations.
RF system concepts for a muon cooling experiment
Turner, W.C.; Corlett, J.N.; Li, D.; Moretti, A.; Kirk, H.G.; Palmer, R.B.; Zhao, Y.
The feasibility of muon colliders for high energy physics experiments has been under intensive study for the past few years and recent activity has focused on defining an R and D program that would answer the critical issues. An especially critical issue is developing practical means of cooling the phase space of the muons once they have been produced and captured in a solenoidal magnetic transport channel. Concepts for the rf accelerating cavities of a muon cooling experiment are discussed.
Jet production in muon scattering at Fermilab E665
Salgado, C.W.; E665 Collaboration
Measurements of multi-jet production rates from Muon-Nucleon and Muon-Nuclei scattering at Fermilab-E665 are presented. Jet rates are defined by the JADE clustering algorithm. Rates in Muon-Nucleon deep-inelastic scattering are compared to Monte Carlo model predictions. Preliminary results from jet production on heavy targets, in the shadowing region, show a higher suppression of two-forward jets as compared to one-forward jet production.
Muon Cooling R&D Progress in the US
NASA Astrophysics Data System (ADS)
Li, Derun
Muon ionization cooling R&D is important for a neutrino factory and future muon collider. In addition to theoretical studies, much progress has been made in muon cooling channel hardware R&D since NuFact-2006. This paper reports the progress on hardware R&D that includes experimental RF test programs using 805-MHz RF cavity, superconducting (SC) solenoids (coupling coils), 201-MHz RF cavity, liquid hydrogen absorber and MUCOOL Test Area (MTA) experiment preparation for beam tests.
An OPERA-3D Model of Muon Injection in the Muon g - 2 Storage Ring
NASA Astrophysics Data System (ADS)
Vallina, Lia
The muon g - 2 experiment at Fermilab will measure the anomalous magnetic moment of the muon to 140 parts-per-billion. The modern experimental technique utilizes a superconducting storage ring to produce an extremely uniform magnetic field. Since the experimental systematic uncertainties scales with the non-uniformity of the magnetic field, care must be taken to minimize distortions to the field. The injection point of the muon beam into the storage ring requires special attention. In this talk, the experimental concept and the use of a superconducting inflector magnet at the injection point will be outlined. Our efforts to model this critical region in the electromagnetic simulation software, OPERA, will be described.
Muon Bunching and Phase-Energy Rotation for a Neutrino Factory and Muon Collider
NASA Astrophysics Data System (ADS)
Neuffer, David; Yoshikawa, Cary
We have developed scenarios for capture, bunching and phase-energy rotation of muons from a proton source, using high-frequency rf systems. The method captures a maximal number of muons into a string of rf bunches with initial application in the neutrino factory design studies. For a muon collider, these bunches must be recombined for maximal luminosity, and our initial design produced a relatively long bunch train. In this paper we present more compact scenarios that obtain a smaller number of bunches, and, after some optimization, obtain cases that are better for both neutrino-factory and collider scenarios. We also consider further modification by incorporating hydrogen gas-filled rf cavities for bunching and cooling. We describe these examples and consider variations toward an optimal factory + collider scenario.
Muon dynamics in superprotonic conductors
NASA Astrophysics Data System (ADS)
Ikedo, Yutaka; Sugiyama, Jun; Nozaki, Hiroshi; Nishiyama, Kusuo; Matsuo, Yasumitsu; Lord, James S.
In order to clarify the mechanism of high proton conductivity ( σ) for superprotonic conductors, MHXO4, where M=Cs and Rb, X=S and Se, μ+SR experiments have been performed in the temperature range between 250 and 450 K using single crystal samples. Here, MHXO4 exhibits extraordinary high σ at T above its structural phase transition ( Tc=414 K for CsHSO4) from a low- T monoclinic phase (Phase II) to a high- T tetragonal phase (Phase I). Since the asymmetry of weak transverse field (wTF) spectrum does not reach its maximum at ambient T, muonium (Mu) state is found to exist in both CsHSO4 and CsHSeO4. The Mu fraction in wTF spectrum for CsHSO4 is still a finite value even in Phase I, while the Mu state disappears in Phase I of CsHSeO4. The longitudinal field μ+SR measurements for observing the Mu state and its dynamics in CsHSO4, show fast Mu diffusion and the conversion from Mu to diamagnetic μ+ in whole T range measured. Considering the fact that the σ in Phase I of CsHSO4 is about 10 times larger than that of CsHSeO4, the Mu formation in Phase I implies the presence of the atomic hydrogen state and play a possible crucial role for the high σ in Phase I of CsHSO4.
Toroidal magnetic detector for high resolution measurement of muon momenta
Bonanos, Peter
A muon detector system including central and end air-core superconducting toroids and muon detectors enclosing a central calorimeter/detector. Muon detectors are positioned outside of toroids and all muon trajectory measurements are made in a nonmagnetic environment. Internal support for each magnet structure is provided by sheets, located at frequent and regularly spaced azimuthal planes, which interconnect the structural walls of the toroidal magnets. In a preferred embodiment, the shape of the toroidal magnet volume is adjusted to provide constant resolution over a wide range of rapidity.
Toroidal magnetic detector for high resolution measurement of muon momenta
Bonanos, P.
A muon detector system including central and end air-core superconducting toroids and muon detectors enclosing a central calorimeter/detector. Muon detectors are positioned outside of toroids and all muon trajectory measurements are made in a nonmagnetic environment. Internal support for each magnet structure is provided by sheets, located at frequent and regularly spaced azimuthal planes, which interconnect the structural walls of the toroidal magnets. In a preferred embodiment, the shape of the toroidal magnet volume is adjusted to provide constant resolution over a wide range of rapidity. 4 figs.
Multiple muons of conventional and exotic origin in DUMAND
NASA Technical Reports Server (NTRS)
Grieder, K. F.
A first summary of results from a theoretical analysis, based on hadron - muon cascade calculations, that yield relative intensities of very high energy multiple muons originating from ultra high energy interactions initiated by primary protons and iron nuclei in the atmosphere, under consideration of normal as well as direct and exotic production channels is presented. Lateral density distributions and target diagrams will be presented which show that only very large detectors, such as DUMAND, will be able to record multiple muons of conventional origin reliably. This, however, is a prerequisite for any primary mass determination based on multiple muon data.
Asymmetry of Charge Ratio for Low Energetic Muons
Mitrica, Bogdan
The WILLI calorimeter, installed in NIPNE Bucharest, is operated since several years for measuring charge ratio of atmospheric muons at low energies (E<1 GeV), particularly exploring its directional dependence. Measurements of the muon flux are compared with Monte-Carlo simulation with CORSIKA code. Recently WILLI detector is proposed to get extended with a by mini-array of 12 scintillators (WILLI-EAS) in order to measure muon charge ratio of the muon density of EAS lateral distributions. Experimental studies of this kind could provide detailed information on the shower development under the influence of the geomagnetic field and also on features of the hadronic interaction.
Cosmic muon flux measurements at the Kimballton Underground Research Facility
NASA Astrophysics Data System (ADS)
Kalousis, L. N.; Guarnaccia, E.; Link, J. M.; Mariani, C.; Pelkey, R.
In this article, the results from a series of muon flux measurements conducted at the Kimballton Underground Research Facility (KURF), Virginia, United States, are presented. The detector employed for these investigations, is made of plastic scintillator bars readout by wavelength shifting fibers and multianode photomultiplier tubes. Data was taken at several locations inside KURF, spanning rock overburden values from ~ 200 to 1450 m.w.e. From the extracted muon rates an empirical formula was devised, that estimates the muon flux inside the mine as a function of the overburden. The results are in good agreement with muon flux calculations based on analytical models and MUSIC.
A complete scheme for production and cooling a muon beam for three specified muon colliders is presented. Parameters for these muon colliders are given. The scheme starts with the front end of a proposed neutrino factory that yields bunch trains of both muon signs. Emittance exchange cooling in slow helical lattices reduces the longitudinal emittance until it becomes possible to merge the trains into single bunches, one of each sign. Further cooling in all dimensions is applied to the single bunches in further slow helical lattices. Final transverse cooling to the required parameters is achieved in 50 T solenoids using high TC superconductor at 4 K. Preliminary simulations of each element are presented.
Muon SR Newsletter, No. 29, April 5, 1984
Crowe, K.M.; Portis, A.M.; Yamazaki, T.
Muon SR stands for Muon Spin Relaxation, Rotation, Resonance, Research, or what have you. The intention of the mnemonic acronym is to draw attention to the analogy with NMR and ESR, the range of whose applications is well known. Any study of the interactions of the muon spin by virtue of the asymmetric decay is considered ..mu..SR, but this definition is not intended to exclude any peripherally related phenomena, especially if relevant to the use of the muon's mganetic moment as a delicate probe of matter. Abstracts of individual items from this issue were prepared separately for the data base.
Measurement of cosmic-ray muons and muon-induced neutrons in the Aberdeen Tunnel Underground Laboratory
NASA Astrophysics Data System (ADS)
Blyth, S. C.; Chan, Y. L.; Chen, X. C.; Chu, M. C.; Cui, K. X.; Hahn, R. L.; Ho, T. H.; Hsiung, Y. B.; Hu, B. Z.; Kwan, K. K.; Kwok, M. W.; Kwok, T.; Lau, Y. P.; Leung, J. K. C.; Leung, K. Y.; Lin, G. L.; Lin, Y. C.; Luk, K. B.; Luk, W. H.; Ngai, H. Y.; Ngan, S. Y.; Pun, C. S. J.; Shih, K.; Tam, Y. H.; Tsang, R. H. M.; Wang, C. H.; Wong, C. M.; Wong, H. L. H.; Wong, K. K.; Yeh, M.; Zhang, B. J.; Aberdeen Tunnel Experiment Collaboration
We have measured the muon flux and production rate of muon-induced neutrons at a depth of 611 m water equivalent. Our apparatus comprises three layers of crossed plastic scintillator hodoscopes for tracking the incident cosmic-ray muons and 760 L of a gadolinium-doped liquid scintillator for producing and detecting neutrons. The vertical muon intensity was measured to be Iμ=(5.7 ±0.6 )×10-6 cm-2 s-1 sr-1 . The yield of muon-induced neutrons in the liquid scintillator was determined to be Yn=(1.19 ±0.08 (stat)±0.21 (syst))×10-4 neutrons /(μ .g .cm-2 ) . A fit to the recently measured neutron yields at different depths gave a mean muon energy dependence of ⟨Eμ⟩ 0.76 ±0.03 for liquid-scintillator targets.
Measurement of cosmic-ray muons and muon-induced neutrons in the Aberdeen Tunnel Underground Laboratory
Yeh, M.; Chan, Y. L.; Chen, X. C.; Chu, M. C.; Cui, K. X.; Hahn, R. L.; Ho, T. H.; Hsiung, Y. B.; Hu, B. Z.; Kwan, K. K.; et al
In this study, we have measured the muon flux and production rate of muon-induced neutrons at a depth of 611 m water equivalent. Our apparatus comprises three layers of crossed plastic scintillator hodoscopes for tracking the incident cosmic-ray muons and 760 L of a gadolinium-doped liquid scintillator for producing and detecting neutrons. The vertical muon intensity was measured to be Iμ = (5.7±0.6)×10–6 cm–2 s–1 sr–1. The yield of muon-induced neutrons in the liquid scintillator was determined to be Yn = (1.19 ± 0.08(stat) ± 0.21(syst)) × 10–4 neutrons/(μ•g•cm–2). A fit to the recently measured neutron yields at different depthsmore » gave a mean muon energy dependence of < Eμ >0.76±0.03 for liquid-scintillator targets.« less
Density dependent stopping power and muon sticking in muon catalyzed D-T fusion
Rafelski, H.E.; Mueller, B.
The origin of the experimentally observed (1) density dependence of the muon alpha sticking fraction ..omega../sub s/ in muon catalyzed deuterium- tritium fusion is investigated. We show that the reactivation probability depends sensitively on the target stopping power at low ion velocities. The density dependence of the stopping power for a singly charged projectile in liquid heavy hydrogen is parametrized to simulate possible screening effects and a density dependent effective ionization potential. We find that, in principle, a description of the measured density dependence is possible, but the required parameters appear too large. Also, the discrepancy with observed (He..mu..) X-ray data widens.
Studies on Muon Induction Acceleration and an Objective Lens Design for Transmission Muon Microscope
NASA Astrophysics Data System (ADS)
Artikova, Sayyora; Yoshida, Mitsuhiro; Naito, Fujio
Muon acceleration will be accomplished by a set of induction cells, where each increases the energy of the muon beam by an increment of up to 30 kV. The cells are arranged in a linear way resulting in total accelerating voltage of 300 kV. Acceleration time in the linac is about hundred nanoseconds. Induction field calculation is based on an electrostatic approximation. Beam dynamics in the induction accelerator is investigated and final beam focusing on specimen is realized by designing a pole piece lens.
The Muon Portal Project: A large-area tracking detector for muon tomography
NASA Astrophysics Data System (ADS)
Riggi, F.
The Muon Portal Project [1] is a joint initiative between research and industrial partners, aimed at the construction of a real size detector protoype to search for hidden high-Z fissile materials inside containers by the muon scattering technique. The detector is based on a set of 48 detection modules (1 m × 3 m), so as to provide four X-Y detection planes, two placed above and two below the container to be inspected. After a research and development phase, which led to the choice and test of the individual components, the construction of the full size detector has already started and will be completed in a few months.
Helical muon beam cooling channel engineering design
Johnson, Rolland
The Helical Cooling Channel (HCC) achieves effective ionization cooling of the six-dimensional (6d) phase space of a muon beam by means of a series of 21st century inventions. In the HCC, hydrogen-pressurized RF cavities enable high RF gradients in strong external magnetic fields. The theory of the HCC, which requires a magnetic field with solenoid, helical dipole, and helical quadrupole components, demonstrates that dispersion in the gaseous hydrogen energy absorber provides effective emittance exchange to enable longitudinal ionization cooling. The 10-year development of a practical implementation of a muon-beam cooling device has involved a series of technical innovations and experiments that imply that an HCC of less than 300 m length can cool the 6d emittance of a muon beam by six orders of magnitude. We describe the design and construction plans for a prototype HCC module based on oxygen-doped hydrogen-pressurized RF cavities that are loaded with dielectric, fed by magnetrons, and operate in a superconducting helical solenoid magnet. The first phase of this project saw the development of a conceptual design for the integration of 805 MHz RF cavities into a 10 T Nb3Sn based HS test section. Two very novel ideas are required to realize the design. The first idea is the use of dielectric inserts in the RF cavities to make them smaller for a given frequency so that the cavities and associated plumbing easily fit inside the magnet cryostat. Calculations indicate that heat loads will be tolerable, while RF breakdown of the dielectric inserts will be suppressed by the pressurized hydrogen gas. The second new idea is the use of a multi-layer Nb3Sn helical solenoid. The technology demonstrations for the two aforementioned key components of a 10T, 805 MHz HCC were begun in this project. The work load in the Fermilab Technical Division made it difficult to test a multi-layer Nb3Sn solenoid as originally planned. Instead, a complementary project was approved by the DOE
Measurement of muon g-2 and EDM with an ultra-cold muon beam at J-PARC
NASA Astrophysics Data System (ADS)
Mibe, Tsutomu; J-PARC g-2 Collaboration
A new measurement of the anomalous magnetic moment ( g-2) and electric dipole moment (EDM) of the positive muon is proposed with a novel technique utilizing an ultra-cold muons accelerated to 300 MeV/c and a 66 cm-diameter compact muon storage ring without focusing-electric field. It requires an intense source of muonium to achieve the design intensity of the ultra-cold muon beam. Test experiments at TRIUMF aims to measure the muonium production rate as well as its space-time distribution in the vacuum for the development of the intense muonium source.
Lorentz structure of weak current in ν interactions and inverse muon decay
NASA Astrophysics Data System (ADS)
Mishra, Sanjib R.
Neutrino interactions uniquely convey the Lorentz structure of weak current. Two studies that probe this structure are reviewed: structure functions from νμ -and ν μ - induced charged current events; and the inverse muon decay process, νμ+e -→ μ-+ νe. In the first study, the relative absence of νμ-induced charged current events with respect to νμ-induced events at large z (> 0.45) and large y (> 0.70) (investigated by CDHS and CCFR) restricts |η| 2 = |g R/g L| 2 < 0.0015 with 90 % CL (CCFR). Within the framework of left-right symmetric models, this measurement imposes a limit upon the mixing angle of the left and right handed bosons. Unlike the limits imposed by the μ-decay and the nuclear β-decay experiments, the present limit is valid irrespective of the mass of the right handed neutrino. In the second study, recent high statistics measurements of inverse muon decay by CCFR and CHARM II yield a total cross section, σ( νμ+e -→ μ-+ νe) = (17.3±0.72(stat)±0.39(syst)]E ν10 -42 cm 2/GeV. This restricts the scalar coupling of the muon | gLLS| < 0.25 with 90% CL.
Precise determination of muon and electromagnetic shower contents from a shower universality property
Yushkov, A.; Ambrosio, M.; Aramo, C.; D'Urso, D.; Valore, L.; Guarino, F.
We consider two new aspects of extensive air shower development universality allowing to make an accurate estimation of muon and electromagnetic (EM) shower contents in two independent ways. In the first case, to get the muon (or EM) signal in water Cherenkov tanks or in scintillator detectors, it is enough to know the vertical depth of the shower maximum X{sub max}{sup v} and the total signal in the ground detector. In the second case, the EM signal can be calculated from the primary particle energy and the zenith angle. In both cases, the parametrizations of muon and EM signals are almost independent on the primary particle nature, energy and zenith angle. Implications of the considered properties for mass composition and hadronic interaction studies are briefly discussed. The present study is performed on 28 000 proton, oxygen, and iron showers, generated with CORSIKA 6.735 for the E{sup -1} spectrum in the energy range lg (E/eV)=18.5-20 and uniformly distributed in cos{sup 2{theta}} in the zenith angle interval {theta}=0 deg. - 65 deg. for QGSJET II/Fluka interaction models.