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18F-Labeling Using Click Cycloadditions
Ross, Tobias L.
Due to expanding applications of positron emission tomography (PET) there is a demand for developing new techniques to introduce fluorine-18 (t1/2 = 109.8 min). Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of 18F in those molecules poses an exceeding challenge. Two major challenges during 18F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel 18F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click 18F-cycloadditions. PMID:25003110
One-step (18)F labeling of biomolecules using organotrifluoroborates.
Liu, Zhibo; Lin, Kuo-Shyan; Bénard, François; Pourghiasian, Maral; Kiesewetter, Dale O; Perrin, David M; Chen, Xiaoyuan
Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous (18)F fluoride ((18)F(-)) and used for positron emission tomography (PET) imaging. Among the β(+)-emitting radionuclides, fluorine-18 ((18)F) is the isotope of choice for PET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be (18)F-labeled in one step in aqueous conditions via (18)F-(19)F isotope exchange. This protocol features a recently designed ammoniomethyltrifluoroborate, and it describes the following: (i) a synthetic strategy that affords modular synthesis of radiolabeling precursors via a copper-catalyzed 'click' reaction; and (ii) a one-step (18)F-labeling method that obviates the need for HPLC purification. Within 30 min, (18)F-labeled PET imaging probes, such as peptides, can be synthesized in good chemical and radiochemical purity (>98%), satisfactory radiochemical yield of 20-35% (n > 20, non-decay corrected) and high specific activity of 40-111 GBq/μmol (1.1-3.0 Ci/μmol). The entire procedure, including the precursor preparation and (18)F radiolabeling, takes 7-10 d. PMID:26313478
18F-Labelled Intermediates for Radiosynthesis by Modular Build-Up Reactions: Newer Developments
Ermert, Johannes
This brief review gives an overview of newer developments in 18F-chemistry with the focus on small 18F-labelled molecules as intermediates for modular build-up syntheses. The short half-life (<2 h) of the radionuclide requires efficient syntheses of these intermediates considering that multistep syntheses are often time consuming and characterized by a loss of yield in each reaction step. Recent examples of improved synthesis of 18F-labelled intermediates show new possibilities for no-carrier-added ring-fluorinated arenes, novel intermediates for tri[18F]fluoromethylation reactions, and 18F-fluorovinylation methods. PMID:25343144
Convergent synthesis and evaluation of 18F-labeled azulenic COX2 probes for cancer imaging
Nolting, Donald D.; Nickels, Michael; Tantawy, Mohammed N.; Yu, James Y. H.; Xie, Jingping; Peterson, Todd E.; Crews, Brenda C.; Marnett, Larry; Gore, John C.; Pham, Wellington
The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and
Enhanced Aqueous Suzuki–Miyaura Coupling Allows Site-Specific Polypeptide 18F-Labeling
The excesses of reagents used in protein chemistry are often incompatible with the reduced or even inverse stoichiometries used for efficient radiolabeling. Analysis and screening of aqueous Pd(0) ligand systems has revealed the importance of a guanidine core and the discovery of 1,1-dimethylguanidine as an enhanced ligand for aqueous Suzuki–Miyaura cross-coupling. This novel Pd catalyst system has now allowed the labeling of small molecules, peptides, and proteins with the fluorine-18 prosthetic [18F]4-fluorophenylboronic acid. These findings now enable site-specific protein 18F-labeling under biologically compatible conditions using a metal-triggered reaction. PMID:23991754
(18)F-labeling syntheses and preclinical evaluation of functionalized nanoliposomes for Alzheimer's disease.
Rokka, Johanna; Snellman, Anniina; Kaasalainen, Martti; Salonen, Jarno; Zona, Cristiano; La Ferla, Barbara; Nicotra, Francesco; Re, Francesca; Masserini, Massimo; Forsback, Sarita; Lopez-Picon, Francisco; Rinne, Juha O; Haaparanta-Solin, Merja; Solin, Olof
The aim of the present study was to synthesize functionalized (18)F-labeled NLs ((18)F-NLs) and evaluate their biological behavior in mouse models of Alzheimer's disease (AD) using positron emission tomography (PET) and ex vivo brain autoradiography. (18)F-fluorine was introduced to (18)F-NLs either by using a core forming (18)F-lipid or by encapsulating a (18)F-tracer, (18)F-treg-curcumin inside the NLs. Phosphatidic acid (PA) and curcumin derivative (Curc) functionalized (18)F-NLs with or without additional mApoE functionalization were produced using thin film hydration. The biodistribution and β-amyloid plaque-binding ability of (18)F-NLs were studied in wild type mice and AD mouse models using in vivo PET imaging and ex vivo brain autoradiography at 60min after (18)F-NL injection. Functionalized (18)F-NLs were successfully synthesized. The preclinical evaluation in mice showed that the functional group affected the biodistribution of (18)F-NLs. Further functionalization with mApoE increased the brain-to-blood ratio of (18)F-NLs but the overall brain uptake remained low with all functionalized (18)F-NLs. The liposomal encapsulation of (18)F-treg-curcumin was not successful and preclinical results of encapsulated (18)F-treg-curcumin and plain (18)F-treg-curcumin were identical. Although the studied functionalized (18)F-NLs were not suitable for PET imaging as such, the synthesis techniques introduced in this study can be utilized to modify the biological behavior of (18)F-labeled NLs. PMID:26993963
Efficient 18F-Labeling of Large 37-Amino Acid pHLIP Peptide Analogues and their Biological Evaluation
Daumar, Pierre; Wanger-Baumann, Cindy A.; Pillarsetty, NagaVaraKishore; Fabrizio, Laura; Carlin, Sean D.; Andreev, Oleg A.; Reshetnyak, Yana K.; Lewis, Jason S.
control [18F]-L-K-pHLIP revealed pH-dependent tumor retention. This reliable and efficient protocol promises to be useful for the 18F-labeling of large peptides such as pHLIP and will accelerate the evaluation of numerous [18F]-pHLIP analogues as potential PET tracers. PMID:22784215
Radiosynthesis and preliminary biological evaluation of a new (18)F-labeled triethylene glycol derivative of triphenylphosphonium.
Tominaga, Takahiro; Ito, Hiroaki; Ishikawa, Yoichi; Iwata, Ren; Ishiwata, Kiichi; Furumoto, Shozo
Delocalized lipophilic cations such as [(18)F]fluorobenzyltriphenylphosphonium ([(18)F]FBnTP) can accumulate in mitochondria and have been used in myocardial perfusion imaging (MPI). In this study, we established a simplified method for [(18)F]FBnTP synthesis using triphenylphosphine hydrobromide (PPh3 •HBr) without preparing an intermediate that contains benzyl bromide structure. Applying this new method, we synthesized and evaluated a novel (18)F-labeled PEGylated BnTP derivative ([(18)F]FPEGBnTP). In vitro cellular uptake study demonstrated that [(18)F]FPEGBnTP accumulated in cells in proportion to the relative intensity of mitochondrial membrane potential. Biodistribution study revealed that the heart : liver uptake ratio of [(18)F]FPEGBnTP (4.00 at 60 min) was superior to that of [(18)F]FBnTP (1.50 at 60 min). However, [(18)F]FPEGBnTP showed slow blood clearance and high radioactivity uptake in bone at 120-min post-injection. These results imply the possibility of [(18)F]FPEGBnTP being used as a MPI agent. However, there is a need of further structural optimization and flow-dependent uptake study. PMID:26861736
High-yielding aqueous 18F-labeling of peptides via Al18F chelation.
D'Souza, Christopher A; McBride, William J; Sharkey, Robert M; Todaro, Louis J; Goldenberg, David M
The coordination chemistry of a new pentadentate bifunctional chelator (BFC), NODA-MPAA 1, containing the 1,4,7-triazacyclononane-1,4-diacetate (NODA) motif with a methylphenylacetic acid (MPAA) backbone, and its ability to form stable Al(18)F chelates were investigated. The organofluoroaluminates were easily accessible from the reaction of 1 and AlF(3). X-ray diffraction studies revealed aluminum at the center of a slightly distorted octahedron, with fluorine occupying one of the axial positions. The tert-butyl protected prochelator 7, which can be synthesized in one step, is useful for coupling to biomolecules on solid phase or in solution. High yield (55-89%) aqueous (18)F-labeling was achieved in 10-15 min with a tumor-targeting peptide 4 covalently linked to 1. Defluorination was not observed for at least 4 h in human serum at 37 °C. These results demonstrate the facile application of Al(18)F chelation using BFC 1 as a versatile labeling method for radiofluorinating other heat-stable peptides for positron emission imaging. PMID:21805975
Synthesis and characterization of (18)F-labeled active site inhibited factor VII (ASIS).
Erlandsson, Maria; Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Jesper B; Petersen, Lars C; Madsen, Jacob; Kjaer, Andreas
Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an (18)F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[(18)F]fluorobenzoate, and the [(18)F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [(18)F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [(18)F]ASIS and ASIS could be detected. Furthermore, [(18)F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [(18)F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [(18)F]ASIS are in progress. PMID:25820758
sup 18 F-labeled insulin: A prosthetic group methodology for incorporation of a positron emitter into peptides and proteins
Shai, Y.; Kirk, K.L.; Channing, M.A.; Dunn, B.B.; Lesniak, M.A.; Eastman, R.C.; Finn, R.D.; Roth, J.; Jacobson, K.A. )
In the present study we synthesize {sup 18}F-labeled insulin of high specific radioactivity. A new prosthetic group methodology, in which ({sup 18}F)fluoride displaces a bromide group of 4-(bromomethyl)-benzoylamine intermediates, was used. The 4-(fluoromethyl)benzoyl product was chemically stable. {sup 18}F-Labeled insulin retains the essential biological properties of native insulin, as measured in vitro by binding to insulin receptors on human cells and stimulation of glucose metabolism in rat adipocytes. The overall process can be carried out speedily to yield a product of sufficient purity to permit in vivo studies. The method appears to be applicable to a wide variety of peptides.
Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection
Namavari, Mohammad; Gowrishankar, Gayatri; Hoehne, Aileen; Jouannot, Erwan; Gambhir, Sanjiv S
Purpose To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections. Procedures It is known that maltose and maltodextrins are energy sources for bacteria. Hence, 18F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[18F]fluoro-D-glucopyranoside (6-[18F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[18F]fluoro-D-glucopyranoside (1-[18F]fluoromaltose) as bacterial infection PET imaging agents. 6-[18F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2′,3′,-di-O-acetyl-4′,6′-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[18F]fluoromaltose. In an analogous procedure, 1-[18F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2′,3′,4′,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[18F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[18F]fluoromaltose was examined. Results A reliable synthesis of 1- and 6-[18F]fluoromaltose has been accomplished with 4–6 and 5–8 % radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[18F]fluoromaltose was sufficiently stable over the time span needed for PET studies (~96 % intact compound after 1-h and ~65 % after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[18F]fluoromaltose. Competition assays showed that the uptake of 6-[18F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose. Conclusion We have successfully synthesized 1- and 6-[18F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake
Comparison of two site-specifically (18)F-labeled affibodies for PET imaging of EGFR positive tumors.
Su, Xinhui; Cheng, Kai; Jeon, Jongho; Shen, Bin; Venturin, Gianina Teribele; Hu, Xiang; Rao, Jianghong; Chin, Frederick T; Wu, Hua; Cheng, Zhen
The epidermal growth factor receptor (EGFR) serves as an attractive target for cancer molecular imaging and therapy. Our previous positron emission tomography (PET) studies showed that the EGFR-targeting affibody molecules (64)Cu-DOTA-ZEGFR:1907 and (18)F-FBEM-ZEGFR:1907 can discriminate between high and low EGFR-expression tumors and have the potential for patient selection for EGFR-targeted therapy. Compared with (64)Cu, (18)F may improve imaging of EGFR-expression and is more suitable for clinical application, but the labeling reaction of (18)F-FBEM-ZEGFR:1907 requires a long synthesis time. The aim of the present study is to develop a new generation of (18)F labeled affibody probes (Al(18)F-NOTA-ZEGFR:1907 and (18)F-CBT-ZEGFR:1907) and to determine whether they are suitable agents for imaging of EGFR expression. The first approach consisted of conjugating ZEGFR:1907 with NOTA and radiolabeling with Al(18)F to produce Al(18)F-NOTA-ZEGFR:1907. In a second approach the prosthetic group (18)F-labeled-2-cyanobenzothiazole ((18)F-CBT) was conjugated to Cys-ZEGFR:1907 to produce (18)F-CBT-ZEGFR:1907. Binding affinity and specificity of Al(18)F-NOTA-ZEGFR:1907 and (18)F-CBT-ZEGFR:1907 to EGFR were evaluated using A431 cells. Biodistribution and PET studies were conducted on mice bearing A431 xenografts after injection of Al(18)F-NOTA-ZEGFR:1907 or (18)F-CBT-ZEGFR:1907 with or without coinjection of unlabeled affibody proteins. The radiosyntheses of Al(18)F-NOTA-ZEGFR:1907 and (18)F-CBT-ZEGFR:1907 were completed successfully within 40 and 120 min with a decay-corrected yield of 15% and 41% using a 2-step, 1-pot reaction and 2-step, 2-pot reaction, respectively. Both probes bound to EGFR with low nanomolar affinity in A431 cells. Although (18)F-CBT-ZEGFR:1907 showed instability in vivo, biodistribution studies revealed rapid and high tumor accumulation and quick clearance from normal tissues except the bones. In contrast, Al(18)F-NOTA-ZEGFR:1907 demonstrated high in
Imaging integrin alpha-v-beta-3 expression in tumors with an 18F-labeled dimeric RGD peptide
Dijkgraaf, Ingrid; Terry, Samantha; McBride, William J.; Goldenberg, David M.; Laverman, Peter; Franssen, Gerben M.; Oyen, Wim J. G.; Boerman, Otto C.
Integrin αvβ3 receptors are expressed on activated endothelial cells during neovascularization to maintain tumor growth. Many radiolabeled probes utilize the tight and specific association between the arginine-glycine-aspartatic acid (RGD) peptide and integrin αvβ3, but one main obstacle for any clinical application of these probes is the laborious multistep radiosynthesis of 18F. In this study, the dimeric RGD peptide, E-[c(RGDfK)]2, was conjugated with NODAGA and radiolabeled with 18F in a simple one-pot process with a radiolabeling yield of 20%; the whole process lasting only 45 min. NODAGA-E-[c(RGDfK)]2 labeled with 18F at a specific activity of 1.8 MBq/nmol and a radiochemical purity of 100% could be achieved. Log P value of 18F-labeled NODAGA-E-[c(RGDfK)]2 was −4.26 ± 0.02. In biodistribution studies, 18F-NODAGA-E-[c(RGDfK)]2 cleared rapidly from the blood with 0.03 ± 0.01 %ID/g in the blood at 2 h p.i., mainly via the kidneys and showed good in vivo stability. Tumor uptake of 18F-NODAGA-E-[c(RGDfK)]2 (3.44 ± 0.20 %ID/g, 2 h p.i.) was significantly lower than that of reference compounds 68Ga-labeled NODAGA-E-[c(RGDfK)]2 (6.26 ± 0.76 %ID/g; P <0.001) and 111In-labeled NODAGA-E-[c(RGDfK)]2 (4.99 ± 0.64 %ID/g; P < 0.01). Co-injection of an excess of unlabeled NODAGA-E-[c(RGDfK)]2 along with 18F-NODAGA-E-[c(RGDfK)]2 resulted in significantly reduced radioactivity concentrations in the tumor (0.85 ± 0.13 %ID/g). The αvβ3 integrin-expressing SK-RC-52 tumor could be successfully visualized by microPET with 18F-labeled NODAGA-E-[c(RGDfK)]2. In conclusion, NODAGA-E-[c(RGDfK)]2 could be labeled rapidly with 18F using a direct aqueous, one-pot method and it accumulated specifically in αvβ3 integrin-expressing SK-RC-52 tumors, allowing for visualization by microPET. PMID:23606427
Single-scan rest/stress imaging 18F-labeled flow tracers
Alpert, Nathaniel; Dean Fang, Yu-Hua; Fakhri, Georges El
Purpose: The authors report a novel measurement strategy to obtain both rest and stress blood flow during a single, relatively short, scan session. Methods: Measurement of rest-stress myocardial blood flow with long-lived tracers usually requires separate scan sessions to remove the confounding effects of residual radioactivity concentration in the blood and tissue. The innovation of this method is to treat the rest-stress scan as a single entity in which the flow parameters change due to pharmacological challenge. With this approach the fate of a tracer molecule is naturally accounted for, no matter if it was introduced during the rest or stress phase of the study. Two new dual-injection kinetic models are considered that represent the response to pharmacological stress as a transitional or transient increase of myocardial blood flow. The authors present the theory of the method followed by the specific application of the theory to 18F-Flurpiridaz, a new myocardial flow-imaging agent. Results: Myocardial blood flow was accurately and precisely estimated from a single-scan rest/stress study for the long half-lived tracer 18F-Flurpiridaz. By accounting for the time-dependence of the kinetic parameters, the proposed models achieved good accuracy and precision (5%) under different vasodilators and different ischemic states. Conclusions: Detailed simulations predict that accurate and precise rest-stress blood flow measurements can be obtained in 20–30 min. PMID:23127055
Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging.
Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan
Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers. PMID:27390067
Synthesis and evaluation of 18F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression
Daumar, Pierre; Zeglis, Brian M.; Ramos, Nicholas; Divilov, Vadim; Sevak, Kuntal Kumar; Pillarsetty, NagaVaraKishore; Lewis, Jason S.
Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, 18F-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [18F]-18 and [18F]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression. PMID:25240701
Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods.
Drerup, Christian; Ermert, Johannes; Coenen, Heinz H
Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and (18)F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be (18)F-labelled in no-carrier-added (n.c.a.) form. For preparation of the (18)F-labelled nNOS-Inhibitor [(18)F]10 a "build-up" radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [(18)F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified "late-stage" (18)F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. (18)F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [(18)F]10 as probe for preclinical in vivo studies. PMID:27598109
A high-affinity [18F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer
Ganguly, Tanushree; Dannoon, Shorouk; Hopkins, Mark R.; Murphy, Stephanie; Cahaya, Hendry; Blecha, Joseph E.; Jivan, Salma; Drake, Christopher R.; Barinka, Cyril; Jones, Ella F.; VanBrocklin, Henry F.; Berkman, Clifford E.
Introduction In this study, a structurally modified phosphoramidate scaffold, with improved prostate-specific membrane antigen (PSMA) avidity, stability and in vivo characteristics, as a PET imaging agent for prostate cancer (PCa), was prepared and evaluated. Methods p-Fluorobenzoyl-aminohexanoate and 2-(3-hydroxypropyl)glycine were introduced into the PSMA-targeting scaffold yielding phosphoramidate 5. X-ray crystallography was performed on the PSMA/5 complex. [18F]5 was synthesized, and cell uptake and internalization studies were conducted in PSMA(+) LNCaP and CWR22Rv1 cells and PSMA(−) PC-3 cells. In vivo PET imaging and biodistribution studies were performed at 1 and 4 h post injection in mice bearing CWR22Rv1 tumor, with or without blocking agent. Results The crystallographic data showed interaction of the p-fluorobenzoyl group with an arene-binding cleft on the PSMA surface. In vitro studies revealed elevated uptake of [18F]5 in PSMA(+) cells (2.2% in CWR22Rv1 and 12.1% in LNCaP) compared to PSMA(−) cells (0.08%) at 4 h. In vivo tumor uptake of 2.33% ID/g and tumor-to-blood ratio of 265:1 was observed at 4 h. Conclusions We have successfully synthesized, radiolabeled and evaluated a new PSMA-targeted PET agent. The crystal structure of the PSMA/5 complex highlighted the interactions within the arene-binding cleft contributing to the overall complex stability. The high target uptake and rapid non-target clearance exhibited by [18F]5 in PSMA(+) xenografts substantiates its potential use for PET imaging of PCa. Advances in Knowledge The only FDA-approved imaging agent for PCa, Prostascint®, targets PSMA but suffers from inherent shortcomings. The data acquired in this manuscript confirmed that our new generation of [18F]-labeled PSMA inhibitor exhibited promising in vivo performance as a PET imaging agent for PCa and is well-positioned for subsequent clinical trials. Implications for Patient Care Our preliminary data demonstrate that this tracer possesses
Preparation of 18F-labeled peptides using the copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition.
Gill, Herman S; Marik, Jan
An optimized procedure for preparing fluorine-18 ((18)F)-labeled peptides by the copper-catalyzed azide-alkyne 1,3-dipolar cyloaddition (CuAAC) is presented here. The two-step radiosynthesis begins with the microwave-assisted nucleophilic (18)F-fluorination of a precursor containing a terminal p-toluenesulfonyl, terminal azide and polyethylene glycol backbone. The resulting (18)F-fluorinated azide-containing building block is coupled to an alkyne-decorated peptide by the CuAAC. The reaction is accelerated by the copper(I)-stabilizing ligand bathophenanthroline disulfonate and can be performed in either reducing or nonreducing conditions (e.g., to preserve disulfide bonds). After an HPLC purification, (18)F-labeled peptide can be obtained with a 31 ± 6% radiochemical yield (n = 4, decay-corrected from (18)F-fluoride elution) and a specific activity of 39.0 ± 12.4 Ci μmol(-1) within 77 ± 4 min. PMID:22011654
Synthesis and Bio-Evaluation of New (18) F-Labeled Pyridaben Analogs with Improved Stability for Myocardial Perfusion Imaging in Mice.
Mou, Tiantian; Zhao, Zuoquan; Zhang, Pu; Fang, Wei; Peng, Cheng; Lu, Jie; Wang, Qian; Ma, Yunchuan; Zhang, Xianzhong
To improve the stability of (18) F-labeled pyridaben analogs for myocardial perfusion imaging, three new analogs of pyridaben ([(18) F]FPTP2, [(18) F]FPTP-P2, and [(18) F]FPTP-P3) were synthesized with 'side chain' modifications. The radiolabeled tracers and corresponding non-radioactive compounds were obtained by substituting tosyl group with (18/19) F. The effect of structure modification on myocardial targeting and physicochemical properties of new tracers were evaluated in vitro and in vivo. The total radiosynthesis time of these tracers was approximately 70-90 min with high decay-corrected radiochemical yields (36-65%) and good radiochemical purity (> 98%). These lipophilic tracers exhibited obvious improved stability in water. Studies of their biodistribution in normal Kunming mice demonstrated that [(18) F]FPTP2 exhibited very high initial heart uptake (39.70 ± 2.81 %ID/g at 2 min after injection) and low background in the liver, blood, and soft tissues. The heart-to-liver, heart-to-lung, and heart-to-blood ratios were 3.59, 19.34, and 67.34 at 15 min postinjection, respectively. Favorable myocardial targeting property and remarkable improvement of stability of [(18) F]FPTP2 suggest that the substitution of the phenyl 'sidechain' with other non-phenyl rings has no effect on the myocardial targeting property of (18) F-labeled pyridaben analogs. PMID:25529021
In vivo biodistribution of two [18F]-labelled muscarinic cholinergic receptor ligands: 2-[18F]- and 4-[18F]-fluorodexetimide.
Wilson, A A; Scheffel, U A; Dannals, R F; Stathis, M; Ravert, H T; Wagner, H N
Two [18F]-labelled analogues of the potent muscarinic cholinergic receptor (m-AChR) antagonist, dexetimide, were evaluated as potential ligands for imaging m-AChR by positron emission tomography (PET). Intravenous administration of both 2-[18F]- or 4-[18F]-fluorodexetimide resulted in high brain uptake of radioactivity in mice. High binding levels were observed in m-AChR rich areas, such as cortex and striatum, with low levels in the receptor-poor cerebellum. Uptake of radioactivity was saturable and could be blocked by pre-administration of dexetimide or atropine. Drugs with different sites of action were ineffective at blocking receptor binding. The results indicate that both radiotracers are promising candidates for use in PET studies. PMID:2008155
Synthesis and Evaluation of 4-[18F]Fluoropropoxy-3-iodobenzylguanidine ([18F]FPOIBG): A Novel 18F-labeled Analogue of MIBG
Vaidyanathan, Ganesan; McDougald, Darryl; Koumarianou, Eftychia; Choi, Jaeyeon; Hens, Marc; Zalutsky, Michael R.
Introduction Radioiodinated meta-iodobenzylguanidine (MIBG), a norepinephrine transporter (NET) substrate, has been extensively used as an imaging agent to study the pathophysiology of the heart and for the diagnosis and treatment of neuroendocrine tumors. The goal of this study was to develop an 18F-labeled analogue of MIBG that like MIBG itself could be synthesized in a single radiochemical step. Towards this end, we designed 4-fluoropropoxy-3-iodobenzylguanidine (FPOIBG). Methods Standards of FPOIBG and 4-fluoropropoxy-3-bromobenzylguanidine (FPOBBG) as well as their tosylate precursors for labeling with 18F, and a tin precursor for the preparation of radioiodinated FPOIBG were synthesized. Radiolabeled derivatives were synthesized by nucleophilic substitution and electrophilic iododestannylation from the corresponding precursors. Labeled compounds were evaluated for NET transporter recognition in in vitro assays using three NET-expressing cell lines and in biodistribution experiments in normal mice, with all studies performed in a paired-label format. Competitive inhibition of [125I]MIBG uptake by unlabeled benzylguanidine compounds was performed in UVW-NAT cell line to determine IC50 values. Results [18F]FPOIBG was synthesized from the corresponding tosylate precursor in 5.2 ± 0.5% (n = 6) overall radiochemical yields starting with aqueous fluoride in about 105 min. In a paired-label in vitro assay, the uptake of [18F]FPOIBG at 2 h was 10.2 ± 1.5%, 39.6 ± 13.4%, and 13.3 ± 2.5%, in NET-expressing SK-N-SH, UVW-NAT, and SK-N-BE(2c) cells, respectively, while these values for [125I]MIBG were 57.3 ± 8.1%, 82.7 ± 8.9%, and 66.3 ± 3.6%. The specificity of uptake of both tracers was demonstrated by blocking with desipramine. The 125I-labeled congener of FPOIBG gave similar results. On the other hand, [18F]FPOBBG, a compound recently reported in the literature, demonstrated much higher uptake, albeit less than that of co-incubated [125I]MIBG. IC50 values for
Synthesis and pre-clinical evaluation of an 18F-labeled single-chain antibody fragment for PET imaging of epithelial ovarian cancer
Sharma, Sai Kiran; Wuest, Melinda; Way, Jenilee D; Bouvet, Vincent R; Wang, Monica; Wuest, Frank R
Anti-CA125 antibodies have been used in immunoassays to quantify levels of shed antigen in the serum of patients who are under surveillance for epithelial ovarian cancer (EOC). However, there is currently no molecular imaging probe in the clinic for the assessment of CA125 expression in vivo. The present study describes the development of an 18F-labeled single-chain variable fragment (scFv) for PET imaging of CA125 in preclinical EOC models. Anti-CA125 scFv was derived from MAb-B43.13 by recombinant expression of the fragment in E.coli. Fragment scFv-B43.13 was purified via immobilized metal affinity chromatography and characterized for antigen binding via immuno-staining and flow cytometry. Prosthetic group N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) was used for radiolabeling of scFv-B43.13. Preclinical ovarian cancer models were developed based on ovarian cancer cell lines OVCAR3 (CA125-positive) and SKOV3 (CA125-negative) in NIH-III mice. The radiopharmacological profile of 18F-labeled scFv-B43.13 ([18F]FBz-scFv-B43.13) was studied with PET. [18F]FBz-scFv-B43.13 was prepared in radiochemical yields of 3.7 ± 1.8% (n = 5) at an effective specific activity of 3.88 ± 0.76 GBq/µmol (n = 5). The radiotracer demonstrated selective uptake in CA125-positive OVCAR3 cells and virtually no uptake in CA125-negative SKOV3 cells. Standardized uptake values (SUV) of radioactivity uptake in OVCAR3 tumors was 0.5 (n = 3) and 0.3 (n = 2) in SKOV3 tumors after 60 min post injection (p.i.). PMID:27508105
Synthesis and pre-clinical evaluation of an (18)F-labeled single-chain antibody fragment for PET imaging of epithelial ovarian cancer.
Sharma, Sai Kiran; Wuest, Melinda; Way, Jenilee D; Bouvet, Vincent R; Wang, Monica; Wuest, Frank R
Anti-CA125 antibodies have been used in immunoassays to quantify levels of shed antigen in the serum of patients who are under surveillance for epithelial ovarian cancer (EOC). However, there is currently no molecular imaging probe in the clinic for the assessment of CA125 expression in vivo. The present study describes the development of an (18)F-labeled single-chain variable fragment (scFv) for PET imaging of CA125 in preclinical EOC models. Anti-CA125 scFv was derived from MAb-B43.13 by recombinant expression of the fragment in E.coli. Fragment scFv-B43.13 was purified via immobilized metal affinity chromatography and characterized for antigen binding via immuno-staining and flow cytometry. Prosthetic group N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB) was used for radiolabeling of scFv-B43.13. Preclinical ovarian cancer models were developed based on ovarian cancer cell lines OVCAR3 (CA125-positive) and SKOV3 (CA125-negative) in NIH-III mice. The radiopharmacological profile of (18)F-labeled scFv-B43.13 ([(18)F]FBz-scFv-B43.13) was studied with PET. [(18)F]FBz-scFv-B43.13 was prepared in radiochemical yields of 3.7 ± 1.8% (n = 5) at an effective specific activity of 3.88 ± 0.76 GBq/µmol (n = 5). The radiotracer demonstrated selective uptake in CA125-positive OVCAR3 cells and virtually no uptake in CA125-negative SKOV3 cells. Standardized uptake values (SUV) of radioactivity uptake in OVCAR3 tumors was 0.5 (n = 3) and 0.3 (n = 2) in SKOV3 tumors after 60 min post injection (p.i.). PMID:27508105
Synthesis and preliminary evaluation in tumor bearing mice of new (18)F-labeled arylsulfone matrix metalloproteinase inhibitors as tracers for positron emission tomography.
Casalini, Francesca; Fugazza, Lorenza; Esposito, Giovanna; Cabella, Claudia; Brioschi, Chiara; Cordaro, Alessia; D'Angeli, Luca; Bartoli, Antonietta; Filannino, Azzurra M; Gringeri, Concetta V; Longo, Dario L; Muzio, Valeria; Nuti, Elisa; Orlandini, Elisabetta; Figlia, Gianluca; Quattrini, Angelo; Tei, Lorenzo; Digilio, Giuseppe; Rossello, Armando; Maiocchi, Alessandro
New fluorinated, arylsulfone-based matrix metalloproteinase (MMP) inhibitors containing carboxylate as the zinc binding group were synthesized as radiotracers for positron emission tomography. Inhibitors were characterized by Ki for MMP-2 in the nanomolar range and by a fair selectivity for MMP-2/9/12/13 over MMP-1/3/14. Two of these compounds were obtained in the (18)F-radiolabeled form, with radiochemical purity and yield suitable for preliminary studies in mice xenografted with a human U-87 MG glioblastoma. Target density in xenografts was assessed by Western blot, yielding Bmax/Kd = 14. The biodistribution of the tracer was dominated by liver uptake and hepatobiliary clearance. Tumor uptake of (18)F-labeled MMP inhibitors was about 30% that of [(18)F]fluorodeoxyglucose. Accumulation of radioactivity within the tumor periphery colocalized with MMP-2 activity (evaluated by in situ zimography). However, specific tumor uptake accounted for only 18% of total uptake. The aspecific uptake was ascribed to the high binding affinity between the radiotracer and serum albumin. PMID:23458498
Radiosynthesis and evaluation of an 18F-labeled positron emission tomography (PET) radioligand for metabotropic glutamate receptor subtype 4 (mGlu4).
Kil, Kun-Eek; Poutiainen, Pekka; Zhang, Zhaoda; Zhu, Aijun; Choi, Ji-Kyung; Jokivarsi, Kimmo; Brownell, Anna-Liisa
Four 4-phthalimide derivatives of N-(3-chlorophenyl)-2-picolinamide were synthesized as potential ligands for the PET imaging of mGlu4 in the brain. Of these compounds, N-(3-chloro-4-(4-fluoro-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide (3, KALB001) exhibited improved binding affinity (IC50 = 5.1 nM) compared with ML128 (1) and was subsequently labeled with (18)F. When finally formulated in 0.1 M citrate buffer (pH 4) with 10% ethanol, the specific activity of [(18)F]3 at the end of synthesis (EOS) was 233.5 ± 177.8 GBq/μmol (n = 4). The radiochemical yield of [(18)F]3 was 16.4 ± 4.8% (n = 4), and the purity was over 98%. In vivo imaging studies in a monkey showed that the radiotracer quickly penetrated the brain with the highest accumulation in the brain areas known to express mGlu4. Despite some unfavorable radiotracer properties like fast washout in rodent studies, [(18)F]3 is the first (18)F-labeled mGlu4 radioligand, which can be further modified to improve pharmacokinetics and brain penetrability for future human studies. PMID:25330258
Design, Synthesis, and In Vitro and In Vivo Evaluation of an (18)F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer.
Rosenberg, Adam J; Liu, Hui; Jin, Hongjun; Yue, Xuyi; Riley, Sean; Brown, Steven J; Tu, Zhude
Sphingosine 1-phosphate receptor 1 (S1P1) plays a pivotal signaling role in inflammatory response; because S1P1 modulation has been identified as a therapeutic target for various diseases, a PET tracer for S1P1 would be a useful tool. Fourteen fluorine-containing analogues of S1P ligands were synthesized and their in vitro binding potency measured; four had high potency and selectivity for S1P1 (S1P1 IC50 < 10 nM, >100-fold selectivity for S1P1 over S1P2 and S1P3). The most potent ligand, 28c (IC50 = 2.63 nM for S1P1) was (18)F-labeled and evaluated in a mouse model of LPS-induced acute liver injury to determine its S1P1-binding specificity. The results from biodistribution, autoradiography, and microPET imaging showed higher [(18)F]28c accumulation in the liver of LPS-treated mice than controls. Increased expression of S1P1 in the LPS model was confirmed by immunohistochemical analysis (IHC). These data suggest that [(18)F]28c is a S1P1 PET tracer with high potential for imaging S1P1 in vivo. PMID:27280499
Synthesis and evaluation of new (18)F-labelled acetamidobenzoxazolone-based radioligands for imaging of the translocator protein (18 kDa, TSPO) in the brain.
Tiwari, Anjani K; Fujinaga, Masayuki; Yui, Joji; Yamasaki, Tomoteru; Xie, Lin; Kumata, Katsushi; Mishra, Anil K; Shimoda, Yoko; Hatori, Akiko; Ji, Bin; Ogawa, Masanao; Kawamura, Kazunori; Wang, Feng; Zhang, Ming-Rong
The visualization of the activated microglia/TSPO is one of the main aspects of neuroimaging. Here we describe two new (18)F-labelled molecules, 2-[5-(4-[(18)F]fluoroethoxyphenyl)- ([(18)F]2) and 2-[5-(4-[(18)F]fluoropropyloxyphenyl)- ([(18)F]3) -2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenylacetamide as novel PET ligands for imaging the translocator protein (18 kDa, TSPO) in the brain. The three-D pharmacophore evaluation and docking studies suggested their high affinity for the TSPO and in vitro binding assays of the TSPO showed binding affinities 6.6 ± 0.7 nM and 16.7 ± 2.5 nM for 2 and 3, respectively. The radiochemical yields for [(18)F]2 and [(18)F]3 were found to be 22 ± 4% (n = 8) and 5 ± 2% (n = 5), respectively at EOB. The radiochemical purity for both was found ≥98% and the specific activity was in the range of 98-364 GBq μmol(-1) at EOS. In vitro autoradiography with an ischemic rat brain showed significantly increased binding on the ipsilateral side compared to the contralateral side. The specificity of [(18)F]2 and [(18)F]3 for binding TSPO was confirmed using the TSPO ligands PK11195 and MBMP. The biodistribution patterns of both PET ligands were evaluated in normal mice by 1 h dynamic PET imaging. In the brain, regional radioactivity reached the maximum very rapidly within 0-4 min for both ligands, similar to (R)[(11)C]PK11195. The metabolite study of [(18)F]2 also favoured a more favourable profile for quantification in comparison to (R)[(11)C]PK11195. In summary, these data indicated that [(18)F]2 and [(18)F]3 have good potential to work as PET ligands, therefore there are merits to use these radioligands for the in vivo evaluation in animal models to see their efficacy in the living brain. PMID:25339090
18F-Labeled NaF PET-CT in Detection of Bone Metastases in Patients With Preoperative Lung Cancer
Rao, Liangjun; Zong, Zhen; Chen, Zhifeng; Wang, Xiaoyan; Shi, Xinchong; Yi, Chang; Zhang, Xiangsong
Abstract We compared the diagnostic accuracy of 18F-labeled sodium fluoride (18F-NaF) PET-CT with 99m-technetium methylene diphosphonate (99mTc-MDP) single photon emission computed tomography (SPECT) to detect bone metastases (BMs) in patients with preoperative lung cancer. Patients with lung cancer (n = 181) were examined with 18F-NaF PET-CT, and another 167 patients with lung cancer were examined with 99mTc-MDP SPECT. 18F-NaF PET-CT and 99mTc-MDP SPECT were evaluated by 2 experienced readers. Lesions were graded on a scale of 0 (degenerative lesion) to 4 (definite BM), and equivocal lesions were determined as indifferent (grade 3). Based on patient-based analysis, there were only 4 equivocal patients in 18F-NaF PET-CT detection. However, in 99mTc-MDP SPECT detection, there were 19 equivocal patients, which indicated a significant difference in terms of occurrence ratio (χ2 = 9.005, P = 0.03). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). Based on lesions-based analysis, SPECT produced 26 equivocal lesions of 333 lesions, but PET-CT produced only 5 equivocal lesions of 991 lesions. PET-CT was significantly better than SPECT in the aspect of producing equivocal patients (χ2 = 58.141, P < 0.001). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). 18F-NaF PET-CT is a highly sensitive and specific modality for the detection of BM in patients with preoperative lung cancer. It is better than conventional 99mTc-MDP SPECT in detecting BM in patients with preoperative lung cancer. PMID:27100456
Radiosynthesis and preliminary PET evaluation of (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors.
Yuan, Gengyang; Jones, Graham B; Vasdev, Neil; Liang, Steven H
To prompt the development of (18)F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile ([(18)F]8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the (18)F-labeled 1-bromo-3-fluorobenzene ([(18)F]15) intermediate with K(18)F. A subsequent copper(I) iodide mediated coupling reaction was carried out with 2-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile (10) to [(18)F]8 in 10±2% uncorrected radiochemical yield relative to starting (18)F-fluoride with >99% radiochemical purity and 29.6±7.4Gbq/μmol specific activity at the time of injection. PET imaging studies with the title radiotracer in normal mice demonstrated good brain uptake (peak standardized uptake value (SUV)=2.3±0.1) and warrants further in vivo validation. PMID:27546294
Distribution and binding of 18F-labeled and 125I-labeled analogues of ACI-80, a prospective molecular imaging biomarker of disease: a whole hemisphere post mortem autoradiography study in human brains obtained from Alzheimer's disease patients.
Gulyás, Balázs; Spenger, Christian; Beliczai, Zsuzsa; Gulya, Károly; Kása, Péter; Jahan, Mahabuba; Jia, Zhisheng; Weber, Urs; Pfeifer, Andrea; Muhs, Andreas; Willbold, Dieter; Halldin, Christer
One of the major pathological landmarks of Alzheimer's disease and other neurodegenerative diseases is the presence of amyloid deposits in the brain. The early non-invasive visualization of amyloid is a major objective of recent diagnostic neuroimaging approaches, including positron emission tomography (PET), with an eye on follow-up of disease progression and/or therapy efficacy. The development of molecular imaging biomarkers with binding affinity to amyloid in the brain is therefore in the forefront of imaging biomarker and radiochemistry research. Recently, a dodecamer peptide (amino acid sequence=QSHYRHISPAQV; denominated D1 or ACI-80) was identified as a prospective ligand candidate, binding with high ex vivo affinity to L-Aβ-amyloid (K(d): 0.4 μM). In order to assess the ligand's capacity to visualize amyloid in Alzheimer's disease (AD), two (125)I labeled and three (18)F labeled analogues of the peptide were synthesized and tested in post mortem human autoradiography experiments using whole hemisphere brain slices obtained from deceased AD patients and age matched control subjects. The (18)F-labeled radioligands showed more promising visualization capacity of amyloid that the (125)I-labeled radioligands. In the case of each (18)F radioligands the grey matter uptake in the AD brains was significantly higher than that in control brains. Furthermore, the grey matter: white matter uptake ratio was over ~2, the difference being significant for each (18)F-radioligands. The regional distribution of the uptake of the various radioligands systematically shows a congruent pattern between the high uptake regions and spots in the autoradiographic images and the disease specific signals obtained in adjacent or identical brain slices labeled with histological, immunohistochemical or autoradiographic stains for amyloid deposits or activated astrocytes. The present data, using post mortem human brain autoradiography in whole hemisphere human brains obtained from deceased
18F: Labeling Chemistry and Labeled Compounds
NASA Astrophysics Data System (ADS)
Ross, T. L.; Wester, H. J.
Positron emission tomography (PET) is a unique tool for the investigation, localization, and quantification of physiological activities in vivo by tracing the involved or accompanying biochemical processes. Because of its nuclear and chemical properties, fluorine-18, which is commonly produced by a cyclotron using the 18O(p,n)18F or the 20Ne(d,α)18F nuclear process, is a nearly ideal positron emitting radionuclide. Its half-life of 109.7 min permits tracer syntheses and imaging protocols extending over hours and allows distribution of 18F-radiopharmaceuticals to hospitals and facilities lacking a cyclotron. The low maximum positron energy of 635 keV results in low radiation doses, short ranges in tissue, and therefore in excellent imaging resolution. Introduction of 18F-fluorine, either via nucleophilic strategies using [18F]F- or electrophilic routes using molecular [18F]F2, permits the synthesis of a broad spectrum of compounds within a time compatible with the half-life. Although fluorine is only slightly larger than a hydrogen atom, changes in the physiological behavior of bioactive compounds as a result of alteration in metabolic stability, lipophilicity, affinity to the target, or other structures, etc., are often observed even after F-for-H or F-for-OH substitutions. In this chapter, an overview of the scope and limitations of the 18F-chemistry is given. Fluorination strategies, routes, and synthetic aspects are exemplified, as far as possible, by established and selected 18F-radiopharmaceuticals with clinical relevance or with potential for further clinical application.
Enantioselective synthesis of L-(-)-4- boronophenylalanine (L-BPA)
Samsel, Edward G.
A method of making substantially pure L-BPA is disclosed. The method includes the steps of reacting 4-bromobenzaldehyde with ethylene glycol to form 4-bromobenzaldehyde ethylene glycol acetal, sequentially reacting 4-bromobenzaldehyde ethyleneglycol acetal with Mg to produce the Grignard reagent and thereafter reacting with tributyl borate and then converting to an acid environment to form 4-boronobenzaldehyde, reacting 4-boronobenzaldehyde with diethanol amine to form 4-boronobenzaldehyde diethanolamine ester, condensing the 4-boronobenzaldehyde diethanolamine ester with 2-phenyl-2-oxazolin-5-one to form an azlactone, reacting the azlactone with an alkali metal hydroxide to form z-.alpha.-benzoylamino-4-boronocinnamic acid, asymmetrically hydrogenating the z-.alpha.-benzoylamino-4-boronocinnamic acid in the presence of a catalyst of a cheltate complex of rhodium (I) with chiral bisphosphines to form L-(+)-N-benzoyl-4-boronophenylalanine, and thereafter acidifying the L-(+)-N-benzoyl-4-boronophenylalanine in an organic medium to produce L-BPA.
Enantioselective synthesis of L-(-)-4- boronophenylalanine (L-BPA)
Samsel, E.G.
A method of making substantially pure L-BPA is disclosed. The method includes the steps of reacting 4-bromobenzaldehyde with ethylene glycol to form 4-bromobenzaldehyde ethylene glycol acetal, sequentially reacting 4-bromobenzaldehyde ethyleneglycol acetal with Mg to produce the Grignard reagent and thereafter reacting with tributyl borate and then converting to an acid environment to form 4-boronobenzaldehyde, reacting 4-boronobenzaldehyde with diethanol amine to form 4-boronobenzaldehyde diethanolamine ester, condensing the 4-boronobenzaldehyde diethanolamine ester with 2-phenyl-2-oxazolin-5-one to form an azlactone, reacting the azlactone with an alkali metal hydroxide to form z-[alpha]-benzoylamino-4boronocinnamic acid, asymmetrically hydrogenating the z-[alpha]-benzoylamino-4-boronocinnamic acid in the presence of a catalyst of a cheltate complex of rhodium (I) with chiral bisphosphines to form L-(+)-N-benzoyl-4-boronophenylalanine, and thereafter acidifying the L-(+)-N-benzoyl-4-boronophenylalanine in an organic medium to produce L-BPA. 3 figs.
A Phase 1 biodistribution study of p-boronophenylalanine
Coderre, J.A.
The objectives of the Phase I BPA biodistribution study are as follows: Objective 1: To establish the safety of orally administered boronophenylalanine (BPA) as determined by monitoring of patient's vital signs and by clinical analysis of blood before and after BPA administration. Objective 2: To establish BPA pharmacokinetics by monitoring the rates of boron absorption into and clearance from the blood and the rate of urinary excretion of boron. Objective 3: To measure the amount of boron incorporated into human tumors (melanoma, glioma, and breast carcinoma) using samples obtained at surgery or biopsy. This report presents the results obtained from the first thirteen patients entered into the study. Three additional glioblastoma patients have been studied recently at Stony Brook, the tissues are still being analyzed.
A Phase 1 biodistribution study of p-boronophenylalanine
Coderre, J.A.
The objectives of the Phase I BPA biodistribution study are as follows: Objective 1: To establish the safety of orally administered boronophenylalanine (BPA) as determined by monitoring of patient`s vital signs and by clinical analysis of blood before and after BPA administration. Objective 2: To establish BPA pharmacokinetics by monitoring the rates of boron absorption into and clearance from the blood and the rate of urinary excretion of boron. Objective 3: To measure the amount of boron incorporated into human tumors (melanoma, glioma, and breast carcinoma) using samples obtained at surgery or biopsy. This report presents the results obtained from the first thirteen patients entered into the study. Three additional glioblastoma patients have been studied recently at Stony Brook, the tissues are still being analyzed.
N-Succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([18F]SFBTMGMB): A Residualizing Label for 18F-labeling of internalizing biomolecules
Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Pruszynski, Marek; Koumarianou, Eftychia; Zhou, Zhengyuan; Zalutsky, Michael R.
Residualizing labeling methods for internalizing peptides and proteins are designed to trap the radionuclide inside the cell after intracellular degradation of the biomolecule. The goal of this work was to develop a residualizing label for the 18F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate (Boc2-[18F]SFBTMGMB) was synthesized by click reaction of an azide precursor and [18F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n =15). An anti-HER2 nanobody 5F7 was labeled with 18F using [18F]SFBTMGMB ([18F]RL-I), obtained by the deprotection of Boc2-[18F]SFBTMGMB, in 31.2 ± 6.7% (n =5) conjugation efficiency. Thus labeled nanobody had a radiochemical purity of >95%, bound to the HER2-expressing BT474M1 breast cancer cells with an affinity of 4.7 ± 0.9 nM, and had an immunoreactive fraction of 62–80%. In summary, a novel residualizing prosthetic agent for labeling biomolecules with 18F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2. PMID:26645790
Improved treatment planning for boron neutron capture therapy for glioblastoma multiforme using fluorine-18 labeled boronophenylalanine and positron emission tomography.
Nichols, Trent L; Kabalka, George W; Miller, Laurence F; Khan, Mohammad K; Smith, Gary T
Boron neutron capture therapy (BNCT) is a cancer brachytherapy based upon the thermal neutron reaction: 10B(n,alpha)7Li. The efficacy of the treatment depends primarily upon two conditions being met: (a) the preferential concentration of a boronated compound in the neoplasm and (b) an adequate fluence of thermal neutrons delivered to the neoplasm. The boronated amino acid, para-boronophenylalanine (BPA), is the agent widely used in clinical trials to deliver 10B to the malignancy. Positron emission tomography (PET) can be used to generate in vivo boron distribution maps by labeling BPA with the positron emitting nuclide fluorine-18. The incorporation of the PET-derived boron distribution maps into current treatment planning protocols is shown to provide improved treatment plans. Using previously established protocols, six patients with glioblastoma had 18BPA PET scans. The PET distribution maps obtained were used in the conventional BNCT treatment codes. The isodose curves derived from the PET data are shown to differ both qualitatively and quantitatively from the conventional isodose curves that were derived from calculations based upon the assumption of uniform uptake of the pharmaceutical in tumor and normal brain regions. The clinical course of each of the patients who eventually received BNCT (five of the six patients) was compared using both sets of isodose calculations. The isodose contours based upon PET derived distribution data appear to be more consistent with the patients' clinical course. PMID:12408309
A Phase 1 trial of intravenous boronophenylalanine-fructose complex in patients with glioblastoma multiforme
Bergland, R.; Elowitz, E.; Chadha, M.; Coderre, J.A.; Joel, D.
Boron neutron capture therapy (BNCT) of glioblastoma multiforme was initially performed at the Brookhaven National Laboratory in the early 1950`s While this treatment for malignant brain tumors has continued in Japan, new worldwide interest has been stimulated by the development of new and more selective boron compounds. Boronophenylalanine (BPA) is a blood-brain barrier penetrating compound that has been used in BNCT of malignant melanomas. SPA has been employed experimentally in BNCT of rat gliosarcoma and has potential use in the treatment of human glioblastoma. As a preface to clinical BNCT trials, we studied the biodistribution of SPA in patients with glioblastoma.
The overall goal of this research is to combine two powerful methodologies, boron neutron capture therapy (BNCT) and positron emission tomography (PET), to advance the treatment of patients with malignant brain tumors. BNCT is a method to selectively deliver lethal alpha radiation to a tumor through the administration of a boron-10 containing drug, and irradiation of the tumor area with neutrons [1]. L-Boronophenylalanine (L-{sup 10}BPA) is a boron-10 containing amino acid currently used for BNCT [4]. In order to perform neutron dosimetry, it is essential to determine tumor boron-10 levels in the course of the therapy. PET has the ability to measure the concentration of drugs labeled with positron-emitting isotopes in the human body [2]. 2-Fluoro-4-borono-phenylalanine ([{sup 18}F]FBPA) has been labeled as a surrogate marker for L-BPA for pharmacokinetic studies in brain tumor patients [3]. However, [{sup 18}F]FBPA is a different drug than L-BPA because it contains a fluorine atom. We report here the labeling of L-BPA with C-11, which has the advantage of being chemically identical to L-BPA. Carbon-11 is also well suited to repeated studies within the same PET scanning session.
Boron neutron capture therapy of ocular melanoma and intracranial glioma using p-boronophenylalanine
Coderre, J.A.; Greenberg, D.; Micca, P.L.; Joel, D.D.; Saraf, S. ); Packer, S. . Div. of Ophthalmology)
During conventional radiotherapy, the dose that can be delivered to the tumor is limited by the tolerance of the surrounding normal tissue within the treatment volume. Boron Neutron Capture Therapy (BNCT) represents a promising modality for selective tumor irradiation. The key to effective BNCT is selective localization of {sup 10}B in the tumor. We have shown that the synthetic amino acid p-boronophenylalanine (BPA) will selectively deliver boron to melanomas and other tumors such as gliosarcomas and mammary carcinomas. Systemically delivered BPA may have general utility as a boron delivery agent for BNCT. In this paper, BNCT with BPA is used in treatment of experimentally induced gliosarcoma in rats and nonpigmented melanoma in rabbits. The tissue distribution of boron is described, as is response to the BNCT. 6 refs., 4 figs., 1 tab.
Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents
Wang, Limin; Zha, Zhihao; Qu, Wenchao; Qiao, Hongwen; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.
Introduction This paper reports the synthesis and labeling of 18F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine-serine-cysteine preferring (ASC) transporter system. Methods Three new 18F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labelling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[18F]fluoromethyl)-L-alanine (L[18F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma). Results New 18F alanine derivatives were prepared with 7–34% uncorrected radiochemical yields, excellent enantiomeric purity (>99%) and good radiochemical purity (>99%). In vitro uptake of the L-[18F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than those observed for other two alanine derivatives and [18F]FDG in first 1 h. Inhibition of cell uptake studies suggested that L-[18F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[18F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[18F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[18F]FMA in both 9L rat and transgenic mouse. Conclusion L-[18F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor proliferation. PMID:22542392
Synthesis and evaluation of 18F labeled FET prodrugs for tumor imaging
Wang, Limin; Lieberman, Brian P.; Ploessl, Karl; Kung, Hank F.
Introduction O-(2-[18F]fluoroethyl)-L-tyrosine (FET, [18F]1) is a useful amino-acid-based imaging agent for brain tumors. This paper reports the synthesis and evaluation of three FET prodrugs, O-(2-[18F]fluoroethyl)-L-tyrosyl-L-glycine (FET-Gly, [18F]2), O-(2-[18F]fluoroethyl)-L-tyrosyl-L-alanine (FET-Ala, [18F]3) and N-acetyl O-(2-[18F]fluoroethyl)-L-tyrosine (AcFET, [18F]4), which could be readily hydrolyzed to FET in vivo for tumor imaging. We investigated their metabolism in the blood and imaging properties in comparison to FET ([18F]1). Methods Three new [18F]FET derivatives, 2 – 4, were prepared from their corresponding tosylate-precursors through nucleophilic fluorination and subsequent deprotection reactions. In vitro uptake studies were carried out in 9L glioma cancer cell lines. In vitro and in vivo hydrolysis studies were conducted to evaluate the hydrolysis of FET prodrugs in blood and in Fisher 344 rats. Biodistribution and PET imaging studies were then performed in rats bearing 9L tumors. Results New FET prodrugs were prepared with 3 – 28 % decay corrected radiochemical yields, good enantiomeric purity (> 95 %) and high radiochemical purity (> 95 %). FET-Gly ([18F]2), FET-Ala ([18F]3), and AcFET ([18F]4) exhibited negligible uptake in comparison to the high uptake of FET ([18F]1) in 9L cells. Metabolism studies of FET-Gly ([18F]2), FET-Ala ([18F]3), and AcFET ([18F]4) in rat and human blood showed that FET-Ala ([18F]3) was hydrolyzed to FET ([18F]1) faster than FET-Gly ([18F]2) or AcFET ([18F]4). Most of the FET-Ala (79 %) was converted to FET ([18F]1) within 5 min in blood in vivo. Biodistribution studies demonstrated that FET-Ala ([18F]3) displayed the highest tumor uptake. The tumor-to-background ratios of FET-Ala ([18F]3) and FET ([18F]1) were comparable and appeared to be better than those of FET-Gly ([18F]2) and AcFET ([18F]4). PET imaging studies showed that both FET ([18F]1) and FET-Ala ([18F]3) could visualize tumors effectively, and that they share similar imaging characteristics. Conclusions FET-Ala ([18F]3) demonstrated promising properties as a prodrug of FET ([18F]1), which could be used in PET imaging of tumor amino acid metabolism. PMID:24183614
18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals
Bernard-Gauthier, Vadim; Wängler, Carmen; Wängler, Bjoern; Schirrmacher, Ralf
Background. Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET). These "nonclassical" labeling methodologies based on silicon-, boron-, and aluminium-18F chemistry deviate from commonplace bonding of an [18F]fluorine atom (18F) to either an aliphatic or aromatic carbon atom. One method in particular, the silicon-fluoride-acceptor isotopic exchange (SiFA-IE) approach, invalidates a dogma in radiochemistry that has been widely accepted for many years: the inability to obtain radiopharmaceuticals of high specific activity (SA) via simple IE. Methodology. The most advantageous feature of IE labeling in general is that labeling precursor and labeled radiotracer are chemically identical, eliminating the need to separate the radiotracer from its precursor. SiFA-IE chemistry proceeds in dipolar aprotic solvents at room temperature and below, entirely avoiding the formation of radioactive side products during the IE. Scope of Review. A great plethora of different SiFA species have been reported in the literature ranging from small prosthetic groups and other compounds of low molecular weight to labeled peptides and most recently affibody molecules. Conclusions. The literature over the last years (from 2006 to 2014) shows unambiguously that SiFA-IE and other silicon-based fluoride acceptor strategies relying on 18F− leaving group substitutions have the potential to become a valuable addition to radiochemistry. PMID:25157357
An improved strategy for the synthesis of [18F]-labeled arabinofuranosyl nuclosides
Zhang, Hanwen; Cantorias, Melchor V.; Pillarsetty, NagaVaraKishore; Burnazi, Eva M.; Cai, Shangde; Lewis, Jason S.
The expression of the herpes simplex virus type-1 thymidine kinase (HSV1-tk) gene can be imaged efficaciously using a variety of 2′-[18F]fluoro-2′-deoxy-1-b-D-arabinofuranosyl-uracil derivatives [[18F]-FXAU, X= I(iodo), E(ethyl), and M(methyl)]. However, the application of these derivatives in clinical and translational studies has been impeded by their complicated and long syntheses (3–5 h). To remedy these issues, in the study at hand we have investigated whether microwave or combined catalysts could facilitate the coupling reaction between sugar and nucleobase and, further, have probed the feasibility of establishing a novel approach for [18F]-FXAU synthesis. We have demonstrated that the rate of the trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed coupling reaction between the 2-deoxy-sugar and uracil derivatives at 90°C can be significantly accelerated by microwave-driven heating or by the addition of Lewis acid catalyst (SnCl4). Further, we have observed that the stability of the α- and β-anomers of [18F]-FXAU derivatives differs during the hydrolysis step. Using the microwave-driven heating approach, overall decay-corrected radiochemical yields of 19–27% were achieved for [18F]-FXAU in 120 min at a specific activity of >22 MBq/nmol (595 Ci/mmol). Ultimately, we believe that these high yielding syntheses of [18F]-FIAU, [18F]-FMAU and [18F]-FEAU will facilitate routine production for clinical applications. PMID:22819195
Improved 18F labeling of peptides with a fluoride-aluminum-chelate complex.
McBride, William J; D'Souza, Christopher A; Sharkey, Robert M; Karacay, Habibe; Rossi, Edmund A; Chang, Chien-Hsing; Goldenberg, David M
We reported previously the feasibility to radiolabel peptides with fluorine-18 ((18)F) using a rapid one-pot method that first mixes (18)F(-) with Al(3+) and then binds the (Al(18)F)(2+) complex to a NOTA ligand on the peptide. In this report, we examined several new NOTA ligands and determined how temperature, reaction time, and reagent concentration affected the radiolabeling yield. Four structural variations of the NOTA ligand had isolated radiolabeling yields ranging from 5.8% to 87% under similar reaction conditions. All of the Al(18)F NOTA complexes were stable in vitro in human serum, and those that were tested in vivo also were stable. The radiolabeling reactions were performed at 100 degrees C, and the peptides could be labeled in as little as 5 min. The IMP467 peptide could be labeled up to 115 GBq/micromol (3100 Ci/mmol), with a total reaction and purification time of 30 min without chromatographic purification. PMID:20540570
Rapid (18)F-labeling and loading of PEGylated gold nanoparticles for in vivo applications.
Zhu, Jun; Chin, Joshua; Wängler, Carmen; Wängler, Bjoern; Lennox, R Bruce; Schirrmacher, Ralf
Water-soluble 3 nm maleimide-terminated PEGylated gold nanoparticles (maleimide-AuNP) were synthesized in both partially hydrolyzed and nonhydrolyzed forms. Both of these maleimide-AuNPs, when reacted with the silicon-fluorine prosthetic group [(18)F]SiFA-SH, resulted in radiolabeled AuNPs. These NPs were readily purified with high radiochemical yields (RCY) of 60-80% via size exclusion chromatography. Preliminary small animal positron emission tomography (PET) measurements in healthy rats gives information about the pathway of excretion and the stability of the radioactive label in vivo. The partially hydrolyzed [(18)F]SiFA-maleimide-AuNPs shows uptake in the brain region of interest (ROI) (> 0.13%ID/g) which was confirmed by ex vivo examination of the thoroughly perfused rat brain. The multiple maleimide end groups on the AuNP surface also allows for the simultaneous incorporation of [(18)F]SiFA-SH and a bioactive peptide (cysteine-modified octreotate, cys-TATE, which can bind to somatostatin receptor subtypes 2 and 5) in a proof-of-concept study. The well-defined Michael addition reaction between various thiol containing molecules and the multifunctionalized maleimide-AuNPs thus offers an opportunity to develop a new bioconjugation platform for new diagnostics as well as therapeutics. PMID:24807200
Dose-response analysis for boron neutron capture therapy of the B16 murine melanoma using p-boronophenylalanine
Coderre, J.A.; Micca, P.L.; Slatkin, D.N.; Makar, M.S.
Boron Neutron Capture Therapy (BNCT) of a well-pigmented B16 melanoma implanted subcutaneously in the mouse thigh has been carried out at the Brookhaven Medical Research Reactor (BMRR) using the synthetic amino acid p-boronophenylalanine (BPA) as the boron delivery agent. The response of the B16 melanoma to BNCT was compared with the response to 250 kVp x-rays using both tumor growth delay and in vivo/in vitro assay that measures clonogenic survival. These experiments allow a comparison of tumor growth delay, log cell kill and damage to normal tissues produced by BNCT or photon irradiation.
Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons
Coderre, J.A.; Chanana, A.D.; Joel, D.D.; Liu, H.B.; Slatkin, D.N.; Wielopolski, L.; Bergland, R.; Elowitz, E.; Chadha, M.
The amino acid analogue p-boronophenylalanine (BPA) is under investigation as a neutron capture agent for BNCT of glioblastoma multiforme. A series of patients undergoing surgical removal of tumor received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT. BPA can be solubilized at neutral pH by complexation with fructose (BPA-F). Studies with rats suggest that intraperitoneal injection of BPA-F complex produces a much higher tumor boron concentration to rat intracerebral 9L gliosarcoma that were possible with oral BPA. Higher boron concentrations have allowed higher tumor radiation doses to be delivered while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. The experience to date of the administration of BPA-F to one patient is provided in this report.
Cruickshank, Garth; Detta, Allah; Green, Stuart; Lockyer, Nick; Ngoga, Desire; Ghani, Zahir; Phoenix, Ben
BNCT is a biologically targeted radiotherapy where preferential boron uptake interacts with a neutron beam in cancerous cells causing irreparable alpha DNA damage. This requires the delivery of at least 30 parts per million (ppm) of 10B into tumour tissue and <10ppm 10B in healthy tissue. Renewed interest arises from the advent of 'accelerator' technology and the recognition of specific uptake transporter in tumour cells. We report an optimising pharmacokinetic and tissue uptake study in glioblastoma patients to determine the route of delivering a new formulation of (p-boronophenylalanine, BPA), its pharmacokinetics, toxicity profile, and LAT1 dependent cellular uptake for a clinical trial. Using inductively-coupled plasma mass spectrometry (ICP-MS), secondary ion mass spectrometry (SIMS) and immunohistochemistry (IHC), boron was measured in blood, urine, cerebrospinal fluid (CSF), extracellular fluid (ECFmicrodialysis), and tissue prior to, during and post BPA infusions in newly-diagnosed patients (n = 10). Tumour and brain-around tumour (BAT) tissue were sampled at 2.5h and 3.5h post-infusion. Tumour and BAT, IHC expression levels of the BPA transporter L-amino acid transporter 1 (LAT-1) were recorded, and cellular boron levels, estimated in SIMS images.LAT1 dependent BPA uptake was also determined. There was no toxicity with BPA given at 375mg/kg as a 2h intravenous or intracarotid infusion with or without pre-infusion mannitol-induced BBB disruption. The Pk profile indicates highest plasma-to-brain concentration gradient from intracarotid infusion and BBB manipulation,with high boron concentrations in the brain compartment. SIMS boron ratio in tumour vs BAT was 0.96 intravenous,1.85 IV + mannitol BBB-D and 2.40 intracarotid cohorts, confirming improved delivery of boron. Tumour and BAT uptake varied, but sustained uptake in BAT (>30ppm boron) indicates potential BNCT targeting after surgery. Tumour boron uptake is governed by LAT-1 behaviour rather than BBB
Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2.
Wongthai, Printip; Hagiwara, Kohei; Miyoshi, Yurika; Wiriyasermkul, Pattama; Wei, Ling; Ohgaki, Ryuichi; Kato, Itsuro; Hamase, Kenji; Nagamori, Shushi; Kanai, Yoshikatsu
The efficacy of boron neutron capture therapy relies on the selective delivery of boron carriers to malignant cells. p-Boronophenylalanine (BPA), a boron delivery agent, has been proposed to be localized to cells through transporter-mediated mechanisms. In this study, we screened aromatic amino acid transporters to identify BPA transporters. Human aromatic amino acid transporters were functionally expressed in Xenopus oocytes and examined for BPA uptake and kinetic parameters. The roles of the transporters in BPA uptake were characterized in cancer cell lines. For the quantitative assessment of BPA uptake, HPLC was used throughout the study. Among aromatic amino acid transporters, ATB(0,+), LAT1 and LAT2 were found to transport BPA with Km values of 137.4 ± 11.7, 20.3 ± 0.8 and 88.3 ± 5.6 μM, respectively. Uptake experiments in cancer cell lines revealed that the LAT1 protein amount was the major determinant of BPA uptake at 100 μM, whereas the contribution of ATB(0,+) became significant at 1000 μM, accounting for 20-25% of the total BPA uptake in MCF-7 breast cancer cells. ATB(0,+), LAT1 and LAT2 transport BPA at affinities comparable with their endogenous substrates, suggesting that they could mediate effective BPA uptake in vivo. The high and low affinities of LAT1 and ATB(0,+), respectively, differentiate their roles in BPA uptake. ATB(0,+), as well as LAT1, could contribute significantly to the tumor accumulation of BPA at clinical dose. PMID:25580517
18F-labeled Single-Stranded DNA Aptamer for PET Imaging of Protein Tyrosine Kinase-7 Expression
Wang, Lu; Wang, Zhe; Yang, Xiangyu; Dewhurst, Andrew; Ma, Ying; Zhu, Guizhi; Niu, Gang; Kiesewetter, Dale O.; Vasdev, Neil; Liang, Steven H.; Chen, Xiaoyuan
Protein tyrosine kinase-7 (PTK7), a member of receptor tyrosine kinase superfamily initially identified as colon carcinoma kinase-4 (CCK-4), is highly expressed in various human malignancies. Its expression was found to correlate with aggressive biological behaviors such as increased cell proliferation, invasiveness and migration. Despite the importance and unmet need of imaging PTK7 in vivo, there is currently no clinically-relevant method to visualize tumoral PTK7 expression noninvasively such as PET or SPECT. This study aims to develop a specific, selective and high affinity PET radioligand based on single-stranded DNA (ssDNA) aptamer to address this challenge. Methods Sgc8, a 41-oligonucleotide that targets to PTK7, was labeled with F-18 using a two-step radiochemical synthesis, which featured a direct one-step radiofluorination on the distinctive spirocyclic hypervalent iodine(III) precursor to give 18F-fluorobenzyl azide followed by copper mediated "click" conjugation with Sgc8-alkyne. 18F-Sgc8 was evaluated in vitro and in vivo in two cell lines, HCT116 and U87MG, which express high and low amounts of PTK7, respectively. Results Sgc8 was labeled efficiently with F-18 in an isolated radiochemical yield of 62 ± 2%, non-decay-corrected (ndc) based on 18F-fluorobenzyl azide. 18F-Tr-Sgc8 was found to possess high affinity binding to both cell lines, with IC50 values for HCT116 as 2.7 ± 0.6 nM and U87MG as 16.9 ± 2.1 nM. In vivo PET imaging clearly visualized PTK7 expression in HCT116 xenografted mice with tumor uptake of 0.76 ± 0.09 %ID/g at 30 min post-injection (p.i.) for the subcutaneous tumor model and greater than 1.5 %ID/g for the liver metastasis model. U87MG xenograft tumors had much lower tracer accumulation (0.13 ± 0.06 %ID/g at 30 min p.i.), which was consistent with the lower expression of PTK7 in this tumor model. The labeled aptamer was rapidly cleared from the blood through the kidneys and bladder to give high tumor-to-blood and tumor-to-muscle ratios of 7.29 ± 1.51 and 10.25 ± 2.08, respectively. Conclusions The F-18 radiolabeling methodology shown here is a very robust procedure for labeling aptamers and similar chemical moieties, and can be applied to many different targets. Quantification of PTK7 using 18F-Tr-Sgc8 may be suitable for clinical translation and might help in the future to select and monitor appropriate therapies. PMID:26315836
Dosimetry of 18F-Labeled Tyrosine Kinase Inhibitor SKI-249380, a Dasatinib-Tracer for PET Imaging
Dunphy, Mark P. S.; Zanzonico, Pat; Veach, Darren; Somwar, Romel; Pillarsetty, Nagavarakishore; Lewis, Jason; Larson, Steven
Purpose To obtain estimates of human normal-organ radiation doses of 18F-SKI-249380, as a prerequisite step towards first-in-human trial. 18F-SKI-249380 is a first-of-its-kind PET tracer for imaging the in vivo pharmacokinetics of dasatinib, an investigational targeted therapy for solid malignancies. Procedures Isoflurane-anesthetized mice received tracer dose via tail vein. Organ time-integrated activity coefficients, fractional urinary and hepatobiliary excretion, and total-body clearance kinetics were derived from PET data, with allometric extrapolation to the Standard Man anatomic model and normal-organ-absorbed dose calculations using OLINDA/EXM software. Results The human effective dose was 0.031 mSv/MBq. The critical organ was the upper large intestine, with a dose equivalent of 0.25 mSv/MBq. A 190-MBq administered activity of 18F-SKI-249380 is thus predicted to expose an adult human to radiation doses generally comparable to those of routinely used diagnostic radiopharmaceuticals. Conclusions Animal-based human dose estimates support first-in-human testing of 18F-SKI-249380. PMID:21161687
Synthesis, uptake mechanism characterization and biological evaluation of 18F labeled fluoroalkyl phenylalanine analogs as potential PET imaging agents
Wang, Limin; Qu, Wenchao; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.
Introduction Amino acids based tracers represent a promising class of tumor metabolic imaging agents with successful clinical applications. Two new phenylalanine derivatives, p-(2-[18F]fluoroethyl)-L-phenylalanine (FEP, [18F]2) and p-(3-[18F]fluoropropyl)-L-phenylalanine (FPP, [18F]3) were synthesized and evaluated in comparison to clinically utilized O-(2-[18F]fluoroethyl)-L-tyrosine (FET, [18F]1). Methods FEP ([18F]2) and FPP ([18F]3) were successfully synthesized by a rapid and efficient two-step nucleophilic fluorination of tosylate precursors and deprotection reaction. In vitro cell uptake studies were carried out in 9L glioma cells. In vivo studies, 9L tumor xenografts were implanted in Fisher 344 rats. Results FEP ([18F]2) and FPP ([18F]3) could be efficiently labeled within 90 min with good enantiomeric purity (>95%), good yield (11–37%) and high specific activity (21–69 GBq/μmol). Cell uptake studies showed FEP had higher uptake than FPP as well as reference ligand FET ([18F]1). Uptake mechanism studies suggested that FEP is a selective substrate for system L and prefers its subtype LAT1. In vivo biodistribution studies demonstrated FEP had specific accumulation in tumor cells and tumor to background ratio reached 1.45 at 60 min. Small animal PET imaging studies showed FEP was comparable to FET for imaging rats bearing 9L tumor model. FEP had high uptake in 9L tumor compared to surrounding tissue and was quickly excreted through urinary tract. Conclusion Biological evaluations indicate that FEP ([18F]2) is a potential useful tracer for tumor imaging with PET. PMID:21220129
Synthesis, In Vitro and In Vivo Evaluation of 18F-labeled PET Ligands for Imaging the Vesicular Acetylcholine Transporter
Tu, Zhude; Efange, Simon M. N.; Xu, Jinbin; Li, Shihong; Jones, Lynne A.; Parsons, Stanley M.; Mach, Robert H.
A new class of vesicular acetylcholine transporter inhibitor that incorporates a carbonyl group into the benzovesamicol structure was synthesized and analogs were evaluated in vitro. (±)-trans-2-Hydroxy-3-(4-(4-[18F]fluorobenzoyl)piperidino)tetralin (9e) has Ki values of 2.70 nM for VAChT, 191 nM for σ1 and 251 nM for σ2. The racemic precursor (9d) was resolved via chiral HPLC and (±)-[18F]9e, (-)-[18F]9e, and (+)-[18F]9e were respectively radiolabeled via microwave irradiation of the appropriate precursors with [18F]/F- and Kryptofix/K2CO3 in DMSO with radiochemical yields ∼50-60% and specific activities >2000 mCi/μmol. (-)-[18F]9e uptake in rat brain was consistent with in vivo selectivity for the VAChT with an initial uptake of 0.911 %ID/g in rat striatum and a striatum: cerebellum ratio of 1.88 by 30 min p.i.. MicroPET imaging of macaques demonstrated a 2.1 ratio of (-)-[18F]9e in putamen versus cerebellum at 2 h. p.i. (-)-[18F]9e has potential to be a PET tracer for clinical imaging of the VAChT. PMID:19203271
Novel 18F labeling strategy for polyester-based NPs for in vivo PET-CT imaging.
Di Mauro, Primiano Pio; Gómez-Vallejo, Vanessa; Baz Maldonado, Zuriñe; Llop Roig, Jordi; Borrós, Salvador
Drug-loaded nanocarriers and nanoparticulate systems used for drug release require a careful in vivo evaluation in terms of physicochemical and pharmacokinetic properties. Nuclear imaging techniques such as positron emission tomography (PET) are ideal and noninvasive tools to investigate the biodistribution and biological fate of the nanostructures, but the incorporation of a positron emitter is required. Here we describe a novel approach for the (18)F-radiolabeling of polyester-based nanoparticles. Our approach relies on the preparation of the radiolabeled active agent 4-[(18)F]fluorobenzyl-2-bromoacetamide ([(18)F]FBBA), which is subsequently coupled to block copolymers under mild conditions. The labeled block copolymers are ultimately incorporated as constituent elements of the NPs by using a modified nano coprecipitation method. This strategy has been applied in the current work to the preparation of peptide-functionalized NPs with potential applications in drug delivery. According to the measurements of particle size and zeta potential, the radiolabeling process did not result in a statistically significant alteration of the physicochemical properties of the NPs. Moreover, radiochemical stability studies showed no detachment of the radioactivity from NPs even at 12 h after preparation. The radiolabeled NPs enabled the in vivo quantification of the biodistribution data in rats using a combination of imaging techniques, namely, PET and computerized tomography (CT). Low accumulation of the nanoparticles in the liver and their elimination mainly via urine was found. The different biodistribution pattern obtained for the "free" radiolabeled polymer suggests chemical and radiochemical integrity of the NPs under investigation. The strategy reported here may be applied to any polymeric NPs containing polymers bearing a nucleophile, and hence our novel strategy may find application for the in vivo and noninvasive investigation of a wide range of NPs. PMID:25710619
One-step (18)F-labeling of peptides for positron emission tomography imaging using the SiFA methodology.
Wängler, Carmen; Niedermoser, Sabrina; Chin, Joshua; Orchowski, Katy; Schirrmacher, Esther; Jurkschat, Klaus; Iovkova-Berends, Liuba; Kostikov, Alexey P; Schirrmacher, Ralf; Wängler, Björn
Here we present a procedure to label peptides with the positron-emitting radioisotope fluorine-18 ((18)F) using the silicon-fluoride acceptor (SiFA) labeling methodology. Positron emission tomography (PET) has gained high importance in noninvasive imaging of various diseases over the past decades, and thus new specific imaging probes for PET imaging, especially those labeled with (18)F, because of the advantageous properties of this nuclide, are highly sought after. N-terminally SiFA-modified peptides can be labeled with (18)F(-) in one step at room temperature (20-25 °C) or below without forming side products, thereby producing satisfactory radiochemical yields of 46 ± 1.5% (n = 10). The degree of chemoselectivity of the (18)F-introduction, which is based on simple isotopic exchange, allows for a facile cartridge-based purification fully devoid of HPLC implementation, thereby yielding peptides with specific activities between 44.4 and 62.9 GBq μmol(-1) (1,200-1,700 Ci mmol(-1)) within 25 min. PMID:23037309
Quantitative bioimaging of p-boronophenylalanine in thin liver tissue sections as a tool for treatment planning in boron neutron capture therapy.
Reifschneider, Olga; Schütz, Christian L; Brochhausen, Christoph; Hampel, Gabriele; Ross, Tobias; Sperling, Michael; Karst, Uwe
An analytical method using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to assess enrichment of 10B-containing p-boronophenylalanine-fructose (BPA-f) and its pharmacokinetic distribution in human tissues after application for boron neutron capture therapy (BNCT). High spatial resolution (50 μm) and limits of detection in the low parts-per-billion range were achieved using a Nd:YAG laser of 213 nm wavelength. External calibration by means of 10B-enriched standards based on whole blood proved to yield precise quantification results. Using this calibration method, quantification of 10B in cancerous and healthy tissue was carried out. Additionally, the distribution of 11B was investigated, providing 10B enrichment in the investigated tissues. Quantitative imaging of 10B by means of LA-ICP-MS was demonstrated as a new option to characterise the efficacy of boron compounds for BNCT. PMID:25015045
L-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study
Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna; Vaelimaeki, Petteri; Beule, Annette; Collan, Juhani; Kortesniemi, Mika; Uusi-Simola, Jouni; Kotiluoto, Petri; Auterinen, Iiro; Seren, Tom; Paetau, Anders; Saarilahti, Kauko; Savolainen, Sauli; Joensuu, Heikki
Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of L-boronophenylalanine-fructose (L-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of L-BPA-F, either 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated L-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of L-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an L-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.
Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2
Wongthai, Printip; Hagiwara, Kohei; Miyoshi, Yurika; Wiriyasermkul, Pattama; Wei, Ling; Ohgaki, Ryuichi; Kato, Itsuro; Hamase, Kenji; Nagamori, Shushi; Kanai, Yoshikatsu
The efficacy of boron neutron capture therapy relies on the selective delivery of boron carriers to malignant cells. p-Boronophenylalanine (BPA), a boron delivery agent, has been proposed to be localized to cells through transporter-mediated mechanisms. In this study, we screened aromatic amino acid transporters to identify BPA transporters. Human aromatic amino acid transporters were functionally expressed in Xenopus oocytes and examined for BPA uptake and kinetic parameters. The roles of the transporters in BPA uptake were characterized in cancer cell lines. For the quantitative assessment of BPA uptake, HPLC was used throughout the study. Among aromatic amino acid transporters, ATB0,+, LAT1 and LAT2 were found to transport BPA with Km values of 137.4 ± 11.7, 20.3 ± 0.8 and 88.3 ± 5.6 μM, respectively. Uptake experiments in cancer cell lines revealed that the LAT1 protein amount was the major determinant of BPA uptake at 100 μM, whereas the contribution of ATB0,+ became significant at 1000 μM, accounting for 20–25% of the total BPA uptake in MCF-7 breast cancer cells. ATB0,+, LAT1 and LAT2 transport BPA at affinities comparable with their endogenous substrates, suggesting that they could mediate effective BPA uptake in vivo. The high and low affinities of LAT1 and ATB0,+, respectively, differentiate their roles in BPA uptake. ATB0,+, as well as LAT1, could contribute significantly to the tumor accumulation of BPA at clinical dose. PMID:25580517
SIMS ion microscopy imaging of boronophenylalanine (BPA) and 13C15N-labeled phenylalanine in human glioblastoma cells: Relevance of subcellular scale observations to BPA-mediated boron neutron capture therapy of cancer
NASA Astrophysics Data System (ADS)
Chandra, Subhash; Lorey, Daniel R., II
p-Boronophenylalanine (BPA) is a clinically approved boron neutron capture therapy (BNCT) agent currently being used in clinical trials of glioblastoma multiforme, melanoma and liver metastases. Secondary ion mass spectrometry (SIMS) observations from the Cornell SIMS Laboratory provided support for using a 6 h infusion of BPA, instead of a 2 h infusion, for achieving higher levels of boron in brain tumor cells. These observations were clinically implemented in Phase II experimental trials of glioblastoma multiforme in Sweden. However, the mechanisms for higher BPA accumulation with longer infusions have remained unknown. In this work, by using 13C15N-labeled phenylalanine and T98G human glioblastoma cells, comparisons between the 10B-delivery of BPA and the accumulation of labeled phenylalanine after 2 and 6 h treatments were made with a Cameca IMS-3f SIMS ion microscope at 500 nm spatial resolution in fast frozen, freeze-fractured, freeze-dried cells. Due to the presence of the Na-K-ATPase in the plasma membrane of most mammalian cells, the cells maintain an approximately 10/1 ratio of K/Na in the intracellular milieu. Therefore, the quantitative imaging of these highly diffusible species in the identical cell in which the boron or labeled amino acid was imaged provides a rule-of-thumb criterion for validation of SIMS observations and the reliability of the cryogenic sampling. The labeled phenylalanine was detected at mass 28, as the 28(13C15N)- molecular ion. Correlative analysis with optical and confocal laser scanning microscopy revealed that fractured freeze-dried glioblastoma cells contained well-preserved ultrastructural details with three discernible subcellular regions: a nucleus or multiple nuclei, a mitochondria-rich perinuclear cytoplasmic region and the remaining cytoplasm. SIMS analysis revealed that the overall cellular signals of both 10B from BPA and 28CN- from labeled phenylalanine increased approximately 1.6-fold between the 2 and 6 h exposures
Evaluation of treatment response using integrated 18F-labeled choline positron emission tomography/magnetic resonance imaging in adolescents with intracranial non-germinomatous germ cell tumours.
Tsouana, Eva; Stoneham, Sara; Fersht, Naomi; Kitchen, Neil; Gaze, Mark; Bomanji, Jamshed; Fraioli, Francesco; Hargrave, Darren; Shankar, Ananth
The efficacy of hybrid 18F-Fluroethyl-Choline (FEC) positron emission tomography (PET)/magnetic resonance imaging (MRI) was investigated as an imaging modality for diagnosis and assessment of treatment response and remission status in four patients with proven or suspected intracranial non-germinomatous germ cell tumours (NGGCT). In two patients faint or absent choline avidity correlated with negative histology, whereas in other two patients, persistent choline avidity in the residual mass was suggestive of presence of viable tumour, subsequently confirmed histologically. We conclude that FEC-PET/MRI may be an effective imaging tool in detecting viable residual tumour in patients with intracranial NGGCT post treatment. PMID:25854508
Development of Purine-Derived 18F-Labeled Pro-drug Tracers for Imaging of MRP1 Activity with PET
Multidrug resistance-associated protein 1 (MRP1) is a drug efflux transporter that has been implicated in the pathology of several neurological diseases and is associated with development of multidrug resistance. To enable measurement of MRP1 function in the living brain, a series of 6-halopurines decorated with fluorinated side chains have been synthesized and evaluated as putative pro-drug tracers. The tracers were designed to undergo conjugation with glutathione within the brain and hence form the corresponding MRP1 substrate tracers in situ. 6-Bromo-7-(2-[18F]fluoroethyl)purine showed good brain uptake and rapid metabolic conversion. Dynamic PET imaging demonstrated a marked difference in brain clearance rates between wild-type and mrp1 knockout mice, suggesting that the tracer can allow noninvasive assessment of MRP1 activity in vivo. PMID:24456310
Fast 18F Labeling of a Near-Infrared Fluorophore Enables Positron Emission Tomography and Optical Imaging of Sentinel Lymph Nodes
We combine a novel boronate trap for F− with a near-infrared fluorophore into a single molecule. Attachment to targeting ligands enables localization by positron emission tomography (PET) and near-infrared fluorescence (NIRF). Our first application of this generic tag is to label Lymphoseek (tilmanocept), an agent designed for receptor-specific sentinel lymph node (SLN) mapping. The new conjugate incorporates 18F− in a single, aqueous step, targets mouse SLN rapidly (1 h) with reduced distal lymph node accumulation, permits PET or scintigraphic imaging of SLN, and enables NIRF-guided excision and histological verification even after 18F decay. This embodiment is superior to current SLN mapping agents such as nontargeted [99mTc]sulfur colloids and Isosulfan Blue, as well as the phase III targeted ligand [99mTc]SPECT Lymphoseek counterpart, species that are visible by SPECT or visible absorbance separately. Facile incorporation of 18F into a NIRF probe should promote many synergistic PET and NIRF combinations. PMID:20873712
Structure-Activity Relationship of (18)F-Labeled Phosphoramidate Peptidomimetic Prostate-Specific Membrane Antigen (PSMA)-Targeted Inhibitor Analogues for PET Imaging of Prostate Cancer.
Dannoon, Shorouk; Ganguly, Tanushree; Cahaya, Hendry; Geruntho, Jonathan J; Galliher, Matthew S; Beyer, Sophia K; Choy, Cindy J; Hopkins, Mark R; Regan, Melanie; Blecha, Joseph E; Skultetyova, Lubica; Drake, Christopher R; Jivan, Salma; Barinka, Cyril; Jones, Ella F; Berkman, Clifford E; VanBrocklin, Henry F
A series of phosphoramidate-based prostate specific membrane antigen (PSMA) inhibitors of increasing lipophilicity were synthesized (4, 5, and 6), and their fluorine-18 analogs were evaluated for use as positron emission tomography (PET) imaging agents for prostate cancer. To gain insight into their modes of binding, they were also cocrystallized with the extracellular domain of PSMA. All analogs exhibited irreversible binding to PSMA with IC50 values ranging from 0.4 to 1.3 nM. In vitro assays showed binding and rapid internalization (80-95%, 2 h) of the radiolabeled ligands in PSMA(+) cells. In vivo distribution demonstrated significant uptake in CWR22Rv1 (PSMA(+)) tumor, with tumor to blood ratios of 25.6:1, 63.6:1, and 69.6:1 for [(18)F]4, [(18)F]5, and [(18)F]6, respectively, at 2 h postinjection. Installation of aminohexanoic acid (AH) linkers in the phosphoramidate scaffold improved their PSMA binding and inhibition and was critical for achieving suitable in vivo imaging properties, positioning [(18)F]5 and [(18)F]6 as favorable candidates for future prostate cancer imaging clinical trials. PMID:27228467
Reusable electrochemical cell for rapid separation of [18F]fluoride from [18O]water for flow-through synthesis of 18F-labeled tracers
Sadeghi, Saman; Liang, Vincent; Cheung, Shilin; Woo, Suh; Wu, Curtis; Ly, Jimmy; Deng, Yuliang; Eddings, Mark; van Dam, R. Michael
A brass-platinum electrochemical micro flow cell was developed to extract [18F]fluoride from an aqueous solution and release it into an organic based solution, suitable for subsequent radio-synthesis, in a fast and reliable manner. This cell does not suffer electrode erosion and is thus reusable while operating faster by enabling increased voltages. By optimizing temperature, trapping and release potentials, flow rates, and electrode materials, an overall [18F]fluoride trapping and release efficiency of 84±5% (n=7) was achieved. X-ray photoelectron spectroscopy (XPS) was used to analyze electrode surfaces of various metal-metal systems and the findings were correlated with the performance of the electrochemical cell. To demonstrate the reactivity of the released [18F]fluoride, the cell was coupled to a flow-through reactor and automated synthesis of [18F]FDG with a repeatable decay-corrected yield of 56±4% (n=4) was completed in <15 min. A multi-human dose of 5.92 GBq [18F]FDG was also demonstrated. PMID:23474380
Design, Synthesis, and Evaluation of an (18)F-Labeled Radiotracer Based on Celecoxib-NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase-2 (COX-2).
Kaur, Jatinder; Tietz, Ole; Bhardwaj, Atul; Marshall, Alison; Way, Jenilee; Wuest, Melinda; Wuest, Frank
A series of novel fluorine-containing cyclooxygenase-2 (COX-2) inhibitors was designed and synthesized based on the previously reported fluorescent COX-2 imaging agent celecoxib-NBD (3; NBD=7-nitrobenzofurazan). In vitro COX-1/COX-2 inhibitory data show that N-(4-fluorobenzyl)-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (5; IC50 =0.36 μM, SI>277) and N-fluoromethyl-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (6; IC50 =0.24 μM, SI>416) are potent and selective COX-2 inhibitors. Compound 5 was selected for radiolabeling with the short-lived positron emitter fluorine-18 ((18) F) and evaluated as a positron emission tomography (PET) imaging agent. Radiotracer [(18) F]5 was analyzed in vitro and in vivo using human colorectal cancer model HCA-7. Although radiotracer uptake into COX-2-expressing HCA-7 cells was high, no evidence for COX-2-specific binding was found. Radiotracer uptake into HCA-7 tumors in vivo was low and similar to that of muscle, used as reference tissue. PMID:26287271
(11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain.
Funke, Uta; Vugts, Danielle J; Janssen, Bieneke; Spaans, Arnold; Kruijer, Perry S; Lammertsma, Adriaan A; Perk, Lars R; Windhorst, Albert D
The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, the H1 R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1 R occupancy. The H3 R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3 R PET imaging studies in humans have been reported. The H4 R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4 R-specific (11) C-labeled ligands have been synthesized, and the imaging of the H4 R in vivo is in the early stage. PMID:24285318
In vivo 19F MRI and 19F MRS of 19F-labelled boronophenylalanine fructose complex on a C6 rat glioma model to optimize boron neutron capture therapy (BNCT)
NASA Astrophysics Data System (ADS)
Porcari, Paola; Capuani, Silvia; D'Amore, Emanuela; Lecce, Mario; La Bella, Angela; Fasano, Fabrizio; Campanella, Renzo; Migneco, Luisa Maria; Saverio Pastore, Francesco; Maraviglia, Bruno
Boron neutron capture therapy (BNCT) is a promising binary modality used to treat malignant brain gliomas. To optimize BNCT effectiveness a non-invasive method is needed to monitor the spatial distribution of BNCT carriers in order to estimate the optimal timing for neutron irradiation. In this study, in vivo spatial distribution mapping and pharmacokinetics evaluation of the 19F-labelled boronophenylalanine (BPA) were performed using 19F magnetic resonance imaging (19F MRI) and 19F magnetic resonance spectroscopy (19F MRS). Characteristic uptake of 19F-BPA in C6 glioma showed a maximum at 2.5 h after compound infusion as confirmed by both 19F images and 19F spectra acquired on blood samples collected at different times after infusion. This study shows the ability of 19F MRI to selectively map the bio-distribution of 19F-BPA in a C6 rat glioma model, as well as providing a useful method to perform pharmacokinetics of BNCT carriers.
Capillary electrophoresis-electrospray mass spectrometry and HR-ICP-MS for the detection and quantification of 10B-boronophenylalanine (10B-BPA) used in boron neutron capture therapy.
Pitois, Aurélien; de las Heras, Laura Aldave; Zampolli, Antonella; Menichetti, Luca; Carlos, Ramon; Lazzerini, Guido; Cionini, Luca; Salvatori, Pietro Alberto; Betti, Maria
Boron neutron capture therapy (BNCT) is a bimodal radiotherapeutic treatment based on the irradiation of neoplastic tissues with neutrons after the tissues have selectively accumulated molecules loaded with nuclides with large neutron capture cross-sections (such boron-10). Boron-10 carriers have been tested to a limited extent, and clinical trials have been conducted on sulfhydryl borane (10B-BSH) and boronophenylalanine (10B-BPA). However, precise and accurate measurements of boron-10 concentrations (0.1-100 microg/g) in specimens and samples of limited size (microg scale) are needed in order to be able to biologically characterise new compounds in predictive tissue dosimetry, toxicology and pharmacology studies as well as in clinical investigations. A new approach based on fast separation and detection of 10B-BPA performed by coupling capillary electrophoresis to electrospray mass spectrometry is reported. This method allows the quantitative analysis and characterisation of 10B-BPA in a short time with a high separation efficiency. Detection limits of 3 microM for 10B-BPA and 30 ng/mL for 10B were obtained with CE-ESI-MS. A quantification limit of 10 microM for 10B-BPA (100 ng/mL for 10B) was attained. The total boron-10 concentration was determined by high-resolution inductively coupled mass spectrometry in order to validate the method. Boron-10 isotope measurements were carried out by HR-ICP-MS at medium resolution (R=4000) due to the presence of an isobaric interference at mass 10. Good agreement was obtained between the values from CE-ESI-MS and those from HR-ICP-MS. The method has been successfully used to determine the 10B-BPA in two lines of cultured cells. PMID:16372182
Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs.
Walter, Bernd; Brust, Peter; Füchtner, Frank; Müller, Marco; Hinz, Rainer; Kuwabara, Hiroto; Fritz, Harald; Zwiener, Ulrich; Bauer, Reinhard
There is evidence that the dopaminergic system is sensitive to traumatic brain injury (TBI). However, the age-dependency of this sensitivity has not been studied together with brain oxidative metabolism. We postulate that the acute effects of severe TBI on brain dopamine turnover are age-dependent. Therefore 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with Positron-Emission-Tomography (PET) was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) in the brain of 11 newborn piglets (7-10 days old) and nine juvenile pigs (6-7 weeks old). Six newborn and five juvenile animals were subjected to a severe fluid-percussion (FP) induced TBI. The remaining animals were used as sham operated untreated control groups. Simultaneously, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rates of oxygen and glucose were determined. At 1 h after FP-TBI, [18F]FDOPA was infused and PET scanning was performed for 2 h. At 2 h after FP-TBI administration, a second series of measurements of physiological values including CBF and brain oxidative metabolism data had been obtained. Severe FP-TBI elicited a marked increase in the rate constant for fluorodopamine production (k3FDOPA) in all brain regions of newborn piglets studied by between 97% (mesencephalon) and 143% (frontal cortex) (p < 0.05). In contrast, brain hemodynamics and cerebral oxidative metabolism remained unaltered after TBI. Furthermore, the permeability-surface area product of FDOPA (PSFDOPA) was unchanged. In addition, regional blood flow differences between corresponding ipsi- and contralateral brain regions did not occur after TBI. Thus, it is suggested that severe FP-TBI induces an upregulation of AADC activity of newborn piglets that is not related to alterations in brain oxidative metabolism. PMID:15319007
Scantamburlo, G; Pitchot, W; Ansseau, M
Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could
Samokhvalov, Andriy V; Paton-Gay, C Lindsay; Balchand, Kam; Rehm, Jürgen
Phenibut is a γ-aminobutyric acid (GABA) agonist designed and used as an anxiolytic in Russia. In Western countries, phenibut is not a registered medication but is available through online stores as a supplement. We present a case of a patient who used phenibut to self-medicate anxiety, insomnia and cravings for alcohol. While phenibut was helpful initially, the patient developed dependence including tolerance, significant withdrawal symptoms within 3–4 h of last use and failure to fulfil his roles at work and at home. He finally sought medical assistance in our addictions clinic. We have gradually, over the course of 9 weeks, substituted phenibut with baclofen, which has similar pharmacological properties, and then successfully tapered the patient off baclofen. This required approximately 10 mg of baclofen for each gram of phenibut. PMID:23391959
Samokhvalov, Andriy V; Paton-Gay, C Lindsay; Balchand, Kam; Rehm, Jürgen
Phenibut is a γ-aminobutyric acid (GABA) agonist designed and used as an anxiolytic in Russia. In Western countries, phenibut is not a registered medication but is available through online stores as a supplement. We present a case of a patient who used phenibut to self-medicate anxiety, insomnia and cravings for alcohol. While phenibut was helpful initially, the patient developed dependence including tolerance, significant withdrawal symptoms within 3-4 h of last use and failure to fulfil his roles at work and at home. He finally sought medical assistance in our addictions clinic. We have gradually, over the course of 9 weeks, substituted phenibut with baclofen, which has similar pharmacological properties, and then successfully tapered the patient off baclofen. This required approximately 10 mg of baclofen for each gram of phenibut. PMID:23391959
Chemical dependence - resources
Drug abuse - resources; Resources - chemical dependence ... The following organizations are a good resource for information on drug dependence: National Council on Alcoholism and Drug Dependence -- ncadd.org National Institute on Drug Abuse -- www.drugabuse.gov ...
Dependent personality disorder
Dependent personality disorder is a mental condition in which people depend too much on others to meet their emotional ... Causes of dependent personality disorder are unknown. The disorder usually ... It is one of the most common personality disorders and ...
Dependency, Empathy, and Altruism.
ERIC Educational Resources Information Center
Miller, Shirley Matile
This study examined the relationship of dependency, empathy, and altruism. It was hypothesized that: (1) dependency would be related in a curvilinear manner to empathy, with children who are moderate in dependency scoring highest in empathy; (2) dependency would be positively related to visible altruism when such prosocial behavior results in…
Dependent personality disorder
[Cannabis: Use and dependence].
Dervaux, Alain; Laqueille, Xavier
The main characteristics of cannabis dependence are craving, persistent desire or unsuccessful efforts to cut down or control cannabis use and important social, occupational, or recreational activities given up or reduced because of cannabis use. Withdrawal symptoms include insomnia, irritability, anger, restlessness, depression, mood swings and cravings. Regular cannabis use induces cognitive impairment, especially of attention, episodic memory and working memory. Alcohol and other substances abuse or dependence are frequently found in patients with cannabis dependence. Psychiatric comorbidities are frequent in patients with cannabis dependence, in particular anxiety disorders, mood disorders, and personality disorders. The treatment of cannabis dependence includes behavioral psychotherapy, especially motivational interviewing and cognitive-behavioral therapy, alongside treatment of co-occurring mental health and substance use conditions. There are currently no available pharmacological treatment interventions for cannabis dependence. The treatment of cannabis dependence and withdrawal remains nonspecific. PMID:23040955
Decisions Concerning Directional Dependence
ERIC Educational Resources Information Center
von Eye, Alexander; DeShon, Richard P.
In this rejoinder, von Eye and DeShon discuss the decision strategies proposed in their original article ("Directional Dependence in Developmental Research," this issue), as well as the ones proposed by the authors of the commentary (Pornprasertmanit and Little, "Determining Directional Dependency in Causal Associations," this issue). In addition,…
ERIC Educational Resources Information Center
Edwards, William F.; Shiflett, Ray C.; Shultz, Harris
The mathematical model used to describe independence between two events in probability has a non-intuitive consequence called dependent spaces. The paper begins with a very brief history of the development of probability, then defines dependent spaces, and reviews what is known about finite spaces with uniform probability. The study of finite…
Ozler, Sule
The focus of this paper is the works and life of Adam Smith, who is widely recognized as the father and founder of contemporary economics. Latent content analysis is applied to his seminal text in economics, An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The results reveal that Smith considers dependence on others a problem and sees the solution to this problem in impersonalized interdependence. In addition, his views on social dependency and personal dependency, reflected in his Lectures on Jurisprudence (1963) and The Theory of Moral Sentiments (1759), are analyzed. This analysis suggests a central tension between dependence and independence in Smith's writings. The personal dependency patterns he exhibited in his life, which also suggest a tension between dependence and independence, are identified through a reading of his biographies. Based on insights from psychoanalytic literature, this paper proposes that developing the ideas in the Wealth of Nations was part of Smith's creative solution to this tension. In particular, his solution to one individual's dependence on another was through a system of impersonalized interdependence. In other words, Smith defended against his personal dependence through his economic theorizing. PMID:22712591
Interactive Visualization of Dependencies
ERIC Educational Resources Information Center
Moreno, Camilo Arango; Bischof, Walter F.; Hoover, H. James
We present an interactive tool for browsing course requisites as a case study of dependency visualization. This tool uses multiple interactive visualizations to allow the user to explore the dependencies between courses. A usability study revealed that the proposed browser provides significant advantages over traditional methods, in terms of…
Buprenorphine for opioid dependence.
Ling, Walter
As a treatment agent for opioid dependence, buprenorphine is a nearly ideal medication at our current stage of medication development. Unlike methadone, buprenorphine dosage can be rapidly adjusted with minimal potential for inducing severe consequences. In addition to its intrinsic safety, buprenorphine's relatively low abuse liability in the combination product (i.e., with naloxone as Suboxone) makes it even more acceptable in regulatory quarters as well as to prescribing physicians. The approval of buprenorphine as a pharmacotherapy for opioid dependence returns to physicians the ability to treat their opioid-dependent patients with an effective opioid-based treatment for the first time in nearly 100 years. Buprenorphine is an opioid, however, and potential for misuse remains, even in combination with naloxone. Whether buprenorphine will be increasingly accepted as a treatment for opioid-dependent patients depends on clinicians recognizing the advantages of its uniquely useful properties while still heeding the need to manage their patients' therapy with reasonable vigilance. PMID:19402772
High Performance, Dependable Multiprocessor
NASA Technical Reports Server (NTRS)
Ramos, Jeremy; Samson, John R.; Troxel, Ian; Subramaniyan, Rajagopal; Jacobs, Adam; Greco, James; Cieslewski, Grzegorz; Curreri, John; Fischer, Michael; Grobelny, Eric; George, Alan; Aggarwal, Vikas; Patel, Minesh; Some, Raphael
With the ever increasing demand for higher bandwidth and processing capacity of today's space exploration, space science, and defense missions, the ability to efficiently apply commercial-off-the-shelf (COTS) processors for on-board computing is now a critical need. In response to this need, NASA's New Millennium Program office has commissioned the development of Dependable Multiprocessor (DM) technology for use in payload and robotic missions. The Dependable Multiprocessor technology is a COTS-based, power efficient, high performance, highly dependable, fault tolerant cluster computer. To date, Honeywell has successfully demonstrated a TRL4 prototype of the Dependable Multiprocessor [I], and is now working on the development of a TRLS prototype. For the present effort Honeywell has teamed up with the University of Florida's High-performance Computing and Simulation (HCS) Lab, and together the team has demonstrated major elements of the Dependable Multiprocessor TRLS system.
Measurement of Tanning Dependence
Heckman, C.J.; Darlow, S.; Kloss, J.D.; Cohen-Filipic, J.; Manne, S.L.; Munshi, T.; Yaroch, A.L.; Perlis, C.
Background Indoor tanning has been found to be addictive. However, the most commonly-used tanning dependence measures have not been well-validated. Objective The study's purpose was to explore the psychometric characteristics of and compare the mCAGE (modified Cut-down, Annoyed, Guilty, Eye-opener Scale), mDSM-IV-TR (modified Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition - Text Revised), and TAPS (Tanning Pathology Scale) measures of tanning dependence and provide recommendations for research and practice. Methods This study was a cross-sectional online survey with 18–25 year old female university students. The main outcome variable was tanning dependence measured by the mCAGE, mDSM-IV-TR, and TAPS. Results Internal consistency of the TAPS subscales was good but was poor for the mCAGE and mDSM-IV-TR, except when their items were combined. Agreement between the mCAGE and mDSM-IV-TR was fair. Factor analysis of the TAPS confirmed the current four-factor structure. All of the tanning dependence scales were significantly correlated with one another. Likewise, most of the tanning dependence scales were significantly correlated with other measures of tanning attitudes and behaviors. However, the tolerance to tanning TAPS subscale was not significantly correlated with any measure of tanning attitudes or behaviors and had the lowest subscale internal reliability and eigenvalues. Conclusion Based on the data and existing literature, we make recommendations for the continued use of tanning dependence measures. Intervention may be needed for the approximately 5% of college women who tend to be classified as tanning dependent across measures. Monitoring of individuals reporting tanning dependence symptoms is warranted. PMID:23980870
Buprenorphine for opioid dependence
Ling, Walter
As a treatment agent for opioid dependence, buprenorphine is a nearly ideal medication at our current stage of medication development. Unlike methadone, buprenorphine dosage can be rapidly adjusted with minimal potential for inducing severe consequences. In addition to its intrinsic safety, buprenorphine's relatively low abuse liability in the combination product (i.e., with naloxone as Suboxone®) makes it even more acceptable in regulatory quarters as well as to prescribing physicians. The approval of buprenorphine as a pharmacotherapy for opioid dependence returns to physicians the ability to treat their opioid-dependent patients with an effective opioid-based treatment for the first time in nearly 100 years. Buprenorphine is an opioid, however, and potential for misuse remains, even in combination with naloxone. Whether buprenorphine will be increasingly accepted as a treatment for opioid-dependent patients depends on clinicians recognizing the advantages of its uniquely useful properties while still heeding the need to manage their patients' therapy with reasonable vigilance. PMID:19402772
Dependability and performability analysis
NASA Technical Reports Server (NTRS)
Trivedi, Kishor S.; Ciardo, Gianfranco; Malhotra, Manish; Sahner, Robin A.
Several practical issues regarding specifications and solution of dependability and performability models are discussed. Model types with and without rewards are compared. Continuous-time Markov chains (CTMC's) are compared with (continuous-time) Markov reward models (MRM's) and generalized stochastic Petri nets (GSPN's) are compared with stochastic reward nets (SRN's). It is shown that reward-based models could lead to more concise model specifications and solution of a variety of new measures. With respect to the solution of dependability and performability models, three practical issues were identified: largeness, stiffness, and non-exponentiality, and a variety of approaches are discussed to deal with them, including some of the latest research efforts.
Evolution of Metabolic Dependency
NASA Astrophysics Data System (ADS)
Shou, Wenying
Microbes are often found to have lost their ability to make essential metabolites (auxotrophs) and instead rely on other individuals for these metabolites. How might metabolic dependency evolve to be so common? When microbes live inside a host (endosymbionts), amply host metabolites support auxotrophic endosymbionts. If the host transmits only a small number of endosymbionts to its offspring, then auxotrophic endosymbionts can rise to high frequency simply by chance. On the other hand, auxotrophs have also been observed in abundant free-living bacteria found in ocean water where nutrient supply is low. How might auxotrophs rise to an appreciable frequency in a large population when nutrient supply is low? We have found commonly-encountered conditions that facilitate the evolution of metabolic dependency. Metabolic interactions can in turn shape spatial organization of microbial communities (Momeni et al. (2013) eLife 2, 00230; Momeni et al. (2013) eLife 2, 00960; Estrela and Brown (2013) PLoS Comput Biol 9, e1003398; Muller et al. (2014) PNAS 111, 1037-1042). Rapid evolution of metabolic dependency can contribute to the complexity of microbial communities. Evolution of metabolic dependency.
ERIC Educational Resources Information Center
Collyer, A. A.
Discusses the flow characteristics of thixotropic and negative thixotropic fluids; various theories underlying the thixotropic behavior; and thixotropic phenomena exhibited in drilling muds, commercial paints, pastes, and greases. Inconsistencies in the terminology used to label time dependent effects are revealed. (CC)
ERIC Educational Resources Information Center
Valentich, Mary
Presents a feminist perspective which offers a social structural framework for examining women's problematic behavior in traditional gender roles. Examines implications for treatment of women with drug dependence problems including developing the helping agent's awareness of the pervasiveness of sexism and its potentially negative effects.…
Measurement dependent locality
NASA Astrophysics Data System (ADS)
Pütz, Gilles; Gisin, Nicolas
The demonstration and use of Bell-nonlocality, a concept that is fundamentally striking and is at the core of applications in device independent quantum information processing, relies heavily on the assumption of measurement independence, also called the assumption of free choice. The latter cannot be verified or guaranteed. In this paper, we consider a relaxation of the measurement independence assumption. We briefly review the results of Pütz et al (2014 Phys. Rev. Lett. 113 190402), which show that with our relaxation, the set of so-called measurement dependent local (MDL) correlations is a polytope, i.e. it can be fully described using a finite set of linear inequalities. Here we analyze this polytope, first in the simplest case of two parties with binary inputs and outputs, for which we give a full characterization. We show that partially entangled states are preferable to the maximally entangled state when dealing with measurement dependence in this scenario. We further present a method which transforms any Bell-inequality into an MDL inequality and give valid inequalities for the case of arbitrary number of parties as well as one for arbitrary number of inputs. We introduce the assumption of independent sources in the measurement dependence scenario and give a full analysis for the bipartite scenario with binary inputs and outputs. Finally, we establish a link between measurement dependence and another strong hindrance in certifying nonlocal correlations: nondetection events.
ERIC Educational Resources Information Center
Small, Deborah A.
Natural disasters and other traumatic events often draw a greater charitable response than do ongoing misfortunes, even those that may cause even more widespread misery, such as famine or malaria. Why is the response disproportionate to need? The notion of reference dependence critical to Prospect Theory (Kahneman & Tversky, 1979) maintains that…
[Prevention of alcohol dependence].
Trova, A C; Paparrigopoulos, Th; Liappas, I; Ginieri-Coccossis, M
With the exception of cardiovascular diseases, no other medical condition causes more serious dysfunction or premature deaths than alcohol-related problems. Research results indicate that alcohol dependent individuals present an exceptionally poor level of quality of life. This is an outcome that highlights the necessity of planning and implementing preventive interventions on biological, psychological or social level, to be provided to individuals who make alcohol abuse, as well as to their families. Preventive interventions can be considered on three levels of prevention: (a) primary prevention, which is focused on the protection of healthy individuals from alcohol abuse and dependence, and may be provided on a universal, selective or indicated level, (b) secondary prevention, which aims at the prevention of deterioration regarding alcoholic dependence and relapse, in the cases of individuals already diagnosed with the condition and (c) tertiary prevention, which is focused at minimizing deterioration of functioning in chronically sufferers from alcoholic dependence. The term "quaternary prevention" can be used for the prevention of relapse. As for primary prevention, interventions focus on assessing the risk of falling into problematic use, enhancing protective factors and providing information and health education in general. These interventions can be delivered in schools or in places of work and recreation for young people. In this context, various programs have been applied in different countries, including Greece with positive results (Preventure, Alcolocks, LST, SFP, Alcohol Ignition Interlock Device). Secondary prevention includes counseling and structured help with the delivery of programs in schools and in high risk groups for alcohol dependence (SAP, LST). These programs aim at the development of alcohol refusal skills and behaviors, the adoption of models of behaviors resisting alcohol use, as well as reinforcement of general social skills. In the
Intensity dependent spread theory
NASA Technical Reports Server (NTRS)
Holben, Richard
The Intensity Dependent Spread (IDS) procedure is an image-processing technique based on a model of the processing which occurs in the human visual system. IDS processing is relevant to many aspects of machine vision and image processing. For quantum limited images, it produces an ideal trade-off between spatial resolution and noise averaging, performs edge enhancement thus requiring only mean-crossing detection for the subsequent extraction of scene edges, and yields edge responses whose amplitudes are independent of scene illumination, depending only upon the ratio of the reflectance on the two sides of the edge. These properties suggest that the IDS process may provide significant bandwidth reduction while losing only minimal scene information when used as a preprocessor at or near the image plane.
Lokiarchaeon is hydrogen dependent.
Sousa, Filipa L; Neukirchen, Sinje; Allen, John F; Lane, Nick; Martin, William F
The nature of the host that acquired the mitochondrion at the eukaryote origin is an important microbial evolutionary issue. Modern phylogenetics indicates that the host was an archaeon. The metagenome sequence of Candidatus Lokiarchaeon has identified it as being the closest relative of the host yet known. Here, we report comparative genomic evidence indicating that Lokiarchaeon is hydrogen dependent, as one theory for the eukaryote origin-the hydrogen hypothesis-predicts for the host lineage. PMID:27572645
Doran, N.A.; Arnold, A.J.; Parker, W.C.; Huffer, F.W.
Age-dependent extinction is an observation with important biological implications. Van Valen's Red Queen hypothesis triggered three decades of research testing its primary implication: that age is independent of extinction. In contrast to this, later studies with species-level data have indicated the possible presence of age dependence. Since the formulation of the Red Queen hypothesis, more powerful tests of survivorship models have been developed. This is the first report of the application of the Cox Proportional Hazards model to paleontological data. Planktonic foraminiferal morphospecies allow the taxonomic and precise stratigraphic resolution necessary for the Cox model. As a whole, planktonic foraminiferal morphospecies clearly show age-dependent extinction. In particular, the effect is attributable to the presence of shorter-ranged species (range < 4 myr) following extinction events. These shorter-ranged species also possess tests with unique morphological architecture. The morphological differences are probably epiphenomena of underlying developmental and heterochronic processes of shorter-ranged species that survived various extinction events. Extinction survivors carry developmental and morphological characteristics into postextinction recovery times, and this sets them apart from species populations established independently of extinction events. Copyright ?? 2006, SEPM (Society for Sedimentary Geology).
Neurobiology of Alcohol Dependence
Gilpin, Nicholas W.; Koob, George F.
Alcoholism is a debilitating disorder for the individual and very costly for society. A major goal of alcohol research is to understand the neural underpinnings associated with the transition from alcohol use to alcohol dependence. Positive reinforcement is important in the early stages of alcohol use and abuse. Negative reinforcement can be important early in alcohol use by people self-medicating coexisting affective disorders, but its role likely increases following the transition to dependence. Chronic exposure to alcohol induces changes in neural circuits that control motivational processes, including arousal, reward, and stress. These changes affect systems utilizing the signaling molecules dopamine, opioid peptides, γ-aminobutyric acid, glutamate, and serotonin, as well as systems modulating the brain's stress response. These neuroadaptations produce changes in sensitivity to alcohol's effects following repeated exposure (i.e., sensitization and tolerance) and a withdrawal state following discontinuation of alcohol use. Chronic alcohol exposure also results in persistent neural deficits, some of which may fully recover following extended periods of abstinence. However, the organism remains susceptible to relapse, even after long periods of abstinence. Recent research focusing on brain arousal, reward, and stress systems is accelerating our understanding of the components of alcohol dependence and contributing to the development of new treatment strategies. PMID:19881886
NASA Astrophysics Data System (ADS)
Das, Diptarka
One of the most important results emerging from string theory is the gauge gravity duality (AdS/CFT correspondence) which tells us that certain problems in particular gravitational backgrounds can be exactly mapped to a particular dual gauge theory a quantum theory very similar to the one explaining the interactions between fundamental subatomic particles. The chief merit of the duality is that a difficult problem in one theory can be mapped to a simpler and solvable problem in the other theory. The duality can be used both ways. Most of the current theoretical framework is suited to study equilibrium systems, or systems where time dependence is at most adiabatic. However in the real world, systems are almost always out of equilibrium. Generically these scenarios are described by quenches, where a parameter of the theory is made time dependent. In this dissertation I describe some of the work done in the context of studying quantum quench using the AdS/CFT correspondence. We recover certain universal scaling type of behavior as the quenching is done through a quantum critical point. Another question that has been explored in the dissertation is time dependence of the gravity theory. Present cosmological observations indicate that our universe is accelerating and is described by a spacetime called de-Sitter(dS). In 2011 there had been a speculation over a possible duality between de-Sitter gravity and a particular field theory (Euclidean SP(N) CFT). However a concrete realization of this proposition was still lacking. Here we explicitly derive the dS/CFT duality using well known methods in field theory. We discovered that the time dimension emerges naturally in the derivation. We also describe further applications and extensions of dS/CFT. KEYWORDS: Holography, AdS/CFT correspondence, Quantum Quench, dS/CFT correspondence, Chaos.
Bleakley, Hoyt; Lin, Jeffrey
We examine portage sites in the U.S. South, Mid-Atlantic, and Midwest, including those on the fall line, a geomorphological feature in the southeastern U.S. marking the final rapids on rivers before the ocean. Historically, waterborne transport of goods required portage around the falls at these points, while some falls provided water power during early industrialization. These factors attracted commerce and manufacturing. Although these original advantages have long since been made obsolete, we document the continuing importance of these portage sites over time. We interpret these results as path dependence and contrast explanations based on sunk costs interacting with decreasing versus increasing returns to scale. PMID:23935217
Bleakley, Hoyt; Lin, Jeffrey
We examine portage sites in the U.S. South, Mid-Atlantic, and Midwest, including those on the fall line, a geomorphological feature in the southeastern U.S. marking the final rapids on rivers before the ocean. Historically, waterborne transport of goods required portage around the falls at these points, while some falls provided water power during early industrialization. These factors attracted commerce and manufacturing. Although these original advantages have long since been made obsolete, we document the continuing importance of these portage sites over time. We interpret these results as path dependence and contrast explanations based on sunk costs interacting with decreasing versus increasing returns to scale. PMID:23935217
Velocity dependant splash behaviour
NASA Astrophysics Data System (ADS)
Hamlett, C. A. E.; Shirtcliffe, N. J.; McHale, G.; Ahn, S.; Doerr, S. H.; Bryant, R.; Newton, M. I.
Extreme soil water repellency can occur in nature via condensation of volatile organic compounds released during wildfires and can lead to increased erosion rate. Such extreme water repellent soil can be classified as superhydrophobic and shares similar chemical and topographical features to specifically designed superhydrophobic surfaces. Previous studies using high speed videography to investigate single droplet impact behaviour on artificial superhydrophobic have revealed three distinct modes of splash behaviour (rebound, pinned and fragmentation) which are dependent on the impact velocity of the droplet. In our studies, using high-speed videography, we show that such splash behaviour can be replicated on fixed 'model' water repellent soils (hydrophobic glass beads/particles). We show that the type of splash behaviour is dependent on both the size and chemical nature of the fixed particles. The particle shape also influences the splash behaviour as shown by drop impact experiments on fixed sand samples. We have also studied soil samples, as collected from the field, which shows that the type of droplet splash behaviour can lead to enhanced soil particle transport.
4-[18F]Fluorophenylpiperazines by improved Hartwig-Buchwald N-arylation of 4-[18F]fluoroiodobenzene, formed via hypervalent λ3-iodane precursors: application to build-up of the dopamine D4 ligand [18F]FAUC 316.
Kügler, Fabian; Ermert, Johannes; Kaufholz, Peter; Coenen, Heinz H
Substituted phenylpiperazines are often neuropharmacologically active compounds and in many cases are essential pharmacophores of neuroligands for different receptors such as D2-like dopaminergic, serotoninergic and other receptors. Nucleophilic, no-carrier-added (n.c.a.) 18F-labelling of these ligands in an aromatic position is desirable for studying receptors with in vivo molecular imaging. 1-(4-[18F]Fluorophenyl)piperazine was synthesized in two reaction steps starting by 18F-labelling of a iodobenzene-iodonium precursor, followed by Pd-catalyzed N-arylation of the intermediate 4-[18F]fluoro-iodobenzene. Different palladium catalysts and solvents were tested with particular attention to the polar solvents dimethylformamide (DMF) and dimethylsulfoxide (DMSO). Weak inorganic bases like potassium phosphate or cesium carbonate seem to be essential for the arylation step and lead to conversation rates above 70% in DMF which is comparable to those in typically used toluene. In DMSO even quantitative conversation was observed. Overall radiochemical yields of up to 40% and 60% in DMF and DMSO, respectively, were reached depending on the labelling yield of the first step. The fluorophenylpiperazine obtained was coupled in a third reaction step with 2-formyl-1H-indole-5-carbonitrile to yield the highly selective dopamine D4 ligand [18F]FAUC 316. PMID:25558857
Comparison of the biological effects of {sup 18}F at different intracellular levels
Kashino, Genro; Hayashi, Kazutaka; Douhara, Kazumasa; Kobashigawa, Shinko; Mori, Hiromu
Highlights: • We estimated the inductions of DNA DSB in cell treated with {sup 18}F-FDG. • We found that inductions of DNA DSB are dependent on accumulation of {sup 18}F in cell. • Accumulation of {sup 18}F in cell may be indispensable for risk estimation of PET. - Abstract: We herein examined the biological effects of cells treated with {sup 18}F labeled drugs for positron emission tomography (PET). The relationship between the intracellular distribution of {sup 18}F and levels of damaged DNA has yet to be clarified in detail. We used culture cells (Chinese Hamster Ovary cells) treated with two types of {sup 18}F labeled drugs, fluorodeoxyglucose (FDG) and fluorine ion (HF). FDG efficiently accumulated in cells, whereas HF did not. To examine the induction of DNA double strand breaks (DSB), we measured the number of foci for 53BP1 that formed at the site of DNA DSB. The results revealed that although radioactivity levels were the same, the induction of 53BP1 foci was stronger in cells treated with {sup 18}F-FDG than in those treated with {sup 18}F-HF. The clonogenic survival of cells was significantly lower with {sup 18}F-FDG than with {sup 18}F-HF. We concluded that the efficient accumulation of {sup 18}F in cells led to stronger biological effects due to more severe cellular lethality via the induction of DNA DSB.
NASA Astrophysics Data System (ADS)
Polidoro, B.; Iervolino, I.; Chioccarelli, E.; Giorgio, M.
Probabilistic seismic hazard is usually computed trough a homogeneous Poisson process that even though it is a time-independent process it is widely used for its very convenient properties. However, when a single fault is of concern and/or the time scale is different from that of the long term, time-dependent processes are required. In this paper, different time-dependent models are reviewed with working examples. In fact, the Paganica fault (in central Italy) has been considered to compute both the probability of occurrence of at least one event in the lifespan of the structure, as well as the seismic hazard expressed in terms of probability of exceedance of an intensity value in a given time frame causing the collapse of the structure. Several models, well known or novel application to engineering hazard have been considered, limitation and issues in their applications are also discussed. The Brownian Passage Time (BPT) model is based on a stochastic modification of the deterministic stick-slip oscillator model for characteristic earthquakes; i.e., based on the addition of random perturbations (a Gaussian white noise) to the deterministic load path predicted by elastic rebound theory. This model assumes that the load state is at some ground level immediately after an event, increases steadly over time, reaches a failure threshold and relaxes instantaneously back to the ground level. For this model also a variable threshold has been considered to take into account the uncertainty of the threshold value. For the slip-predictable model it is assumed that the stress accumulates at a constant rate starting from some initial stress level. Stress is assumed to accumulate for a random period of time until an earthquake occurs. The size of the earthquake is governed by the stress release and it is a function of the elapsed time since the last event. In the time-predictable model stress buildup occurs at a constant rate until the accumulated stress reaches a threshold
Parenthood and opioid dependence
Pihkala, Heljä; Sandlund, Mikael
Introduction Many patients in maintenance treatment programs for opioid dependence are parents to underage children. Objective The aim of this study was to explore how parents who are regular patients in maintenance treatment perceive their parenthood. Methods The study used a qualitative approach. The informants were recruited by staff at a substance abuse clinic in Sweden. Criteria for inclusion were participation in the local maintenance treatment program, having a child or children younger than 18 years, and being in contact with the child or children. Data were collected in 2012–2013 by in-depth interviews of seven fathers and five mothers and analyzed using concepts and procedures of qualitative content analysis. Results The central findings of the study were: 1) the parents' concerns about possible future discrimination against their children, ie, stigma by association; and 2) the patients' own parents' role as the most important support in parenthood. Conclusion The issue of anticipated discrimination against the children of parents undergoing maintenance treatment might be an aspect to consider in the development of interventions and support. Considering the role of the patients' own parents also seems important. PMID:25709518
Summary Cyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. CDKs play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. This review summarizes how, although CDKs are traditionally separated into cell-cycle or transcriptional CDKs, these activities are frequently combined in many family members. Not surprisingly, deregulation of this family of proteins is a hallmark of several diseases, including cancer, and drug-targeted inhibition of specific members has generated very encouraging results in clinical trials. PMID:25180339
Wavelength dependent mask defects
NASA Astrophysics Data System (ADS)
Badger, Karen; Butt, Shahid; Burnham, Jay; Faure, Tom; Hibbs, Michael; Rankin, Jed; Thibault, David; Watts, Andrew
For years there has been a mismatch between the photomask inspection wavelength and the usage conditions. While the non-actinic inspection has been a source for concern, there has been essentially no evidence that a defect "escaped" the mask production process due to the inspection mismatch. This paper will describe the discovery of one such defect, as well as the diagnostic and inspection techniques used to identify the location, analyze the composition, and determine the source of the printed wafer defect. Conventional mask inspection techniques revealed no defects, however an actinic Aerial Image Metrology System (AIMS) revealed a 1.5 mm region on the mask with up to 59% transmission reduction at 193 nm. Further diagnostics demonstrated a strong wavelength dependence which accounted for the near invisibility of the defect at I line (365 nm) or even DUV (248 nm) wavelengths, which had 0% and 5% respective transmission reductions. Using some creative imaging techniques via AIMS tool and modeling, the defect was deduced to have a three dimensional Gaussian absorption character, with total width approximately 1.5 mm. Several non-destructive diagnostic techniques were developed to determine the composition and location of the defect within the substrate. These results will be described in addition to identifying methods for ensuring product quality in the absence of actinic inspection.
Pharmacotherapies for cannabis dependence
Marshall, Kushani; Gowing, Linda; Ali, Robert; Le Foll, Bernard
Background Cannabis is the most prevalent illicit drug in the world. Demand for treatment of cannabis use disorders is increasing. There are currently no pharmacotherapies approved for treatment of cannabis use disorders. Objectives To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or supportive care for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to 4 March 2014), MEDLINE (to week 3 February 2014), EMBASE (to 3 March 2014) and PsycINFO (to week 4 February 2014). We also searched reference lists of articles, electronic sources of ongoing trials and conference proceedings, and contacted selected researchers active in the area. Selection criteria Randomised and quasi-randomised controlled trials involving the use of medications to reduce the symptoms and signs of cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in participants diagnosed as cannabis dependent or who were likely to be dependent. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two review authors assessed studies for inclusion and extracted data. All review authors confirmed the inclusion decisions and the overall process. Main results We included 14 randomised controlled trials involving 958 participants. For 10 studies the average age was 33 years; two studies targeted young people; and age data were not available for two studies. Approximately 80% of study participants were male. The studies were at low risk of selection, performance, detection and selective outcome reporting bias. Three studies were at risk of attrition bias. All studies involved comparison of active medication and placebo. The medications included preparations containing
Texting Dependence, iPod Dependence, and Delay Discounting.
Ferraro, F Richard; Weatherly, Jeffrey N
We gave 127 undergraduates questionnaires about their iPod and texting dependence and 2 hypothetical delay discounting scenarios related to free downloaded songs and free texting for life. Using regression analyses we found that when iPod dependence was the dependent variable, Text2-excessive use, Text4-psychological and behavioral symptoms, iPod2-excessive use, and iPod3-relationship disruption were significant predictors of discounting. When texting dependence was the dependent variable, Text4-psychological and behavioral symptoms and iPod3-relationship disruption were significant predictors of discounting. These are the first data to show that delay discounting relates to certain aspects of social media, namely iPod and texting dependence. These data also show that across these 2 dependencies, both psychological and behavioral symptoms and relationship disruptions are affected. PMID:27424418
Pharmacological Intervention of Nicotine Dependence
Jain, Raka; Gupta, Tina
Nicotine dependence is a major cause of mortality and morbidity all over the world. Various medications have been tried to treat nicotine dependence including nicotine replacement therapy, bupropion, and varenicline. A newer venture to nicotine dependence treatment is a nicotine vaccine which is yet to get footsteps in common practice. The present review assimilates various pharmacotherapeutic measures to address nicotine dependence. However, it is to be noted that psychological interventions, when combined with pharmacotherapy, offer the greatest benefits to the patients. PMID:24490153
Gupta, Sumit; Garg, Bhavuk
Etizolam is a thienodiazepine anxiolytic which is said to have lower dependence potential than other benzodiazepines. We report a case of etizolam dependence in a young male with social anxiety disorder and moderate depression. This case report highlights the fact that the same caution be exercised while prescribing etizolam with respect to its potential to cause dependence as with any other benzodiazepine. PMID:25538342
A case of etizolam dependence.
Gupta, Sumit; Garg, Bhavuk
Etizolam is a thienodiazepine anxiolytic which is said to have lower dependence potential than other benzodiazepines. We report a case of etizolam dependence in a young male with social anxiety disorder and moderate depression. This case report highlights the fact that the same caution be exercised while prescribing etizolam with respect to its potential to cause dependence as with any other benzodiazepine. PMID:25538342
Study designs for dependent happenings.
Halloran, M E; Struchiner, C J
In 1916, Sir Ronald Ross defined "dependent happenings" as events where the number affected in a unit of time depends on the number already affected. That is, the incidence depends on the prevalence, a characteristic of many infectious diseases. Because of this dependence, interventions against infectious diseases can have not only direct protective effects for the person receiving an intervention, but also indirect effects resulting from changes in the intensity of transmission in the population. This paper develops the conceptual framework for four types of study designs that differentiate and account for direct and indirect effects of intervention programs in dependent happenings. PMID:1742381
Dependent failures of diesel generators
Mankamo, T.; Pulkkinen, U.
This survey of dependent failures (common-cause failures) is based on the data of diesel generator failures in U. S. nuclear power plants as reported in Licensee Event Reports. Failures were classified into random and potentially dependent failures. All failures due to design errors, manufacturing or installation errors, maintenance errors, or deviations in the operational environment were classified as potentially dependent failures.The statistical dependence between failures was estimated from the relative portion of multiple failures. Results confirm the earlier view of the significance of statistical dependence, a strong dependence on the age of the diesel generator was found in each failure class excluding random failures and maintenance errors, which had a nearly constant frequency independent of diesel generator age.
A case of pheniramine dependence.
Saatcioglu, Omer; Evren, Cuneyt
Abuse and addiction of histaminergic agonists and antagonists were investigated. The withdrawal signs may become after using drugs such as L-histidine, histamine-N-methyl, promethazine, pheniramine, astemizole, etc. Some medicines which include these active metabolites could lead to dependence cause different side effects. This case suggests that pheniramine abuse also could to dependence. We should pay attention to trend of pheniramine and other histaminergic drugs dependence and need to regulate the market by law more severely. PMID:16492663
Measuring Dependence on Imported Oil
U.S. dependence on imported oil can be measured in at least two ways. The differences hinge largely on whether oil imports are defined as net imports (total imports minus exports) or as total imports. EIA introduces a revised table that expresses dependence on imports in terms of both measures.
ERIC Educational Resources Information Center
Weippl, Edgar R.
E-learning systems are used by many universities for both blended learning and distance education. In both cases the success of courses depends, among many other factors, on e-learning applications that work reliably. For e-assessments the expected level of reliability and dependability is even higher. By clearly analyzing technical and…
Detecting Mood-Dependent Retrieval.
ERIC Educational Resources Information Center
Mayer, John D.; Bower, Gordon H.
The mood-dependent retrieval hypothesis states that mood will enhance recall by acting as a recall cue if the stimuli have been learned initially in the same mood. Material learned in a happy mood will be best recalled when the person returns to a happy mood; the same holds for a sad mood. Mood-dependent retrieval effect has been regulary…
Momentum dependence of symmetry energy
NASA Astrophysics Data System (ADS)
Coupland, Daniel D.; Youngs, Michael; Chajecki, Zbigniew; Lynch, William; Tsang, Betty; Zhang, Yingxun; Famiano, Michael; Ghosh, Tilak; Giacherio, B.; Kilburn, Micha; Lee, Jenny; Lu, Fei; Russotto, Paulo; Sanetullaev, Alisher; Showalter, Rachel; Verde, Giuseppe; Winkelbauer, Jack
One of the main uncertainties in the Equation of State of neutron-rich nuclear matter concerns the density and momentum dependence of the nuclear symmetry energy. Some constraints on the density dependence of the symmetry energy at sub-saturation densities have been recently obtained. However questions remain, especially concerning the momentum dependence of the symmetry mean-field potential that can make the neutron and proton effective masses different. We probe the momentum dependence of this isovector mean-field potential by comparing the energy spectra of neutrons and protons emitted in 112Sn+112Sn and 124Sn +124Sn collisions at incident energies of E/A = 50 and 120 MeV. We achieve an experimental precision that can discriminate between transport model predictions for the n/p double ratio for different momentum dependencies of the symmetry mean-field potential. One of the main uncertainties in the Equation of State of neutron-rich nuclear matter concerns the density and momentum dependence of the nuclear symmetry energy. Some constraints on the density dependence of the symmetry energy at sub-saturation densities have been recently obtained. However questions remain, especially concerning the momentum dependence of the symmetry mean-field potential that can make the neutron and proton effective masses different. We probe the momentum dependence of this isovector mean-field potential by comparing the energy spectra of neutrons and protons emitted in 112Sn+112Sn and 124Sn+124Sn collisions at incident energies of E/A = 50 and 120 MeV. We achieve an experimental precision that can discriminate between transport model predictions for the n/p double ratio for different momentum dependencies of the symmetry mean-field potential. PHY-1102511.
Early recognition of chemical dependence.
Maly, R C
Chemical dependence is a leading cause of morbidity and death in the United States. At least 20% of patients seen by primary care physicians in both the outpatient and inpatient setting are chemically dependent. Up to 90% of these patients go undiagnosed by their primary physicians. Chemical dependence is defined as a chronic, progressive illness characterized by the repeated and persistent use of alcohol or drugs despite negative health, family, work, financial, or legal consequences. Primary care physicians are in an ideal position to detect chemical dependence at its earliest stages, when irreversible medical consequences and death are most likely preventable. Alcohol is the most common drug of abuse. Improving the rate of recognition of chemical dependence depends on being familiar with the constellation of physical, mental, and social indicators. Early medical manifestations of alcoholism common in the primary care setting include: gastric complaints, elevated blood pressure, palpitations, traumatic injuries, headaches, impotence, and gout. Early psychosocial manifestations common in both alcohol and drug dependence include anxiety, depression, insomnia, persistent relationship conflicts, work or school problems, and financial or legal problems. Particularly useful laboratory indicators of alcoholism include elevated levels of GGT and MCV, both displaying high specificity, with the GGT level being the most sensitive. Similarly specific laboratory tests for drug dependence are not available. Any patient presenting with any of the above medical, psychosocial, or laboratory manifestations should be screened for chemical dependence. The CAGE questionnaire for alcoholism, a four-question test, is particularly well suited to the primary care setting, where it can be administered in fewer than 60 seconds. The CAGE has demonstrated high sensitivity (in the 80% range) and specificity (approximately 85%) for alcoholism. Comparably convenient instruments do not yet exist
Evaluating Dependence Criteria for Caffeine.
Striley, Catherine L W; Griffiths, Roland R; Cottler, Linda B
Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who reported caffeine use in the last 7 days and also reported use of alcohol, nicotine, or illicit drugs within the past year (n=167). Results: Thirty-five percent met the criteria for dependence when all seven of the adopted DSM dependence criteria were used. Rates of endorsement of several of the most applicable diagnostic criteria were as follows: 26% withdrawal, 23% desire to cut down or control use, and 44% continued use despite harm. In addition, 34% endorsed craving, 26% said they needed caffeine to function, and 10% indicated that they talked to a physician or counselor about problems experienced with caffeine. There was a trend towards increased caffeine dependence among those dependent on nicotine or alcohol. Within a subgroup that had used caffeine, alcohol, and nicotine in the past year, 28% fulfilled criteria for caffeine dependence compared to 50% for alcohol and 80% for nicotine. Conclusion: The present study adds to a growing literature suggesting the reliability, validity, and clinical utility of the caffeine dependence diagnosis. Recognition of caffeine dependence in the DSM-V may be clinically useful. PMID:24761264
Statistical dependency in visual scanning
NASA Technical Reports Server (NTRS)
Ellis, Stephen R.; Stark, Lawrence
A method to identify statistical dependencies in the positions of eye fixations is developed and applied to eye movement data from subjects who viewed dynamic displays of air traffic and judged future relative position of aircraft. Analysis of approximately 23,000 fixations on points of interest on the display identified statistical dependencies in scanning that were independent of the physical placement of the points of interest. Identification of these dependencies is inconsistent with random-sampling-based theories used to model visual search and information seeking.
[Tests for evaluating tobacco dependence].
Underner, M; Le Houezec, J; Perriot, J; Peiffer, G
The primary reason why there is such a heavy burden of tobacco smoking induced illness and death is dependence on nicotine which makes it difficult for smokers to quit. For clinical or research purposes, the degree of dependence, the intensity of the withdrawal syndrome and/or craving have been evaluated by different scales. This review provides a list of questionnaires that are used in smoking cessation. It pays particular attention to the validated and translated resources that are available in French. Research should be conducted in order to provide French speaking smoking cessation specialists with all the relevant scales allowing better evaluation of tobacco dependence. PMID:22542405
The Cost of Technological Dependence
ERIC Educational Resources Information Center
Patel, Surendra J.
Technological transfer often exacts a definite price, with the developing countries in an obvious situation of dependency. But today it is possible to appraise the economic and social cost of transference. (BL)
NASA Astrophysics Data System (ADS)
Ferreira, H.; Pereira, L.
We evaluate the dependence among large values of a spatial process of maxima trough a coefficient that can be applied in natural, technical and societal extreme phenomena. Its main properties are: a) k locations can be taken into account; b) it takes values in [0,1] and higher values indicate stronger dependence; c) it is independent of the univariate marginal distributions of the random field; d) it can be related with other coefficients in the literature such as the tail dependence and the extremal coefficients; e) it agrees with the concordance property for multivariate distributions; f) it has as a particular case the variogram from geostatistics; g) it can be easily estimated. We illustrate the application of the introduced coefficient with the estimation of the degree of dependence among large values of the amount of tritium in drinking water for tree cities.
Time-dependent drift Hamiltonian
Boozer, A.H.
The lowest-order drift equations are given in a canonical magnetic coordinate form for time-dependent magnetic and electric fields. The advantages of the canonical Hamiltonian form are also discussed.
[Helping the highly dependent smokers].
Perriot, J; Mathern, G; André, E; Schmitt, A; Merson, F; Brousse, G; Underner, M
Many smokers have difficulty in stopping smoking, either motivated to stop or forced for health, economic or statutory reasons. They have in common a heavy tobacco dependence and a high level of cigarette consumption. Often they combined factors impairing success in the attempt to stop smoking : e. g. anxio-depressive disorders, use of psychoactive substances, socio-economic deprivation. Smoking cessation specialists must optimize their interventions in order to improve the care of these highly dependent smokers. PMID:23888574
Scale-dependent halo bias from scale-dependent growth
Parfrey, Kyle; Hui, Lam; Sheth, Ravi K.
We derive a general expression for the large-scale halo bias, in theories with a scale-dependent linear growth, using the excursion set formalism. Such theories include modified-gravity models, and models in which the dark energy clustering is non-negligible. A scale dependence is imprinted in both the formation and evolved biases by the scale-dependent growth. Mergers are accounted for in our derivation, which thus extends earlier work which focused on passive evolution. There is a simple analytic form for the bias for those theories in which the nonlinear collapse of perturbations is approximately the same as in general relativity. As an illustration, we apply our results to a simple Yukawa modification of gravity, and use Sloan Digital Sky Survey measurements of the clustering of luminous red galaxies to constrain the theory's parameters.
[In dependence on process of the act].
Watanabe, Noboru
The author explains the concept of dependence and classifies dependence into two categories: mutually supporting dependence (good dependence) and selfish dependence (bad dependence). Then, three types of bad dependence (interpersonal dependence, process dependence, substance dependence) are outlined. Among them, process dependence is as follows. Some people find temporary relief when they become involved in the process of doing something, such as gambling, shopping, and stealing. However, they soon start to regret their actions and attempt to refrain from repeating the process, but this exacerbates their feeling of internal tension. They then repeat the process to relieve the tension, resulting in a vicious cycle of tension and relief. PMID:26394520
[Genetic vulnerability of methamphetamine dependence].
Moriya, Yuki; Kasahara, Yoshiyuki; Sora, Ichiro
Methamphetamine (METH) dependence show strong familial and genetic influences in family and twin studies. METH exerts its reinforcing effects by modulating monoaminergic transmission, of which dopamine is supposed to be important. Previously, experimental animals were being used to identify mechanisms of action of METH that are related to its abuse and toxicity, and genetic mouse models have also been used to define genes that may predict risk for the development of drug addiction. We found that genetic variances of dopamine transporter, dopamine receptor, micro-opioid receptor, serotonin 1A receptor, serotonin 6 receptor, and adenosine 2A adenosine receptor could be vulnerability factors for METH dependence or psychosis in the Japanese population. Genetic analysis with a genome-wide association study (GWAS)-based approach has been successful for investigating the genetic influences of METH dependence and other complex features. Collaborative studies with JGIDA and NIDA/NIH have obtained the results that the genetic vulnerability to METH dependence contributes to other major drug addiction. The genetic studies for METH dependence might help to identify the risk of individuals and to develop treatments that take advantage of individual genetic information in the future. PMID:25069251
Dependency Structures for Statistical Machine Translation
ERIC Educational Resources Information Center
Bach, Nguyen
Dependency structures represent a sentence as a set of dependency relations. Normally the dependency structures from a tree connect all the words in a sentence. One of the most defining characters of dependency structures is the ability to bring long distance dependency between words to local dependency structures. Another the main attraction of…
[Drug dependence and psychotropic drugs].
Giraud, M J; Lemonnier, E; Bigot, T
Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941
Effectiveness of data dependence analysis
Maydan, D.E.; Hennessy, J.L.; Lam, M.S.
Data dependence testing is the basic step in detecting loop level parallelism in numerical programs. The problem is undecidable in the general case. Therefore, work has been concentrated on a simplified problems, affine memory disambiguation. In this simpler domain, array references and loops bounds are assumed to be linear integer functions of loop variables. Dataflow information is ignored. For this domain, we have shown that in practice the problem can be solved accurately and efficiently. This paper studies empirically the effectiveness of this domain restriction, however many real references are affine and flow insensitive. We use Larus`s llpp system to find all the data dependences dynamically. We compare these to the results given by our affine memory disambiguation system. This system is exact for all the cases we see in practice. We show that while the affine approximation is reasonable, memory disambiguation is not a sufficient approximation for data dependence analysis. We propose extensions to improve the analysis.
Anabolic steroid abuse and dependence.
Brower, Kirk J
Anabolic-androgenic steroids (AAS) are mainly used to treat androgen deficiency syndromes and, more recently, catabolic states such as AIDS-associated wasting. There is no evidence in the reviewed literature that AAS abuse or dependence develops from the therapeutic use of AAS. Conversely, 165 instances of AAS dependence have been reported among weightlifters and bodybuilders who, as part of their weight training regimens, chronically administered supraphysiologic doses, often including combinations of injected and oral AAS as well as other drugs of abuse. A new model is proposed in which both the "myoactive" and psychoactive effects of AAS contribute to the development of AAS dependence. The adverse consequences of AAS are reviewed, as well as their assessment by means of a history and physical, mental status examination, and laboratory testing. When patients with AAS use disorders are compared with patients with other substance use disorders, both similarities and differences become apparent and have implications for treatment. PMID:12230967
Developing Tests of Visual Dependency
NASA Technical Reports Server (NTRS)
Kindrat, Alexandra N.
Astronauts develop neural adaptive responses to microgravity during space flight. Consequently these adaptive responses cause maladaptive disturbances in balance and gait function when astronauts return to Earth and are re-exposed to gravity. Current research in the Neuroscience Laboratories at NASA-JSC is focused on understanding how exposure to space flight produces post-flight disturbances in balance and gait control and developing training programs designed to facilitate the rapid recovery of functional mobility after space flight. In concert with these disturbances, astronauts also often report an increase in their visual dependency during space flight. To better understand this phenomenon, studies were conducted with specially designed training programs focusing on visual dependency with the aim to understand and enhance subjects ability to rapidly adapt to novel sensory situations. The Rod and Frame test (RFT) was used first to assess an individual s visual dependency, using a variety of testing techniques. Once assessed, subjects were asked to perform two novel tasks under transformation (both the Pegboard and Cube Construction tasks). Results indicate that head position cues and initial visual test conditions had no effect on an individual s visual dependency scores. Subjects were also able to adapt to the manual tasks after several trials. Individual visual dependency correlated with ability to adapt manual to a novel visual distortion only for the cube task. Subjects with higher visual dependency showed decreased ability to adapt to this task. Ultimately, it was revealed that the RFT may serve as an effective prediction tool to produce individualized adaptability training prescriptions that target the specific sensory profile of each crewmember.
Mixture Models for Dependent Observations
NASA Technical Reports Server (NTRS)
Peters, C.
Parametric mixture models appropriate for data presented in homogeneous blocks of varying sizes from several unidentified source populations are considered. For most applications, the data elements within each block are dependent. Models are proposed for multivariate normal data incorporating two types of dependence, exchangeability of elements within blocks, and a Markov structure for blocks. The consequences of assuming exchangeability, when in fact the Markov structure holds, are explored. Computational problems for each model are considered, and results of a simple test of the exchangeability hypothesis for LANDSAT data are presented.
Time dependent view factor methods
Kirkpatrick, R.C.
View factors have been used for treating radiation transport between opaque surfaces bounding a transparent medium for several decades. However, in recent years they have been applied to problems involving intense bursts of radiation in enclosed volumes such as in the laser fusion hohlraums. In these problems, several aspects require treatment of time dependence.
Dependency Structures and Transformational Rules.
ERIC Educational Resources Information Center
Robinson, Jane J.
In this paper the author shows that dependency grammars are not only equivalent to structure-free phrase-structure grammars (i.e., equally adequate), but are even more informative: they express both the "is a" relation which phrase-structure grammars express and the "governs" relation which phrase-structure grammars obscure. It is shown that…
Network-timing-dependent plasticity.
Delattre, Vincent; Keller, Daniel; Perich, Matthew; Markram, Henry; Muller, Eilif B
Bursts of activity in networks of neurons are thought to convey salient information and drive synaptic plasticity. Here we report that network bursts also exert a profound effect on Spike-Timing-Dependent Plasticity (STDP). In acute slices of juvenile rat somatosensory cortex we paired a network burst, which alone induced long-term depression (LTD), with STDP-induced long-term potentiation (LTP) and LTD. We observed that STDP-induced LTP was either unaffected, blocked or flipped into LTD by the network burst, and that STDP-induced LTD was either saturated or flipped into LTP, depending on the relative timing of the network burst with respect to spike coincidences of the STDP event. We hypothesized that network bursts flip STDP-induced LTP to LTD by depleting resources needed for LTP and therefore developed a resource-dependent STDP learning rule. In a model neural network under the influence of the proposed resource-dependent STDP rule, we found that excitatory synaptic coupling was homeostatically regulated to produce power law distributed burst amplitudes reflecting self-organized criticality, a state that ensures optimal information coding. PMID:26106298
The Study of Curricular Dependency
ERIC Educational Resources Information Center
Anastasiu, Dragos
In the educational process, the disciplines D1, D2,...,Dn have a succession which is generated by the content and the final objective--the student formation. In this work, the disciplines are presented as structured text entities. The graph associated to the disciplines is established. A method for dependencies evaluation is proposed. The testing…
Network-timing-dependent plasticity
Delattre, Vincent; Keller, Daniel; Perich, Matthew; Markram, Henry; Muller, Eilif B.
Bursts of activity in networks of neurons are thought to convey salient information and drive synaptic plasticity. Here we report that network bursts also exert a profound effect on Spike-Timing-Dependent Plasticity (STDP). In acute slices of juvenile rat somatosensory cortex we paired a network burst, which alone induced long-term depression (LTD), with STDP-induced long-term potentiation (LTP) and LTD. We observed that STDP-induced LTP was either unaffected, blocked or flipped into LTD by the network burst, and that STDP-induced LTD was either saturated or flipped into LTP, depending on the relative timing of the network burst with respect to spike coincidences of the STDP event. We hypothesized that network bursts flip STDP-induced LTP to LTD by depleting resources needed for LTP and therefore developed a resource-dependent STDP learning rule. In a model neural network under the influence of the proposed resource-dependent STDP rule, we found that excitatory synaptic coupling was homeostatically regulated to produce power law distributed burst amplitudes reflecting self-organized criticality, a state that ensures optimal information coding. PMID:26106298
Analytic Time Depending Galaxy Models
NASA Astrophysics Data System (ADS)
Sala, F.
RESUMEN. Considerando las hip6tesis de Chandrasekhar para el estudjo de la GalActicaq se han desarrollado varios modelos analiticos integrables con simetria axial y dependientes del . . By considering Chandrasekhar hypotheses +or the study o+ Galactic Dynamics, several integrable analytic axisymmetric time-depending galactic models have been developed. Ke ords; GALAXY-DYNAMICS - GALAXY-STRUCTURE
We Depend on Illinois' Environment.
ERIC Educational Resources Information Center
Illinois Environmental Protection Agency, Springfield.
This teachers guide contains information and activities to provide 5th-grade students with a hands-on experience with air, land, and water pollution in Illinois. This booklet incorporates previous documents entitled: "Water the Liquid of Life,""The Land We Depend On," and "The Air We Breathe." The materials are designed to develop research,…
Time-Dependent Reliability Analysis
FRANTIC-3 was developed to evaluate system unreliability using time-dependent techniques. The code provides two major options: to evaluate standby system unavailability or, in addition to the unavailability to calculate the total system failure probability by including both the unavailability of the system on demand as well as the probability that it will operate for an arbitrary time period following the demand. The FRANTIC-3 time dependent reliability models provide a large selection of repair and testingmore » policies applicable to standby or continously operating systems consisting of periodically tested, monitored, and non-repairable (non-testable) components. Time-dependent and test frequency dependent failures, as well as demand stress related failure, test-caused degradation and wear-out, test associated human errors, test deficiencies, test override, unscheduled and scheduled maintenance, component renewal and replacement policies, and test strategies can be prescribed. The conditional system unavailabilities associated with the downtimes of the user specified failed component are also evaluated. Optionally, the code can perform a sensitivity study for system unavailability or total failure probability to the failure characteristics of the standby components.« less
Directional Dependence in Developmental Research
ERIC Educational Resources Information Center
von Eye, Alexander; DeShon, Richard P.
In this article, we discuss and propose methods that may be of use to determine direction of dependence in non-normally distributed variables. First, it is shown that standard regression analysis is unable to distinguish between explanatory and response variables. Then, skewness and kurtosis are discussed as tools to assess deviation from…
Quick Time-dependent Ionization Calculations Depending on MHD Simulations
NASA Astrophysics Data System (ADS)
Shen, Chengcai; Raymond, John C.; Murphy, Nicholas Arnold
Time-dependent ionization is important in astrophysical environments where the thermodynamic time scale is shorter than ionization time scale. In this work, we report a FORTRAN program that performs fast non-equilibrium ionization calculations based on parallel computing. Using MHD simulation results, we trace the movements of plasma in a Lagrangian framework, and obtain evolutionary history of temperature and electron density. Then the time-dependent ionization equations are solved using the eigenvalue method. For any complex temperature and density histories, we introduce a advanced time-step strategy to improve the computational efficiency. Our tests show that this program has advantages of high numerical stability and high accuracy. In addition, it is also easy to integrate this solver with the other MHD routines.
Nalmefene. Alcohol dependence: no advance.
Alcohol dependence is a chronic, severe and sometimes fatal disease. Psychological and social support is a crucial element of patient management. Acamprosate and naltrexone are the drugs of choice to help patients remain abstinent, but they are only moderately effective. Nalmefene, an opioid receptor antagonist related to naltrexone, has been authorised in the European Union to help alcohol-dependent patients reduce their alcohol consumption. Nalmefene has not been compared with naltrexone or acamprosate in clinical trials. Clinical evaluation is mainly based on two double-blind, randomised, placebo-controlled trials in which nalmefene was taken "on demand" at a dose of one tablet per day. The trials lasted 6 months and included a total of 1322 patients. During an initial two-week period in which all patients received medical and psychosocial support, about one-third of patients in both trials reduced their alcohol consumption without medication. Depending on the subgroup and the trial, about one-third to one-half of patients discontinued medical treatment before the end of the study period. In both trials, patients taking nalmefene had two fewer "heavy drinking days" per month than patients in the placebo groups. However, at the end of the study, they continued to drink heavily at least one week per month on average. Daily alcohol consumption was 5 to 9 grams lower with nalmefene than with placebo. The most frequent adverse effects observed in clinical trials were insomnia, dizziness, headache and nausea, which were severe in more than 10% of patients. Other serious but less frequent adverse effects included confusion, hallucinations and dissociation, usually at the beginning of treatment. These adverse effects affected about 3% of patients treated with nalmefene, a proportion three times higher than in the placebo groups. The consequences of mixing nalmefene with large amounts of alcohol are not known. In practice, the effects of nalmefene in alcohol-dependent
Refraction effects and wavelength dependence
NASA Astrophysics Data System (ADS)
Claverie, J.; Dion, D.
The performances of Electro-Optical (EO) systems such as visible or infrared cameras, lasers, operating within the Marine Surface Boundary Layer (MSBL), i.e. at heights up to a few tens of meters above the sea surface, are disturbed by various propagation mechanisms: molecular attenuation, aerosol extinction, refraction and turbulence. Refraction is responsible for focusing and defocusing of rays, detection range limitations, mirage formation and angular deviation. The refractive index depends on atmospheric pressure, air temperature and air humidity. Within the optical transmission bands, it also depends on the wavelength. In this paper, the results provided by two different formulations of the refractive index associated with the same ray tracing program are compared and discussed.
Genetic factors influencing alcohol dependence
Mayfield, R D; Harris, R A; Schuckit, M A
Plentiful data from both animal and human studies support the importance of genetic influences in substance abuse and dependence (Bierut et al., 1998; Tsuang et al., 1998; Kendler et al., 2003). This review summarizes the evidence supporting such genetic influences, places them into perspective regarding animal and human studies, discusses the importance of both genes and environment, and highlights some specific genes of interest regarding the vulnerabilities for problems associated with alcohol use disorders. A long history of repetitive heavy use of alcohol exists across generations as well as the high prevalence of alcohol-related problems in Western societies. Moreover, the information offered here addresses the importance of more general issues regarding genetics and gene expression related to alcohol abuse and dependence. PMID:18362899
Dependency Ordering of Atomic Observables
NASA Astrophysics Data System (ADS)
Cīrulis, Jānis
The notion of atomic observable was introduced by S.Gudder for effect test spaces in 1997. In this paper an observable is a σ-homomorphism from the Borel algebra on a line to some logic. Roughly, an observable on a logic is atomic, if it is completely determined by its restriction to one-element subsets of its point spectrum. In particular, every discrete observable is atomic. We study some elementary properties of such observables, and discuss a possible notion of functional dependency between them. Algebraically, a dependency is a certain preorder relation on the set of all atomic observables, which induces an order relation on the set of all maximal orthogonal subsets of the logic. Several properties, as well as characteristics in terms of the underlying logic, of these relations are stated.
Serial dependence in visual perception
Fischer, Jason; Whitney, David
Visual input often arrives in a noisy and discontinuous stream, owing to head and eye movements, occlusion, lighting changes, and many other factors. Yet the physical world is generally stable—objects and physical characteristics rarely change spontaneously. How then does the human visual system capitalize on continuity in the physical environment over time? Here we show that visual perception is serially dependent, using both prior and present input to inform perception at the present moment. Using an orientation judgment task, we found that even when visual input changes randomly over time, perceived orientation is strongly and systematically biased toward recently seen stimuli. Further, the strength of this bias is modulated by attention and tuned to the spatial and temporal proximity of successive stimuli. These results reveal a serial dependence in perception characterized by a spatiotemporally tuned, orientation-selective operator—which we call a continuity field—that may promote visual stability over time. PMID:24686785
Nuclear dependence of charm production
NASA Astrophysics Data System (ADS)
Blanco-Covarrubias, A.; Engelfried, J.; Akgun, U.; Alkhazov, G.; Amaro-Reyes, J.; Atamantchouk, A. G.; Ayan, A. S.; Balatz, M. Y.; Bondar, N. F.; Cooper, P. S.; Dauwe, L. J.; Davidenko, G. V.; Dersch, U.; Dolgolenko, A. G.; Dzyubenko, G. B.; Edelstein, R.; Emediato, L.; Endler, A. M. F.; Eschrich, I.; Escobar, C. O.; Estrada, N.; Evdokimov, A. V.; Filimonov, I. S.; Flores-Castillo, A.; Garcia, F. G.; Golovtsov, V. L.; Gouffon, P.; Gülmez, E.; Iori, M.; Jun, S. Y.; Kaya, M.; Kilmer, J.; Kim, V. T.; Kochenda, L. M.; Konorov, I.; Kozhevnikov, A. P.; Krivshich, A. G.; Krüger, H.; Kubantsev, M. A.; Kubarovsky, V. P.; Kulyavtsev, A. I.; Kuropatkin, N. P.; Kurshetsov, V. F.; Kushnirenko, A.; Lach, J.; Landsberg, L. G.; Larin, I.; Leikin, E. M.; López-Hinojosa, G.; Lungov, T.; Maleev, V. P.; Mao, D.; Mathew, P.; Mattson, M.; Matveev, V.; McCliment, E.; Moinester, M. A.; Molchanov, V. V.; Morelos, A.; Nemitkin, A. V.; Neoustroev, P. V.; Newsom, C.; Nilov, A. P.; Nurushev, S. B.; Ocherashvili, A.; Onel, Y.; Ozkorucuklu, S.; Penzo, A.; Petrenko, S. V.; Procario, M.; Prutskoi, V. A.; Razmyslovich, B. V.; Rud, V. I.; Russ, J.; Sánchez-López, J. L.; Simon, J.; Sitnikov, A. I.; Smith, V. J.; Srivastava, M.; Steiner, V.; Stepanov, V.; Stutte, L.; Svoiski, M.; Terentyev, N. K.; Torres, I.; Uvarov, L. N.; Vasiliev, A. N.; Vavilov, D. V.; Vázquez-Jáuregui, E.; Verebryusov, V. S.; Victorov, V. A.; Vishnyakov, V. E.; Vorobyov, A. A.; Vorwalter, K.; You, J.; Zukanovich-Funchal, R.
Using data taken by SELEX during the 1996-1997 fixed target run at Fermilab, we study the production of charmed hadrons on copper and carbon targets with Σ -, p, π -, and π + beams. Parametrizing the dependence of the inclusive production cross section on the atomic number A as A α , we determine α for D +, D 0, D {/s +}, D +(2010), Λ {/c +}, and their respective anti-particles, as a function of their transverse momentum p t and scaled longitudinal momentum x F . Within our statistics there is no dependence of α on x F for any charm species for the interval 0.1< x F <1.0. The average value of α for charm production by pion beams is α meson=0.850±0.028. This is somewhat larger than the corresponding average α baryon=0.755±0.016 for charm production by baryon beams ( Σ -, p).
Student Assistance Guide for Chemical Dependency.
ERIC Educational Resources Information Center
Saint Vincent Medical Center, Toledo, OH. Tennyson Center.
This document presents practical suggestions for student assistance workers who might work with chemically dependent adolescents. It illustrates the stages of chemical dependency, discusses the progression of dependency in adolescents, and provides guidelines for identifying a chemically dependent adolescent. Since chemically dependent persons…
Time-dependent interstellar chemistry
NASA Technical Reports Server (NTRS)
Glassgold, A. E.
Some current problems in interstellar chemistry are considered in the context of time-dependent calculations. The limitations of steady-state models of interstellar gas-phase chemistry are discussed, and attempts to chemically date interstellar clouds are reviewed. The importance of studying the physical and chemical properties of interstellar dust is emphasized. Finally, the results of a series of studies of collapsing clouds are described.
Geometry Dependence of Stellarator Turbulence
H.E. Mynick, P. Xanthopoulos and A.H. Boozer
Using the nonlinear gyrokinetic code package GENE/GIST, we study the turbulent transport in a broad family of stellarator designs, to understand the geometry-dependence of the microturbulence. By using a set of flux tubes on a given flux surface, we construct a picture of the 2D structure of the microturbulence over that surface, and relate this to relevant geometric quantities, such as the curvature, local shear, and effective potential in the Schrodinger-like equation governing linear drift modes.
Genus dependence of superstring amplitudes
Davis, Simon
The problem of the consistency of the finiteness of the supermoduli space integral in the limit of vanishing super-fixed point distance and the genus-dependence of the integral over the super-Schottky coordinates in the fundamental region containing a neighborhood of |K{sub n}|=0 is resolved. Given a choice of the categories of isometric circles representing the integration region, the exponential form of bounds for superstring amplitudes is derived.
Energy dependence of fission observables
NASA Astrophysics Data System (ADS)
Paşca, Horia
The mass, charge and isotopic distributions of fission fragments are studied within an improved scission-point statistical model in the reaction 235U+n at different energies of the incident neutron. The available experimental data are well reproduced and the energy-dependencies of the observable characteristics of fission are predicted for future experiments. The calculated mass distribution of 238U+n is also compared with experimental data.
Non-transfusion-dependent thalassemias
Musallam, Khaled M.; Rivella, Stefano; Vichinsky, Elliott; Rachmilewitz, Eliezer A.
Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration. PMID:23729725
Dopamine-dependent responses to morphine depend on glucocorticoid receptors
Marinelli, Michela; Aouizerate, Bruno; Barrot, Michel; Le Moal, Michel; Piazza, Pier Vincenzo
Previous work has shown that glucocorticoid hormones facilitate the behavioral and dopaminergic effects of morphine. In this study we examined the possible role in these effects of the two central corticosteroid receptor types: mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). To accomplish this, specific antagonists of these receptors were infused intracerebroventricularly and 2 hr later we measured: (i) locomotor activity induced by a systemic injection of morphine (2 mg/kg); (ii) locomotor activity induced by an infusion of morphine (1 μg per side) into the ventral tegmental area, which is a dopamine-dependent behavioral response to morphine; (iii) morphine-induced dopamine release in the nucleus accumbens, a dopaminergic projection site mediating the locomotor and reinforcing effects of drugs of abuse. Blockade of MRs by spironolactone had no significant effects on locomotion induced by systemic morphine. In contrast, blockade of GRs by either RU38486 or RU39305, which is devoid of antiprogesterone effects, reduced the locomotor response to morphine, and this effect was dose dependent. GR antagonists also reduced the locomotor response to intraventral tegmental area morphine as well as the basal and morphine-induced increase in accumbens dopamine, as measured by microdialysis in freely moving rats. In contrast, spironolactone did not modify dopamine release. In conclusion, glucocorticoids, via GRs, facilitate the dopamine-dependent behavioral effects of morphine, probably by facilitating dopamine release. The possibility of decreasing the behavioral and dopaminergic effects of opioids by an acute administration of GR antagonists may open new therapeutic strategies for treatment of drug addiction. PMID:9636221
Fluorine-18 labeling of proteins
Kilbourn, M.R.; Dence, C.S.; Welch, M.J.; Mathias, C.J.
Two fluorine-18-labeled reagents, methyl 3-(/sup 18/F)fluoro-5-nitrobenzimidate and 4-(/sup 18/F)fluorophenacyl bromide, have been prepared for covalent attachment of fluorine-18 to proteins. Both reagents can be prepared in moderate yields (30-50%, EOB) in synthesis times of 50-70 min. Reaction of these reagents with proteins (human serum albumin, human fibrinogen, and human immunoglobulin A) is pH independent, protein concentration dependent, and takes 5-60 min at mild pH (8.0) and temperature (25-37 degrees C), in yields up to 95% (corrected). The /sup 18/F-labeled proteins are purified by size exclusion chromatography.
Genetics Home Reference: pyridoxine-dependent epilepsy
Scale-Dependent Dispersivity Explained Without Scale-Dependent Heterogeneity
NASA Astrophysics Data System (ADS)
Dhaliwal, P.; Engdahl, N. B.; Fogg, G. E.
The observed scale-dependence of dispersivity has often been attributed to the scale-dependence of porous media heterogeneity. However, mass transfer between areas of high and low hydraulic conductivity and preferential solute migration may provide an alternative explanation for this phenomenon. To illustrate this point, we used geostatistical models representing the heterogeneity and interconnectedness of a typical aquifer system and plume modeling via a highly accurate random walk particle tracking method. The apparent dispersivity values were calculated using the statistical moments of the plumes. Apparent dispersivity was seen to grow from 0.01(m)to 100(m) over length scales of 0.06(m) to 500(m) even though heterogeneity scales and facies proportions were stationary and invariant with scale in the simulations. The results suggest that the increase in dispersivity was due solely to a stretching of the plume by two mechanisms. The first mechanism results from the diffusion of solute into areas of low conductivity and the second comes from the movement of solute through well-connected high K zone channels. Under such conditions, an "asymptotic dispersivity" may never be reached.
Helper-Dependent Adenoviral Vectors
Rosewell, Amanda; Vetrini, Francesco; Ng, Philip
Helper-dependent adenoviral vectors are devoid of all viral coding sequences, possess a large cloning capacity, and can efficiently transduce a wide variety of cell types from various species independent of the cell cycle to mediate long-term transgene expression without chronic toxicity. These non-integrating vectors hold tremendous potential for a variety of gene transfer and gene therapy applications. Here, we review the production technologies, applications, obstacles to clinical translation and their potential resolutions, and the future challenges and unanswered questions regarding this promising gene transfer technology. PMID:24533227
Renormalization in momentum dependent resummations
Jakovac, Antal
At finite temperature and in nonequilibrium environments we have to resum perturbation theory to avoid infrared divergences. Since resummation shuffles the perturbative orders, renormalizability is a nontrivial issue. In this paper we demonstrate that one can modify any type of resummations--even if it is momentum dependent, or it resums higher point functions - in a way that it is renormalizable with the usual zero temperature counterterms. To achieve this goal we reformulate resummation in form of a renormalization scheme. We apply this technique to perform a 2PI resummation in the six dimensional cubic scalar model in equilibrium.
Time-Dependent Photodissociation Regions
NASA Technical Reports Server (NTRS)
Hollenbach, David; Natta, Antonella
We present theoretical models of the time-dependent thermal and chemical structure of molecular gas suddenly exposed to far-ultraviolet (FUV) (6 eV less than hv less than 13.6 eV) radiation fields and the consequent time- dependent infrared emission of the gas. We focus on the response of molecular hydrogen for cloud densities ranging from n = 10(exp 3) to 10(exp 6)/cu cm and FUV fluxes G(sub 0) = 10(exp 3)-10(exp 6) times the local FUV interstellar flux. For G(sub 0)/n greater than 10(exp -2) cu cm, the emergent H(sub 2) vibrational line intensities are initially larger than the final equilibrium values. The H(sub 2) lines are excited by FUV fluorescence and by collisional excitation in warm gas. Most of the H(sub 2) intensity is generated at a characteristic hydrogen column density of N approximately 10(exp 21)/sq cm, which corresponds to an FUV optical depth of unity caused by dust opacity. The time dependence of the H(sub 2) intensities arises because the initial abundances of H(sub 2) at these depths is much higher than the equilibrium values, so that H(sub 2) initially competes more effectively with dust in absorbing FUV photons. Considerable column densities of warm (T approximately 1000) K H(sub 2) gas can be produced by the FUV pumping of H(sub 2) vibrational levels followed by collisional de-excitation, which transfers the energy to heat. In dense (n greater than or approximately 10(exp 5)/cu cm) gas exposed to high (G(sub 0) greater than or approximately 10(exp 4)) fluxes, this warm gas produces a 2-1 S(1)/1-0 S(l) H(sub 2) line ratio of approximately 0.1, which mimics the ratio found in shocked gas. In lower density regions, the FUV pumping produces a pure-fluorescent ratio of approximately 0.5. We also present calculations of the time dependence of the atomic hydrogen column densities and of the intensities of 0 I 6300 A, S II 6730 A, Fe II 1.64 microns, and rotational OH and H20 emission. Potential applications include star-forming regions, clouds
Dependent video coding using a tree representation of pixel dependencies
NASA Astrophysics Data System (ADS)
Amati, Luca; Valenzise, Giuseppe; Ortega, Antonio; Tubaro, Stefano
Motion-compensated prediction induces a chain of coding dependencies between pixels in video. In principle, an optimal selection of encoding parameters (motion vectors, quantization parameters, coding modes) should take into account the whole temporal horizon of a GOP. However, in practical coding schemes, these choices are made on a frame-by-frame basis, thus with a possible loss of performance. In this paper we describe a tree-based model for pixelwise coding dependencies: each pixel in a frame is the child of a pixel in a previous reference frame. We show that some tree structures are more favorable than others from a rate-distortion perspective, e.g., because they entail a large descendance of pixels which are well predicted from a common ancestor. In those cases, a higher quality has to be assigned to pixels at the top of such trees. We promote the creation of these structures by adding a special discount term to the conventional Lagrangian cost adopted at the encoder. The proposed model can be implemented through a double-pass encoding procedure. Specifically, we devise heuristic cost functions to drive the selection of quantization parameters and of motion vectors, which can be readily implemented into a state-of-the-art H.264/AVC encoder. Our experiments demonstrate that coding efficiency is improved for video sequences with low motion, while there are no apparent gains for more complex motion. We argue that this is due to both the presence of complex encoder features not captured by the model, and to the complexity of the source to be encoded.
The genetics of nicotine dependence.
Li, Ming D
Despite almost two decades of intensive tobacco-control efforts, approximately 23% of American adults continue to smoke, and 13% are nicotine-dependent. Cigarette smoking is the greatest preventable cause of cancer, accounting for at least 30% of all cancer deaths and 87% of lung cancer deaths. Smoking behavior is influenced by both genetic and environmental factors. Many years of twin and adoption studies have demonstrated that the heritability of liability for nicotine dependence (ND) is at least 50%. During the past several years, significant efforts have been made to identify susceptibility genes for ND using both genome-wide linkage and association analysis approaches. It is expected that identification of susceptibility genes for ND will allow the development and tailoring of both prevention strategies for individuals at risk and effective treatment programs and medicines for individuals who use tobacco products. This review summarizes the recent progress in genetic studies of ND. As genotyping technology is being improved and well-characterized clinical samples on smoking behavior become available, more and more genes and genetic variants responsible for ND will be identified in the near future. PMID:16539894
Selfsimilar time dependent shock structures
NASA Technical Reports Server (NTRS)
Beck, R.; Drury, L. O.
Diffusive shock acceleration as an astrophysical mechanism for accelerating charged particles has the advantage of being highly efficient. This means however that the theory is of necessity nonlinear; the reaction of the accelerated particles on the shock structure and the acceleration process must be self-consistently included in any attempt to develop a complete theory of diffusive shock acceleration. Considerable effort has been invested in attempting, at least partially, to do this and it has become clear that in general either the maximum particle energy must be restricted by introducing additional loss processes into the problem or the acceleration must be treated as a time dependent problem (Drury, 1984). It is concluded that stationary modified shock structures can only exist for strong shocks if additional loss processes limit the maximum energy a particle can attain. This is certainly possible and if it occurs the energy loss from the shock will lead to much greater shock compressions. It is however equally possible that no such processes exist and we must then ask what sort of nonstationary shock structure develops. The ame argument which excludes stationary structures also rules out periodic solutions and indeed any solution where the width of the shock remains bounded. It follows that the width of the shock must increase secularly with time and it is natural to examine the possibility of selfsimilar time dependent solutions.
Selfsimilar time dependent shock structures
NASA Astrophysics Data System (ADS)
Beck, R.; Drury, L. O.
Diffusive shock acceleration as an astrophysical mechanism for accelerating charged particles has the advantage of being highly efficient. This means however that the theory is of necessity nonlinear; the reaction of the accelerated particles on the shock structure and the acceleration process must be self-consistently included in any attempt to develop a complete theory of diffusive shock acceleration. Considerable effort has been invested in attempting, at least partially, to do this and it has become clear that in general either the maximum particle energy must be restricted by introducing additional loss processes into the problem or the acceleration must be treated as a time dependent problem (Drury, 1984). It is concluded that stationary modified shock structures can only exist for strong shocks if additional loss processes limit the maximum energy a particle can attain. This is certainly possible and if it occurs the energy loss from the shock will lead to much greater shock compressions. It is however equally possible that no such processes exist and we must then ask what sort of nonstationary shock structure develops. The ame argument which excludes stationary structures also rules out periodic solutions and indeed any solution where the width of the shock remains bounded. It follows that the width of the shock must increase secularly with time and it is natural to examine the possibility of selfsimilar time dependent solutions.
Pharmacological Treatment of Cannabis Dependence
Weinstein, A.M.; Gorelick, David A.
Cannabis is the most frequently used illegal psychoactive substance in the world. There is a significant increase in the number of treatment admissions for cannabis use disorders in the past few years, and the majority of cannabis-dependent individuals who enter treatment have difficulty in achieving and maintaining abstinence. Thus, there is increased need for medications that can be used to treat this population. So far, no medication has been shown broadly and consistently effective; none has been approved by any national regulatory authority. Medications studied have included those that alleviate symptoms of cannabis withdrawal (e.g., dysphoric mood, irritability), those that directly affect endogenous cannabinoid receptor function, and those that have shown efficacy in treatment of other drugs of abuse or psychiatric conditions. Buspirone is the only medication to date that has shown efficacy for cannabis dependence in a controlled clinical trial. Results from controlled human laboratory studies and small open-label clinical trials suggest that dronabinol, the COMT inhibitor entacapone, and lithium may warrant further study. Recent pre-clinical studies suggest the potential of fatty acid amide hydrolase (FAAH) inhibitors such as URB597, endocannabinoid-metabolizing enzymes, and nicotinic alpha7 receptor antagonists such as methyllycaconitine (MLA). Controlled clinical trials are needed to evaluate the clinical efficacy of these medications and to validate the laboratory models being used to study candidate medications. PMID:21524266
Pharmacological treatment of cannabis dependence.
Weinstein, A M; Gorelick, David A
Cannabis is the most frequently used illegal psychoactive substance in the world. There is a significant increase in the number of treatment admissions for cannabis use disorders in the past few years, and the majority of cannabis-dependent individuals who enter treatment have difficulty in achieving and maintaining abstinence. Thus, there is increased need for medications that can be used to treat this population. So far, no medication has been shown broadly and consistently effective; none has been approved by any national regulatory authority. Medications studied have included those that alleviate symptoms of cannabis withdrawal (e.g., dysphoric mood, irritability),those that directly affect endogenous cannabinoid receptor function, and those that have shown efficacy in treatment of other drugs of abuse or psychiatric conditions. Buspirone is the only medication to date that has shown efficacy for cannabis dependence in a controlled clinical trial. Results from controlled human laboratory studies and small open-label clinical trials suggest that dronabinol, the COMT inhibitor entacapone, and lithium may warrant further study. Recent pre-clinical studies suggest the potential of fatty acid amide hydrolase (FAAH) inhibitors such as URB597, endocannabinoid-metabolizing enzymes, and nicotinic alpha 7 receptor antagonists such as methyllycaconitine (MLA).Controlled clinical trials are needed to evaluate the clinical efficacy of these medications and to validate the laboratory models being used to study candidate medications. PMID:21524266
Suicidal Behavior in Chemically Dependent Adolescents.
ERIC Educational Resources Information Center
Cavaiola, Alan A.; Lavender, Neil
Study explores distinctions between chemically dependent suicide attempters, chemically dependent nonsuicidal adolescents, and high school students with no history of chemical dependency (N=250). Results reveal that there were significant differences between the chemically dependent groups. It was also found that the majority of suicidal gestures…
Reprogramming Roadblocks Are System Dependent
Chantzoura, Eleni; Skylaki, Stavroula; Menendez, Sergio; Kim, Shin-Il; Johnsson, Anna; Linnarsson, Sten; Woltjen, Knut; Chambers, Ian; Kaji, Keisuke
Summary Since the first generation of induced pluripotent stem cells (iPSCs), several reprogramming systems have been used to study its molecular mechanisms. However, the system of choice largely affects the reprogramming efficiency, influencing our view on the mechanisms. Here, we demonstrate that reprogramming triggered by less efficient polycistronic reprogramming cassettes not only highlights mesenchymal-to-epithelial transition (MET) as a roadblock but also faces more severe difficulties to attain a pluripotent state even post-MET. In contrast, more efficient cassettes can reprogram both wild-type and Nanog−/− fibroblasts with comparable efficiencies, routes, and kinetics, unlike the less efficient reprogramming systems. Moreover, we attribute a previously reported variation in the N terminus of KLF4 as a dominant factor underlying these critical differences. Our data establish that some reprogramming roadblocks are system dependent, highlighting the need to pursue mechanistic studies with close attention to the systems to better understand reprogramming. PMID:26278041
Temperature-dependent Luttinger surfaces.
Ito, T; Chainani, A; Haruna, T; Kanai, K; Yokoya, T; Shin, S; Kato, R
The Luttinger surface of an organic metal (TTF-TCNQ), possessing charge order and spin-charge separated band dispersions, is investigated using temperature-dependent angle-resolved photoemission spectroscopy. The Luttinger surface topology, obtained from momentum distribution curves, changes from quasi-2D (dimensional) to quasi-1D with temperature. The high temperature quasi-2D surface exhibits 4kF charge-density-wave (CDW) superstructure in the TCNQ derived holon band, in the absence of 2kF order. Decreasing temperature results in quasi-1D nested 2kF CDW order in the TCNQ spinon band and in the TTF surface. The results establish the link in momentum space between charge order and spin-charge separation in a Luttinger liquid. PMID:16384402
Mass dependence of nitride sputtering
NASA Astrophysics Data System (ADS)
Elovikov, S. S.; Khrustachev, I. K.; Mosunov, A. S.; Yurasova, V. E.
A molecular dynamics simulation was performed to study the sputtering yield Y for BN, AlN and GaN polycrystals of wurtzite structure as a function of the masses m 1 of bombarding ions with energies from 200 to 2000 eV. A nonmonotonic behavior of the Y ( m 1 ) curve was obtained for the irradiation by low-energy ions, the curve having a maximum with a position being dependent on m 2 / m 1 ( m 2 is the average mass of atoms in a compound). For AlN and GaN the maximum was observed at m 2 / m 1 = 2, and for BN at m 2 / m 1 = 1. The effect of the mass of bombarding ions on the mean energies and energy spectra of sputtered particles, the depth of sputtering origin, and the generation of emitted atoms for nitrides was also investigated and discussed.
Phenprobamate dependence: a case report.
Demir, Bahadir; Demir, Yasemin; Aksoy, Ihsan; Kilic, Osman Hasan Tahsin; Gucyetmez, Volkan; Savas, Haluk A
Phenprobamate (3-phenylpropylcarbamate) is a centrally acting muscle relaxant with mild sedative and anticonvulsant effects. Muscle relaxants can enhance and prolong the effect of narcotic drugs and enable to obtain same effect with a smaller amount of alcohol or illicit substance. Almost all of the centrally acting muscle relaxants have varying sedative effects on which their abuse potential mainly depends. Data related to abuse of carisoprodol, meprobamate, baclofen takes place in the literature. However, to our knowledge this is the first case report about abuse of and tolerance to phenprobamate. We aimed to attract attention to important points of prescribing drugs that have abuse potential like in our case who was using up to 16000 mg/day phenprobamate. PMID:25727392
Your morals depend on language.
Costa, Albert; Foucart, Alice; Hayakawa, Sayuri; Aparici, Melina; Apesteguia, Jose; Heafner, Joy; Keysar, Boaz
Should you sacrifice one man to save five? Whatever your answer, it should not depend on whether you were asked the question in your native language or a foreign tongue so long as you understood the problem. And yet here we report evidence that people using a foreign language make substantially more utilitarian decisions when faced with such moral dilemmas. We argue that this stems from the reduced emotional response elicited by the foreign language, consequently reducing the impact of intuitive emotional concerns. In general, we suggest that the increased psychological distance of using a foreign language induces utilitarianism. This shows that moral judgments can be heavily affected by an orthogonal property to moral principles, and importantly, one that is relevant to hundreds of millions of individuals on a daily basis. PMID:24760073
Flavor dependence of quantum chromodynamics
NASA Astrophysics Data System (ADS)
Sui, Chengzhong
We study the dependence of Quantum Chromodynamics (QCD) on the number of light dynamical quarks. We conduct simulations on N3s × 32 (Ns = 16 or 24) lattices with two and four flavors of dynamical staggered quarks of mass 0.01 and 0.02. Most of our simulations have at least 5000 trajectories, which is significantly longer than those in previous studies by other research groups. We reproduce some of our previous 163 x 32 runs using our new supercomputer QCDSP. We complete our four-flavor 163 x 32 simulations. We perform simulations with two and four flavors on 24 3 x 32 lattices. We study the dependence of the nucleon mass on the lattice operators. We measure the pion decay constant using two different methods. We also extract the π - N σ-term. We find that, for four flavors, the masses of most hadrons show strong finite size effects, changing by as much as 10%-15% when the lattice spatial volume increases from 163 to 243. We find, in contrast, that the finite size effects on two-flavor hadron masses are less drastic: In this case all meson masses change by only a few percent; the nucleon mass changes by 10%. We find only quantitative differences in the ratios of physical quantities for the two-flavor and four-flavor QCD. The nucleon to the rho mass ratio for four flavors is about 13% higher than that for two flavors and this is significant to three standard deviations. In addition, we find that the pion decay constant for two flavors agrees well with the experimental value.
Analysis of Critical Infrastructure Dependencies and Interdependencies
Petit, Frederic; Verner, Duane; Brannegan, David; Buehring, William; Dickinson, David; Guziel, Karen; Haffenden, Rebecca; Phillips, Julia; Peerenboom, James
The report begins by defining dependencies and interdependencies and exploring basic concepts of dependencies in order to facilitate a common understanding and consistent analytical approaches. Key concepts covered include; Characteristics of dependencies: upstream dependencies, internal dependencies, and downstream dependencies; Classes of dependencies: physical, cyber, geographic, and logical; and Dimensions of dependencies: operating environment, coupling and response behavior, type of failure, infrastructure characteristics, and state of operations From there, the report proposes a multi-phase roadmap to support dependency and interdependency assessment activities nationwide, identifying a range of data inputs, analysis activities, and potential products for each phase, as well as key steps needed to progress from one phase to the next. The report concludes by outlining a comprehensive, iterative, and scalable framework for analyzing dependencies and interdependencies that stakeholders can integrate into existing risk and resilience assessment efforts.
Size-Dependent Fluid Mechanics
NASA Astrophysics Data System (ADS)
Hadjesfandiari, Ali; Hajesfandiari, Arezoo; Dargush, Gary
Classical fluid mechanics provides a reasonable basis for analyzing the behavior of fluid flow at the macro scale. However, experiments show that the behavior of fluid in small scales is different from their behavior at macro scales. An additional concern relates to the absence of a length scale in the governing Navier-Stokes equations, when the present description of turbulence seems to need the clear definition of a characteristic size. Consequently, there is need for a more complete fluid dynamics, which spans many scales and, of course, must reduce to classical fluid mechanics for flows with macro-scale size. Here we develop the consistent size-dependent fluid mechanics by discovering the skew-symmetric character of couple stress tensor. As a result, the skew-symmetric mean curvature rate vector as the consistent measure of deformation is introduced. It is demonstrated that this theory may provide a basis for fundamental studies of flows at the finest scales for which a continuum representation is valid and, perhaps, for gaining additional insight into the problem of turbulence.
Nuclear Dependence of Charm Production
Blanco-Covarrubias, A.; Engelfried, J.; Akgun, U.; Alkhazov, G.; Amaro-Reyes, J.; Atamantchouk, A.G.; Ayan, A.S.; Balatz, M.Y.; Bondar, N.F.; Cooper, P.S.; Dauwe, Loretta J.; /Michigan U., Flint /Moscow, ITEP
With data taken by SELEX, which accumulated data during the 1996-1997 fixed target run at Fermilab, we study the production of charmed hadrons on copper and carbon targets with {Sigma}{sup -}, p, {pi}{sup -}, and {pi}{sup +} beams. Parameterizing the production cross section {infinity} A{sup {alpha}}, A being the atomic number, we determine {alpha} for D{sup +}, D{sup 0}, D{sub s}{sup +}, D{sup +}(2010), {Lambda}{sub c}{sup +}, and their respective anti-particles, as a function of their transverse momentum p{sub t} and scaled longitudinal momentum x{sub F}. Within our statistics there is no dependence of {alpha} on x{sub F} for any charm species for the interval 0.1 < x{sub F} < 1.0. The average value of {alpha} for charm production by pion beams is {alpha}{sub meson} = 0.850 {+-} 0.028. This is somewhat larger than the corresponding average {alpha}{sub baryon} = 0.755 {+-} 0.016 for charm production by baryon beams ({Sigma}{sup -}, p).
Temperature dependence of basalt weathering
NASA Astrophysics Data System (ADS)
Li, Gaojun; Hartmann, Jens; Derry, Louis A.; West, A. Joshua; You, Chen-Feng; Long, Xiaoyong; Zhan, Tao; Li, Laifeng; Li, Gen; Qiu, Wenhong; Li, Tao; Liu, Lianwen; Chen, Yang; Ji, Junfeng; Zhao, Liang; Chen, Jun
The homeostatic balance of Earth's long-term carbon cycle and the equable state of Earth's climate are maintained by negative feedbacks between the levels of atmospheric CO2 and the chemical weathering rate of silicate rocks. Though clearly demonstrated by well-controlled laboratory dissolution experiments, the temperature dependence of silicate weathering rates, hypothesized to play a central role in these weathering feedbacks, has been difficult to quantify clearly in natural settings at landscape scale. By compiling data from basaltic catchments worldwide and considering only inactive volcanic fields (IVFs), here we show that the rate of CO2 consumption associated with the weathering of basaltic rocks is strongly correlated with mean annual temperature (MAT) as predicted by chemical kinetics. Relations between temperature and CO2 consumption rate for active volcanic fields (AVFs) are complicated by other factors such as eruption age, hydrothermal activity, and hydrological complexities. On the basis of this updated data compilation we are not able to distinguish whether or not there is a significant runoff control on basalt weathering rates. Nonetheless, the simple temperature control as observed in this global dataset implies that basalt weathering could be an effective mechanism for Earth to modulate long-term carbon cycle perturbations.
Psychobiological mechanisms of exercise dependence.
Hamer, Mark; Karageorghis, Costas I
Exercise dependence (ED) is characterised by an obsessive and unhealthy preoccupation with exercise. Previous research has focused largely on identifying behavioural aspects of ED, although the biological mechanisms remain unknown and are under researched. We review various ED hypotheses including affect regulation, anorexia analogue, sympathetic arousal and beta-endorphin. We also present a novel hypothesis pertaining to ED and interleukin (IL)-6, which combines previous hypotheses with literature from the field of psycho-neuroimmunology. We explore the notion that IL-6 provides a link from the periphery to the brain, which may mediate the underlying features of ED. We propose a conceptual model indicating that, in individuals prone to ED, exercise results in a transient reduction in negative affect, but concurrently results in excessive production of IL-6 and the activation of neuroendocrine pathways, which are associated with behavioural and psychological disturbances of exercise withdrawal. Our intention is for this model to serve as a basis for further research in the area of ED, which may eventually lead to the development of successful treatment strategies. Recent developments in methods to reliably assess these biological markers from blood and saliva samples should encourage such research to be undertaken in exercise settings. PMID:17503874
National Council on Alcoholism and Drug Dependence
... Affiliate of the Month NCADD National Council on Alcoholism and Drug Dependence Addiction is a Disease - Treatment ... For over 70 years, The National Council on Alcoholism and Drug Dependence, Inc. (NCADD) has been a ...
Common Surgeries Raise Risk for Opioid Dependence
... fullstory_159815.html Common Surgeries Raise Risk for Opioid Dependence: Study Doctors should explore alternatives for pain ... have an elevated risk of growing dependent on opioid painkillers, a new study finds. These prescription painkillers ...
Partial least squares for dependent data
Singer, Marco; Krivobokova, Tatyana; Munk, Axel; de Groot, Bert
We consider the partial least squares algorithm for dependent data and study the consequences of ignoring the dependence both theoretically and numerically. Ignoring nonstationary dependence structures can lead to inconsistent estimation, but a simple modification yields consistent estimation. A protein dynamics example illustrates the superior predictive power of the proposed method. PMID:27279662
Dependency and Education: Reproduction or Conspiracy?
ERIC Educational Resources Information Center
Velloso, Jacques
The origins and meaning of dependency are examined, how the dependency approach as an analytical tool can be used to advance research in comparative education is illustrated, and two issues raised by the critics of dependency--the issues of reproduction and of conspiracy--are discussed. (RM)
Minimization of Dependency Length in Written English
ERIC Educational Resources Information Center
Temperley, David
Gibson's Dependency Locality Theory (DLT) [Gibson, E. 1998. "Linguistic complexity: locality of syntactic dependencies." "Cognition," 68, 1-76; Gibson, E. 2000. "The dependency locality theory: A distance-based theory of linguistic complexity." In A. Marantz, Y. Miyashita, & W. O'Neil (Eds.), "Image, Language, Brain" (pp. 95-126). Cambridge, MA:…
Generalized Categorial Grammar for Unbounded Dependencies Recovery
ERIC Educational Resources Information Center
Nguyen, Luan Viet
Accurate recovery of predicate-argument dependencies is vital for interpretation tasks like information extraction and question answering, and unbounded dependencies may account for a significant portion of the dependencies in any given text. This thesis describes a Generalized Categorial Grammar (GCG) which, like other categorial grammars,…
Motivational and psychological correlates of bodybuilding dependence
Abstract Background and aims: Exercise may become physically and psychologically maladaptive if taken to extremes. One example is the dependence reported by some individuals who engage in weight training. The current study explored potential psychological, motivational, emotional and behavioural concomitants of bodybuilding dependence, with a particular focus on motives for weight training. Using a path analysis paradigm, putative causal models sought to explain associations among key study variables. Methods: A convenience sample of 101 men aged between 18 and 67 years was assembled from gymnasia in Adelaide, South Australia. Active weight trainers voluntarily completed a questionnaire that included measures of bodybuilding dependence (social dependency, training dependency, and mastery), anger, hostility and aggression, stress and motivations for weight training. Results: Three motives for weight training were identified: mood control, physique anxiety and personal challenge. Of these, personal challenge and mood control were the most directly salient to dependence. Social dependency was particularly relevant to personal challenge, whereas training dependency was associated with both personal challenge and mood control. Mastery demonstrated a direct link with physique anxiety, thus reflecting a unique component of exercise dependence. Conclusions: While it was not possible to determine causality with the available data, the joint roles of variables that influence, or are influenced by, bodybuilding dependence are identified. Results highlight unique motivations for bodybuilding and suggest that dependence could be a result of, and way of coping with, stress manifesting as aggression. A potential framework for future research is provided through the demonstration of plausible causal linkages among these variables. PMID:25317342
Genetics of Nicotine Dependence and Pharmacotherapy
Lessov-Schlaggar, Christina N.; Pergadia, Michele L.; Khroyan, Taline V.; Swan, Gary E.
Nicotine dependence is substantially heritable. Several regions across the genome have been implicated in containing genes that confer liability to nicotine dependence and variation in individual genes has been associated with nicotine dependence. Smoking cessation measures are also heritable, and measured genetic variation is associated with nicotine dependence treatment efficacy. Despite significant strides in the understanding of the relative contribution of genetic and environmental factors to nicotine dependence and treatment, emergent challenges necessitate interdisciplinary coordinated effort for effective problem solving. These challenges include refinement of the nicotine dependence phenotype, better understanding of the dynamic interplay between genes and environment in nicotine dependence etiology, application and development of molecular and statistical methodology that can adequately address vast amounts of data, and continuous translational cross-talk. PMID:17888884
Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment
Carpano, Marina; Perona, Marina; Rodriguez, Carla; Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A.; Brandizzi, Daniel; Cabrini, Romulo; Pisarev, Mario; Juvenal, Guillermo Juan; Dagrosa, Maria Alejandra
Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ({sup 10}BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10{sup 6} MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of {sup 10}B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37°C and 23°C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R{sup 2} = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R{sup 2} = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion.
Biodistribution of the boron carriers boronophenylalanine (BPA) and/or decahydrodecaborate (GB-10) for Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases
D.W. Nigg; Various Others
BNCT was proposed for the treatment of diffuse, non-resectable tumors in the lung. We performed boron biodistribution studies with 5 administration protocols employing the boron carriers BPA and/or GB-10 in an experimental model of disseminated lung metastases in rats. All 5 protocols were non-toxic and showed preferential tumor boron uptake versus lung. Absolute tumor boron concentration values were therapeutically useful (25–76 ppm) for 3 protocols. Dosimetric calculations indicate that BNCT at RA-3 would be potentially therapeutic without exceeding radiotolerance in the lung.
A Multiple Motives Approach to Tobacco Dependence: The Wisconsin Inventory of Smoking Dependence Motives (WISDM-68)
ERIC Educational Resources Information Center
Piper, Megan E.; Piasecki, Thomas M.; Federman, E. Belle; Bolt, Daniel M.; Smith, Stevens S.; Fiore, Michael C.; Baker, Timothy C.
The dependence construct fills an important explanatory role in motivational accounts of smoking and relapse. Frequently used measures of dependence are either atheoretical or grounded in a unidimensional model of physical dependence. This research creates a multidimensional measure of dependence that is based on theoretically grounded motives for…
Assessment of dependency, agreeableness, and their relationship.
Lowe, Jennifer Ruth; Edmundson, Maryanne; Widiger, Thomas A
Agreeableness is central to the 5-factor model conceptualization of dependency. However, 4 meta-analyses of the relationship of agreeableness with dependency have failed to identify a consistent relationship. It was the hypothesis of the current study that these findings might be due in part to an emphasis on the assessment of adaptive, rather than maladaptive, variants of agreeableness. This hypothesis was tested by using experimentally altered NEO Personality Inventory-Revised (Costa & McCrae, 1992) items that were reversed with respect to their implications for maladaptiveness. The predicted correlations were confirmed with the experimentally altered version with measures of dependent personality disorder, measures of trait dependency (including 2 measures of adaptive dependency), and measures of dependency from alternative dimensional models of personality disorder. The theoretical implications of the findings and suggestions for future research are discussed. PMID:19947788
Warming: mechanism and latitude dependence
NASA Astrophysics Data System (ADS)
Barkin, Yury
flows distribution with respect the Earth's hemispheres in first caused by eccentric position of the Earth core with respect to the mantle (displaced in present geological epoch in direction to Brasil). Of course the asymmetric distribution of heat loss is a long-term phenomenon in the geological history. But in present epoch due to drift of the core to the North we must observe some increasing of the heat flow of the Northern hemisphere and decreasing of the heat flow of the Southern hemisphere. In reality mentioned changes of heat flows are contrast (asymmetrical) and can have general tendency of increasing heat flows in both hemispheres (due to activization of relative oscillations of the core and mantle relatively polar axis). Contrast secular warming of Northern and Southern hemispheres of the Earth in present epoch. Dependence of warming from latitude. And warm flows are asymmetrically, more intensively warm is redistributed in northern hemisphere of the Earth and less intensively in a southern hemisphere. From here it follows, that the phenomenon of more intensive warming up of northern hemisphere, rather than southern in present period should be observed. Data of climatic observations (in first temperature trends for various latitude belts). More detailed analysis shows, that the phenomenon of warming in different form is shown in various latitudinal belts of the Earth. This phenomenon is more clearly shown in latitudinal belts further situated on latitude from South Pole, i.e. in high northern latitudes. Really, the trend of increase of temperature in northern hemisphere is characterized by greater rate, than a trend of temperature in a southern hemisphere. And not only trend components of temperatures increase with increasing of latitudes from southern pole to northern pole, but also amplitudes of decade fluctuations of temperature in high northern breadthes are more bigger than in southern hemisphere. Thus again it is necessary to expect a contrast and
Passion and dependency in online shopping activities.
Wang, Chih-Chien; Yang, Hui-Wen
This study examines the influence of harmonious passion (HP) and obsessive passion (OP) to online shopping dependency. The results show that both HP and OP might lead to online shopping dependency and online shoppers with OP are more dependent on online shopping activities. In addition, this study also found out that HP and OP could be denoted as a sequence of different intensities of passion, where HP might be a necessity of OP. PMID:17474850
Spectral methods for time dependent problems
NASA Technical Reports Server (NTRS)
Tadmor, Eitan
Spectral approximations are reviewed for time dependent problems. Some basic ingredients from the spectral Fourier and Chebyshev approximations theory are discussed. A brief survey was made of hyperbolic and parabolic time dependent problems which are dealt with by both the energy method and the related Fourier analysis. The ideas presented above are combined in the study of accuracy stability and convergence of the spectral Fourier approximation to time dependent problems.
Incorporating spatial dependence in regional frequency analysis
Wang, Zhuo; Yan, Jun; Zhang, Xuebin
The efficiency of regional frequency analysis (RFA) is undermined by intersite dependence, which is usually ignored in parameter estimation. We propose a spatial index flood model where marginal generalized extreme value distributions are joined by an extreme-value copula characterized by a max-stable process for the spatial dependence. The parameters are estimated with a pairwise likelihood constructed from bivariate marginal generalized extreme value distributions. The estimators of model parameters and return levels can be more efficient than those from the traditional index flood model when the max-stable process fits the intersite dependence well. Through simulation, we compared the pairwise likelihood method with an L-moment method and an independence likelihood method under various spatial dependence models and dependence levels. The pairwise likelihood method was found to be the most efficient in mean squared error if the dependence model was correctly specified. When the dependence model was misspecified within the max-stable models, the pairwise likelihood method was still competitive relative to the other two methods. When the dependence model was not a max-stable model, the pairwise likelihood method led to serious bias in estimating the shape parameter and return levels, especially when the dependence was strong. In an illustration with annual maximum precipitation data from Switzerland, the pairwise likelihood method yielded remarkable reduction in the standard errors of return level estimates in comparison to the L-moment method. PMID:25745273
Patient Dependency Knowledge-Based Systems.
Soliman, F
The ability of Patient Dependency Systems to provide information for staffing decisions and budgetary development has been demonstrated. In addition, they have become powerful tools in modern hospital management. This growing interest in Patient Dependency Systems has renewed calls for their automation. As advances in Information Technology and in particular Knowledge-Based Engineering reach new heights, hospitals can no longer afford to ignore the potential benefits obtainable from developing and implementing Patient Dependency Knowledge-Based Systems. Experience has shown that the vast majority of decisions and rules used in the Patient Dependency method are too complex to capture in the form of a traditional programming language. Furthermore, the conventional Patient Dependency Information System automates the simple and rigid bookkeeping functions. On the other hand Knowledge-Based Systems automate complex decision making and judgmental processes and therefore are the appropriate technology for automating the Patient Dependency method. In this paper a new technique to automate Patient Dependency Systems using knowledge processing is presented. In this approach all Patient Dependency factors have been translated into a set of Decision Rules suitable for use in a Knowledge-Based System. The system is capable of providing the decision-maker with a number of scenarios and their possible outcomes. This paper also presents the development of Patient Dependency Knowledge-Based Systems, which can be used in allocating and evaluating resources and nursing staff in hospitals on the basis of patients' needs. PMID:9809275
Determining Directional Dependency in Causal Associations
ERIC Educational Resources Information Center
Pornprasertmanit, Sunthud; Little, Todd D.
Directional dependency is a method to determine the likely causal direction of effect between two variables. This article aims to critique and improve upon the use of directional dependency as a technique to infer causal associations. We comment on several issues raised by von Eye and DeShon (2012), including: encouraging the use of the signs of…
Fuzzy Functional Dependencies and Redundancy Elimination.
ERIC Educational Resources Information Center
Bosc, Patrick; Dubois, Didier; Prade, Henri
For about 10 years, several proposals to deal with ill-known information in database management systems have been made, and extensions of the relational data model have been proposed. An overview of functional dependencies is provided, and the connection between fuzzy functional dependencies and database design is discussed. (AEF)
Commitment and Dependence Upon Regular Running.
ERIC Educational Resources Information Center
Sachs, Michael L.; Pargman, David
The linear relationship between intellectual commitment to running and psychobiological dependence upon running is examined. A sample of 540 regular runners (running frequency greater than three days per week for the past year for the majority) was surveyed with a questionnaire. Measures of commitment and dependence on running, as well as…
Assessment of Dependency, Agreeableness, and Their Relationship
ERIC Educational Resources Information Center
Lowe, Jennifer Ruth; Edmundson, Maryanne; Widiger, Thomas A.
Agreeableness is central to the 5-factor model conceptualization of dependency. However, 4 meta-analyses of the relationship of agreeableness with dependency have failed to identify a consistent relationship. It was the hypothesis of the current study that these findings might be due in part to an emphasis on the assessment of adaptive, rather…
Dependent Children and Suicide of Married Parents.
ERIC Educational Resources Information Center
Kozak, Conrad M.; Gibbs, James O.
Single suicides and married suicides with dependent children were compared to similar groups in the general population. Married people with dependent children experienced the lowest average suicide rate, but had a larger mean number of children than the population as a whole. (Author)
The Restorative Recovery School: Countering Chemical Dependency
ERIC Educational Resources Information Center
Riestenberg, Nancy
In a recovery school, the students commit to working on recovery from chemical dependency and addiction while becoming successful students. Since all of the students attending the school have been in chemical dependency treatment, the safety of the environment is the first concern of students, their families and staff. Applying restorative…
Understanding and Teaching the Dependent Retarded Child.
ERIC Educational Resources Information Center
Rosenzweig, Louis E.; Long, Julia
Levels of mental retardation and school admission procedures for the dependent retarded (IQ's 30 to 50) are reviewed. Goals for all retarded and the application of goals to the dependent retarded are considered. Plans and procedures for both teacher and child activities along with suggestions for audiovisual and other materials are provided in the…
Code of Federal Regulations, 2010 CFR
... EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Child Annuities § 843.405 Dependency. To be eligible for survivor annuity benefits, a child must have been dependent on the employee or retiree at the time of the employee's or retiree's death....
Chemical Dependence and Clinical Depression in Pregnancy.
ERIC Educational Resources Information Center
Burns, Kayreen; And Others
Assessed the extent and depth of depression in 54 chemically dependent pregnant women, divided into three groups by age. Results indicated that the older chemically dependent women scored significantly higher on the depression index than did either of the two younger groups, while the teenagers obtained a mean score comparable to that of the…
Escherichia coli survival in waters: Temperature dependence
Knowing the survival rates of water-borne Escherichia coli is important in evaluating microbial contamination and making appropriate management decisions. E. coli survival rates are dependent on temperature, a dependency that is routinely expressed using an analogue of the Q10 mo...
Is ecstasy a drug of dependence?
Degenhardt, Louisa; Bruno, Raimondo; Topp, Libby
This paper examines the evidence for an MDMA or "ecstasy" dependence syndrome. Animal evidence suggests that MDMA may be a less potent reinforcer than other drugs, but that it does have dependence potential. This suggests that (a) ecstasy dependence might be less likely than dependence upon other drugs; and (b) factors related to the behavioural and psychological aspects of reward and dependence may make a relatively greater contribution for ecstasy than for other drugs, where physically centred (and better understood) features of dependence may be more salient. Human evidence supports this proposition. Some people report problems with their use, but the literature suggests that physical features play a more limited role than psychological ones. Tolerance is apparent, and withdrawal is self-reported, but it is unclear whether these reports distinguish sub-acute effects of ecstasy intoxication from symptoms reflective of neuroadaptive processes underlying a "true" withdrawal syndrome. Studies examining the structure of dependence upon ecstasy suggest it may be different from drugs such as alcohol, methamphetamine and opioids. Consistent with studies of hallucinogens, a two-factor structure has been identified with factors suggestive of "compulsive use" and "escalating use". Regardless of the nature of any dependence syndrome, however, there is evidence to suggest that a minority of ecstasy users become concerned about their use and seek treatment. Further controlled studies are required to investigate this phenomenon. PMID:19836170
Risk Management using Dependency Stucture Matrix
NASA Astrophysics Data System (ADS)
Petković, Ivan
An efficient method based on dependency structure matrix (DSM) analysis is given for ranking risks in a complex system or process whose entities are mutually dependent. This rank is determined according to the element's values of the unique positive eigenvector which corresponds to the matrix spectral radius modeling the considered engineering system. For demonstration, the risk problem of NASA's robotic spacecraft is analyzed.
Alcoholism, Field Dependency and Organic Impairment.
ERIC Educational Resources Information Center
Lafferty, Patricia; Kahn, Marvin W.
Although research has suggested that field dependency is a relatively stable characteristic of alcoholics, the results have been confounded by the use of different measures and different time intervals. To investigate the degree of organic brain impairment and its association with measured field dependency amongst alcoholics, 41 male alcoholics,…
E. coli survival in waters: temperature dependence
Technology Transfer Automated Retrieval System (TEKTRAN)
Knowing the survival rates of water-borne Escherichia coli is important for evaluating microbial contamination and in making appropriate management decisions. E. coli survival rates are dependent on temperature; this dependency is routinely expressed using an analog of the Q10 model. This suggestion...
Many hydrologists have observed that dispersion coefficients, when measured in the field, turn out to be scale-dependent. Recently, Guven, et al., (1983) presented a study which contains a basis for understanding the phenomenon of scale-dependent dispersion within a deterministic...
Alcohol dependence in the Naval Service.
Dickie, A K; Coetzee, R H
Alcohol misuse is a significant occupational health issue in the United Kingdom Armed Forces. Dependence associated with alcohol misuse represents the severe end of the clinical and occupational consequences of sustained alcohol misuse. This article aims to explore the diagnosis, management and occupational considerations of alcohol dependence in the Naval Service environment. PMID:25335312
Empirical Evaluation of Directional-Dependence Tests
ERIC Educational Resources Information Center
Thoemmes, Felix
Testing of directional dependence is a method to infer causal direction that recently has attracted some attention. Previous examples by e.g. von Eye and DeShon (2012a) and extensive simulation studies by Pornprasertmanit and Little (2012) have demonstrated that under specific assumptions, directional-dependence tests can recover the true causal…
Chemical Dependency Regional Needs Assessment: Northeastern Minnesota.
ERIC Educational Resources Information Center
Stone, Marylee
The Minnesota Model of Chemical Dependency Treatment, which evolved from a combination of the grassroots Alcoholics Anonymous movement and the State Mental Health Services in the 1960s has made Minnesota an international leader in chemical dependency treatment efforts. Northeastern Minnesota has shared this reputation with the state. In spite of…
Chemical dependency and adolescent self-esteem.
Wasson, D; Anderson, M A
The purpose of this descriptive study is to determine whether self-esteem differs between chemically dependent adolescents and adolescents from the general high school population. The Self-Esteem Inventory (Coopersmith, 1987) was completed by 119 adolescents (31 inpatient, 31 aftercare, and 57 general high school students) aged 13 to 18. Findings suggest that inpatient, chemically dependent adolescents have lower self-esteem than the other two groups. For the chemically dependent adolescent, nursing case management with communication among and between health care providers, school professionals, and family may facilitate successful, long-term recovery. For adolescents at risk for development of chemical dependence, nursing health promotion behaviors, such as early assessment and implementation of self-esteem-building activities, may assist in prevention of chemical dependency. PMID:7633338
Genetic Vulnerability and Susceptibility to Substance Dependence
Bierut, Laura Jean
The development of substance dependence requires the initiation of substance use, the conversion from experimental use to established use, and finally the development of dependence. Numerous large twin studies have indicated a significant genetic contribution to this process. Genetic studies to date have been most successful at identifying genetic factors that influence the transition from regular use to dependence. The availability of large cohort samples for nicotine and alcohol dependence has resulted in significant progress being made in understanding at least some of the genetic contributions to these addictions. Fewer studies have replicated specific genetic contributions to illicit drug use, though it is clear that there is a strong genetic component involved here as well. Substance dependence can be thought of as a pharmacogenetic illness, and most likely hundreds and more probably thousands of genetic variants will be required to fully explain the genetic input to this disease. PMID:21338875
Management of benzodiazepine misuse and dependence
Brett, Jonathan; Murnion, Bridin
Summary There are well-recognised harms from long-term use of benzodiazepines. These include dependency, cognitive decline and falls. It is important to prevent and recognise benzodiazepine dependence. A thorough risk assessment guides optimal management and the necessity for referral. The management of dependence involves either gradual benzodiazepine withdrawal or maintenance treatment. Prescribing interventions, substitution, psychotherapies and pharmacotherapies can all contribute. Unless the patient is elderly, it is helpful to switch to a long-acting benzodiazepine in both withdrawal and maintenance therapy. The dose should be gradually reduced over weeks to lower the risk of seizures. Harms from drugs such as zopiclone and zolpidem are less well characterised. Dependence is managed in the same manner as benzodiazepine dependence. PMID:26648651
Management of benzodiazepine misuse and dependence.
Brett, Jonathan; Murnion, Bridin
There are well-recognised harms from long-term use of benzodiazepines. These include dependency, cognitive decline and falls. It is important to prevent and recognise benzodiazepine dependence. A thorough risk assessment guides optimal management and the necessity for referral. The management of dependence involves either gradual benzodiazepine withdrawal or maintenance treatment. Prescribing interventions, substitution, psychotherapies and pharmacotherapies can all contribute. Unless the patient is elderly, it is helpful to switch to a long-acting benzodiazepine in both withdrawal and maintenance therapy. The dose should be gradually reduced over weeks to lower the risk of seizures. Harms from drugs such as zopiclone and zolpidem are less well characterised. Dependence is managed in the same manner as benzodiazepine dependence. PMID:26648651
N-desmethyldiazepam physical dependence in dogs.
McNicholas, L F; Martin, W R; Pruitt, T A
Dogs, surgically implanted with a chronic gastric fistula, were chronically dosed with N-desmethyldiazepam (32 mg/kg/day) in four divided doses to attain N-desmethyldiazepam plasma levels comparable to those observed in dogs dependent on diazepam (60 mg/kg/day). The time course of N-desmethyldiazepam abstinence was studied, beginning not less than 2 weeks after stabilization levels had been achieved. The abstinence syndrome observed after abrupt discontinuation of N-desmethyldiazepam was similar to the diazepam abstinence syndrome but differed in several important aspects. In diazepam-dependent dogs, there was a short burst of tremor very early in withdrawal (approximately 1-2 hr after the last dose of diazepam) that was not seen in N-desmethyldiazepam-dependent dogs. Signs of abstinence such as tremor, hot foot walking and twitches and jerks were more frequently observed in N-desmethyldiazepam-dependent dogs than in diazepam-dependent dogs as were decreases in food and water intake and in body weight. The overall intensity of abstinence, as measured by the Diazepam Withdrawal Abstinence Scale, was greater in N-desmethyldiazepam-dependent dogs than in dogs dependent on either lorazepam or diazepam. Plasma levels of N-desmethyldiazepam and oxazepam were nearly equal in dogs dependent on diazepam or on N-desmethyldiazepam and were 4 to 10 times greater than the plasma levels of diazepam or lorazepam in diazepam- or lorazepam-dependent dogs, respectively. Furthermore, the plasma levels of N-desmethyldiazepam and oxazepam declined much more slowly than the levels of diazepam and lorazepam. These results suggest that physical dependence on diazepam is caused by the accumulation and actions of N-desmethyldiazepam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3932642
Time-dependent photoelectron angular distributions
NASA Astrophysics Data System (ADS)
Wang, Xiangyang
I show that the angular distribution of electrons photoionized from gas phase targets by short light pulses is time-dependent, when the orbital momentum composition of the photocurrent changes with excitation energy so evolves with the time of detection. A theory of time- dependent photoionization is outlined and general formulas of time-dependent photoelectron flux and angular distribution are given. Two general propagator methods suitable to describe the time-dependent photoionization and scattering processes are developed. The photoionization process is viewed as a local excitation followed by a half scattering. The local excitation process is solved theoretically in a small region around the target core. This approach has been generalized to describe the evolution of a wavepacket in an unbound system. An asymptotic propagator theorem is discovered and used to derive analytic expressions for asymptotic propagators. The origin of the time dependence is explored by parameterizing the time delay and orbital momentum coupling in a two channel model. K-shell photoionization of N2 and CO are calculated with this time- dependent photoionization theory, implemented using a multiple scattering model. Numerical results demonstrate that the time dependence of photoelectron angular distributions is a realistic effect.
Birefringence in time-dependent moving media
NASA Astrophysics Data System (ADS)
Lin, Shirong; Zhang, Ruoyang; Zhai, Yanwang; Wei, Jianye; Zhao, Qing
Electromagnetic wave propagation in one- and two-dimensional time-dependent moving media is investigated in this paper. We identify another origin of linear birefringence caused by the component of the flow perpendicular to the wave vector. Previously, birefringence is induced by applying external electric and magnetic fields to non-crystalline material. Here it is shown that the time-varying velocity field also contributes to such a phenomenon. Our results indicate that the parallel component, time-dependent or not, will not yield birefringence. Furthermore, the time-dependent flow also results in a frequency shift. One-dimensional simulation is conducted to demonstrate these effects.
Imaging dopamine transmission parameters in cannabis dependence.
Ghazzaoui, Rassil; Abi-Dargham, Anissa
Low striatal dopamine D2/3 receptor (D2/3) availability and low ventrostriatal dopamine release have been observed in alcoholism, cocaine and heroin dependence. Multiple studies to date have examined D2 availability in cannabis dependence and have consistently failed to demonstrate alterations. In addition, the response of the dopamine system to an amphetamine challenge and to a stress challenge has also been examined, and did not show alterations. We review these studies here and conclude that cannabis dependence is an exception among commonly abused drugs in that it is not associated with blunting of the dopamine system. PMID:24513022
Cigarette smoking, nicotine dependence, and treatment.
Sees, K L
Since the 1988 Surgeon General's report on nicotine addiction, more attention is being given to nicotine dependence as a substantial contributing factor in cigarette smokers' inability to quit. Many new medications are being investigated for treating nicotine withdrawal and for assisting in long-term smoking abstinence. Medications alone probably will not be helpful; they should be used as adjuncts in comprehensive smoking abstinence programs that address not only the physical dependence on nicotine but also the psychological dependence on cigarette smoking. PMID:2190425
Process dependent nuclear k⊥ broadening effect
NASA Astrophysics Data System (ADS)
Schäfer, Andreas; Zhou, Jian
We study the process dependent nuclear k⊥ broadening effect by employing the transverse momentum dependent (TMD) factorization approach in combination with the Mclerran-Venugopalan model. More specifically, we investigate how the parton transverse momentum distributions are affected by the process dependent gauge links in cold nuclear matter. In particular, our analysis also applies to the polarized cases including the nuclear quark Boer-Mulders function and the linearly polarized gluon distribution. Our main focus is on the nuclear TMDs at intermediate or large x.
Free Beauty, Dependent Beauty, and Art.
ERIC Educational Resources Information Center
Stecker, Robert
Explains the difference between free and dependent beauty. States that these distinctions, formed by Immanuel Kant, have important implications for aesthetic education. Concludes with a defense of Kant's aesthetics. (JDH)
EDTA-dependent pseudothrombocytopenia in a child.
Akbayram, Sinan; Dogan, Murat; Akgun, Cihangir; Caksen, Hüseyin; Oner, Ahmet Faik
Ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia (PTCP) is the phenomenon of a spurious low platelet count due to antiplatelet antibodies that cause platelet clumping in blood anticoagulated with EDTA. The aggregation of platelets in EDTA-dependent PTCP is usually prevented by other anticoagulants, such as sodium citrate or heparin. EDTA-dependent PTCP has never been associated with hemorrhagic diathesis or platelet dysfunction. In this article, a 10-year-old boy with EDTA- and heparin-dependent PTCP is presented because of rare presentation. We report that EDTA and heparin can induce platelet clumping, and thus spuriously low platelet counts. However, aggregation of platelets was not detected in blood samples with sodium citrate, and platelet count was normal. PMID:20530050
The Nonlinear Dynamics of Pacemaker Dependency
NASA Astrophysics Data System (ADS)
Buechley, Leah
A person is considered pacemaker dependent when most of his or her heartbeats are supplied by a pacemaker. The purpose of this study was to determine whether there are significant differences between the heart dynamics of pacemaker-dependent patients and those of normal patients. Nonlinear dynamics techniques and statistical methods were used to analyze the ECGs of normal patients and pacemaker-dependent patients. Standard embedding of the ECG data yielded inconclusive results, but embedding the beat intervals proved to be much more useful. Lyapunov exponent calculations, recurrence plot analyses, and standard statistical analyses of these data showed significant differences in heart behavior between the two groups of patients. In particular, the beat intervals appear to exhibit chaotic behavior for the normal patients and fixed-point dynamics for pacemaker-dependent patients.
National Council on Alcoholism and Drug Dependence
... the Month NCADD National Council on Alcoholism and Drug Dependence Addiction is a Disease - Treatment is Available - Recovery Brings ... Research Addiction Get the Facts Alcohol Learn More Drugs Learn More Addiction Update Learn More Underage Issues Learn More FAQ ...
▼Nalmefene for alcohol dependence.
The burden of morbidity and mortality resulting from alcohol dependence is high. World Health Organization (WHO) figures suggest that in the UK the prevalence of alcohol use disorders in those aged 15 years and older is around 6.4% for men and 1.5% for women.1 Reduction of harm resulting from alcohol dependence remains a high priority in all four devolved health services in the UK.2-5 Several medicines are licensed for the maintenance of abstinence in alcohol-dependent patients. However, until recently no drug was licensed for the management of alcohol dependence in people who are still drinking. ▼Nalmefene (Selincro, Lundbeck), an opioid modulator licensed for the reduction of alcohol consumption, was launched in the UK in May 2013.6,7 Here we discuss the evidence for its effectiveness and safety and consider its place in therapy. PMID:24809337
Topic 5: Time-Dependent Behavior
Pfeiffer, P.A.; Tanabe, Tada-aki
This chapter is a report of the material presented at the International Workshop on Finite Element Analysis of Reinforced Concrete, Session 4 -- Time Dependent Behavior, held at Columbia University, New York on June 3--6, 1991. Dr. P.A. Pfeiffer presented recent developments in time-dependent behavior of concrete and Professor T. Tanabe presented a review of research in Japan on time-dependent behavior of concrete. The chapter discusses the recent research of time-dependent behavior of concrete in the past few years in both the USA-European and Japanese communities. The author appreciates the valuable information provided by Zdenek P. Bazant in preparing the USA-European Research section.
Polarization Dependent Optical Responses of Graphene Nanoribbons
NASA Astrophysics Data System (ADS)
Cao, Ting; Choi, Sangkook; Louie, Steven
The optical response of an anisotropic system depends on light's polarization direction. In this study, we perform first-principle calculations on polarization dependent optical absorption spectra of graphene nanoribbons at the RPA and GW-BSE level. We observe significant polarization dependent features. We demonstrate the many-body origins of these features. We also discuss the polarization dependent optical responses of other carbon nanostructures, and connect our work to experimental measurements. This work was supported by National Science Foundation Grant No. DMR10-1006184, the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Computational resources have been provided by DOE at Lawrence Berkeley National Laboratory's NERSC facility
Bounds for state-dependent quantum cloning
Han Yongjian; Zhang Yongsheng; Guo Guangcan
Due to the no-cloning theorem, the unknown quantum state can only be cloned approximately or exactly with some probability. There are two types of cloners: universal and state-dependent cloner. The optimal universal cloner has been found and can be viewed as a special state-dependent quantum cloner that has no information about the states. In this paper, we investigate the state-dependent cloning when the state set contains more than two states. We get some bounds of the global fidelity for these processes. This method is not dependent on the number of the states contained in the state set. It is also independent of the numbers of copying.
Implant Proves Effective At Combating Opioid Dependence
... new resource for those addicted to prescription painkillers, heroin To use the sharing features on this page, ... twice as likely to kick their dependence on heroin or prescription painkillers if they receive a new ...
Time dependent breakdown in silicon dioxide films
NASA Technical Reports Server (NTRS)
Svensson, C.; Shumka, A.
An investigation was conducted regarding the possible existence of a time-dependent breakdown mechanism in thermal oxides of the type used as gate oxide in MOS circuits. Questions of device fabrication are discussed along with details concerning breakdown measurements and the determination of C-V characteristics. A relatively large prebreakdown current observed in one of the cases is related to the time-dependent breakdown.
Isotopic dependence of the Casimir force.
Krause, Dennis E; Fischbach, Ephraim
We calculate the dependence of the Casimir force on the isotopic composition of the interacting objects. This dependence arises from the subtle influence of the nuclear masses on the electronic properties of the bodies. We discuss the relevance of these results to current experiments utilizing the isoelectronic effect to search at very short separations for new weak forces suggested by various unification theories. PMID:12443107
Treating drug-dependent patients in hospitals.
Skene, Loane; Keays, David; Gardner, Bruce
Are hospital staff legally permitted to test drug-dependent patients for drugs or infectious disease without the patient's consent in order to treat the patient or to protect themselves or other patients? What should staff do with "suspicious" items in the patient's possession (drugs, credit cards in different names, firearms)? Can drug-dependent patients lawfully use illicit drugs in hospital? Who should supply and administer them? PMID:12242876
Divergences and involution-dependent constants
Nagao, G.
The authors show the cancellation of the dilation divergence in the 1-loop open bosonic string vacuum and N-tachyon scattering amplitude depends upon a set of involution-dependent constants. Such a set of constants exists at each loop level and thus provides a means with which to study the connection between the cancellation of divergences and anomalies for the gauge group SO(2/sup D/2/).
Desai, N.G.; Vaswani, M.; Chavan, B.S.; Tripathi, B.M.; Kaw, N.
Ninety two patients of alcohol dependence were studied for liver function at a specialised drug dependence treatment centre. Biochemical laboratory evidence of liver dysfunction was found in a very large number of patients, including the patients who had no clinical signs or symptoms. The findings from this retrospective study are discussed in the context of the earlier studies from other settings in India. PMID:21584115
[Drugs, a current problem. Alcohol dependency].
Amigó Tadín, Montserrat
Alcohol is a socially accepted drug which is commercialized in multiple products including wine, cognac, gin, beer, anisette, vermouth, rum, etc. and which can be consumed in small quantities without producing harmful effects on one's health; nonetheless, women are more susceptible to alcohol's damages and an abusive consumption of alcohol creates dependence and chronic diseases. Ten percent of those people who consume alcohol develop dependency and comprise the leading group of drug addicts in many countries. PMID:16493852
Profile of liver dysfunction in alchohol dependence.
Desai, N G; Vaswani, M; Chavan, B S; Tripathi, B M; Kaw, N
Ninety two patients of alcohol dependence were studied for liver function at a specialised drug dependence treatment centre. Biochemical laboratory evidence of liver dysfunction was found in a very large number of patients, including the patients who had no clinical signs or symptoms. The findings from this retrospective study are discussed in the context of the earlier studies from other settings in India. PMID:21584115
[Health Technology Dependency: A Concept Analysis].
Chen, Miao-Yi; Chen, Ting-Yu; Kao, Chi-Wen
Health technology dependence is a widely recognized concept that refers to the utilization of technology, including drugs, equipment, instruments, and related devices, to compensate for a physical disability or to prevent the progression of a disability. Although technology may significantly prolong the life of a patient, technology may also increase the psychological pressure of these patients and the burdens of their caregivers. There is a current dearth of related research and discussions related to the concept of "health technology dependency". Therefore, the present paper uses the strategies of concept analysis described by Walker & Avant (2010) to analyze this concept. The characteristic definition of health technology dependence addresses individuals who: (1) currently live with health technology, (2) may perceive physical or psychological burdens due to health technology, and (3) feel physical and psychological well-being when coping positively with their health technology dependency and, further, regard health technology as a part of their body. Further, the present paper uses case examples to help analyze the general concept. It is hoped that nurses may better understand the concept of "health technology dependency", consider the concerns of health-technology-dependent patients and their families, and develop relevant interventions to promote the well-being of these patients and their families. PMID:26813069
Experimental analysis of computer system dependability
NASA Technical Reports Server (NTRS)
Iyer, Ravishankar, K.; Tang, Dong
This paper reviews an area which has evolved over the past 15 years: experimental analysis of computer system dependability. Methodologies and advances are discussed for three basic approaches used in the area: simulated fault injection, physical fault injection, and measurement-based analysis. The three approaches are suited, respectively, to dependability evaluation in the three phases of a system's life: design phase, prototype phase, and operational phase. Before the discussion of these phases, several statistical techniques used in the area are introduced. For each phase, a classification of research methods or study topics is outlined, followed by discussion of these methods or topics as well as representative studies. The statistical techniques introduced include the estimation of parameters and confidence intervals, probability distribution characterization, and several multivariate analysis methods. Importance sampling, a statistical technique used to accelerate Monte Carlo simulation, is also introduced. The discussion of simulated fault injection covers electrical-level, logic-level, and function-level fault injection methods as well as representative simulation environments such as FOCUS and DEPEND. The discussion of physical fault injection covers hardware, software, and radiation fault injection methods as well as several software and hybrid tools including FIAT, FERARI, HYBRID, and FINE. The discussion of measurement-based analysis covers measurement and data processing techniques, basic error characterization, dependency analysis, Markov reward modeling, software-dependability, and fault diagnosis. The discussion involves several important issues studies in the area, including fault models, fast simulation techniques, workload/failure dependency, correlated failures, and software fault tolerance.
Affective Dependence and Aggression: An Exploratory Study
Petruccelli, Filippo; Diotaiuti, Pierluigi; Verrastro, Valeria; Petruccelli, Irene; Federico, Roberta; Martinotti, Giovanni; Fossati, Andrea; Di Giannantonio, Massimo; Janiri, Luigi
Introduction. Emotionally dependent subjects may engage in controlling, restrictive, and aggressive behaviours, which limit their partner's autonomy. The underlying causes of such behaviours are not solely based on levels of aggression, but act as a mean of maintaining the subject's own sense of self-worth, identity, and general functioning. Objective. The aim of the paper is to explore the correlation between affective dependency and reactive/proactive aggression and to evaluate individual differences as predisposing factors for aggressive behaviour and emotional dependency. Methods. The Spouse-Specific Dependency Scale (SSDS) and the Reactive Proactive Questionnaire (RPQ) were administered to a sample of 3375 subjects. Results. In the whole sample, a positive correlation between emotional dependency and proactive aggression was identified. Differences with regard to sex, age group, and geographical distribution were evidenced for the scores of the different scales. Conclusion. A fundamental distinction between reactive and proactive aggression was observed, anchoring proactive aggression more strictly to emotional dependency. Sociocultural and demographical variables, together with the previous structuring of attachment styles, help to determine the scope, frequency, and intensity of the demands made to the partner, as well as to feed the fears of loss, abandonment, or betrayal. PMID:25054147
Alcoholic neurobiology: changes in dependence and recovery.
Crews, Fulton T; Buckley, Tracey; Dodd, Peter R; Ende, Gabriele; Foley, Nina; Harper, Clive; He, Jun; Innes, David; Loh, El-Wui; Pfefferbaum, Adolph; Zou, Jian; Sullivan, Edith V
This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October, 2004. Chronic alcoholism follows a fluctuating course, which provides a naturalistic experiment in vulnerability, resilience, and recovery of human neural systems in response to presence, absence, and history of the neurotoxic effects of alcoholism. Alcohol dependence is a progressive chronic disease that is associated with changes in neuroanatomy, neurophysiology, neural gene expression, psychology, and behavior. Specifically, alcohol dependence is characterized by a neuropsychological profile of mild to moderate impairment in executive functions, visuospatial abilities, and postural stability, together with relative sparing of declarative memory, language skills, and primary motor and perceptual abilities. Recovery from alcoholism is associated with a partial reversal of CNS deficits that occur in alcoholism. The reversal of deficits during recovery from alcoholism indicates that brain structure is capable of repair and restructuring in response to insult in adulthood. Indirect support of this repair model derives from studies of selective neuropsychological processes, structural and functional neuroimaging studies, and preclinical studies on degeneration and regeneration during the development of alcohol dependence and recovery form dependence. Genetics and brain regional specificity contribute to unique changes in neuropsychology and neuroanatomy in alcoholism and recovery. This symposium includes state-of-the-art presentations on changes that occur during active alcoholism as well as those that may occur during recovery-abstinence from alcohol dependence. Included are human neuroimaging and neuropsychological assessments, changes in human brain gene expression, allelic combinations of genes associated with alcohol dependence and preclinical studies investigating mechanisms of
Mixing Pot and Tobacco Increases Dependence Risk: Study
... July 5, 2016 (HealthDay News) -- People who mix marijuana with tobacco are at greater risk for dependency ... likelihood that users become dependent, the researchers found. "Cannabis dependence and tobacco dependence manifest in similar ways, ...
Is frictional healing slip-dependent?
NASA Astrophysics Data System (ADS)
Bhattacharya, P.; Rubin, A. M.; Ryan, K. L.; Riviere, J. V.; Marone, C.
Frictional re-strengthening of bare rock surfaces at very low stresses and near zero slip rate, as observed in the laboratory, is traditionally interpreted as showing support for purely time-dependent healing as embodied in the Aging law. However, while slide-hold-slide experiments on bare surfaces do show an apparent (purely) time-dependent increase in the static friction upon reslide, we show that the stress minima attained during the preceding holds show a strong slip-dependence which contradict the Aging law. A velocity strengthening Slip law explains such data much better. We also show that, large velocity step decreases, which drive the system far below steady state just like long holds, clearly support the slip-dependent response of the Slip law over the time-dependent healing contained in the Aging law. But, while time-dependent healing has an intuitive physical picture in terms of growth of the 'real contact area' with time, it is more difficult to ascribe one to slip-dependent healing. Here, we explore the possibility that the slip-dependence arises out of an interplay between contact `quality' and `quantity' at the scale of the asperity contacts. First, to further study the slip-dependence of healing, we carry out large velocity step decreases and sequences of long slide-hold-slides on both bare rock and gouge. Secondly, to probe the micro-mechanical origins of healing, we complement our mechanical data with amplitudes and travel time data of ultrasonic P- and S- waves transmitted across the sliding interface. While ultrasonic P-wave transmissivity has been used as a proxy for 'real contact area' in friction experiments by Nagata et al. (2012, 2014) before, the simultaneous use of P- and S-phases in our experiments is designed specifically to probe contact rheology. Initial results show strong correlations between changes in friction, transmitted wave amplitudes and travel times in response to changes in slip rate. We also observe important differences
Mapping Groundwater Dependent Ecosystems in California
Howard, Jeanette; Merrifield, Matt
Background Most groundwater conservation and management efforts focus on protecting groundwater for drinking water and for other human uses with little understanding or focus on the ecosystems that depend on groundwater. However, groundwater plays an integral role in sustaining certain types of aquatic, terrestrial and coastal ecosystems, and their associated landscapes. Our aim was to illuminate the connection between groundwater and surface ecosystems by identifying and mapping the distribution of groundwater dependent ecosystems (GDEs) in California. Methodology/Principal Findings To locate where groundwater flow sustains ecosystems we identified and mapped groundwater dependent ecosystems using a GIS. We developed an index of groundwater dependency by analyzing geospatial data for three ecosystem types that depend on groundwater: (1) springs and seeps; (2) wetlands and associated vegetation alliances; and (3) stream discharge from groundwater sources (baseflow index). Each variable was summarized at the scale of a small watershed (Hydrologic Unit Code-12; mean size = 9,570 ha; n = 4,621), and then stratified and summarized to 10 regions of relative homogeneity in terms of hydrologic, ecologic and climatic conditions. We found that groundwater dependent ecosystems are widely, although unevenly, distributed across California. Although different types of GDEs are clustered more densely in certain areas of the state, watersheds with multiple types of GDEs are found in both humid (e.g. coastal) and more arid regions. Springs are most densely concentrated in the North Coast and North Lahontan, whereas groundwater dependent wetlands and associated vegetation alliances are concentrated in the North and South Lahontan and Sacramento River hydrologic regions. The percentage of land area where stream discharge is most dependent on groundwater is found in the North Coast, Sacramento River and Tulare Lake regions. GDE clusters are located at the highest percentage
Linear dependencies in Weyl-Heisenberg orbits
NASA Astrophysics Data System (ADS)
Dang, Hoan Bui; Blanchfield, Kate; Bengtsson, Ingemar; Appleby, D. M.
Five years ago, Lane Hughston showed that some of the symmetric informationally complete positive operator valued measures (SICs) in dimension 3 coincide with the Hesse configuration (a structure well known to algebraic geometers, which arises from the torsion points of a certain elliptic curve). This connection with elliptic curves is signalled by the presence of linear dependencies among the SIC vectors. Here we look for analogous connections between SICs and algebraic geometry by performing computer searches for linear dependencies in higher dimensional SICs. We prove that linear dependencies will always emerge in Weyl-Heisenberg orbits when the fiducial vector lies in a certain subspace of an order 3 unitary matrix. This includes SICs when the dimension is divisible by 3 or equal to 8 mod 9. We examine the linear dependencies in dimension 6 in detail and show that smaller dimensional SICs are contained within this structure, potentially impacting the SIC existence problem. We extend our results to look for linear dependencies in orbits when the fiducial vector lies in an eigenspace of other elements of the Clifford group that are not order 3. Finally, we align our work with recent studies on representations of the Clifford group.
Marijuana dependence: not just smoke and mirrors.
Ramesh, Divya; Schlosburg, Joel E; Wiebelhaus, Jason M; Lichtman, Aron H
Marijuana (Cannabis sativa) is the most commonly used illicit drug worldwide as well as in the Unites States. Prolonged use of marijuana or repeated administration of its primary psychoactive constituent, Δ9-tetrahydrocannabinol (THC), can lead to physical dependence in humans and laboratory animals. The changes that occur with repeated cannabis use include alterations in behavioral, physiological, and biochemical responses. A variety of withdrawal responses occur in cannabis-dependent individuals: anger, aggression, irritability, anxiety and nervousness, decreased appetite or weight loss, restlessness, and sleep difficulties with strange dreams. But the long half-life and other pharmacokinetic properties of THC result in delayed expression of withdrawal symptoms, and because of the lack of contiguity between drug cessation and withdrawal responses the latter are not readily recognized as a clinically relevant syndrome. Over the past 30 years, a substantial body of clinical and laboratory animal research has emerged supporting the assertion that chronic exposure to cannabinoids produces physical dependence and may contribute to drug maintenance in cannabis-dependent individuals. However, no medications are approved to treat cannabis dependence and withdrawal. In this review, we describe preclinical and clinical research that supports the existence of a cannabinoid withdrawal syndrome. In addition, we review research evaluating potential pharmacotherapies (e.g., THC, a variety of antidepressant drugs, and lithium) to reduce cannabis withdrawal responses and examine how expanded knowledge about the regulatory mechanisms in the endocannabinoid system may lead to promising new therapeutic targets. PMID:23382144
Field Dependent Penetration Depth in YBCO
NASA Astrophysics Data System (ADS)
Carrington, A.; Giannetta, R.; Salamon, M. B.; Ginsberg, D. M.; Kim, J. T.
An important step to understanding the nature of superconductivity in cuprate superconductors was the observation of a linear temperature dependence of the penetration depth (λ_ab) in YBCO(W.N. Hardy et al.) Phys. Rev. Lett. 70, 3999 (1993)., which strongly suggests the presence of line nodes in the order parameter, consistent with a d-wave pairing state. Recent theoretical work(S.K. Yip and J.A. Sauls, Phys. Rev. Lett. 69), 2264 (1992). has claimed that the magnetic field dependence of λ_ab at low temperature also uniquely depends on the symmetry of the order parameter. To investigate these effects we have built an apparatus, based on a RF tunnel diode oscillator,to measure with high precision both the temperature and field dependence of λ in small single crystal samples. Particular attention has been paid to reducing extraneous frequency shifts originating from the field/temperature dependence of the oscillator circuit. The sample rests on a moveable stage whose temperature may be varied indepndently of the resonator, so that the background may be measured in-situ. Results will be presented for YBCO at temperatures down to 1.3 K and fields up to H_c1(T), and their implications for the the pairing state in the cuprates discussed. This work was supported by NSF Grant # DMR-89-20538 and STCS/NSF DMR 91-20000.
Representing higher-order dependencies in networks
Xu, Jian; Wickramarathne, Thanuka L.; Chawla, Nitesh V.
To ensure the correctness of network analysis methods, the network (as the input) has to be a sufficiently accurate representation of the underlying data. However, when representing sequential data from complex systems, such as global shipping traffic or Web clickstream traffic as networks, conventional network representations that implicitly assume the Markov property (first-order dependency) can quickly become limiting. This assumption holds that, when movements are simulated on the network, the next movement depends only on the current node, discounting the fact that the movement may depend on several previous steps. However, we show that data derived from many complex systems can show up to fifth-order dependencies. In these cases, the oversimplifying assumption of the first-order network representation can lead to inaccurate network analysis results. To address this problem, we propose the higher-order network (HON) representation that can discover and embed variable orders of dependencies in a network representation. Through a comprehensive empirical evaluation and analysis, we establish several desirable characteristics of HON, including accuracy, scalability, and direct compatibility with the existing suite of network analysis methods. We illustrate how HON can be applied to a broad variety of tasks, such as random walking, clustering, and ranking, and we demonstrate that, by using it as input, HON yields more accurate results without any modification to these tasks. PMID:27386539
Spatial dependences among precipitation maxima over Belgium
NASA Astrophysics Data System (ADS)
Vannitsem, S.; Naveau, P.
For a wide range of applications in hydrology, the probability distribution of precipitation maxima represents a fundamental quantity to build dykes, propose flood planning policies, or more generally, to mitigate the impact of precipitation extremes. Classical Extreme Value Theory (EVT) has been applied in this context by usually assuming that precipitation maxima can be considered as Independent and Identically Distributed (IID) events, which approximately follow a Generalized Extreme Value distribution (GEV) at each recording site. In practice, weather stations records can not be considered as independent in space. Assessing the spatial dependences among precipitation maxima provided by two Belgium measurement networks is the main goal of this work. The pairwise dependences are estimated by a variogram of order one, also called madogram, that is specially tailored to be in compliance with spatial EVT and to capture EVT bivariate structures. Our analysis of Belgium precipitation maxima indicates that the degree of dependence varies greatly according to three factors: the distance between two stations, the season (summer or winter) and the precipitation accumulation duration (hourly, daily, monthly, etc.). Increasing the duration (from one hour to 20 days) strengthens the spatial dependence. The full independence is reached after about 50 km (100 km) for summer (winter) for a duration of one hour, while for long durations only after a few hundred kilometers. In addition this dependence is always larger in winter than in summer whatever is the duration. An explanation of these properties in terms of the dynamical processes dominating during the two seasons is advanced.
Behavioral Dependence of Auditory Cortical Responses
Osmanski, Michael S.; Wang, Xiaoqin
Neural responses in the auditory cortex have historically been measured from either anesthetized or awake but non-behaving animals. A growing body of work has begun to focus instead on recording from auditory cortex of animals actively engaged in behavior tasks. These studies have shown that auditory cortical responses are dependent upon the behavioral state of the animal. The longer ascending subcortical pathway of the auditory system and unique characteristics of auditory processing suggest that such dependencies may have a more profound influence on cortical processing in auditory system compared to other sensory systems. It is important to understand the nature of these dependencies and their functional implications. In this article, we review the literature on this topic pertaining to cortical processing of sounds. PMID:25690831
Flavour-dependent leptogenesis with reheating
Antusch, Stefan
Upper bounds on the reheat temperature of the early universe, as they appear for example in classes of supergravity models, impose severe constraints on the thermal leptogenesis mechanism. To analyse these constraints, we extend the flavour-dependent treatment of leptogenesis to include reheating. We solve the flavour-dependent Boltzmann equations to obtain the leptogenesis efficiency as a function of the flavour dependent washout parameter m-tilde{sub 1,{alpha}} and of m{sub N{sub 1}}/T{sub RH}, the ratio of the mass of the lightest right-handed neutrino over the reheat temperature, and calculate the minimal values of the reheat temperature compatible with thermal leptogenesis in type I and type II seesaw scenarios.
On Capital Dependent Dynamics of Knowledge
NASA Astrophysics Data System (ADS)
Szydlowski, M.; Krawiec, A.
We investigate the dynamics of growth models in terms of dynamical system theory. We analyse some forms of knowledge and its influence on economic growth. We assume that the rate of change of knowledge depends on both the rate of change of physical and human capital. First, we study a model with constant savings. The model with optimised behaviour of households is also considered. We show that the model where the rate of change of knowledge depends only on the rate of change of physical capital can be reduced to the form of the two-dimensional autonomous dynamical system. All possible evolutional paths and the stability of solutions in the phase space are discussed in details. We obtain that the rate of growth of capital, consumption and output are greater in the case of capital dependent rate of change of knowledge.
Predictive a priori pressure-dependent kinetics.
Jasper, Ahren W; Pelzer, Kenley M; Miller, James A; Kamarchik, Eugene; Harding, Lawrence B; Klippenstein, Stephen J
The ability to predict the pressure dependence of chemical reaction rates would be a great boon to kinetic modeling of processes such as combustion and atmospheric chemistry. This pressure dependence is intimately related to the rate of collision-induced transitions in energy E and angular momentum J. We present a scheme for predicting this pressure dependence based on coupling trajectory-based determinations of moments of the E,J-resolved collisional transfer rates with the two-dimensional master equation. This completely a priori procedure provides a means for proceeding beyond the empiricism of prior work. The requisite microcanonical dissociation rates are obtained from ab initio transition state theory. Predictions for the CH4 = CH3 + H and C2H3 = C2H2 + H reaction systems are in excellent agreement with experiment. PMID:25477457
Temperature Dependence of Factors Controlling Isoprene Emissions
NASA Technical Reports Server (NTRS)
Duncan, Bryan N.; Yoshida, Yasuko; Damon, Megan R.; Douglass, Anne R.; Witte, Jacquelyn C.
We investigated the relationship of variability in the formaldehyde (HCHO) columns measured by the Aura Ozone Monitoring Instrument (OMI) to isoprene emissions in the southeastern United States for 2005-2007. The data show that the inferred, regional-average isoprene emissions varied by about 22% during summer and are well correlated with temperature, which is known to influence emissions. Part of the correlation with temperature is likely associated with other causal factors that are temperature-dependent. We show that the variations in HCHO are convolved with the temperature dependence of surface ozone, which influences isoprene emissions, and the dependence of the HCHO column to mixed layer height as OMI's sensitivity to HCHO increases with altitude. Furthermore, we show that while there is an association of drought with the variation in HCHO, drought in the southeastern U.S. is convolved with temperature.
Endothelium-dependent relaxation of blood vessels
Hynes, M.R.
Dilation of blood vessels in response to a large number of agents has been shown to be dependent on an intact vascular endothelium. The present studies examine some aspects of endothelium-dependent vasodilation in blood vessels of the rabbit and rat. Using the rabbit ear artery and the subtype-selective muscarinic antagonist pirenzepine, muscarinic receptors of the endothelium and smooth muscle cells were shown to be of the low affinity M/sub 2/ subtype. Inhibition of (/sup 3/H)(-)quinuclidinyl benzilate was used to determine affinity for the smooth muscle receptors while antagonism of methacholine induced vasodilation yielded the endothelial cell receptor affinity. The effect of increasing age (1-27 months) on endothelium-dependent relaxation was studied in aortic rings, perfused tail artery and perfused mesenteric bed of the Fisher 344 rat. The influence of endothelium on contractile responses was examined using the perfused caudal artery.
Drug dependence: its significance and characteristics
Eddy, Nathan B.; Halbach, H.; Isbell, Harris; Seevers, Maurice H.
It has become impossible in practice, and is scientifically unsound, to maintain a single definition for all forms of drug addiction and/or habituation. A feature common to these conditions as well as to drug abuse in general is dependence, psychic or physical or both, of the individual on a chemical agent. Therefore, better understanding should be attained by substitution of the term drug dependence of this or that type, according to the agent or class of agents involved, in discussions of these conditions, especially inter-disciplinary. Short descriptions, followed by concise listings of their characteristics, are formulated for the various types of dependence on at present widely abused major groups of substances. PMID:5294186
Acamprosate in the treatment of alcohol dependence.
Mason, Barbara J
Acamprosate is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation in combination with psychosocial support. Acamprosate is a synthetic taurine analogue that seems to act centrally to restore the normal activity of glutamatergic neurotransmission altered by chronic alcohol exposure. Over the past 15 years, the safety and efficacy of acamprosate for alcohol dependence have been well established in multiple double-blind, placebo-controlled trials. Overall, acamprosate has been consistently associated with greater beneficial effects on measures of alcohol abstinence compared with placebo. Specifically, patients treated with acamprosate achieve greater rates of complete abstinence, longer times to first drink and/or increased duration of cumulative abstinence when compared with placebo. Acamprosate received approval by the US FDA for the treatment of alcohol dependence in July 2004 and is currently prescribed in 28 countries. PMID:16197362
Peripartum pain management in opioid dependent women
Höflich, Anna S.; Langer, Martin; Jagsch, Reinhold; Bäwert, Andjela; Winklbaur, Bernadette; Fischer, Gabriele; Unger, Annemarie
Increased pain sensitivity and the development of opioid tolerance complicate the treatment of pain experienced by opioid maintained pregnant women during delivery and the perinatal period. The aim of the present study was to investigate differences in pain management of opioid maintained compared to non-dependent pregnant women during delivery and the postpartum period. 40 deliveries of 37 opioid dependent women enrolled in a double-blind, double-dummy randomized controlled trial (RCT) examining the safety and efficacy of methadone (mean dose at the time of delivery = 63.89 mg) and buprenorphine (mean dose at the time of delivery = 14.05 mg) during pregnancy were analyzed and participants were matched to a non-dependent comparison group of 80 pregnant women. Differences in pain management (opioid and non-opioid analgesic medication) during delivery and perinatal period were analyzed. Following cesarean delivery opioid maintained women received significantly less opioid analgesics (day of delivery p = 0.038; day 1: p = 0.02), NSAIDs were administered more frequently to opioid dependent patients than to the comparison group during cesarean section and on the third day postpartum. Significantly higher nicotine consumption in the group of opioid dependent women had a strong influence on the retrieved results, and might be considered as an independent factor of altered pain experience. Differences in pain treatment became evident when comparing opioid maintained women to healthy controls. These differences might be based on psychosocial consequences of opioid addiction along with the lack of an interdisciplinary consensus on pain treatment protocols for opioid dependent patients. PMID:22396085
Rats exhibit reference-dependent choice behavior.
Bhatti, Mehwish; Jang, Hyeran; Kralik, Jerald D; Jeong, Jaeseung
Human preferences depend on whether a chosen outcome appears to be a loss or a gain compared with what had been expected, i.e., in comparison to a reference point. Because reference dependence has such a strong influence on human decision-making, it is important to uncover its origins, which will in turn help delineate the underlying mechanisms. It remains unknown whether rats use reference points in decision-making, and yet, the study of rats could help address the question of whether reference dependence is evolutionarily conserved among mammals and could provide a nonhuman animal model to investigate the neural mechanisms underlying this important cognitive process. The aim of the current study was to determine whether rats show reference-dependent choice behavior. We developed a novel paradigm by modifying the "T" maze by installing "pockets" to the left and right of the "T" stem that held reward pellets so rats would potentially develop reference values for each option prior to choice. We found that the rats were indeed sensitive to the way alternatives were presented. That is, they exhibited reference-dependent choice behavior by avoiding the choice option framed as a loss (e.g., having four reward pellets in the pocket, but receiving only one), at least under conditions with certain outcomes and clear differences between the reference and outcome quantities. Despite the small number of rats in this study, this species-level capacity suggests that reference dependence in general and loss aversion in particular may be conserved traits that evolved at or before the emergence of mammals. PMID:24657593
Temperature Dependence of Radiative and Nonradiative Rates from Time-Dependent Correlation Function Methods.
Banerjee, Shiladitya; Baiardi, Alberto; Bloino, Julien; Barone, Vincenzo
The temperature dependence of the rate constants in radiative and nonradiative decays from excited electronic states has been studied using a time-dependent correlation function approach in the framework of the adiabatic representation and the harmonic oscillator approximation. The present work analyzes the vibrational aspect of the processes, which gives rise to the temperature dependence, with the inclusion of mode-mixing, as well as of frequency change effects. The temperature dependence of the rate constants shows a contrasting nature, depending on whether the process has been addressed within the Franck-Condon approximation or beyond it. The calculation of the Duschinsky matrix and the shift vector between the normal modes of the two states can be done in Cartesian and/or internal coordinates, depending on the flexibility of the investigated molecule. A new computational code has been developed to calculate the rates of intersystem crossing, internal conversion, and fluorescence for selected molecules as functions of temperature. PMID:26683207
Investigations of Low Temperature Time Dependent Cracking
Van der Sluys, W A; Robitz, E S; Young, B A; Bloom, J
The objective of this project was to investigate metallurgical and mechanical phenomena associated with time dependent cracking of cold bent carbon steel piping at temperatures between 327 C and 360 C. Boiler piping failures have demonstrated that understanding the fundamental metallurgical and mechanical parameters controlling these failures is insufficient to eliminate it from the field. The results of the project consisted of the development of a testing methodology to reproduce low temperature time dependent cracking in laboratory specimens. This methodology was used to evaluate the cracking resistance of candidate heats in order to identify the factors that enhance cracking sensitivity. The resultant data was integrated into current available life prediction tools.
Time-Dependent Molecular Reaction Dynamics
Oehrn, Yngve
This paper is a brief review of a time-dependent, direct, nonadiabatic theory of molecular processes called Electron Nuclear Dynamics (END). This approach to the study of molecular reaction dynamics is a hierarchical theory that can be applied at various levels of approximation. The simplest level of END uses classical nuclei and represents all electrons by a single, complex, determinantal wave function. The wave function parameters such as average nuclear positions and momenta, and molecular orbital coefcients carry the time dependence and serve as dynamical variables. Examples of application are given of the simplest level of END to ion-atom and ion-molecule reactions.
Temperature dependence of thermopower in molecular junctions
NASA Astrophysics Data System (ADS)
Kim, Youngsang; Lenert, Andrej; Meyhofer, Edgar; Reddy, Pramod
The thermoelectric properties of molecular junctions are of considerable interest due to their promise for efficient energy conversion. While the dependence of thermoelectric properties of junctions on molecular structure has been recently studied, their temperature dependence remains unexplored. Using a custom built variable temperature scanning tunneling microscope, we measured the thermopower and electrical conductance of individual benzenedithiol junctions over a range of temperatures (100 K-300 K). We find that while the electrical conductance is independent of temperature, the thermopower increases linearly with temperature, confirming the predictions of the Landauer theory.
Does Melissa Officinalis Cause Withdrawal or Dependence?
Demirci, Kadir; Akgönül, Mehmet; Demirdaş, Arif; Akpınar, Abdullah
Introduction: Melissa officinalis is a medical and aromatic plant that is used for its hypnotic, sedative, and spasmolytic effects. This report presents a case study of30-year-old patient who was admitted to an emergency department with restlessness, tremor, distractibility, and sweating following a discontinuation of Melissa officinalis consumption. Case report: In this case, withdrawal symptoms may be related to the dependence effect caused by long-term use of Melissa officinalis. Although Melissa officinalis, a plant, is preferred by many patients as an alternative to pharmaceutical drugs, patients should be made aware that it may have a risk of dependency and can lead to withdrawal symptoms. PMID:25870482
Momentum dependence of the nuclear mean field
Baldo, M.; Bombaci, I.; Giansiracusa, G.; Lombardo, U. Dipartimento di Fisica, Universita di Catania, Corso Italia 57, 95129 Catania, Italy)
The dependence on the momentum of the nuclear mean field is studied in the framework of the self-consistent Bethe-Brueckner theory. It is pointed out that the rearrangement term, coming from the variation of the {ital G} matrix, gives a substantial contribution at the lowest momenta. The resulting single particle potential exhibits a good rate of convergence. Its momentum dependence appears to be negligible up to 2 fm{sup {minus}1}, in contrast with potentials used in calculations of heavy-ion collisions at intermediate energies.
Time-dependent corona models - Scaling laws
NASA Technical Reports Server (NTRS)
Korevaar, P.; Martens, P. C. H.
Scaling laws are derived for the one-dimensional time-dependent Euler equations that describe the evolution of a spherically symmetric stellar atmosphere. With these scaling laws the results of the time-dependent calculations by Korevaar (1989) obtained for one star are applicable over the whole Hertzsprung-Russell diagram and even to elliptic galaxies. The scaling is exact for stars with the same M/R-ratio and a good approximation for stars with a different M/R-ratio. The global relaxation oscillation found by Korevaar (1989) is scaled to main sequence stars, a solar coronal hole, cool giants and elliptic galaxies.
Maximum likelihood clustering with dependent feature trees
NASA Technical Reports Server (NTRS)
Chittineni, C. B. (Principal Investigator)
The decomposition of mixture density of the data into its normal component densities is considered. The densities are approximated with first order dependent feature trees using criteria of mutual information and distance measures. Expressions are presented for the criteria when the densities are Gaussian. By defining different typs of nodes in a general dependent feature tree, maximum likelihood equations are developed for the estimation of parameters using fixed point iterations. The field structure of the data is also taken into account in developing maximum likelihood equations. Experimental results from the processing of remotely sensed multispectral scanner imagery data are included.
Modeling local dependence in longitudinal IRT models.
Olsbjerg, Maja; Christensen, Karl Bang
Measuring change in a latent variable over time is often done using the same instrument at several time points. This can lead to dependence between responses across time points for the same person yielding within person correlations that are stronger than what can be attributed to the latent variable. Ignoring this can lead to biased estimates of changes in the latent variable. In this paper we propose a method for modeling local dependence in the longitudinal 2PL model. It is based on the concept of item splitting, and makes it possible to correctly estimate change in the latent variable. PMID:25552424
Benzodiazepines consumption: does dependence vary with age?
Gérardin, Marie; Victorri-Vigneau, Caroline; Guerlais, Marylène; Guillou-Landreat, Morgane; Grall-Bronnec, Marie; Jolliet, Pascale
We have compared two groups of chronic benzodiazepines (or zolpidem/zopiclone) users: "Seniors," aged 65 years or more, and "Adults," aged less than 65 years. The study took place in the Pays de Loire region. The questionnaire assesses dependence based on items from the DSM-IV. The analysis was based on 176 Senior questionnaires and 212 Adult questionnaires. Whereas Senior patients take benzodiazepines routinely with little negative consequences, Adults suffer from underlying psychological trouble, mention a higher consumption than planned, which causes negative consequences. 35.2% of Seniors are dependent on benzodiazepines versus 49.8% of Adults. PMID:24810390
Wave function for time-dependent harmonically confined electrons in a time-dependent electric field.
Li, Yu-Qi; Pan, Xiao-Yin; Sahni, Viraht
The many-body wave function of a system of interacting particles confined by a time-dependent harmonic potential and perturbed by a time-dependent spatially homogeneous electric field is derived via the Feynman path-integral method. The wave function is comprised of a phase factor times the solution to the unperturbed time-dependent Schrödinger equation with the latter being translated by a time-dependent value that satisfies the classical driven equation of motion. The wave function reduces to that of the Harmonic Potential Theorem wave function for the case of the time-independent harmonic confining potential. PMID:24070284
Regulation of hippocampus-dependent memory by cyclic AMP-dependent protein kinase
Abel, Ted; Nguyen, Peter V.
The hippocampus is crucial for the consolidation of new declarative long-term memories. Genetic and behavioral experimentation have revealed that several protein kinases are critical for the formation of hippocampus-dependent long-term memories. Cyclic-AMP dependent protein kinase (PKA) is a serine–threonine kinase that has been strongly implicated in the expression of specific forms of hippocampus-dependent memory. We review evidence that PKA is required for hippocampus-dependent memory in mammals, and we highlight some of the proteins that have been implicated as targets of PKA. Future directions and open questions regarding the role of PKA in memory storage are also described. PMID:18394470
Context-Dependent Control over Attentional Capture
ERIC Educational Resources Information Center
Cosman, Joshua D.; Vecera, Shaun P.
A number of studies have demonstrated that the likelihood of a salient item capturing attention is dependent on the "attentional set" an individual employs in a given situation. The instantiation of an attentional set is often viewed as a strategic, voluntary process, relying on working memory systems that represent immediate task priorities.…
It All Depends on Your Attitude.
ERIC Educational Resources Information Center
Kastner, Bernice
Presents six learning exercises that introduce students to the mathematics used to control and track spacecraft attitude. Describes the geocentric system used for Earthbound location and navigation, the celestial sphere, the spacecraft-based celestial system, time-dependent angles, observer-fixed coordinate axes, and spacecraft rotational axes.…
The path dependence of deformation texture development
Takeshita, T.; Kocks, U.F.; Wenk, H.R.
It is demonstrated for the case of three different strain paths, all of which end up with the same, elongated specimen shape, that the texture developed during straining is path dependent. This is true both for experiments on aluminum polycrystals and for simulations using the LApp code.
Time-dependent nanomechanics of cartilage.
Han, Lin; Frank, Eliot H; Greene, Jacqueline J; Lee, Hsu-Yi; Hung, Han-Hwa K; Grodzinsky, Alan J; Ortiz, Christine
In this study, atomic force microscopy-based dynamic oscillatory and force-relaxation indentation was employed to quantify the time-dependent nanomechanics of native (untreated) and proteoglycan (PG)-depleted cartilage disks, including indentation modulus E(ind), force-relaxation time constant τ, magnitude of dynamic complex modulus |E(∗)|, phase angle δ between force and indentation depth, storage modulus E', and loss modulus E″. At ∼2 nm dynamic deformation amplitude, |E(∗)| increased significantly with frequency from 0.22 ± 0.02 MPa (1 Hz) to 0.77 ± 0.10 MPa (316 Hz), accompanied by an increase in δ (energy dissipation). At this length scale, the energy dissipation mechanisms were deconvoluted: the dynamic frequency dependence was primarily governed by the fluid-flow-induced poroelasticity, whereas the long-time force relaxation reflected flow-independent viscoelasticity. After PG depletion, the change in the frequency response of |E(∗)| and δ was consistent with an increase in cartilage local hydraulic permeability. Although untreated disks showed only slight dynamic amplitude-dependent behavior, PG-depleted disks showed great amplitude-enhanced energy dissipation, possibly due to additional viscoelastic mechanisms. Hence, in addition to functioning as a primary determinant of cartilage compressive stiffness and hydraulic permeability, the presence of aggrecan minimized the amplitude dependence of |E(∗)| at nanometer-scale deformation. PMID:21463599
Perceiving sequential dependencies in auditory streamsa
Kidd, Gerald; Mason, Christine R.; Streeter, Timothy; Thompson, Eric R.; Best, Virginia; Wakefield, Gregory H.
This study examined the ability of human listeners to detect the presence and judge the strength of a statistical dependency among the elements comprising sequences of sounds. The statistical dependency was imposed by specifying transition matrices that determined the likelihood of occurrence of the sound elements. Markov chains were constructed from these transition matrices having states that were pure tones/noise bursts that varied along the stimulus dimensions of frequency and/or interaural time difference. Listeners reliably detected the presence of a statistical dependency in sequences of sounds varying along these stimulus dimensions. Furthermore, listeners were able to discriminate the relative strength of the dependency in pairs of successive sound sequences. Random variation along an irrelevant stimulus dimension had small but significant adverse effects on performance. A much greater decrement in performance was found when the sound sequences were concurrent. Likelihood ratios were computed based on the transition matrices to specify Ideal Observer performance for the experimental conditions. Preliminary modeling efforts were made based on degradations of Ideal Observer performance intended to represent human observer limitations. This experimental approach appears to be useful for examining auditory "stream" formation and maintenance over time based on the predictability of the constituent sound elements. PMID:23927120
Dependency Traits Among Parents of Drug Abusers
ERIC Educational Resources Information Center
Tennant, Forest S., Jr.
Studies question whether there is a significant association between parents' dependency traits and drug habits in their offspring. Reported here is a survey of 1,091 young males. The reported occurrence of parents' alcohol consumption, smoking, use of stimulants and sedatives, and overeating were compared among abusers and non-users of hashish,…
Satisfaction with life and opioid dependence
Luty, Jason; Arokiadass, Sujaa Mary Rajagopal
Background Serious substance misuse and dependence is widely seen as damaging to an individual and to society in general. Whereas the medical and society effects of substance misuse are widely described, some commentators suggest substance misuse may be an "alternative lifestyle". Aim To assess general life satisfaction amongst treatment-seeking people with substance dependence. Methods The Satisfaction With Life Scale (SWLS) was administered to a sample of opioid-dependent people receiving substitute medication. Results 105 subjects and 105 age-sex matched subjects in a comparison group completed the questionnaire. The mean SWLS score was 7.12 (SD = 10.6; median = 6) for patients compared to 22.6 (SD = 6.8) in the comparison group. (Two sided p < 0.0001; Median difference = -13.5; Wilcoxon signed rank test.) Conclusion The study used a validated instrument and objective reports to confirm significantly higher rates of dissatisfaction with life among opioid dependent people in treatment when compared to members of the general population. PMID:18226241
Grain size dependence of wear in ceramics
Wu, C.CM.; Rice, R.W.; Johnson, D.; Platt, B.A.
Pin-on-disk (POD) microwear tests of Al2O3, MgO, MgAl2O4, and ZrO2 crystalline structures were conducted as a function of grain size and the results compared with data from single crystals of the same materials. Extrapolation to infinite grain size in the Hall-Petch type relationship for the structures resulted in lower intercepts than the single-crystal values. In addition, the macrowear grain-size dependence appears to decrease with increased wear. It is suggested that thermal expansion anisotropy (of Al2O3) significantly affects the grain size dependence of POD wear, giving a negative intercept, while elastic anisotropy is a factor in the grain-size dependence of the cubic (MgO, MgAl2O4, and ZrO2 materials. The reduced grain-size dependence is attributed to overlapping wear tracks, reducing the effects of enhanced wear damage. 9 references.
The chain-length dependence test.
Stone, Matthew T; Heemstra, Jennifer M; Moore, Jeffrey S
Trends obtained from systematic studies based on chain-length variation have provided valuable insight and understanding into the behavior of m-phenylene ethynylene foldamers. The generalization of this experimental approach, the chain-length dependence test, is useful for studying solution conformation, packing in the solid state, specific intrachain interactions, and the contributions of end groups to a particular property. PMID:16411735
Correlates of Baclofen Effectiveness in Alcohol Dependence
Shukla, Lekhansh; Shukla, Tulika; Bokka, Spandana; Kandasamy, Arun; Benegal, Vivek; Murthy, Pratima; Chand, Prabhat
Alcohol dependence is a global concern. Baclofen has shown promise as an anti-craving agent but its efficiency remains to be settled. We reviewed 549 male cases diagnosed with alcohol dependence who received Acamprosate (201) or Baclofen (348). 'Time to first drink' was compared between two groups and multiple regression analysis was done in baclofen group to identify correlates of effectiveness. There was a significant difference in outcome measure between Baclofen (M = 4.44, SD = 3.75) and Acamprosate group (M = 3.73, SD = 2.19); t (547) = 2.45, P = 0.01. Initial regression analysis with six predictor variables (average daily alcohol units, current age, age at onset of dependence, family history, duration of dependence and dose of baclofen in mg/day) showed significant correlation of outcome variable with only two predictor variables — dose of baclofen and average daily intake. Using the hierarchical method it was found that 'dose of baclofen' and 'average alcohol intake' explain a significant amount of variance in 'time to first drink'. [F (1, 345) = 182.8, P < 0.001, R2 = 0.52, R2adjusted = 0.51]. This information can be used to select patients in long term longitudinal studies and may explain variable results seen in clinical trials of baclofen done earlier. PMID:26664095
Problems Identifying Independent and Dependent Variables
ERIC Educational Resources Information Center
Leatham, Keith R.
This paper discusses one step from the scientific method--that of identifying independent and dependent variables--from both scientific and mathematical perspectives. It begins by analyzing an episode from a middle school mathematics classroom that illustrates the need for students and teachers alike to develop a robust understanding of…
Stress Disrupts Context-Dependent Memory
ERIC Educational Resources Information Center
Schwabe, Lars; Bohringer, Andreas; Wolf, Oliver T.
Memory is facilitated when the retrieval context resembles the learning context. The brain structures underlying contextual influences on memory are susceptible to stress. Whether stress interferes with context-dependent memory is still unknown. We exposed healthy adults to stress or a control procedure before they learned an object-location task…
Context dependent anti-aliasing image reconstruction
NASA Technical Reports Server (NTRS)
Beaudet, Paul R.; Hunt, A.; Arlia, N.
Image Reconstruction has been mostly confined to context free linear processes; the traditional continuum interpretation of digital array data uses a linear interpolator with or without an enhancement filter. Here, anti-aliasing context dependent interpretation techniques are investigated for image reconstruction. Pattern classification is applied to each neighborhood to assign it a context class; a different interpolation/filter is applied to neighborhoods of differing context. It is shown how the context dependent interpolation is computed through ensemble average statistics using high resolution training imagery from which the lower resolution image array data is obtained (simulation). A quadratic least squares (LS) context-free image quality model is described from which the context dependent interpolation coefficients are derived. It is shown how ensembles of high-resolution images can be used to capture the a priori special character of different context classes. As a consequence, a priori information such as the translational invariance of edges along the edge direction, edge discontinuity, and the character of corners is captured and can be used to interpret image array data with greater spatial resolution than would be expected by the Nyquist limit. A Gibb-like artifact associated with this super-resolution is discussed. More realistic context dependent image quality models are needed and a suggestion is made for using a quality model which now is finding application in data compression.
Field Dependency and Performance in Mathematics
ERIC Educational Resources Information Center
Onwumere, Onyebuchi; Reid, Norman
Mathematics is an important school subject but one which often poses problems for learners. It has been found that learners do not possess the cognitive capacity to handle understanding procedures, representations, concepts, and applications at the same time. while the extent of field dependency may hold the key to one way by which the working…
Pearson and Pedagogy: Countering Co-Dependency
ERIC Educational Resources Information Center
Fielder, John
Noel Pearson and Marcia Langton have both used the terms "co-dependency" and "rescuing" as part of their challenge to the rights-based focus informing Indigenous policies in Australia since the 1960s. Their premise is that the liberal/Left welfare-based agenda, for decades, has largely overlooked Indigenous responsibility. At the same time, they…
Chewing Maintains Hippocampus-Dependent Cognitive Function
Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya
Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research. PMID:26078711
Socioeconomic Heterogeneity of Mining-Dependent Counties.
ERIC Educational Resources Information Center
Nord, Mark; Luloff, A. E.
Although the socioeconomic well-being of all U.S. mining-dependent counties was slightly above the national average in 1990, disaggregation reveals substantial effects of region and mining subsector. In particular, southern and Great Lakes coal-mining counties had significantly lower high school graduation rates and higher poverty and unemployment…
Cost of Oil Dependence: A 2000 Update
Greene, D.L.; Tishchishyna, N.I.
Oil dependence remains a potentially serious economic and strategic problem for the United States. This report updates previous estimates of the costs of oil dependence to the U.S. economy and introduces several methodological enhancements. Estimates of the costs to the U.S. economy of the oil market upheavals of the last 30 years are in the vicinity of $7 trillion, present value 1998 dollars, about as large as the sum total of payments on the national debt over the same period. Simply adding up historical costs in 1998 dollars without converting to present value results in a Base Case cost estimate of $3.4 trillion. Sensitivity analysis indicates that cost estimates are sensitive to key parameters. A lower bound estimate of $1.7 trillion and an upper bound of $7.1 trillion (not present value) indicate that the costs of oil dependence have been large under almost any plausible set of assumptions. These cost estimates do not include military, strategic or political costs associated with U.S. and world dependence on oil imports.
Costs of Oil Dependence: A 2000 Update
Greene, D.L.
Oil dependence remains a potentially serious economic and strategic problem for the United States. This report updates previous estimates of the costs of oil dependence to the U.S. economy and introduces several methodological enhancements. Estimates of the costs to the U.S. economy of the oil market upheavals of the last 30 years are in the vicinity of $7 trillion, present value 1998 dollars, about as large as the sum total of payments on the national debt over the same period. Simply adding up historical costs in 1998 dollars without converting to present value results in a Base Case cost estimate of $3.4 trillion. Sensitivity analysis indicates that cost estimates are sensitive to key parameters. A lower bound estimate of $1.7 trillion and an upper bound of $7.1 trillion (not present value) indicate that the costs of oil dependence have been large under almost any plausible set of assumptions. These cost estimates do not include military, strategic or political costs associated with U.S. and world dependence on oil imports.
Activity Therapy Services and Chemical Dependency Rehabilitation.
ERIC Educational Resources Information Center
James, Mark R.; Townsley, Robin K.
Discusses how music, occupational, and recreation therapies can contribute to comprehensive treatment programs for chemical dependency. Sees prime contribution of activity therapy as lying in nature of experiential education, applying insight gained in counseling sessions and discussion groups to practical real-life situations. (Author/NB)
Attachment and Dependency in Developmental Perspective.
ERIC Educational Resources Information Center
Sroufe, L. Alan; And Others
Distinguishes between attachment (the relationship between infant and caregiver) and dependency (the reliance of the child on adults for nurturance, attention, or assistance). Assesses preschool children with varying attachment histories and suggests that the roots of overdependency lie in the quality of the early infant-caregiver relationship.…
Comparing the Variances of Two Dependent Groups.
ERIC Educational Resources Information Center
Wilcox, Rand R.
Recently, C. E. McCulloch (1987) suggested a modification of the Morgan-Pitman test for comparing the variances of two dependent groups. This paper demonstrates that there are situations where the procedure is not robust. A subsample approach, similar to the Box-Scheffe test, and the Sandvik-Olsson procedure are also assessed. (TJH)
Percolation of networks with directed dependency links
NASA Astrophysics Data System (ADS)
Niu, Dunbiao; Yuan, Xin; Du, Minhui; Stanley, H. Eugene; Hu, Yanqing
The self-consistent probabilistic approach has proven itself powerful in studying the percolation behavior of interdependent or multiplex networks without tracking the percolation process through each cascading step. In order to understand how directed dependency links impact criticality, we employ this approach to study the percolation properties of networks with both undirected connectivity links and directed dependency links. We find that when a random network with a given degree distribution undergoes a second-order phase transition, the critical point and the unstable regime surrounding the second-order phase transition regime are determined by the proportion of nodes that do not depend on any other nodes. Moreover, we also find that the triple point and the boundary between first- and second-order transitions are determined by the proportion of nodes that depend on no more than one node. This implies that it is maybe general for multiplex network systems, some important properties of phase transitions can be determined only by a few parameters. We illustrate our findings using Erdős-Rényi networks.
Kasugamycin-dependent mutants of Escherichia coli.
Dabbs, E R
Kasugamycin-dependent mutants have been isolated from Escherichia coli B. They were obtained through mutagenesis with ethyl methane sulfonate or nitrosoguanidine in conjunction with an antibiotic underlay technique. In the case of nitrosoguanidine, dependent mutants were obtained at a frequency of about 3% of survivors growing up in the selection. In the case of ethyl methane sulfonate, the corresponding value was 1%. Nineteen mutants showing a kasugamycin-dependent phenotype were studied. In terms of response to various temperatures and antibiotic concentrations, they were very heterogeneous, although most fell into two general classes. Genetic analysis indicated that in at least some cases, the kasugamycin-dependent phenotype was the product of two mutations. Two-dimensional gel electropherograms revealed alterations in the ribosomal proteins of seven mutants. One mutant had an alteration in protein S13, and one had an alteration in protein L14. Three showed changes in protein S9. Each of two mutants had changes in two proteins, S18 and L11. Three of these mutants additionally had protein S18 occurring in a partly altered, partly unaltered form. Images PMID:363701
Size dependent adsorption on nanocrystal surfaces
NASA Astrophysics Data System (ADS)
Lu, H. M.; Wen, Z.; Jiang, Q.
A quantitative thermodynamic correlation method to describe the size dependent Langmuir adsorption isotherm is developed. According to the model, the equilibrium adsorption constant increases as material size decreases, which is in agreement with the literature data of acetic acid, valeric acid, oxalic acid, and adipic acid on anatase nanoparticles.
Organizational Change, Absenteeism, and Welfare Dependency
ERIC Educational Resources Information Center
Roed, Knut; Fevang, Elisabeth
Based on Norwegian register data, we set up a multivariate mixed proportional hazard model (MMPH) to analyze nurses' pattern of work, sickness absence, nonemployment, and social insurance dependency from 1992 to 2000, and how that pattern was affected by workplace characteristics. The model is estimated by means of the nonparametric…
Evaluation Framework for Dependable Mobile Learning Scenarios
ERIC Educational Resources Information Center
Bensassi, Manel; Laroussi, Mona
The goal of the dependability analysis is to predict inconsistencies and to reveal ambiguities and incompleteness in the designed learning scenario. Evaluation, in traditional learning design, is generally planned after the execution of the scenario. In mobile learning, this stage becomes too difficult and expensive to apply due to the complexity…
Curvature Dependent Reactivity of Fullerenes and Nanotubes
NASA Technical Reports Server (NTRS)
Park, Seongjun; Cho, Kyeongjae; Srivastava, Deepak
Dependence of pyramidalization angle, examples of nanotube surfaces, internal and external reactivity, and binding energies are some of the topics discussed in this conference presentation preprint. Final conclusions include the relationship between the pyramidal angle of the surface and its associated external reaction energy.
Instructional Media, Attitude Change and Field Dependence.
ERIC Educational Resources Information Center
Kloock, Terryl R.; And Others
The effectiveness of two media types (sound film and still slides with audiotape) in changing student attitudes, and their impact on students varying in field dependency levels was examined. Subjects, 82 college students scoring at the high and low extremes of the Group Embedded Figures Test (GEFT), were randomly assigned to either a (1) multi-cue…
Physical Education Objectives. DOD Dependents Schools.
ERIC Educational Resources Information Center
Dependents Schools (DOD), Washington, DC.
These program objectives were developed to support the Department of Defense Dependent Schools Five Year Curriculum Development Plan and are designed to provide a basis for elementary, middle, and secondary school physical education curricula. A balance of psychomotor, cognitive, and affective aspects is emphasized. General, program, and…
Gravity-dependent transport in industrial processes
NASA Technical Reports Server (NTRS)
Ostrach, Simon; Kamotani, Yasuhiro
Gravity-dependent transport phenomena in various industrial processes are investigated in order to address a broader range of microgravity phenomena and to develop new applications of microgravity. A number of important topics are identified and analyzed in detail. The present article describes results on coating flow, zeolite growth, and rotating electrochemical system.
Prevention of Welfare Dependency--An Overview.
ERIC Educational Resources Information Center
Kaplan, Jan
This document examines strategies for preventing working families and disadvantaged youth from needing cash assistance and becoming dependent on welfare. The document begins with a brief discussion of the tenuous nature of the boundary between families who need public assistance and families who don't and factors contributing to welfare…
Term Dependence: Truncating the Bahadur Lazarsfeld Expansion.
ERIC Educational Resources Information Center
Losee, Robert M., Jr.
Studies the performance of probabilistic information retrieval systems using differing statistical dependence assumptions when estimating the probabilities inherent in the retrieval model. Experimental results using the Bahadur Lazarsfeld expansion on the Cystic Fibrosis database are discussed that suggest that incorporating term dependence…
Time-Dependent Nanomechanics of Cartilage
Han, Lin; Frank, Eliot H.; Greene, Jacqueline J.; Lee, Hsu-Yi; Hung, Han-Hwa K.; Grodzinsky, Alan J.; Ortiz, Christine
In this study, atomic force microscopy-based dynamic oscillatory and force-relaxation indentation was employed to quantify the time-dependent nanomechanics of native (untreated) and proteoglycan (PG)-depleted cartilage disks, including indentation modulus Eind, force-relaxation time constant τ, magnitude of dynamic complex modulus |E∗|, phase angle δ between force and indentation depth, storage modulus E′, and loss modulus E″. At ∼2 nm dynamic deformation amplitude, |E∗| increased significantly with frequency from 0.22 ± 0.02 MPa (1 Hz) to 0.77 ± 0.10 MPa (316 Hz), accompanied by an increase in δ (energy dissipation). At this length scale, the energy dissipation mechanisms were deconvoluted: the dynamic frequency dependence was primarily governed by the fluid-flow-induced poroelasticity, whereas the long-time force relaxation reflected flow-independent viscoelasticity. After PG depletion, the change in the frequency response of |E∗| and δ was consistent with an increase in cartilage local hydraulic permeability. Although untreated disks showed only slight dynamic amplitude-dependent behavior, PG-depleted disks showed great amplitude-enhanced energy dissipation, possibly due to additional viscoelastic mechanisms. Hence, in addition to functioning as a primary determinant of cartilage compressive stiffness and hydraulic permeability, the presence of aggrecan minimized the amplitude dependence of |E∗| at nanometer-scale deformation. PMID:21463599
Temperature dependence of polymer photovoltaic devices
NASA Astrophysics Data System (ADS)
Nakazawa, Yuko
One of many steps to develop a sustainable society is to reduce the use of fossil fuels by replacing them with renewable energy sources, such as solar energy. This dissertation concerns one of the most contemporary methods to harvest solar radiation and covert it to electricity, using thin polymer films. The photovoltaic devices in this study consisted of a thin layer of p-phenylenevinylene (PPV) based semiconducting polymer sandwiched between two metals (semi-transparent ITO and evaporated metal electrode). Two modified device structures were studied, an interfacial heterojunction device, which includes an additional layer of inorganic n-type semiconductor (Ti-oxides) and a bulk heterojunction device, which is formed by blending electron-attracting materials. Both modifications resulted in higher device performances under ambient conditions due to an increased number of dissociation sites. From studies of inorganic solar cells, it is well known that temperature has a large effect on device performance. However, there are only a few studies on organic Solar cells, concerning the temperature dependence. This thesis focuses on understanding the temperature dependent behaviors of polymer photovoltaic devices. Temperature dependence study allows us to examine how the device parameters such as short circuit current (Isc) and open circuit voltage (Voc) are affected by the material properties and the device architectures. The current-voltage relationships were measured in a temperature controlled OXFORD cryostat operating between 150K and 404K. From the dark current-voltage measurements, the field-independent hole mobility (mu0) was extracted, using a space charge limited current analysis. From the photocurrent-voltage measurements, the temperature dependence on Isc, Voc, and fill factor were studied. The temperature characteristics of Isc (T) were compared to that of mu0(T), and two different dependencies were obtained for different device architectures. The temperature
Condition-dependent, phenotype-dependent and genetic-dependent factors in the natal dispersal of a solitary rodent.
Selonen, Vesa; Hanski, Ilpo K
1. Dispersal can be condition- and phenotype-dependent and related to individual genetic differences. Few studies have addressed the relative importance of these factors on dispersal. We studied the factors behind philopatry and dispersal in juvenile Siberian flying squirrels, Pteromys volans L. 2. The dispersal distance and the distances explored before abandoning the natal nest were not related to any of the condition-dependent factors studied such as the area of high-quality habitat or the number of conspecifics near the natal area. In addition, the body mass (a phenotypic trait) of individuals was not related to philopatry and dispersal in flying squirrels. 3. Genetic variability, measured by microsatellite heterozygosity, was positively correlated with dispersal. The correlation was mainly driven by one locus related to the distances explored before abandoning the natal nest. 4. We conclude that condition- and phenotype-dependent factors did not have detectable effects on philopatry and dispersal, but individual heterozygosity was related to dispersal in flying squirrels. Our results suggest that genetic variability is important behind the dispersal of the species. PMID:20561101
Cascading failures in coupled networks with both inner-dependency and inter-dependency links
NASA Astrophysics Data System (ADS)
Liu, Run-Ran; Li, Ming; Jia, Chun-Xiao; Wang, Bing-Hong
We study the percolation in coupled networks with both inner-dependency and inter-dependency links, where the inner- and inter-dependency links represent the dependencies between nodes in the same or different networks, respectively. We find that when most of dependency links are inner- or inter-ones, the coupled networks system is fragile and makes a discontinuous percolation transition. However, when the numbers of two types of dependency links are close to each other, the system is robust and makes a continuous percolation transition. This indicates that the high density of dependency links could not always lead to a discontinuous percolation transition as the previous studies. More interestingly, although the robustness of the system can be optimized by adjusting the ratio of the two types of dependency links, there exists a critical average degree of the networks for coupled random networks, below which the crossover of the two types of percolation transitions disappears, and the system will always demonstrate a discontinuous percolation transition. We also develop an approach to analyze this model, which is agreement with the simulation results well.
Cascading failures in coupled networks with both inner-dependency and inter-dependency links
Liu, Run-Ran; Li, Ming; Jia, Chun-Xiao; Wang, Bing-Hong
We study the percolation in coupled networks with both inner-dependency and inter-dependency links, where the inner- and inter-dependency links represent the dependencies between nodes in the same or different networks, respectively. We find that when most of dependency links are inner- or inter-ones, the coupled networks system is fragile and makes a discontinuous percolation transition. However, when the numbers of two types of dependency links are close to each other, the system is robust and makes a continuous percolation transition. This indicates that the high density of dependency links could not always lead to a discontinuous percolation transition as the previous studies. More interestingly, although the robustness of the system can be optimized by adjusting the ratio of the two types of dependency links, there exists a critical average degree of the networks for coupled random networks, below which the crossover of the two types of percolation transitions disappears, and the system will always demonstrate a discontinuous percolation transition. We also develop an approach to analyze this model, which is agreement with the simulation results well. PMID:27142883
Cascading failures in coupled networks with both inner-dependency and inter-dependency links.
Liu, Run-Ran; Li, Ming; Jia, Chun-Xiao; Wang, Bing-Hong
We study the percolation in coupled networks with both inner-dependency and inter-dependency links, where the inner- and inter-dependency links represent the dependencies between nodes in the same or different networks, respectively. We find that when most of dependency links are inner- or inter-ones, the coupled networks system is fragile and makes a discontinuous percolation transition. However, when the numbers of two types of dependency links are close to each other, the system is robust and makes a continuous percolation transition. This indicates that the high density of dependency links could not always lead to a discontinuous percolation transition as the previous studies. More interestingly, although the robustness of the system can be optimized by adjusting the ratio of the two types of dependency links, there exists a critical average degree of the networks for coupled random networks, below which the crossover of the two types of percolation transitions disappears, and the system will always demonstrate a discontinuous percolation transition. We also develop an approach to analyze this model, which is agreement with the simulation results well. PMID:27142883
Time-Dependent Behaviors of Granite: Loading-Rate Dependence, Creep, and Relaxation
NASA Astrophysics Data System (ADS)
Hashiba, K.; Fukui, K.
To assess the long-term stability of underground structures, it is important to understand the time-dependent behaviors of rocks, such as their loading-rate dependence, creep, and relaxation. However, there have been fewer studies on crystalline rocks than on tuff, mudstone, and rock salt, because the high strength of crystalline rocks makes the detection of their time-dependent behaviors much more difficult. Moreover, studies on the relaxation, temporal change of stress and strain (TCSS) conditions, and relations between various time-dependent behaviors are scarce for not only granites, but also other rocks. In this study, previous reports on the time-dependent behaviors of granites were reviewed and various laboratory tests were conducted using Toki granite. These tests included an alternating-loading-rate test, creep test, relaxation test, and TCSS test. The results showed that the degree of time dependence of Toki granite is similar to other granites, and that the TCSS resembles the stress-relaxation curve and creep-strain curve. A viscoelastic constitutive model, proposed in a previous study, was modified to investigate the relations between the time-dependent behaviors in the pre- and post-peak regions. The modified model reproduced the stress-strain curve, creep, relaxation, and the results of the TCSS test. Based on a comparison of the results of the laboratory tests and numerical simulations, close relations between the time-dependent behaviors were revealed quantitatively.
Age of Alcohol-Dependence Onset: Associations with Severity of Dependence and Seeking Treatment
ERIC Educational Resources Information Center
Hingson, Ralph W.; Heeren, Timothy; Winter, Michael R.
Objective: We explored whether people who become alcohol dependent at younger ages are more likely to seek alcohol-related help or treatment or experience chronic relapsing dependence. Methods: In 2001-2002 the National Institute on Alcohol Abuse and Alcoholism completed a face-to-face interview survey with a multistage probability sample of 43…
Genetics of Opioid Dependence: A Review of the Genetic Contribution to Opioid Dependence
Mistry, Chetna J; Bawor, Monica; Desai, Dipika; Marsh, David C; Samaan, Zainab
This narrative review aims to provide an overview of the impact of opioid dependence and the contribution of genetics to opioid dependence. Epidemiological data demonstrate that opioid dependence is a global trend with far-reaching effects on the social, economic, and health care systems. A review of classical genetic studies of opioid use suggests significant heritability of drug use behavior, however the evidence from molecular genetic studies is inconclusive. Nonetheless, certain genetic variants are important to consider given their role in the pathophysiology of addictive behavior. We undertook a literature review to identify the current state of knowledge regarding the role of genes in opioid dependence. Determining the association of genetic markers could change the current understanding of the various factors contributing to opioid dependence and therefore may improve recognition of individuals at risk for the disorder and prevention and treatment strategies. PMID:25242908
Sleep-dependent motor memory consolidation in older adults depends on task demands.
Gudberg, Christel; Wulff, Katharina; Johansen-Berg, Heidi
It is often suggested that sleep-dependent consolidation of motor learning is impaired in older adults. The current study challenges this view and suggests that the degree of motor consolidation seen with sleep in older age groups depends on the kinematic demands of the task. We show that, when tested with a classic sequence learning task, requiring individuated finger movements, older adults did not show sleep-dependent consolidation. By contrast, when tested with an adapted sequence learning task, in which movements were performed with the whole hand, sleep-dependent motor improvement was observed in older adults. We suggest that age-related decline in fine motor dexterity may in part be responsible for the previously described deficit in sleep-dependent motor consolidation with aging. PMID:25618616
Local density dependent potential for compressible mesoparticles
NASA Astrophysics Data System (ADS)
Faure, Gérôme; Maillet, Jean-Bernard; Stoltz, Gabriel
This work proposes a coarse grained description of molecular systems based on mesoparticles representing several molecules, where interactions between mesoparticles are modelled by an interparticle potential of molecular type. Since strong non-equilibrium situations over a wide range of pressure and density are targeted, the internal compressibility of the mesoparticles has to be considered. This is done by introducing a dependence of the potential on the local environment of the mesoparticles. To define local densities, we resort to a three-dimensional Voronoi tessellation instead of standard local, spherical averages. As an example, a local density dependent potential is fitted to reproduce the Hugoniot curve of a model of nitromethane over a large range of pressures and densities.
Reducing US Oil Dependence Using Simulation
NASA Technical Reports Server (NTRS)
Ayoub, Fadi; Arnaout, Georges M.
People across the world are addicted to oil; as a result, the instability of oil prices and the shortage of oil reserves have influenced human behaviors and global businesses. Today, the United States makes up only 5% of the global population but consumes 25% of the. world total energy. Most of this energy is generated from fossil fuels in the form of electricity. The contribution of this paper is to examine the possibilities of replacing fossil fuel with renewable energies to generate electricity as well as to examine other methods to reduce oil and gas consumption. We propose a system dynamics model in an attempt to predict the future US dependence on fossil fuels by using renewable energy resources such as, nuclear, wind, solar, and hydro powers. Based on the findings of our model, the study expects to provide insights towards promising solutions of the oil dependency problem.
Curvature Dependence of Hydrophobic Hydration Dynamics
NASA Astrophysics Data System (ADS)
Weiß, R. Gregor; Heyden, Matthias; Dzubiella, Joachim
We investigate the solute curvature dependence of water dynamics in the vicinity of hydrophobic spherical solutes using molecular dynamics simulations. For both the lateral and perpendicular diffusivity, as well as for H-bond kinetics of water in the first hydration shell, we find a nonmonotonic solute-size dependence, exhibiting extrema close to the well-known structural crossover length scale for hydrophobic hydration. Additionally, we find an apparent anomalous diffusion for water moving parallel to the surface of small solutes, which, however, can be explained by topology effects. Our findings regarding the intimate connection between solute curvature and water dynamics has implications for our understanding of hydration dynamics at heterogeneous biomolecular surfaces.
Brain Pathways to Recovery from Alcohol Dependence
Cui, Changhai; Noronha, Antonio; Warren, Kenneth; Koob, George F.; Sinha, Rajita; Thakkar, Mahesh; Matochik, John; Crews, Fulton T.; Chandler, L. Judson; Pfefferbaum, Adolf; Becker, Howard C.; Lovinger, David; Everitt, Barry; Egli, Mark; Mandyam, Chitra; Fein, George; Potenza, Marc N.; Harris, R. Adron; Grant, Kathleen A.; Roberto, Marisa; Meyerhoff, Dieter J.; Sullivan, Edith V.
This article highlights the research presentations at the satellite symposium on "Brain Pathways to Recovery from Alcohol Dependence" held at the 2013 Society for Neuroscience Annual Meeting. The purpose of this symposium was to provide an up to date overview of research efforts focusing on understanding brain mechanisms that contribute to recovery from alcohol dependence. A panel of scientists from the alcohol and addiction research field presented their insights and perspectives on brain mechanisms that may underlie both recovery and lack of recovery from alcohol dependence. The four sessions of the symposium encompassed multilevel studies exploring mechanisms underlying relapse and craving associated with sustained alcohol abstinence, cognitive function deficit and recovery, and translational studies on preventing relapse and promoting recovery. Gaps in our knowledge and research opportunities were also discussed. PMID:26074423
Small-molecule-dependent split aptamer ligation.
Sharma, Ashwani K; Heemstra, Jennifer M
Here we describe the first use of small-molecule binding to direct a chemical reaction between two nucleic acid strands. The reported reaction is a ligation between two fragments of a DNA split aptamer using strain-promoted azide-alkyne cycloaddition. Utilizing the split aptamer for cocaine, we demonstrate small-molecule-dependent ligation that is dose-dependent over a wide range of cocaine concentrations and is compatible with complex biological fluids such as human blood serum. Moreover, studies of split aptamer ligation at varying salt concentrations and using structurally similar analogues of cocaine have revealed new insight into the assembly and small-molecule binding properties of the cocaine split aptamer. The ability to translate the presence of a small-molecule target into the output of DNA ligation is anticipated to enable the development of new, broadly applicable small-molecule detection assays. PMID:21761903
Size-Dependent Raman Shifts for nanocrystals
Gao, Yukun; Zhao, Xinmei; Yin, Penggang; Gao, Faming
Raman spectroscopy is a very sensitive tool for probing semiconductor nanocrystals. The underlying mechanism behind the size-dependent Raman shifts is still quite controversial. Here we offer a new theoretical method for the quantum confinement effects on the Raman spectra of semiconductor nanocrystals. We propose that the shift of Raman spectra in nanocrystals can result from two overlapping effects: the quantum effect shift and surface effect shift. The quantum effect shift is extracted from an extended Kubo formula, the surface effect shift is determined via the first principles calculations. Fairly good prediction of Raman shifts can be obtained without the use of any adjustable parameter. Closer analysis shows that the size-dependent Raman shifts in Si nanocrystals mainly result from the quantum effect shifts. For nanodiamond, the proportion of surface effect shift in Raman shift is up to about 40%. Such model can also provide a good baseline for using Raman spectroscopy as a tool to measure size. PMID:27102066
Human copper-dependent amine oxidases.
Finney, Joel; Moon, Hee-Jung; Ronnebaum, Trey; Lantz, Mason; Mure, Minae
Copper amine oxidases (CAOs) are a class of enzymes that contain Cu(2+) and a tyrosine-derived quinone cofactor, catalyze the conversion of a primary amine functional group to an aldehyde, and generate hydrogen peroxide and ammonia as byproducts. These enzymes can be classified into two non-homologous families: 2,4,5-trihydroxyphenylalanine quinone (TPQ)-dependent CAOs and the lysine tyrosylquinone (LTQ)-dependent lysyl oxidase (LOX) family of proteins. In this review, we will focus on recent developments in the field of research concerning human CAOs and the LOX family of proteins. The aberrant expression of these enzymes is linked to inflammation, fibrosis, tumor metastasis/invasion and other diseases. Consequently, there is a critical need to understand the functions of these proteins at the molecular level, so that strategies targeting these enzymes can be developed to combat human diseases. PMID:24407025
Frequency-dependent selection by predators.
Allen, J A
Sometimes predators tend to concentrate on common varieties of prey and overlook rare ones. Within prey species, this could result in the fitness of each variety being inversely related to its frequency in the population. Such frequency-dependent or 'apostatic' selection by predators hunting by sight could maintain polymorphism for colour pattern, and much of the supporting evidence for this idea has come from work on birds and artificial prey. These and other studies have shown that the strength of the observed selection is affected by prey density, palatability, coloration and conspicuousness. When the prey density is very high, selection becomes 'anti-apostatic': predators preferentially remove rare prey. There is still much to be learned about frequency-dependent selection by predators on artificial prey: work on natural polymorphic prey has hardly begun. PMID:2905488
Analysis of frequency dependent pump light absorption
NASA Astrophysics Data System (ADS)
Wohlmuth, Matthias; Pflaum, Christoph
Simulations have to accurately model thermal lensing in order to help improving resonator design of diode pumped solid state lasers. To this end, a precise description of the pump light absorption is an important prerequisite. In this paper, we discuss the frequency dependency of the pump light absorption in the laser crystal and its influence on the simulated laser performance. The results show that the pump light absorption has to include the spectral overlap of the emitting pump source and the absorbing laser material. This information can either be used for a fully frequency dependent absorption model or, at least in the shown examples, to compute an effective value for an exponential Beer-Lambert law of absorption. This is particularly significant at pump wavelengths coinciding with a peak of absorption. Consequences for laser stability and performance are analyzed for different pump wavelengths in a Nd:YAG laser.
Kinship as a frequency dependent strategy.
Ji, Ting; Zheng, Xiu-Deng; He, Qiao-Qiao; Wu, Jia-Jia; Mace, Ruth; Tao, Yi
Humans divide themselves up into separate cultures, which is a unique and ubiquitous characteristic of our species. Kinship norms are one of the defining features of such societies. Here we show how norms of marital residence can evolve as a frequency-dependent strategy, using real-world cases from southwestern China and an evolutionary game model. The process of kinship change has occurred in the past and is also occurring now in southwestern China. Our data and models show how transitions between residence types can occur both as response to changing costs and benefits of co-residence with kin, and also due to the initial frequency of the strategies adopted by others in the population: patrilocal societies can become matrilocal, and neolocal societies can become duolocal. This illustrates how frequency-dependent selection plays a role both in the maintenance of group-level cultural diversity and in cultural extinction. PMID:26998333
Two-frequency-dependent Gauss quadrature rules
NASA Astrophysics Data System (ADS)
Kim, Kyung Joong
We construct two-frequency-dependent Gauss quadrature rules which can be applied for approximating the integration of the product of two oscillatory functions with different frequencies [beta]1 and [beta]2 of the forms,yi(x)=fi,1(x) cos([beta]ix)+fi,2(x) sin([beta]ix), i=1,2,where the functions fi,j(x) are smooth. A regularization procedure is presented to avoid the singularity of the Jacobian matrix of nonlinear system of equations which is induced as one frequency approaches the other frequency. We provide numerical results to compare the accuracy of the classical Gauss rule and one- and two-frequency-dependent rules.
Integral dependent spin couplings in CI calculations
NASA Astrophysics Data System (ADS)
Iberle, K.; Davidson, E. R.
Although the number of ways to combine Slater determinants to form spin eigenfunctions increases rapidly with the number of open shells, most of these spin couplings will make only a small contribution to a given state, provided the spin coupling is chosen judiciously. The technique of limiting calculations to the interacting subspace pioneered by Bunge (1970) was employed by Munch and Davidson (1975) to the vanadium atom. The use of an interacting space looses its advantage in more complex cases. However, the problem can always be reduced to only one interacting spin coupling by making the coefficients integral dependent. The present investigation is concerned with the performance of integral dependent interacting couplings, taking into account the results of three test calculations.
Kinship as a frequency dependent strategy
Ji, Ting; Zheng, Xiu-Deng; He, Qiao-Qiao; Wu, Jia-Jia; Tao, Yi
Humans divide themselves up into separate cultures, which is a unique and ubiquitous characteristic of our species. Kinship norms are one of the defining features of such societies. Here we show how norms of marital residence can evolve as a frequency-dependent strategy, using real-world cases from southwestern China and an evolutionary game model. The process of kinship change has occurred in the past and is also occurring now in southwestern China. Our data and models show how transitions between residence types can occur both as response to changing costs and benefits of co-residence with kin, and also due to the initial frequency of the strategies adopted by others in the population: patrilocal societies can become matrilocal, and neolocal societies can become duolocal. This illustrates how frequency-dependent selection plays a role both in the maintenance of group-level cultural diversity and in cultural extinction. PMID:26998333
Decomposing climate dependency of forest dynamics
NASA Astrophysics Data System (ADS)
Lines, Emily
Forest simulation models have proved extremely useful in understanding forest dynamics by scaling from tree-level processes to landscape scales, but typically contain no climate dependency in their subprocesses. Forest inventory databases may be used to investigate the role of climate on tree-level processes, and the climate drivers of geographical ranges of different species, by making a space-for-time substitution. We demonstrate the value of inventory data for determining the climate drivers of forest processes. By scaling up from individual demographic rates using a forest simulation model, parameterised for mainland Spain, we determine the key climate dependencies driving emergent forest properties, allowing defensible predictions of the impacts of climate change.
Simultaneous Measurement of Temperature Dependent Thermophysical Properties
NASA Astrophysics Data System (ADS)
Czél, Balázs; Gróf, Gyula; Kiss, László
A new evaluation method for a transient measurement of thermophysical properties is presented in this paper. The aim of the research was to couple a new automatic evaluation procedure to the BICOND thermophysical property measurement method to enhance the simultaneous determination of the temperature dependent thermal conductivity and volumetric heat capacity. The thermophysical properties of two different polymers were measured and compared with the literature data and with the measurement results that were done by well-known, traditional methods. The BICOND method involves a step-down cooling, recording the temperature histories of the inner and the outer surfaces of a hollow cylindrical sample and the thermophysical properties are evaluated from the solution of the corresponding inverse heat conduction using a genetic algorithm-based method (BIGEN) developed by the authors. The BIGEN is able to find the material properties with any kind of temperature dependency, that is illustrated through the measurement results of poly(tetrafluoroethylene) (PTFE) and polyamide (PA) samples.
Temperature dependence of standard model CP violation.
Brauner, Tomáš; Taanila, Olli; Tranberg, Anders; Vuorinen, Aleksi
We analyze the temperature dependence of CP violation effects in the standard model by determining the effective action of its bosonic fields, obtained after integrating out the fermions from the theory and performing a covariant gradient expansion. We find nonvanishing CP violating terms starting at the sixth order of the expansion, albeit only in the C-odd-P-even sector, with coefficients that depend on quark masses, Cabibbo-Kobayashi-Maskawa matrix elements, temperature and the magnitude of the Higgs field. The CP violating effects are observed to decrease rapidly with temperature, which has important implications for the generation of a matter-antimatter asymmetry in the early Universe. Our results suggest that the cold electroweak baryogenesis scenario may be viable within the standard model, provided the electroweak transition temperature is at most of order 1 GeV. PMID:22400822
Dependent personality disorder: a critical review.
Disney, Krystle L
Dependent personality disorder (DPD) has evolved from an abstract idea rooted in a historic and psychoanalytic context to a codified diagnosis in the DSM-IV-TR. This comprehensive review paper chronicles the evolution of DPD through each version of the DSM. Major topics relevant to the disorder are also investigated, including gender and cultural considerations, stability and manifestations of DPD across different developmental stages, comorbidity issues, and others. The purpose of this review is to provide a broad yet comprehensive examination of the complex angles of maladaptive dependency and to identify essential next steps in furthering our knowledge of this disorder. The paper concludes with a discussion of shortcomings in the body of research relevant to DPD, along with specific suggestions for improvement in this field of study. PMID:24185092
Photochemotherapy: Light Dependent Therapies in Medicine
NASA Astrophysics Data System (ADS)
Zovinka, Edward P.; Sunseri, Danielle R.
Light-dependent therapies, such as photodynamic therapy and extracorporeal photopheresis, are not new, but have remained of interest to chemists and health care professionals since the middle of the twentieth century. While most people link light-dependent therapies only to the treatment of cancer, these therapies may be of use for a diverse set of medical conditions, from acne to AIDS. The techniques arise directly from the application of chemical concepts, such as spectroscopy, MO theory, and organic chemical reactions. Because of its application to health care, the field of photochemistry provides a tool to demonstrate the significance of chemistry to a socially important issue.
Scale Dependence of Spatiotemporal Intermittence of Rain
NASA Technical Reports Server (NTRS)
Kundu, Prasun K.; Siddani, Ravi K.
It is a common experience that rainfall is intermittent in space and time. This is reflected by the fact that the statistics of area- and/or time-averaged rain rate is described by a mixed distribution with a nonzero probability of having a sharp value zero. In this paper we have explored the dependence of the probability of zero rain on the averaging space and time scales in large multiyear data sets based on radar and rain gauge observations. A stretched exponential fannula fits the observed scale dependence of the zero-rain probability. The proposed formula makes it apparent that the space-time support of the rain field is not quite a set of measure zero as is sometimes supposed. We also give an ex.planation of the observed behavior in tenus of a simple probabilistic model based on the premise that rainfall process has an intrinsic memory.
Density dependence: an ecological Tower of Babel.
Herrando-Pérez, Salvador; Delean, Steven; Brook, Barry W; Bradshaw, Corey J A
The concept of density dependence represents the effect of changing population size on demographic rates and captures the demographic role of social and trophic mechanisms (e.g. competition, cooperation, parasitism or predation). Ecologists have coined more than 60 terms to denote different statistical and semantic properties of this concept, resulting in a formidable lexicon of synonymies and polysemies. We have examined the vocabulary of density dependence used in the modern ecological literature from the foundational lexicon developed by Smith, Allee, Haldane, Neave and Varley. A few simple rules suffice to abate terminological inconsistency and to enhance the biological meaning of this important concept. Correct citation of original references by ecologists and research journals could ameliorate terminological standards in our discipline and avoid linguistic confusion of mathematically and theoretically complex patterns. PMID:22648068
Profile sampling dependence of the MLAYER program
NASA Astrophysics Data System (ADS)
Chang, Ting-Hsun
The dependence of the predictions of the MLAYER program on the set of heights at which the refractive index value are sampled from a fixed reference profile are analyzed. A refractivity profile with a four-meter evaporation duct is adopted as a reference. Two variable piecewise linear profiles of four and five segments, respectively, are used to approximate the reference profile for MLAYER computations. The sensitivities of the waveguide mode location, the range attenuation rate, and the height-gain function to the changes of the piece-wise linear profiles are investigated at the frequencies 3, 6, 10, and 15 GHz. The frequency dependence of the dominant mode for one profile is also studied to investigate the fact that the sensitivity to changes in sampling point location is lower at GHz than at other frequencies. A general rule-of-thumb for the change in range attenuation rate due to a slight change in refractivity is suggested.
Time-Dependent Erosion of Ion Optics
NASA Technical Reports Server (NTRS)
Wirz, Richard E.; Anderson, John R.; Katz, Ira; Goebel, Dan M.
The accurate prediction of thruster life requires time-dependent erosion estimates for the ion optics assembly. Such information is critical to end-of-life mechanisms such as electron backstreaming. CEX2D was recently modified to handle time-dependent erosion, double ions, and multiple throttle conditions in a single run. The modified code is called "CEX2D-t". Comparisons of CEX2D-t results with LDT and ELT post-tests results show good agreement for both screen and accel grid erosion including important erosion features such as chamfering of the downstream end of the accel grid and reduced rate of accel grid aperture enlargement with time.
Protocol dependence of the jamming transition
NASA Astrophysics Data System (ADS)
Bertrand, Thibault; Behringer, Robert P.; Chakraborty, Bulbul; O'Hern, Corey S.; Shattuck, Mark D.
We propose a theoretical framework for predicting the protocol dependence of the jamming transition for frictionless spherical particles that interact via repulsive contact forces. We study isostatic jammed disk packings obtained via two protocols: isotropic compression and simple shear. We show that for frictionless systems, all jammed packings can be obtained via either protocol. However, the probability to obtain a particular jammed packing depends on the packing-generation protocol. We predict the average shear strain required to jam initially unjammed isotropically compressed packings from the density of jammed packings, shape of their basins of attraction, and path traversed in configuration space. We compare our predictions to simulations of shear strain-induced jamming and find quantitative agreement. We also show that the packing fraction range, over which shear strain-induced jamming occurs, tends to zero in the large system limit for frictionless packings with overdamped dynamics.
Conformation Dependence of Backbone Geometry in Proteins
Berkholz, Donald S.; Shapovalov, Maxim V.; Dunbrack, Roland L.; Karplus, P. Andrew
Summary Protein structure determination and predictive modeling have long been guided by the paradigm that the peptide backbone has a single, context-independent ideal geometry. Both quantum-mechanics calculations and empirical analyses have shown this is an incorrect simplification in that backbone covalent geometry actually varies systematically as a function of the Φ and Ψ backbone dihedral angles. Here, we use a nonredundant set of ultrahigh-resolution protein structures to define these conformation-dependent variations. The trends have a rational, structural basis that can be explained by avoidance of atomic clashes or optimization of favorable electrostatic interactions. To facilitate adoption of this new paradigm, we have created a conformation-dependent library of covalent bond lengths and bond angles and shown that it has improved accuracy over existing methods without any additional variables to optimize. Protein structures derived both from crystallographic refinement and predictive modeling both stand to benefit from incorporation of the new paradigm. PMID:19836332
Anchorage Dependent Cells Attached to a Polymer
NASA Technical Reports Server (NTRS)
Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Anchorage dependent cells on STS-95 will be grown on beads, similar to these cells produced during previous investigations. Recombinant proteins may offer the possibility of reducing or eliminating transplant rejections. Research by Synthecon, Inc. using the BioDyn Bioreactor will focus on the preliminary process for growing a proprietary recombinant protein that can decrease rejection of transplanted tissue. The cells producing this protein are anchorage dependent, meaning that they must attach to something to grow. These cells will be cultured in the bioreactor in a medium containing polymer microbeads. Synthecon hopes that the data from this mission will lead to the development of a commercial protein that will aid in prevention of transplant rejection.
Anchorage Dependent Cells Attached to a Polymer
NASA Technical Reports Server (NTRS)
Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Anchorage dependent cells on STS-95 will be grown on beads similar to these cells produced during previous investigations. Recombinant proteins may offer the possibility of reducing or eliminating transplant rejections. Research by Synthecon, Inc. using the BioDyn Bioreactor will focus on the preliminary process for growing a proprietary recombinant protein that can decrease rejection of transplanted tissue. The cells producing this protein are anchorage dependent, meaning that they must attach to something to grow. These cells will be cultured in the bioreactor in a medium containing polymer microbeads. Synthecon hopes that the data from this mission will lead to the development of a commercial protein that will aid in prevention of transplant rejection.
Isotope Dependence of Chemical Erosion of Carbon
Reinhold, Carlos O; Krstic, Predrag S; Stuart, S. J.; Zhang, Hengda; Harris, Peter R; Meyer, Fred W
We study the chemical erosion of hydrogen-supersaturated carbon due to bombardment by hydrogen isotopes H, D, and T at energies of 1 30 eV using classical molecular dynamics simulations. The chemical structure at the hydrogen-saturated interface (the distribution of terminal hydrocarbon moieties, in particular) shows a weak dependence on the mass of the impinging atoms. However the sputtering yields increase considerably with increasing projectile mass. We analyze the threshold energies of chemical sputtering reaction channels and show that they are nearly mass independent, as expected from elementary bond-breaking chemical reactions involving hydrocarbons. Chemical sputtering yields for D impact are compared with new experimental data. Good agreement is found for small hydrocarbons but the simulations overestimate the production of large hydrocarbons for energies larger than 15 eV. We present a thorough analysis of the dependence of our simulations on the parameters of the bombardment schemes and discuss open questions and possible avenues for development.
Mode-dependent characterization of photonic lanterns.
Yu, Dawei; Fu, Songnian; Cao, Zizheng; Tang, Ming; Liu, Deming; Giles, Ian; Koonen, Ton; Okonkwo, Chigo
We propose and experimentally demonstrate a simple method for characterizing the power transfer matrix of photonic lanterns (PLs) used for mode division multiplexing (MDM) transmission. Due to the optical reflection arising at output facet of the few-mode fiber (FMF), we are able to detect the power at the individual single-mode fiber (SMF) input port and exploit a series of equations based on the theory of energy conservation to obtain mode-dependent characteristics of the PL, including the property of mode selectivity, insertion loss (IL), and channel-dependent loss (CDL). The proposed method is experimentally verified for both the mode selective and the nonmode selective photonic lanterns. PMID:27176988
Integral dependent spin couplings in CI calculations
NASA Technical Reports Server (NTRS)
Iberle, K.; Davidson, E. R.
Although the number of ways to combine Slater determinants to form spin eigenfunctions increases rapidly with the number of open shells, most of these spin couplings will make only a small contribution to a given state, provided the spin coupling is chosen judiciously. The technique of limiting calculations to the interacting subspace pioneered by Bunge (1970) was employed by Munch and Davidson (1975) to the vanadium atom. The use of an interacting space looses its advantage in more complex cases. However, the problem can always be reduced to only one interacting spin coupling by making the coefficients integral dependent. The present investigation is concerned with the performance of integral dependent interacting couplings, taking into account the results of three test calculations.
Biperiden Dependence: Case Report and Literature Review
Espi Martinez, Fernando; Espi Forcen, Fernando; Shapov, Arlenne; Martinez Moya, Amparo
Anticholinergic drugs are frequently used in psychiatry for the prophylaxis and treatment of extrapiramidal symptoms caused by neuroleptics. Abuse of anticholinergic agents has been reported in patients with psychotic disorders, on treatment with neuroleptics, and polysubstance use disorders. We are reporting the case of a patient who presented with hypoactive delirium as a consequence of biperiden dependence. The clinician must pay special attention to detect anticholinergic misuse in patients presenting with delirium of unknown cause. PMID:22937420
Renewable Energy Can Help Reduce Oil Dependency
Arvizu, Dan
In a speech to the Economic Club of Kansas City on June 23, 2010, NREL Director Dan Arvizu takes a realistic look at how renewable energy can help reduce America's dependence on oil, pointing out that the country gets as much energy from renewable sources now as it does from offshore oil production. For a transcript, visit http://www.nrel.gov/director/pdfs/energy_overview_06_10.pdf
Spatial dependence of pairing in deformed nuclei
Balbutsev, E. B.; Malov, L. A.; Schuck, P.
The solution of time-dependent Hartree-Fock-Bogoliubov equations by the Wignerfunction-moments method leads to the appearance of refined low-lying modes whose description requires the accurate knowledge of the anomalous density matrix. It is shown that calculations with Woods-Saxon potential satisfy this requirement, producing an anomalous density matrix of the same quality as more complicated calculations with realistic forces.
Transverse Momentum Dependent Hadron Multiplicities at COMPASS
NASA Astrophysics Data System (ADS)
Makke, Nour
Unpolarised semi-inclusive deep inelastic scattering is receiving a growing interest as a powerful tool to access poorly known transverse momentum dependent parton distributions and fragmentation functions that play a key role in many processes, in particular in the study of the spin structure of the nucleon. These functions can be investigated through experimental observables. New results on these observables by the COMPASS experiment at CERN will be shown and discussed.
Correlation dependences of electromagnetic and deformation parameters
NASA Astrophysics Data System (ADS)
Bataleva, E. A.
In-situ monitoring observations are carried out, and correlation analysis aimed at estimating the dependences between the electromagnetic parameters (variations of apparent resistivity, the impedance phase, components of the impedance tensor, and deformations of the daylight surface on the territory of the Bishkek geodynamic polygon) is performed. A new approach to the explanation of the physical mechanism forming variations in electrical conductivity of the medium is proposed on this basis.
Environment-Dependent Payoffs in Finite Populations
NASA Astrophysics Data System (ADS)
Xu, Wei-Hong; Zhang, Yan-Ling; Xie, Guang-Ming; Feng, Xue
In finite population games with weak selection and large population size, when the payoff matrix is constant, the one-third law serves as the condition of a strategy to be advantageous. We generalize the result to the cases of environment-dependent payoff matrices which exhibit the feedback from the environment to the population. Finally, a more general law about cooperation-dominance is obtained.
Time-dependent oral absorption models
NASA Technical Reports Server (NTRS)
Higaki, K.; Yamashita, S.; Amidon, G. L.
The plasma concentration-time profiles following oral administration of drugs are often irregular and cannot be interpreted easily with conventional models based on first- or zero-order absorption kinetics and lag time. Six new models were developed using a time-dependent absorption rate coefficient, ka(t), wherein the time dependency was varied to account for the dynamic processes such as changes in fluid absorption or secretion, in absorption surface area, and in motility with time, in the gastrointestinal tract. In the present study, the plasma concentration profiles of propranolol obtained in human subjects following oral dosing were analyzed using the newly derived models based on mass balance and compared with the conventional models. Nonlinear regression analysis indicated that the conventional compartment model including lag time (CLAG model) could not predict the rapid initial increase in plasma concentration after dosing and the predicted Cmax values were much lower than that observed. On the other hand, all models with the time-dependent absorption rate coefficient, ka(t), were superior to the CLAG model in predicting plasma concentration profiles. Based on Akaike's Information Criterion (AIC), the fluid absorption model without lag time (FA model) exhibited the best overall fit to the data. The two-phase model including lag time, TPLAG model was also found to be a good model judging from the values of sum of squares. This model also described the irregular profiles of plasma concentration with time and frequently predicted Cmax values satisfactorily. A comparison of the absorption rate profiles also suggested that the TPLAG model is better at prediction of irregular absorption kinetics than the FA model. In conclusion, the incorporation of a time-dependent absorption rate coefficient ka(t) allows the prediction of nonlinear absorption characteristics in a more reliable manner.
Renewable Energy Can Help Reduce Oil Dependency
Arvizu, Dan
In a speech to the Economic Club of Kansas City on June 23, 2010, NREL Director Dan Arvizu takes a realistic look at how renewable energy can help reduce America's dependence on oil, pointing out that the country gets as much energy from renewable sources now as it does from offshore oil production. For a transcript, visit http://www.nrel.gov/director/pdfs/energy_overview_06_10.pdf
Dry process dependency of dupic fuel cycle
Park, Kwangheon; Whang, Juho; Kim, Yun-goo; Kim, Heemoon
During the Dry Process, volatile and semi-volatile elements are released from the fuel. The effects of these released radioactive nuclides on DUPIC fuel cycle are analyzed from the view-point of radiation hazard, decay beat, and hazard index. Radiation hazard of fresh and spent DUPIC fuel is sensitive to the method of Dry Process. Decay beat of the fuel is also affected. Hazard index turned out not to be dependent on Dry Process.
Apolipoprotein E isoform-dependent microglia migration
Cudaback, Eiron; Li, Xianwu; Montine, Kathleen S.; Montine, Thomas J.; Keene, C. Dirk
Complement component C5a and ATP are potent effectors of microglial movement and are increased in diverse neurodegenerative diseases and at sites of injury. Apolipoprotein E (apoE) influences microglial function, and different human apoE isoforms confer variable risk for development of neurodegenerative disorders, especially Alzheimer's disease. The purpose of this investigation was to test the hypothesis that mouse apoE and human apoE isoforms influence microglial migration. Using primary wild-type and apoE-deficient microglia, we show that C5a- and ATP-stimulated chemotaxis are largely apoE-dependent processes with different molecular bases. Although the C5a-dependent chemotaxis of wild-type microglia was completely blocked by receptor-associated protein (RAP), suggesting apoE receptor involvement, ATP-stimulated migration was unaffected by RAP but was associated with differential ERK phosphorylation. Studies using primary microglia derived from targeted replacement mice "humanized" for the coding exons (protein isoform) of human ε2 (apoE2), ε3 (apoE3), or ε4 (apoE4) allele of APOE revealed that primary mouse microglia expressing apoE4 or apoE2 exhibited significantly reduced C5a- and ATP-stimulated migration compared with microglia expressing human apoE3. This study, for the first time, demonstrates apoE dependence and apoE isoform-specific modulation of microglial migration in response to distinct chemotactic stimuli commonly associated with neurodegenerative disease.—Cudaback, E., Li, X., Montine, K. S., Montine, T. J., Keene, C. D. Apolipoprotein E isoform-dependent microglia migration. PMID:21385991
Road rage among drug dependent patients.
Benavidez, Daniela C; Flores, Antonio Marcos; Fierro, Inmaculada; Alvarez, F Javier
The consumption of alcohol, cocaine and cannabis is associated with aggressive behaviour, being a victim of injuries from various causes, and suffering traffic accidents. On the other hand, there is a significant association between road rage and traffic accidents, yet this has not been studied in persons suffering a substance dependence disorder. This study analyses the prevalence of road rage in substance dependent patients undergoing treatment. 100 patients randomly selected at an outpatient treatment centre were included in the study. 63% of the patients had experienced road rage in the year prior to the interview, and 18% were serious perpetrators. There was a higher frequency among drivers and those who were starting treatment for cocaine and cocaine+heroin. The study shows that road rage is very frequent among patients with disorders due to substance dependence who are undergoing treatment, in particular the most severe form ("serious perpetrators"). Special attention should be addressed to the issue of driving and road rage during the treatment of these patients. PMID:22840213
Temperature Dependent Kinetics DNA Charge Transport
NASA Astrophysics Data System (ADS)
Wohlgamuth, Chris; McWilliams, Marc; Slinker, Jason
Charge transport (CT) through DNA has been extensively studied, and yet the mechanism of this process is still not yet fully understood. Besides the benefits of understanding charge transport through this fundamental molecule, further understanding of this process will elucidate the biological implications of DNA CT and advance sensing technology. Therefore, we have investigated the temperature dependence of DNA CT by measuring the electrochemistry of DNA monolayers modified with a redox-active probe. By using multiplexed electrodes on silicon chips, we compare square wave voltammetry of distinct DNA sequences under identical experimental conditions. We vary the probe length within the well matched DNA duplex in order to investigate distance dependent kinetics. This length dependent study is a necessary step to understanding the dominant mechanism behind DNA CT. Using a model put forth by O'Dea and Osteryoung and applying a nonlinear least squares analysis we are able to determine the charge transfer rates (k), transfer coefficients (α), and the total surface concentration (&*circ;) of the DNA monolayer. Arrhenius like behavior is observed for the multiple probe locations, and the results are viewed in light of and compared to the prominent charge transport mechanisms.
Interactive dependency curves for resilience management.
Petit, Frédéric; Wallace, Kelly; Phillip, Julia
Physical dependencies are a fundamental consideration when assessing the resilience of an organisation and, ultimately, the resilience of a region. Every organisation needs specific resources for supporting its operations. A disruption in the supply of these resources can severely impact business continuity. It is important to characterise dependencies thoroughly when seeking to reduce the extent an organisation is directly affected by the missions, functions and operations of other organisations. The general protocol when addressing each critical resource is to determine the use for the resource, whether there are redundant services providing the resource, and what protections, backup equipment and arrangements are in place to maintain service. Finally, the criticality of the resource is determined by estimating the time it will take for the facility to experience a severe impact once primary service is lost and what percentage of facility operations can be maintained without backup service in place, as well as identifying whether any external regulations/policies are in place that require shutdown of the facility because of service disruption owing to lack of a critical resource. All of this information can be presented in the form of interactive dependency curves that help anticipate and manage the effect(s) of a disruption on critical resources supply. PMID:25416376
Influence of Sensory Dependence on Postural Control
NASA Technical Reports Server (NTRS)
Santana, Patricia A.; Mulavara, Ajitkumar P.; Fiedler, Matthew J.
The current project is part of an NSBRI funded project, "Development of Countermeasures to Aid Functional Egress from the Crew Exploration Vehicle Following Long-Duration Spaceflight." The development of this countermeasure is based on the use of imperceptible levels of electrical stimulation to the balance organs of the inner ear to assist and enhance the response of a person s sensorimotor function. These countermeasures could be used to increase an astronaut s re-adaptation rate to Earth s gravity following long-duration space flight. The focus of my project is to evaluate and examine the correlation of sensory preferences for vision and vestibular systems. Disruption of the sensorimotor functions following space flight affects posture, locomotion and spatial orientation tasks in astronauts. The Group Embedded Figures Test (GEFT), the Rod and Frame Test (RFT) and the Computerized Dynamic Posturography Test (CDP) are measurements used to examine subjects visual and vestibular sensory preferences. The analysis of data from these tasks will assist in relating the visual dependence measures recognized in the GEFT and RFT with vestibular dependence measures recognized in the stability measures obtained during CDP. Studying the impact of sensory dependence on the performance in varied tasks will help in the development of targeted countermeasures to help astronauts readapt to gravitational changes after long duration space flight.
GABA receptors, alcohol dependence and criminal behavior.
Terranova, Claudio; Tucci, Marianna; Sartore, Daniela; Cavarzeran, Fabiano; Di Pietra, Laura; Barzon, Luisa; Palù, Giorgio; Ferrara, Santo D
The aim of this study was to analyze the connection between alcohol dependence and criminal behavior by an integrated genetic-environmental approach. The research, structured as a case-control study, examined 186 alcohol-dependent males; group 1 (N = 47 convicted subjects) was compared with group 2 (N = 139 no previous criminal records). Genetic results were innovative, highlighting differences in genotype distribution (p = 0.0067) in group 1 for single-nucleotide polymorphism rs 3780428, located in the intronic region of subunit 2 of the GABA B receptor gene (GABBR2). Some environmental factors (e.g., grade repetition) were associated with criminal behavior; others (e.g., attendance at Alcoholics Anonymous) were inversely related to convictions. The concomitant presence of the genetic and environmental factors found to be associated with the condition of alcohol-dependent inmate showed a 4-fold increase in the risk of antisocial behavior. The results need to be replicated on a larger population to develop new preventive and therapeutic proposals. PMID:23822588
Software dependability in the Tandem GUARDIAN system
NASA Technical Reports Server (NTRS)
Lee, Inhwan; Iyer, Ravishankar K.
Based on extensive field failure data for Tandem's GUARDIAN operating system this paper discusses evaluation of the dependability of operational software. Software faults considered are major defects that result in processor failures and invoke backup processes to take over. The paper categorizes the underlying causes of software failures and evaluates the effectiveness of the process pair technique in tolerating software faults. A model to describe the impact of software faults on the reliability of an overall system is proposed. The model is used to evaluate the significance of key factors that determine software dependability and to identify areas for improvement. An analysis of the data shows that about 77% of processor failures that are initially considered due to software are confirmed as software problems. The analysis shows that the use of process pairs to provide checkpointing and restart (originally intended for tolerating hardware faults) allows the system to tolerate about 75% of reported software faults that result in processor failures. The loose coupling between processors, which results in the backup execution (the processor state and the sequence of events) being different from the original execution, is a major reason for the measured software fault tolerance. Over two-thirds (72%) of measured software failures are recurrences of previously reported faults. Modeling, based on the data, shows that, in addition to reducing the number of software faults, software dependability can be enhanced by reducing the recurrence rate.
Time-dependent diffusion in stellar atmospheres
NASA Astrophysics Data System (ADS)
Alecian, G.; Stift, M. J.; Dorfi, E. A.
The chemical peculiarities of Ap stars are due to abundance stratifications produced by atomic diffusion in their outer layers. Theoretical models can predict such stratifications, but so far only provide equilibrium solutions which correspond to the maximum depth-dependent abundances for each element that can be supported by the radiation field. However, these stratifications are actually built up through a non-linear, time-dependent process which has never been modelled for realistic stellar atmospheres. Here, we present the first numerical simulations of time-dependent diffusion. We solve the continuity equation after having computed, as accurately as possible, atomic diffusion velocities (with and without a magnetic field) for a simplified fictitious - but still realistic - chemical element: cloudium. The direct comparison with existing observations is not the immediate aim of this work but rather a general understanding of how the stratification build-up proceeds in time and space. Our results raise serious questions as to the relevance of equilibrium solutions and reinforce the suspicion that certain accumulations of chemical elements might prove unstable.
Time-dependent projected Hartree-Fock
Tsuchimochi, Takashi; Van Voorhis, Troy
Projected Hartree-Fock (PHF) has recently emerged as an alternative approach to describing degenerate systems where static correlation is abundant, when the spin-symmetry is projected. Here, we derive a set of linearized time-dependent equations for PHF in order to be able to access excited states. The close connection of such linear-response time-dependent PHF (TDPHF) to the stability condition of a PHF wave function is discussed. Expanding this analysis also makes it possible to give analytical expressions for the projected coupling terms of Hamiltonian and overlaps between excited Slater determinants. TDPHF with spin-projection (TDSUHF) and its Tamm-Dancoff approximation are benchmarked for several electronically degenerate molecules including the dissociating H{sub 2}, F{sub 2} and O{sub 3} at equilibrium, and the distorted ethylene. It is shown that they give consistently better descriptions of excited states than does time-dependent HF (TDHF). Furthermore, we demonstrate that they offer not only singly but also doubly excited states, which naturally arise upon spin-projection. We also address the thermodynamic limit of TDSUHF, using non-interacting He gas. While TDPHF singly excited states tend to converge to those of HF with the size of the system due to the lack of size-extensivity of PHF, doubly excited states remain reasonable even at the thermodynamic limit. We find that the overall performance of our method is systematically better than the regular TDHF in many cases at the same computational scaling.
Coherent aspect-dependent SAR image formation
NASA Astrophysics Data System (ADS)
Chaney, Ronald D.; Willsky, Alan S.; Novak, Leslie M.
An adaptive image formation algorithm is proposed to exploit the aspect-angle dependence of man-made scatterers in foliage penetrating (FOPEN) synthetic aperture radar (SAR). Man-made scatterers often exhibit a strong dependence on the aspect angle between the orientation of the scatterer and the line of sight of the radar. More specifically, the return from a man-made target is greater when the target is oriented broadside with respect to the radar. Conventional SAR image formation processing assumes that backscatter is independent of the aspect angle; by relaxing this assumption, it is possible to reformulate the image formation process to improve the separability of man-made scatterers vs. natural clutter. We propose an image formation process that adapts the length and position of the aperture used during the cross-range compression stage. The algorithm identifies the locations that are likely to correspond to aspect- dependent scatterers. In the vicinity of such scatterers, the algorithm chooses the aperture to match the expected return from a man-made scatterer. Elsewhere, the algorithm uses the full aperture. The resulting imagery enhances man-made targets relative to the background clutter and facilitates improved detection performance.
Reward-dependent modulation of movement variability.
Pekny, Sarah E; Izawa, Jun; Shadmehr, Reza
Movement variability is often considered an unwanted byproduct of a noisy nervous system. However, variability can signal a form of implicit exploration, indicating that the nervous system is intentionally varying the motor commands in search of actions that yield the greatest success. Here, we investigated the role of the human basal ganglia in controlling reward-dependent motor variability as measured by trial-to-trial changes in performance during a reaching task. We designed an experiment in which the only performance feedback was success or failure and quantified how reach variability was modulated as a function of the probability of reward. In healthy controls, reach variability increased as the probability of reward decreased. Control of variability depended on the history of past rewards, with the largest trial-to-trial changes occurring immediately after an unrewarded trial. In contrast, in participants with Parkinson's disease, a known example of basal ganglia dysfunction, reward was a poor modulator of variability; that is, the patients showed an impaired ability to increase variability in response to decreases in the probability of reward. This was despite the fact that, after rewarded trials, reach variability in the patients was comparable to healthy controls. In summary, we found that movement variability is partially a form of exploration driven by the recent history of rewards. When the function of the human basal ganglia is compromised, the reward-dependent control of movement variability is impaired, particularly affecting the ability to increase variability after unsuccessful outcomes. PMID:25740529
Communication imperialism and dependency: a conceptual clarification.
Lee, P S
Communications imperialism has to do with the domination of a country's media activities by another. The ownership, structure, distribution or content of the media in 1 country are affected by pressures from media interests of another country or group out of proportion with those of that country. To determine if this is happening we should consider the country's policies, the private sector;s efforts to export communications elements, and actions of the dominant country against the dominated. The 4 aspects of international media in this situation are television program exportation, foreign ownership and control of media distribution, the infringement of capital opinions on other societies, and the transfer of commercialism and broadcasting norms. In addition to the software and hardware and the other forms of communication such as satellites, computers, and transportation of the mass media, there are the cultural effects on the developing countries. In the case of involuntary of voluntary dependency of the recipient country, the effect of the unbalanced international communication can be harmful or beneficial. Communication dependency may not be harmful to the culture of the recipient country. In determining the theory of unbalanced international communications 3 factors should be considered. There are: the role of the interacting countries, the nature of the dependency of the recipient country, and the beneficial or harmful effect of unbalanced communication pattern on that country. PMID:12283101
Scaling temperature dependent rheology of magnetorheological fluids
NASA Astrophysics Data System (ADS)
Sherman, Stephen G.; Powell, Louise A.; Becnel, Andrew C.; Wereley, Norman M.
Magnetorheological (MR) fluids are suspensions of micron-scale magnetizable particles suspended in a carrier fluid. When field is applied, MR fluids develop a field controllable yield stress and a field independent post-yield viscosity. However, this viscosity has substantial temperature dependence, varying by up to an order of magnitude over the operating temperature range of MR fluid devices. We apply non-Brownian suspension theory to explain this result and find that the majority of this effect should be caused by the temperature dependent behavior of the carrier fluid. Thus, if two fluids share the same carrier fluid, then their fluid properties should scale in temperature similarly. This result is first validated by measuring viscosity across temperature for custom model fluids designed to conform to theory, showing temperature scaling within 5% for both the MR fluids and their carrier fluid. Then, on a series of related commercially available fluids with unknown additive content, we show that the MR fluids exhibit common scaling to within 4%. We also investigate the effects of magnetic hysteresis and find that it induces a negligible increase in yield stress and no measurable change in viscosity. We conclude that our non-dimensional analysis enables the temperature dependence of novel MR fluids to be characterized with fewer experiments.
Time Dependent Behavior in the Weissenberg Effect
NASA Astrophysics Data System (ADS)
Degen, Michael M.; Andereck, C. David
The Weissenberg effect is the climb of a non-Newtonian fluid up a rotating rod. We have found novel transitional effects in the behavior of a particular climbing fluid, STP(STP Oil Treatment distributed by First Brands Corporation.). The first state is a time-independent axisymmetric concave climb. As the rotation rate of the rod is increased, the first transition is to an axisymmetric climb with an ``onion dome'' shape. At higher rotation rates, the flow undergoes a symmetry breaking bifurcation to a time-dependent state. This time-dependent state exhibits an oscillation with a single frequency. Upon further increase of the rod rotation rate, the oscillation becomes modulated by a second frequency. The nature of each transition will be characterized, including the measurement of oscillation amplitudes and the frequency (or frequencies) of the time dependent states. These results will be compared with previous work.(G.S. Beavers, D.D. Joseph, J. Fluid Mech. 69), 475 (1975).(D.D. Joseph, R.L. Fosdick, Arch. Rational Mech. 49), 321 (1973).
Rate-dependent spallation properties of tantalum
Johnson, J.N.; Hixson, R.S.; Tonks, D.L.; Zurek, A.K.
Spallation experiments are conducted on high-purity tantalum using VISAR instrumentation for impact stresses of 9.5 GPa and 6.0 GPa. The high-amplitude experiment exhibits very rapid initial spall separation, while the low-amplitude shot is only slightly above the threshold for void growth and thus exhibits distinct rate-dependent spallation behavior. These experiments are analyzed in terms of simple tensile fracture criteria, a standard rate-dependent void-growth model, and a rate-dependent void growth model in which the expected plastic volume strain makes no contribution to the relaxation of the mean stress. Recovery tests and VISAR measurements suggest an additional resistance to spallation that follows the rapid coalescence of voids; this effect is termed the secondary spall resistance and is due to the convoluted nature of the spall plane and the resulting interlocking fracture pattern that is developed and for which the stress remains unrelieved until the spall planes have separated several hundred microns.
The biodiversity-dependent ecosystem service debt.
Isbell, Forest; Tilman, David; Polasky, Stephen; Loreau, Michel
Habitat destruction is driving biodiversity loss in remaining ecosystems, and ecosystem functioning and services often directly depend on biodiversity. Thus, biodiversity loss is likely creating an ecosystem service debt: a gradual loss of biodiversity-dependent benefits that people obtain from remaining fragments of natural ecosystems. Here, we develop an approach for quantifying ecosystem service debts, and illustrate its use to estimate how one anthropogenic driver, habitat destruction, could indirectly diminish one ecosystem service, carbon storage, by creating an extinction debt. We estimate that c. 2-21 Pg C could be gradually emitted globally in remaining ecosystem fragments because of plant species loss caused by nearby habitat destruction. The wide range for this estimate reflects substantial uncertainties in how many plant species will be lost, how much species loss will impact ecosystem functioning and whether plant species loss will decrease soil carbon. Our exploratory analysis suggests that biodiversity-dependent ecosystem service debts can be globally substantial, even when locally small, if they occur diffusely across vast areas of remaining ecosystems. There is substantial value in conserving not only the quantity (area), but also the quality (biodiversity) of natural ecosystems for the sustainable provision of ecosystem services. PMID:25430966
Fusing Censored Dependent Data for Distributed Detection
NASA Astrophysics Data System (ADS)
He, Hao; Varshney, Pramod K.
In this paper, we consider a distributed detection problem for a censoring sensor network where each sensor's communication rate is significantly reduced by transmitting only "informative" observations to the Fusion Center (FC), and censoring those deemed "uninformative". While the independence of data from censoring sensors is often assumed in previous research, we explore spatial dependence among observations. Our focus is on designing the fusion rule under the Neyman-Pearson (NP) framework that takes into account the spatial dependence among observations. Two transmission scenarios are considered, one where uncensored observations are transmitted directly to the FC and second where they are first quantized and then transmitted to further improve transmission efficiency. Copula-based Generalized Likelihood Ratio Test (GLRT) for censored data is proposed with both continuous and discrete messages received at the FC corresponding to different transmission strategies. We address the computational issues of the copula-based GLRTs involving multidimensional integrals by presenting more efficient fusion rules, based on the key idea of injecting controlled noise at the FC before fusion. Although, the signal-to-noise ratio (SNR) is reduced by introducing controlled noise at the receiver, simulation results demonstrate that the resulting noise-aided fusion approach based on adding artificial noise performs very closely to the exact copula-based GLRTs. Copula-based GLRTs and their noise-aided counterparts by exploiting the spatial dependence greatly improve detection performance compared with the fusion rule under independence assumption.
Socio-Emotional Factors in Alcohol Dependence
Tikka, Deyashini Lahiri; Ram, Daya; Dubey, Indu; Tikka, Sai Krishna
Background: Alcohol-dependent patients are traditionally believed to have insecure attachment styles, higher anger expression, and lower self-esteem. There is a need to study them together. Aim: To understand the relationships amongst various of the socio-emotional factors. Materials and Methods: Forty male patients with Alcohol dependence syndrome and 40 matched healthy controls (General Health Questionnaire-12 score <3) were compared on attachment styles (on Relationship Scale Questionnaire), anger domains (on State Trait Anger Expression Inventory), and self-esteem (on Rosenberg Self-esteem Scale). Statistics and Analysis: Comparison using independent samples t test and chi square test; correlation using Pearson's correlation coefficient. Results: Patients had significantly higher anger expression, 'anger in' and 'anger out,' and lower self-esteem than healthy controls. Severity of alcohol dependence had significant correlation with 'anger out,' and self-esteem had significant negative correlation with anger expression. Conclusion: The present study suggests that the socio-emotional factors studied are developmentally linked to each other. PMID:24860216
Phase dependencies of the human baroreceptor reflex
NASA Technical Reports Server (NTRS)
Seidel, H.; Herzel, H.; Eckberg, D. L.
We studied the influence of respiratory and cardiac phase on responses of the cardiac pacemaker to brief (0.35-s) increases of carotid baroreceptor afferent traffic provoked by neck suction in seven healthy young adult subjects. Cardiac responses to neck suction were measured indirectly from electrocardiographic changes of heart period. Our results show that it is possible to separate the influences of respiratory and cardiac phases at the onset of a neck suction impulse by a product of two factors: one depending only on the respiratory phase and one depending only on the cardiac phase. This result is consistent with the hypothesis that efferent vagal activity is a function of afferent baroreceptor activity, whereas respiratory neurons modulate that medullary throughput independent of the cardiac phase. Furthermore, we have shown that stimulus broadening and stimulus cropping influence the outcome of neck suction experiments in a way that makes it virtually impossible to obtain information on the phase dependency of the cardiac pacemaker's sensitivity to vagal stimulation without accurate knowledge of the functional shape of stimulus broadening.
Time-dependent projected Hartree-Fock
NASA Astrophysics Data System (ADS)
Tsuchimochi, Takashi; Van Voorhis, Troy
Projected Hartree-Fock (PHF) has recently emerged as an alternative approach to describing degenerate systems where static correlation is abundant, when the spin-symmetry is projected. Here, we derive a set of linearized time-dependent equations for PHF in order to be able to access excited states. The close connection of such linear-response time-dependent PHF (TDPHF) to the stability condition of a PHF wave function is discussed. Expanding this analysis also makes it possible to give analytical expressions for the projected coupling terms of Hamiltonian and overlaps between excited Slater determinants. TDPHF with spin-projection (TDSUHF) and its Tamm-Dancoff approximation are benchmarked for several electronically degenerate molecules including the dissociating H2, F2 and O3 at equilibrium, and the distorted ethylene. It is shown that they give consistently better descriptions of excited states than does time-dependent HF (TDHF). Furthermore, we demonstrate that they offer not only singly but also doubly excited states, which naturally arise upon spin-projection. We also address the thermodynamic limit of TDSUHF, using non-interacting He gas. While TDPHF singly excited states tend to converge to those of HF with the size of the system due to the lack of size-extensivity of PHF, doubly excited states remain reasonable even at the thermodynamic limit. We find that the overall performance of our method is systematically better than the regular TDHF in many cases at the same computational scaling.
Energy dependence corrections to MOSFET dosimetric sensitivity.
Cheung, T; Butson, M J; Yu, P K N
Metal Oxide Semiconductor Field Effect Transistors (MOSFET's) are dosimeters which are now frequently utilized in radiotherapy treatment applications. An improved MOSFET, clinical semiconductor dosimetry system (CSDS) which utilizes improved packaging for the MOSFET device has been studied for energy dependence of sensitivity to x-ray radiation measurement. Energy dependence from 50 kVp to 10 MV x-rays has been studied and found to vary by up to a factor of 3.2 with 75 kVp producing the highest sensitivity response. The detectors average life span in high sensitivity mode is energy related and ranges from approximately 100 Gy for 75 kVp x-rays to approximately 300 Gy at 6 MV x-ray energy. The MOSFET detector has also been studied for sensitivity variations with integrated dose history. It was found to become less sensitive to radiation with age and the magnitude of this effect is dependant on radiation energy with lower energies producing a larger sensitivity reduction with integrated dose. The reduction in sensitivity is however approximated reproducibly by a slightly non linear, second order polynomial function allowing corrections to be made to readings to account for this effect to provide more accurate dose assessments both in phantom and in-vivo. PMID:19400548
DEPEND: A simulation-based environment for system level dependability analysis
NASA Technical Reports Server (NTRS)
Goswami, Kumar; Iyer, Ravishankar K.
The design and evaluation of highly reliable computer systems is a complex issue. Designers mostly develop such systems based on prior knowledge and experience and occasionally from analytical evaluations of simplified designs. A simulation-based environment called DEPEND which is especially geared for the design and evaluation of fault-tolerant architectures is presented. DEPEND is unique in that it exploits the properties of object-oriented programming to provide a flexible framework with which a user can rapidly model and evaluate various fault-tolerant systems. The key features of the DEPEND environment are described, and its capabilities are illustrated with a detailed analysis of a real design. In particular, DEPEND is used to simulate the Unix based Tandem Integrity fault-tolerance and evaluate how well it handles near-coincident errors caused by correlated and latent faults. Issues such as memory scrubbing, re-integration policies, and workload dependent repair times which affect how the system handles near-coincident errors are also evaluated. Issues such as the method used by DEPEND to simulate error latency and the time acceleration technique that provides enormous simulation speed up are also discussed. Unlike any other simulation-based dependability studies, the use of these approaches and the accuracy of the simulation model are validated by comparing the results of the simulations, with measurements obtained from fault injection experiments conducted on a production Tandem Integrity machine.
Heart Rate Dependency of Large Artery Stiffness.
Tan, Isabella; Spronck, Bart; Kiat, Hosen; Barin, Edward; Reesink, Koen D; Delhaas, Tammo; Avolio, Alberto P; Butlin, Mark
Carotid-femoral pulse wave velocity (cfPWV) quantifies large artery stiffness, it is used in hemodynamic research and is considered a useful cardiovascular clinical marker. cfPWV is blood pressure (BP) dependent. Intrinsic heart rate (HR) dependency of cfPWV is unknown because increasing HR is commonly accompanied by increasing BP. This study aims to quantify cfPWV dependency on acute, sympathovagal-independent changes in HR, independent of BP. Individuals (n=52, age 40-93 years, 11 female) with in situ cardiac pacemakers or cardioverter defibrillators were paced at 60, 70, 80, 90, and 100 bpm. BP and cfPWV were measured at each HR. Both cfPWV (mean [95% CI], 0.31 [0.26-0.37] m/s per 10 bpm; P<0.001) and central aortic diastolic pressure (3.78 [3.40-4.17] mm Hg/10 bpm; P<0.001) increased with HR. The HR effect on cfPWV was isolated by correcting the BP effects by 3 different methods: (1) statistically, by a linear mixed model; (2) mathematically, using an exponential relationship between BP and cross-sectional lumen area; and (3) using measured BP dependency of cfPWV derived from changes in BP induced by orthostatic changes (seated and supine) in a subset of subjects (n=17). The BP-independent effects of HR on cfPWV were quantified as 0.20 [0.11-0.28] m/s per 10 bpm (P<0.001, method 1), 0.16 [0.11-0.22] m/s per 10 bpm (P<0.001, method 2), and 0.16 [0.11-0.21] m/s per 10 bpm (P<0.001, method 3). With a mean HR dependency in the range of 0.16 to 0.20 m/s per 10 bpm, cfPWV may be considered to have minimal physiologically relevant changes for small changes in HR, but larger differences in HR must be considered as contributing to significant differences in cfPWV. PMID:27245180
Genetics Home Reference: vitamin D-dependent rickets
Cardiac Fas-dependent and mitochondria-dependent apoptosis after chronic cocaine abuse.
Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Ting, Hua; Lee, Shin-Da
To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day) and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day). After 3 months of treatment, the excised left ventricles were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse. PMID:24722570
Time-dependent Dyson orbital theory.
Gritsenko, O V; Baerends, E J
Although time-dependent density functional theory (TDDFT) has become the tool of choice for real-time propagation of the electron density ρ(N)(t) of N-electron systems, it also encounters problems in this application. The first problem is the neglect of memory effects stemming from the, in TDDFT virtually unavoidable, adiabatic approximation, the second problem is the reliable evaluation of the probabilities P(n)(t) of multiple photoinduced ionization, while the third problem (which TDDFT shares with other approaches) is the reliable description of continuum states of the electrons ejected in the process of ionization. In this paper time-dependent Dyson orbital theory (TDDOT) is proposed. Exact TDDOT equations of motion (EOMs) for time-dependent Dyson orbitals are derived, which are linear differential equations with just static, feasible potentials of the electron-electron interaction. No adiabatic approximation is used, which formally resolves the first TDDFT problem. TDDOT offers formally exact expressions for the complete evolution in time of the wavefunction of the outgoing electron. This leads to the correlated probability of single ionization P(1)(t) as well as the probabilities of no ionization (P(0)(t)) and multiple ionization of n electrons, P(n)(t), which formally solves the second problem of TDDFT. For two-electron systems a proper description of the required continuum states appears to be rather straightforward, and both P(1)(t) and P(2)(t) can be calculated. Because of the exact formulation, TDDOT is expected to reproduce a notorious memory effect, the "knee structure" of the non-sequential double ionization of the He atom. PMID:26987972
Ionic dependence of sulphur mustard cytotoxicity
Sawyer, Thomas W. Nelson, Peggy; Bjarnason, Stephen; Vair, Cory; Shei Yimin; Tenn, Catherine; Lecavalier, Pierre; Burczyk, Andrew
The effect of ionic environment on sulphur mustard (bis 2-chloroethyl sulphide; HD) toxicity was examined in CHO-K1 cells. Cultures were treated with HD in different ionic environments at constant osmolar conditions (320 mOsM, pH 7.4). The cultures were refed with fresh culture medium 1 h after HD exposure, and viability was assessed. Little toxicity was apparent when HD exposures were carried out in ion-free sucrose buffer compared to LC{sub 50} values of {approx} 100-150 {mu}M when the cultures were treated with HD in culture medium. Addition of NaCl to the buffer increased HD toxicity in a salt concentration-dependent manner to values similar to those obtained in culture medium. HD toxicity was dependent on both cationic and anionic species with anionic environment playing a much larger role in determining toxicity. Substitution of NaI for NaCl in the treatment buffers increased HD toxicity by over 1000%. The activity of the sodium hydrogen exchanger (NHE) in recovering from cytosolic acidification in salt-free and in different chloride salts did not correlate with the HD-induced toxicity in these buffers. However, the inhibition by HD of intracellular pH regulation correlated with its toxicity in NaCl, NaI and sucrose buffers. Analytical chemical studies and the toxicity of the iodine mustard derivative ruled out the role of chemical reactions yielding differentially toxic species as being responsible for the differences in HD toxicity observed. This work demonstrates that the early events that HD sets into motion to cause toxicity are dependent on ionic environment, possibly due to intracellular pH deregulation.
Temperature dependent spin structures in Hexaferrite crystal
NASA Astrophysics Data System (ADS)
Chao, Y. C.; Lin, J. G.; Chun, S. H.; Kim, K. H.
In this work, the Hexaferrite Ba0.5Sr1.5Zn2Fe12O22 (BSZFO) is studied due to its interesting characteristics of long-wavelength spin structure. Ferromagnetic resonance (FMR) is used to probe the magnetic states of BSZFO single crystal and its temperature dependence behavior is analyzed by decomposing the multiple lines of FMR spectra into various phases. Distinguished phase transition is observed at 110 K for one line, which is assigned to the ferro(ferri)-magnetic transition from non-collinear to collinear spin state.
Dependable control systems with Internet of Things.
Tran, Tri; Ha, Q P
This paper presents an Internet of Things (IoT)-enabled dependable control system (DepCS) for continuous processes. In a DepCS, an actuator and a transmitter form a regulatory control loop. Each processor inside such actuator and transmitter is designed as a computational platform implementing the feedback control algorithm. The connections between actuators and transmitters via IoT create a reliable backbone for a DepCS. The centralized input-output marshaling system is not required in DepCSs. A state feedback control synthesis method for DepCS applying the self-recovery constraint is presented in the second part of the paper. PMID:26329254
Outboard Motor Maximizes Power and Dependability
NASA Technical Reports Server (NTRS)
Developed by Jonathan Lee, a structural materials engineer at Marshall Space Flight Center, and PoShou Chen, a scientist with Huntsville, Alabama-based Morgan Research Corporation, MSFC-398 is a high-strength aluminum alloy able to operate at high temperatures. MSFC-398 was licensed for marine applications by Bombardier Recreational Products Inc., and is now found in the complete line of Evinrude E-TEC outboard motors, a line of two-stroke motors that maintain the power and dependability of a two-stroke with the refinement of a four-stroke.
Energy dependence of diffractive production at HERA
NASA Astrophysics Data System (ADS)
Gotsman, E.; Levin, E.; Lublinsky, M.; Maor, U.; Tuchin, K.
Intrigued by the unexpected recent results from HERA, that the ratio σdiff/ σtot is only weakly dependent on energy, we have attempted to reproduce this result within the framework of perturbative QCD. To this end we generalize the Kovchegov-McLerran formula for the ratio using Glauber-Mueller approach for shadowing corrections and AGK cutting rules. We investigate several phenomenological approaches and also compare with the successful Golec-Biernat-Wüsthoff model. We have not managed to reproduce the data, and conclude that, apparently, there are soft nonperturbative contributions present at short distances which should be included.
Spatial Heterogeneity Induces Scale Dependent Rock Friction
NASA Astrophysics Data System (ADS)
Yamashita, F.; Fukuyama, E.; Xu, S.; Takizawa, S.; Mizoguchi, K.; Kawakata, H.; Passelègue, F. X.; Schubnel, A.
We carried out large-scale biaxial friction experiments (Fukuyama et al., 2012; 2014) using a pair of meter-sized Indian gabbro as specimens, whose contacting area was 1.5 × 0.1 m2, normal stress was up to 6.7 MPa and loading velocity was up to 3 × 10-2 m/s. After each experiment, we found localized damages (i.e. grooves) were generated on the fault surface and gouges were distributed around them. We confirmed work rate dependency of rock friction as revealed by centimeter-sized rock samples (Di Toro et al., 2011), but further found that the meter-sized rock friction starts to decrease at one order of magnitude smaller work rate than that of the centimeter sized rock (Yamashita et al., 2013, AGU fall meeting). Here, we concluded that this difference is caused by stress localization and associated increase in heterogeneity on the fault as shown by: 1) Total amount of deviations of each local shear stress from the average, which were monitored by strain gauge array, increased with the decrease in friction. 2) Friction coefficients were negatively correlated with degree of spatial heterogeneity evaluated from the distribution of grooves and gouges. 3) Melt textures were found in the collected gouges by microscopic observation using HRSEM. Based on these observations, we propose a stress localization model; the fault surfaces are composed of patched and non-patched areas with high and low normal stress, respectively. The high normal stress patch leads to high shear stress, high mechanical work and thus production of much wear material (gouge), which further causes additional increase in normal stress. Assuming that the local friction follows the results by centimeter-sized gabbro experiments, we numerically simulated a slip-dependent friction for both patched and non-patched areas, and successively reproduced a weakening in macroscopic friction. We confirmed that the work rate dependency of simulated friction was consistent with that of biaxial experiments (Fig. 1
Rickets–vitamin D deficiency and dependency
Sahay, Manisha; Sahay, Rakesh
Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal. PMID:22470851
Spectrally dependent fluctuations of thermal photon sources
NASA Astrophysics Data System (ADS)
Olson, K.; Talghader, J.
Many current quantum optical systems, such as microcavities, interact with thermal light through a small number of widely separated modes. Previous theories for photon number fluctuations of thermal light have been primarily limited to special cases that are appropriate for large volumes or distances, such as single modes, many modes, or modes of uniform spectral distribution. Herein, a theory for the general case of spectrally dependent photon number fluctuations is developed for thermal light. The error in variance of prior art is quantitatively derived for an example cavity in the case where photon counting noise dominates. A method to reduce the spectral impact of this variance is described.
Environmental dependence of masses and coupling constants
Olive, Keith A.; Pospelov, Maxim
We construct a class of scalar field models coupled to matter that lead to the dependence of masses and coupling constants on the ambient matter density. Such models predict a deviation of couplings measured on the Earth from values determined in low-density astrophysical environments, but do not necessarily require the evolution of coupling constants with the redshift in the recent cosmological past. Additional laboratory and astrophysical tests of {delta}{alpha} and {delta}(m{sub p}/m{sub e}) as functions of the ambient matter density are warranted.
Parrondo Games with Spatial Dependence, III
NASA Astrophysics Data System (ADS)
Ethier, S. N.; Lee, Jiyeon
We study Toral's Parrondo games with N players and one-dimensional spatial dependence as modified by Xie et al. Specifically, we use computer graphics to sketch the Parrondo and anti-Parrondo regions for 3 ≤ N ≤ 9. Our work was motivated by a recent paper of Li et al., who applied a state space reduction method to this model, reducing the number of states from 2N to N + 1. We show that their reduced Markov chains are inconsistent with the model of Xie et al.
Temperature dependence of sapphire fiber Raman scattering
Liu, Bo; Yu, Zhihao; Tian, Zhipeng; Homa, Daniel; Hill, Cary; Wang, Anbo; Pickrell, Gary
Anti-Stokes Raman scattering in sapphire fiber has been observed for the first time. Temperature dependence of Raman peaks' intensity, frequency shift, and linewidth were also measured. Three anti-Stokes Raman peaks were observed at temperatures higher than 300°C in a 0.72-m-long sapphire fiber excited by a second-harmonic Nd YAG laser. The intensity of anti-Stokes peaks are comparable to that of Stokes peaks when the temperature increases to 1033°C. We foresee the combination of sapphire fiber Stokes and anti-Stokes measurement in use as a mechanism for ultrahigh temperature sensing.
Escherichia coli survival in waters: temperature dependence.
Blaustein, R A; Pachepsky, Y; Hill, R L; Shelton, D R; Whelan, G
Knowing the survival rates of water-borne Escherichia coli is important in evaluating microbial contamination and making appropriate management decisions. E. coli survival rates are dependent on temperature, a dependency that is routinely expressed using an analogue of the Q₁₀ model. This suggestion was made 34 years ago based on 20 survival curves taken from published literature, but has not been revisited since then. The objective of this study was to re-evaluate the accuracy of the Q₁₀ equation, utilizing data accumulated since 1978. We assembled a database of 450 E. coli survival datasets from 70 peer-reviewed papers. We then focused on the 170 curves taken from experiments that were performed in the laboratory under dark conditions to exclude the effects of sunlight and other field factors that could cause additional variability in results. All datasets were tabulated dependencies "log concentration vs. time." There were three major patterns of inactivation: about half of the datasets had a section of fast log-linear inactivation followed by a section of slow log-linear inactivation; about a quarter of the datasets had a lag period followed by log-linear inactivation; and the remaining quarter were approximately linear throughout. First-order inactivation rate constants were calculated from the linear sections of all survival curves and the data grouped by water sources, including waters of agricultural origin, pristine water sources, groundwater and wells, lakes and reservoirs, rivers and streams, estuaries and seawater, and wastewater. Dependency of E. coli inactivation rates on temperature varied among the water sources. There was a significant difference in inactivation rate values at the reference temperature between rivers and agricultural waters, wastewaters and agricultural waters, rivers and lakes, and wastewater and lakes. At specific sites, the Q₁₀ equation was more accurate in rivers and coastal waters than in lakes making the value of
[The Amygdala in mechanisms of alcohol dependence].
Akhmadeev, A V; Kalimullina, L B
In the present review for the first time systematized literature data about reactive changes, of neurons in the basolateral and medial nuclei of the Amygdala which occur in response to acute and chronic exposure of ethanol. Summarized information about the mechanisms of disturbances in glutamatergic-and GABAergic systems of the basolateral nucleus that determining an increased level of anxiety, which is seen as a main motivating factor of desire for alcohol, thus involved to the manifestation of alcohol dependence. Reviewed molecular and genetic aspects of rsearchs involvement of medial nucleus in the mechanisms of alcoholism. PMID:27530042
Refining and defining the Program Dependence Web
Campbell, P.L. ); Krishna, K.; Ballance, R.A. . Dept. of Computer Science)
The Program Dependence Web (PDW) is an intermediate representation for a computer program, which can be interpreted under control-driven, data-driven or demand-driven disciplines. This document completes the definition for the PDW. This includes operational definitions for the nodes and arcs and a description of how PDWs are interpreted. The general structure for conditionals and loops is shown, accompanied by examples. The definition provided here is a refinement of the original one: a new node, the [beta] node,'' replaces the [mu] node, and the [eta][sup [Tau
Refining and defining the Program Dependence Web
Campbell, P.L.; Krishna, K.; Ballance, R.A.
The Program Dependence Web (PDW) is an intermediate representation for a computer program, which can be interpreted under control-driven, data-driven or demand-driven disciplines. This document completes the definition for the PDW. This includes operational definitions for the nodes and arcs and a description of how PDWs are interpreted. The general structure for conditionals and loops is shown, accompanied by examples. The definition provided here is a refinement of the original one: a new node, the ``{beta} node,`` replaces the {mu} node, and the {eta}{sup {Tau}} node is eliminated.
HIV infection in females dependent on drugs.
Wai, B H; Singh, S; Varma, S L
One hundred and seventy-one drug-dependent females in a drug rehabilitation centre were studied to estimate the prevalence of HIV infection among them. Twenty-four (14%) were positive on the Western Blot test. The presence of HIV infection was significantly correlated with syphilis (p < 0.03) and age (p < 0.001); 83% of those who were HIV positive were intravenous drug users. The need for harm reduction programmes to prevent spread of HIV infection among injecting drug users is stressed. PMID:8867206
Psychoactive Substance Dependence: A Dentist's Challenge.
Millar, Lynsey
Given the number of individuals who are dependent on alcohol and/or drugs, it is inevitable that they will present for dental treatment. They are at an increased risk of dental disease for multiple reasons. This paper aims to provide an overview for general dental practitioners (GDPs) of the challenges that can arise in treating such patients, alongside some suggestions for meeting these challenges. General issues are taken into consideration first, then a focus is made on each of the most common substances, together with their implications in dentistry. PMID:26556258
Temperature dependence of fluid transport in nanopores
NASA Astrophysics Data System (ADS)
Xu, Baoxing; Wang, Binglei; Park, Taehyo; Qiao, Yu; Zhou, Qulan; Chen, Xi
Understanding the temperature-dependent nanofluidic transport behavior is critical for developing thermomechanical nanodevices. By using non-equilibrium molecular dynamics simulations, the thermally responsive transport resistance of liquids in model carbon nanotubes is explored as a function of the nanopore size, the transport rate, and the liquid properties. Both the effective shear stress and the nominal viscosity decrease with the increase of temperature, and the temperature effect is coupled with other non-thermal factors. The molecular-level mechanisms are revealed through the study of the radial density profile and hydrogen bonding of confined liquid molecules. The findings are verified qualitatively with an experiment on nanoporous carbon.
Temperature dependent phonon properties of thermoelectric materials
NASA Astrophysics Data System (ADS)
Hellman, Olle; Broido, David; Fultz, Brent
We present recent developments using the temperature dependent effective potential technique (TDEP) to model thermoelectric materials. We use ab initio molecular dynamics to generate an effective Hamiltonian that reproduce neutron scattering spectra, thermal conductivity, phonon self energies, and heat capacities. Results are presented for (among others) SnSe, Bi2Te3, and Cu2Se proving the necessity of careful modelling of finite temperature properties for strongly anharmonic materials. Supported by the Swedish Research Council (VR) Project Number 637-2013-7296.
Pulsar Electrodynamics: a Time-dependent View
Spitkovsky, Anatoly; /KIPAC, Menlo Park
Pulsar spindown forms a reliable yet enigmatic prototype for the energy loss processes in many astrophysical objects including accretion disks and back holes. In this paper we review the physics of pulsar magnetospheres, concentrating on recent developments in force-free modeling of the magnetospheric structure. In particular, we discuss a new method for solving the equations of time-dependent force-free relativistic MHD in application to pulsars. This method allows to dynamically study the formation of the magnetosphere and its response to perturbations, opening a qualitatively new window on pulsar phenomena. Applications of the method to other magnetized rotators, such as magnetars and accretion disks, are also discussed.
Size-dependent thermopower of nickel nanoparticles
Singh, Jaiveer; Kaurav, N.; Okram, Gunadhor S.
Nickel nanoparticles (Ni-NPs) were prepared by thermal decomposition method using Trioctylphosphine (TOP) and Oleylamine (OA). The average particle size (D) estimated from X-ray diffraction (XRD) using Scherrer equation, to be 1-10nm, systematically decreases with increasing concentration of TOP at constant OA concentration. The observed thermopower strongly depends on particle size particularly at low temperatures reaching a very high value of ∼ 10{sup 5} μV/K (at 20 K), and is attributed to the enhanced grain-boundary scattering combined with quantum confinement.
Isotopic Dependence of the Nuclear Caloric Curve
Sfienti, C.; Adrich, P.; Aumann, T.; Bianchin, S.; Emling, H.; Hellstroem, M.; Henzlova, D.; Johansson, H.; Kezzar, K.; Le Fevre, A.; Leifels, Y.; Luehning, J.; Lynen, U.; Mueller, W. F. J.; Orth, H.; Otte, A. N.; Palit, R.; Sann, H.; Schwarz, C.; Simon, H.
The A/Z dependence of projectile fragmentation at relativistic energies has been studied with the ALADIN forward spectrometer at SIS. A stable beam of {sup 124}Sn and radioactive beams of {sup 124}La and {sup 107}Sn at 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z of the produced spectator sources, consistent with predictions for expanded systems. Small Coulomb effects ({delta}T{approx_equal}0.6 MeV) appear for residue production near the onset of multifragmentation.
Mercury - Wavelength and longitude dependence of polarization
NASA Technical Reports Server (NTRS)
Gehrels, T.; Landau, R.; Coyne, G. V.
The polarization-time variations noted in the present linear polarization observations of the integrated Mercury disk, with filters covering the 0.3-1.0 micron bandpass and between 53-130 deg of phase angle, may be accounted for in terms of longitude dependence through the variation of brightness or other properties over the surface. Kepler's equation for the eccentric anomaly was solved for each observation, and the true anomaly was used to find the subsolar longitude. The difference found in the polarization-albedo relations of Mercury and the moon indicates a difference in surface texture and/or composition.
Calcium-dependent regulation of photosynthesis.
Hochmal, Ana Karina; Schulze, Stefan; Trompelt, Kerstin; Hippler, Michael
The understanding of calcium as a second messenger in plants has been growing intensively over the last decades. Recently, attention has been drawn to the organelles, especially the chloroplast but focused on the stromal Ca2+ transients in response to environmental stresses. Herein we will expand this view and discuss the role of Ca2+ in photosynthesis. Moreover we address of how Ca2+ is delivered to chloroplast stroma and thylakoids. Thereby, new light is shed on the regulation of photosynthetic electron flow and light-dependent metabolism by the interplay of Ca2+, thylakoid acidification and redox status. This article is part of a Special Issue entitled: Chloroplast biogenesis. PMID:25687895
Internal Extinction in Spiral Galaxies. Inclination Dependence
NASA Astrophysics Data System (ADS)
Magris, G. C.; Bruzual, G. A.
. Kent (1986) finds that the surface brightness profiles (r) of spiral galaxies have a weak dependence, if any, on the inclination e with respect to the line of sight. This author also finds a correlation between the MIL ratio and the inclination of a galaxy. The lack of dependence of (r) in , = cos 8 indicates that the disk of these galaxies is optically thick ( .>l), due to the presence of dust grains. For an optically thick system o(r) a + 2.5 log . The cosecant law : 1.086 (Holmberg, 1975) does not explain the observed behaviour of a(r) with . 8ru'ual, Magris and Calvet (1986) solved the radiative transfer equation for a mixture of stars and dispersive dust grains distributed homogeneously in a plane parallel configuration, taking into account the wavelenght dependence of the albedo and , as well as the redistribution in angle of photons scattered by dust grains. The transfer equation is solved for the dimensionless intensity ?( , ) I( , )/I*, where 1* is the intensity emerging from the dust free configuration. The solution, CA -2.5 log (r..=0, ) , includes the correction to the galaxy magnitude due to the excess number 0+ stellar sources along the line o+ sigth (cc -i) with respect to the =I case (face on galaxy). For optically thick systems, does not depend on . The luminosity of a disk galaxy observed with inclination ,q 1 given in our model by L cc , from which log(M/L) = const + (.4 8.N( )'. with G.N . ) = -2.5 log( ). The constant is determined from the mass- luminosity. ratio of a dust free system. In terms of the correction (3(N) we can explain Kent's observations with values of between .3 and 4. These values are consistent with the observation of . -independent surface brightness profiles mentioned above. From this analysis we conclude that the correction terms of Bruzual, Magris and Calvet (1986), which take into account the dispersive properties of interstellar dust, can explain the behaviour of ar) and MIL with galaxy inclination. These correction
Hourly rounding in a high dependency unit.
Lowe, Lynsey; Hodgson, Gillian
The Leeds Teaching Hospitals NHS Trust is one of the many organisations that have signed up to Safety Express, a pilot programme of the Department of Health's Quality, Innovation, Productivity and Prevention safe care coalition. Its aim is to reduce avoidable harm to patients in four areas: trips and falls, pressure ulcers, catheter-associated urinary tract infections and venous thromboembolism. Hourly rounding (hourly checks on patients) has been identified as a means of reducing harm to patients. This article describes the preparation needed to introduce hourly rounding in a high dependency unit. PMID:23189600
Angular momentum dependence of complex fragment emission
Sobotka, L.G.; Sarantites, D.G.; Li, Z.; Dines, E.L.; Halbert, M.L.; Hensley, D.C.; Lisle, J.C.; Schmitt, R.P.; Majka, Z.; Nebbia, G.
The angular momentum dependence of large fragment production in long-lived reactions is studied by measurements of fragment cross sections from reactions with substantially different angular momentum distributions and the coincident ..gamma..-ray multiplicity distributions. The results indicate that the primary l-wave distributions move to larger mean values and decrease in width and skewness with increasing mass symmetry in the decay channel. The results also confirm that the partition of angular momentum kinetic energy relaxed heavy-ion reactions is that expected for a rigidly rotating intermediate.
Topologically nontrivial time-dependent chiral condensates
Suzuki, M.
Topologically nontrivial time-dependent solutions of the classical nonlinear {sigma} model are studied as candidates of the disoriented chiral condensate (DCC) in 3+1 dimensions. Unlike the analytic solutions so far discussed, these solutions cannot be transformed into isospin-uniform ones by chiral rotations. If they are produced as DCC{close_quote}s, they can be detected by a distinct pattern in the angle-rapidity distribution of the neutral-to-charged pion ratio. {copyright} {ital 1996 The American Physical Society.}
Gravity-Dependent Transport in Industrial Processes
NASA Technical Reports Server (NTRS)
Ostrach, Simon; Kamotani, Yasuhiro
Gravity dependent transport phenomena in various industrial processes are investigated in order to indicate new directions for micro-gravity research that enhance the commercial success of the space program. The present article describes the commercialization possibilities of such topics associated with physicochemical transport phenomena. The topics are: coating flow, rotating electrochemical system, and convection in low Plandtl number fluids. The present study is directed to understand these phenomena, and to develop a knowledge base for their applications with emphasis to a micro-gravity environment.
Buprenorphine in the treatment of opiate dependence.
Wesson, Donald R; Smith, David E
Compelling clinical evidence establishes that buprenorphine is similar to methadone in efficacy for opiate detoxification and maintenance but safer than methadone in an overdose situation. The Drug Abuse Treatment Act of 2000 (DATA 2000) enabled US physicians with additional training to prescribe buprenorphine to a limited number of opiate-dependent patients. The sublingual tablets Subutex (buprenorphine alone) and Suboxone (a combination of buprenorphine and naloxone) meet the specifications of DATA 2000. Suboxone is intended to discourage intravenously administration and has less abuse potential than buprenorphine alone. Suboxone is generally recommended for maintenance treatment except for women who are pregnant. Subutex is recommended in treatment of pregnant women. A buprenorphine opiate withdrawal syndrome can occur in newborns. Although intravenous buprenorphine abuse is a significant public health problem in some countries, buprenorphine alone or in combination with naloxone has less potential for abuse than heroin and some prescription opiates, such as oxycodone. Pharmacotherapy from physicians' offices makes buprenorphine treatment acceptable to some opiate-dependent patients who would not accept treatment in traditional opiate-maintenance clinics. For reasons not adequately understood, some patients find discontinuation of buprenorphine following long-term use difficult. This article reviews the pharmacology of buprenorphine, summarizes evidence supporting the safety and efficacy of buprenorphine and provides clinical guidelines for treatment. PMID:20648912
A Case Report of Clonazepam Dependence
Kacirova, Ivana; Grundmann, Milan; Silhan, Petr; Brozmanova, Hana
Abstract Clonazepam is long-acting benzodiazepine agonist used in short-acting benzodiazepine withdrawal; however, recent observations suggest the existence of its abuse. We demonstrate a 40-year-old man with a 20-year history of psychiatric care with recently benzodiazepine dependence (daily intake of ∼60 mg of clonazepam and 10 mg of alprazolam). High serum levels of both drugs were analyzed 3 weeks before admission to hospitalization (clonazepam 543.9 ng/mL, alprazolam 110 ng/mL) and at the time of admission (clonazepam 286.2 ng/mL, alprazolam 140 ng/mL) without any signs of benzodiazepine intoxication. Gradual withdrawal of clonazepam with monitoring of its serum levels and increase of gabapentin dose were used to minimize physical signs and symptoms of clonazepam withdrawal. Alprazolam was discontinued promptly. Clinical consequences of the treatment were controllable tension, intermittent headache, and rarely insomia. It is the first case report showing utilization of therapeutic drug monitoring during withdrawal period in the patient with extreme toleration to severe benzodiazepine dependence. PMID:26945373
Multilevel Cross-dependent Binary Longitudinal Data
Staicu, Ana-Maria; Carroll, Raymond J.
We provide insights into new methodology for the analysis of multilevel binary data observed longitudinally, when the repeated longitudinal measurements are correlated. The proposed model is logistic functional regression conditioned on three latent processes describing the within- and between-variability, and describing the cross-dependence of the repeated longitudinal measurements. We estimate the model components without employing mixed-effects modeling but assuming an approximation to the logistic link function. The primary objectives of this paper are to highlight the challenges in the estimation of the model components, to compare two approximations to the logistic regression function, linear and exponential, and to discuss their advantages and limitations. The linear approximation is computationally efficient whereas the exponential approximation applies for rare events functional data. Our methods are inspired by and applied to a scientific experiment on spectral backscatter from long range infrared light detection and ranging (LIDAR) data. The models are general and relevant to many new binary functional data sets, with or without dependence between repeated functional measurements. PMID:24131242
Dosing time-dependent actions of psychostimulants.
Manev, H; Uz, T
The concept of the dosing time-dependent (DTD) actions of drugs has been used to describe the effects of diurnal rhythms on pharmacological responsiveness. Notwithstanding the importance of diurnal variability in drug pharmacokinetics and bioavailability, it appears that in the central nervous system (CNS), the DTD actions of psychotropic drugs involve diurnal changes in the CNS-specific expression of genes encoding for psychotropic drug targets and transcription factors known as clock genes. In this review, we focused our discussion on the DTD effects of the psychostimulants cocaine and amphetamines. Both cocaine and amphetamines produce differential lasting behavioral alterations, that is, locomotor sensitization, depending on the time of the day they are administered. This exemplifies a DTD action of these drugs. The DTD effects of these psychostimulants correlate with diurnal changes in the system of transcription factors termed clock genes, for example, Period 1, and with changes in the availability of certain subtypes of dopamine receptors, for example, D2 and D3. Diurnal synthesis and release of the pineal hormone melatonin influence the DTD behavioral actions of cocaine and amphetamines. The molecular mechanism of melatonin's effects on the responsiveness of CNS to psychostimulants appears to involve melatonin receptors and clock genes. It is proposed that the DTD characteristics of psychostimulant action and the contributions of the melatonergic system may have clinical implications that include treatments for the attention deficit hyperactivity disorder and possibly neurotoxicity/neuroprotection. PMID:19897073
Frequency dependent thermal expansion in binary viscoelasticcomposites
Berryman, James G.
The effective thermal expansion coefficient beta* of abinary viscoelastic composite is shown to be frequency dependent even ifthe thermal expansion coefficients beta A and beta B of both constituentsare themselves frequency independent. Exact calculations for binaryviscoelastic systems show that beta* is related to constituent valuesbeta A, beta B, volume fractions, and bulk moduli KA, KB, as well as tothe overall bulk modulus K* of the composite system. Then, beta* isdetermined for isotropic systems by first bounding (or measuring) K* andtherefore beta*. For anisotropic systems with hexagonal symmetry, theprincipal values of the thermal expansion beta*perp and beta*para can bedetermined exactly when the constituents form a layered system. In allthe examples studied, it is shown explicitly that the eigenvectors of thethermoviscoelastic system possess non-negative dissipation -- despite thecomplicated analytical behavior of the frequency dependent thermalexpansivities themselves. Methods presented have a variety ofapplications from fluid-fluid mixtures to fluid-solid suspensions, andfrom fluid-saturated porous media to viscoelastic solid-solidcomposites.
The discovery of ubiquitin-dependent proteolysis
Wilkinson, Keith D.
In early 1980, Irwin A. Rose, Avram Hershko, and Aaron Ciechanover published two papers in PNAS that reported the astounding observation that energy-dependent intracellular proteolysis was far more complicated than the previously accepted models of lysosomal proteolysis or the action of ATP-dependent proteases such as bacterial lon. In fact, it has turned out to be even more complicated than they could have suspected. The general model of covalently attaching a small protein as a targeting signal has proved to be every bit as important to eukaryotic cells as the better understood modifications such as phosphorylation or acetylation. The key player in this modification, a small protein called ubiquitin (APF-1 in these papers), is the founding member of a large family of proteins containing the β-grasp fold and is used as a posttranslational targeting signal to modify the structure, function, and/or localization of other proteins. The story of this discovery is a textbook example of the confluence of intellectual curiosity, unselfish collaboration, chance, luck, and preparation. PMID:16230621
The discovery of ubiquitin-dependent proteolysis.
Wilkinson, Keith D
In early 1980, Irwin A. Rose, Avram Hershko, and Aaron Ciechanover published two papers in PNAS that reported the astounding observation that energy-dependent intracellular proteolysis was far more complicated than the previously accepted models of lysosomal proteolysis or the action of ATP-dependent proteases such as bacterial lon. In fact, it has turned out to be even more complicated than they could have suspected. The general model of covalently attaching a small protein as a targeting signal has proved to be every bit as important to eukaryotic cells as the better understood modifications such as phosphorylation or acetylation. The key player in this modification, a small protein called ubiquitin (APF-1 in these papers), is the founding member of a large family of proteins containing the beta-grasp fold and is used as a posttranslational targeting signal to modify the structure, function, and/or localization of other proteins. The story of this discovery is a textbook example of the confluence of intellectual curiosity, unselfish collaboration, chance, luck, and preparation. PMID:16230621
Insulin-dependent diabetes and HLA.
Dausset, J; Hors, J; Contu, L; Busson, M; Schmid, M; Cathelineau, G; Lestradet, H; Baron, D
The study of a hundred and fifteen unrelated insulin-dependent diabetes and eight families with at least two insulin-dependent diabetes members made it possible to confirm the higher frequency of HLA-B8 and B18 (p less than 0.001) among patients, producing a RR of 2.24 and 2.47 respectively. The increased B15 frequency did not achieve statistical significance. B18 whose gametic association (delta = 0.0438) was significant only in diabetic patients was often related to Aw19-2 (Aw30 + Aw31). The B8/B18 genotype gave a relative risk (RR = 4.98) which was significantly higher than that of B8, B18 and B15 heterozygotes (1.50, 1.24 and 1.39 respectively). Pairs of diabetic siblings were more frequently HLA identical than would be expected by chance, and distribution of the pairs of affected sibs into the three categories, identical, semi-identical and different, was closer to the recessive model than to the dominant one. The fact that the B8/B18 individuals had a RR slightly higher than the B8 and B18 homozygotes and distinctly higher than the heterozygotes for only one of these genes, favours the hypothesis of two dominant genes, giving the appearance of recessivity. The gene associated with B18 in Southern Europe seems to play the same part as that of the gene associated with B15 in Northern Europe. PMID:398300
Local Frequency Dependence in Transcranial Ultrasound Transmission
NASA Astrophysics Data System (ADS)
White, P. J.; Clement, G. T.; Hynynen, K.
The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the necessitation of a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of sonication at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, this study examined the frequency dependence of ultrasound transmission in the range of 0.6-1.4 MHz through a series of seventeen points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, it was shown that the reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission.
Generalized parametrization dependence in quantum gravity
NASA Astrophysics Data System (ADS)
Gies, Holger; Knorr, Benjamin; Lippoldt, Stefan
We critically examine the gauge and field-parametrization dependence of renormalization group flows in the vicinity of non-Gaußian fixed points in quantum gravity. While physical observables are independent of such calculational specifications, the construction of quantum gravity field theories typically relies on off-shell quantities such as β functions and generating functionals and thus face potential stability issues with regard to such generalized parametrizations. We analyze a two-parameter class of covariant gauge conditions, the role of momentum-dependent field rescalings and a class of field parametrizations. Using the product of Newton and cosmological constant as an indicator, the principle of minimum sensitivity identifies stationary points in this parametrization space which show a remarkable insensitivity to the parametrization. In the most insensitive cases, the quantized gravity system exhibits a non-Gaußian UV stable fixed point, lending further support to asymptotically safe quantum gravity. One of the stationary points facilitates an analytical determination of the quantum gravity phase diagram and features ultraviolet and infrared complete RG trajectories with a classical regime.
Structure dependent elastic properties of supergraphene
NASA Astrophysics Data System (ADS)
Hou, Juan; Yin, Zhengnan; Zhang, Yingyan; Chang, Tien-Chong
Complete replacement of aromatic carbon bonds in graphene by carbyne chains gives rise to supergraphene whose mechanical properties are expected to depend on its structure. However, this dependence is to date unclear. In this paper, explicit expressions for the in-plane stiffness and Poisson's ratio of supergraphene are obtained using a molecular mechanics model. The theoretical results show that the in-plane stiffness of supergraphene is drastically (at least one order) smaller than that of graphene, whereas its Poisson's ratio is higher than 0.5. As the index number increases (i.e., the length of carbyne chains increases and the bond density decreases), the in-plane stiffness of supergraphene decreases while the Poisson's ratio increases. By analyzing the relation among the layer modulus, in-plane stiffness and Poisson's ratio, it is revealed that the mechanism of the faster decrease in the in-plane stiffness than the bond density is due to the increase of Poisson's ratio. These findings are useful for future applications of supergraphene in nanomechanical systems.
Solvent dependent photophysical properties of dimethoxy curcumin
NASA Astrophysics Data System (ADS)
Barik, Atanu; Indira Priyadarsini, K.
Dimethoxy curcumin (DMC) is a methylated derivative of curcumin. In order to know the effect of ring substitution on photophysical properties of curcumin, steady state absorption and fluorescence spectra of DMC were recorded in organic solvents with different polarity and compared with those of curcumin. The absorption and fluorescence spectra of DMC, like curcumin, are strongly dependent on solvent polarity and the maxima of DMC showed red shift with increase in solvent polarity function (Δf), but the above effect is prominently observed in case of fluorescence maxima. From the dependence of Stokes' shift on solvent polarity function the difference between the excited state and ground state dipole moment was estimated as 4.9 D. Fluorescence quantum yield (ϕf) and fluorescence lifetime (τf) of DMC were also measured in different solvents at room temperature. The results indicated that with increasing solvent polarity, ϕf increased linearly, which has been accounted for the decrease in non-radiative rate by intersystem crossing (ISC) processes.
Diameter-dependent hydrophobicity in carbon nanotubes
NASA Astrophysics Data System (ADS)
Kyakuno, Haruka; Fukasawa, Mamoru; Ichimura, Ryota; Matsuda, Kazuyuki; Nakai, Yusuke; Miyata, Yasumitsu; Saito, Takeshi; Maniwa, Yutaka
Single-wall carbon nanotubes (SWCNTs) are a good model system that provides atomically smooth nanocavities. It has been reported that water-SWCNTs exhibit hydrophobicity depending on the temperature T and the SWCNT diameter D. SWCNTs adsorb water molecules spontaneously in their cylindrical pores around room temperature, whereas they exhibit a hydrophilic-hydrophobic transition or wet-dry transition (WDT) at a critical temperature Twd ≈ 220-230 K and above a critical diameter Dc ≈ 1.4-1.6 nm. However, details of the WDT phenomenon and its mechanism remain unknown. Here, we report a systematic experimental study involving X-ray diffraction, optical microscopy, and differential scanning calorimetry. It is found that water molecules inside thick SWCNTs (D > Dc) evaporate and condense into ice Ih outside the SWCNTs at Twd upon cooling, and the ice Ih evaporates and condenses inside the SWCNTs upon heating. On the other hand, residual water trapped inside the SWCNTs below Twd freezes. Molecular dynamics simulations indicate that upon lowering T, the hydrophobicity of thick SWCNTs increases without any structural transition, while the water inside thin SWCNTs (D < Dc) exhibits a structural transition, forming an ordered ice. This ice has a well-developed hydrogen bonding network adapting to the cylindrical pores of the SWCNTs. Thus, the unusual diameter dependence of the WDT is attributed to the adaptability of the structure of water to the pore dimension and shape.
Michalak, Agnieszka; Biała, Grazyna
The consequences of alcohol dependence concern serious health care, social and economic problems. The scope of many studies is to better understand mechanisms underlying alcohol addiction in order to work out new, more effective treatment strategies. Alcohol affects many neurotransmission systems within the brain. In general, acute alcohol enhances inhibitory transmission, up-regulating the GABAergic system and impairing glutamatergic function, therefore interfering the balance between excitatory and inhibitory synaptic inputs. Chronic alcohol consumption, meanwhile, in order to restore equilibrium leads to neuroadaptive changes caus- ing both decreased GABAergic and increased glutamatergic activity. Also function of other neurotransmitters and modulators is modified by the presence of alcohol, including glycine, adenosine, serotonin and dopamine. Moreover, a significant impact of alcohol on the endogenous opioid system, nicotinic cholinergic transmission and the endocannabinoids system has been also established. At present, only four medications are approved for the treatment of alcohol dependence in Europe, that is naltrexone, acamprosate, disulfiram and the most recent nalmefene. Among other promising strategies the following drugs are mentioned: baclofen, topiramate, ondansetron, aripiprazole, rimonabant and varenicline. Additionally, the role of appetite-regulating hormones, neuroimmune modulators or the body's stress-response system modulators in reducing alcohol consumption is currently of great interest, however, further investigations are needed. PMID:27008795
Heating liquid dielectrics by time dependent fields
NASA Astrophysics Data System (ADS)
Khalife, A.; Pathak, U.; Richert, R.
Steady state and time-resolved dielectric relaxation experiments are performed at high fields on viscous glycerol and the effects of energy absorption from the electric field are studied. Time resolution is obtained by a sinusoidal field whose amplitude is switched from a low to a high level and by recording voltage and current traces with an oscilloscope during this transition. Based on their distinct time and frequency dependences, three sources of modifying the dynamics and dielectric loss via an increase in the effective temperature can be distinguished: electrode temperature, real sample temperature, and configurational temperatures of the modes that absorbed the energy. Isothermal conditions that are desired for focusing on the configurational temperature changes (as in dielectric hole burning and related techniques) are maintained only for very thin samples and for moderate power levels. For high frequencies, say ν > 1 MHz, changes of the real temperature will exceed the effects of configurational temperatures in the case of macroscopic samples. Regarding microwave chemistry, heating via cell phone use, and related situations in which materials are subject to fields involving frequencies beyond the MHz regime, we conclude that changes in the configurational (or fictive) temperatures remain negligible compared with the increase of the real temperature. This simplifies the assessment of how time dependent electric fields modify the properties of materials.
Rate-dependent incompleteness of earthquake catalogs
NASA Astrophysics Data System (ADS)
Hainzl, Sebastian
Important information about the earthquake generation process can be gained from instrumental earthquake catalogs, but this requires complete recordings to avoid biased results. The local completeness magnitude Mc is known to depend on general conditions such as the seismographic network and the environmental noise, which generally limit the possibility to detect small events. The detectability can be additionally reduced by an earthquake-induced increase of the noise-level leading to short-term variations of Mc, which cannot be resolved by traditional methods relying on the analysis of the frequency-magnitude distribution. Based on simple assumptions, I propose a new method to estimate such temporal excursions of Mc solely based on the estimation of the earthquake rate resulting in a high temporal resolution of Mc. The approach is shown to be in agreement with the apparent decrease of the estimated Gutenberg-Richter b-value in high-activity phases of recorded data sets and the observed incompleteness periods after mainshocks. Furthermore, an algorithm to estimate temporal changes of Mc is introduced and applied to empirical aftershock and swarm sequences from California and central Europe, indicating that observed b-value fluctuations are often related to rate-dependent incompleteness of the earthquake catalogs.
Rippled-spectrum resolution dependence on level.
Supin, Alexander Ya; Popov, Vladimir V; Milekhina, Olga N; Tarakanov, Mikhail B
Rippled-density resolution of a rippled sound spectrum (probe band) in both the presence and absence of another band (masker) was studied as a function of sound level in normal listeners. The resolvable ripple density in the probe band was measured by finding the highest ripple density at which an interchange of ripple peak and valley positions was detectable (the phase-reversal test). Probe bands were 0.5 oct wide with center frequencies of 1, 2, and 4 kHz. In the control condition (no masker), the ripple-density resolution was almost independent of sound level within a range of 40-90 dB SPL. When an on-frequency masker coincided with the probe band (that resulted in reduced ripple depth), resolution decreased slightly relative to the control condition but remained little dependent on level. With an off-frequency low-side masker, the ripple-density resolution was a little less than in the control but almost independent of level within a range of 40-60 dB SPL and progressively decreased with level increase from 70 to 90 dB SPL. The dependence on level was qualitatively similar at all probe frequencies and at various widths and positions of the low-side off-frequency masker band. PMID:14599687
KK molecules with momentum-dependent interactions
Lemmer, R. H.
It is shown that the momentum-dependent kaon-antikaon interactions generated via vector-meson exchange from the standard SU{sub V}(3)xSU{sub A}(3) interaction Lagrangian lead to a nonlocal potential in coordinate space that can be incorporated without approximation into a nonrelativistic version of the Bethe-Salpeter wave equation containing a radial-dependent effective kaon mass appearing in a fully symmetrized kinetic energy operator, in addition to a local potential. Estimates of the mass and decay widths of f{sub 0}(980) and a{sub 0}(980), considered as KK molecules of isospin 0 and 1, as well as for K{sup +}K{sup -} atomic bound states (kaonium) are presented and compared with previous studies of a similar nature. It is argued that without a better knowledge of hadronic form factors it is not possible to distinguish between the molecular versus elementary particle models for the structure of the light scalar mesons.
Solvent dependent photophysical properties of dimethoxy curcumin.
Barik, Atanu; Indira Priyadarsini, K
Dimethoxy curcumin (DMC) is a methylated derivative of curcumin. In order to know the effect of ring substitution on photophysical properties of curcumin, steady state absorption and fluorescence spectra of DMC were recorded in organic solvents with different polarity and compared with those of curcumin. The absorption and fluorescence spectra of DMC, like curcumin, are strongly dependent on solvent polarity and the maxima of DMC showed red shift with increase in solvent polarity function (Δf), but the above effect is prominently observed in case of fluorescence maxima. From the dependence of Stokes' shift on solvent polarity function the difference between the excited state and ground state dipole moment was estimated as 4.9 D. Fluorescence quantum yield (φ(f)) and fluorescence lifetime (τ(f)) of DMC were also measured in different solvents at room temperature. The results indicated that with increasing solvent polarity, φ(f) increased linearly, which has been accounted for the decrease in non-radiative rate by intersystem crossing (ISC) processes. PMID:23314392
Temperature dependence of BCF plastic scintillation detectors
NASA Astrophysics Data System (ADS)
Wootton, Landon; Beddar, Sam
We examined temperature dependence in plastic scintillation detectors (PSDs) made of BCF-60 or BCF-12 scintillating fiber coupled to optical fiber with cyanoacrylate. PSDs were subjected to a range of temperatures using a temperature-controlled water bath and irradiated at each temperature while either the dose was measured using a CCD camera or the spectral output was measured using a spectrometer. The spectrometer was used to examine the intensity and spectral distribution of scintillation light emitted by the PSDs, Cerenkov light generated within the PSD, and light transmitted through an isolated optical coupling. BCF-60 PSDs exhibited a 0.50% decrease and BCF-12 PSDs a 0.09% decrease in measured dose per °C increase, relative to dose measured at 22 °C. Spectrometry revealed that the total intensity of the light generated by BCF-60 and BCF-12 PSDs decreased by 0.32% and 0.13%, respectively, per °C increase. The spectral distribution of the light changed slightly with temperature for both PSDs, accounting for the disparity between the change in measured dose and total light output. The generation of Cerenkov light was temperature independent. However, light transmitted through optical coupling between the scintillator and the optical fiber also exhibited temperature dependence.
Perturbative Critical Behavior from Spacetime Dependent Couplings
Dong, Xi; Horn, Bart; Silverstein, Eva; Torroba, Gonzalo
We find novel perturbative fixed points by introducing mildly spacetime-dependent couplings into otherwise marginal terms. In four-dimensional QFT, these are physical analogues of the small-{epsilon} Wilson-Fisher fixed point. Rather than considering 4-{epsilon} dimensions, we stay in four dimensions but introduce couplings whose leading spacetime dependence is of the form {lambda}x{sup {kappa}}{mu}{sup {kappa}}, with a small parameter {kappa} playing a role analogous to {epsilon}. We show, in {phi}{sup 4} theory and in QED and QCD with massless flavors, that this leads to a critical theory under perturbative control over an exponentially wide window of spacetime positions x. The exact fixed point coupling {lambda}{sub *}(x) in our theory is identical to the running coupling of the translationally invariant theory, with the scale replaced by 1/x. Similar statements hold for three-dimensional {phi}{sup 6} theories and two-dimensional sigma models with curved target spaces. We also describe strongly coupled examples using conformal perturbation theory.
Orientation-Dependent Handedness and Chiral Design
NASA Astrophysics Data System (ADS)
Efrati, Efi; Irvine, William T. M.
Chirality occupies a central role in fields ranging from biological self-assembly to the design of optical metamaterials. The definition of chirality, as given by Lord Kelvin, associates chirality with the lack of mirror symmetry: the inability to superpose an object on its mirror image. While this definition has guided the classification of chiral objects for over a century, the quantification of handed phenomena based on this definition has proven elusive, if not impossible, as manifest in the paradox of chiral connectedness. In this work, we put forward a quantification scheme in which the handedness of an object depends on the direction in which it is viewed. While consistent with familiar chiral notions, such as the right-hand rule, this framework allows objects to be simultaneously right and left handed. We demonstrate this orientation dependence in three different systems—a biomimetic elastic bilayer, a chiral propeller, and optical metamaterial—and find quantitative agreement with chirality pseudotensors whose form we explicitly compute. The use of this approach resolves the existing paradoxes and naturally enables the design of handed metamaterials from symmetry principles.
[Cereal-dependent exercise-induced anaphylaxis].
Seoane-Rodríguez, Marta; Caralli, María Elisa; Morales-Cabeza, Cristina; Micozzi, Sarah; De Barrio-Fernández, Manuel; Rojas Pérez-Ezquerra, Patricia
Wheat-dependent exercise-induced anaphylaxis (WDEIA) is increasing. In vitro test such as omega-5-gliadin levels are useful in the diagnosis, while oral single blind challenge tests (OCT) with wheat plus exercise continuous being the gold standard diagnostic method. This paper reports the case of a 38-year-old woman, with several episodes of anaphylaxis after eating different foods and doing exercise after ingestion. An allergy study was performed with positive skin prick tests for wheat, barley and rye. Total IgE 238.0KU/L, positive specific IgE (>100KU/L) to wheat, barley and rye, and negative to rTri-a-19 omega-5 gliadin. OCT with bread and exercise was positive. In this case of wheat-dependent exerciseinduced anaphylaxis (WDEIA) with negative serum specific IgE to omega-5-gliadin, negative results with gamma, alpha, bheta y omega-gliadin doesn't exclude the diagnosis of WDEIA. PMID:26943835
Age-dependent decay in the landscape
Winitzki, Sergei
The picture of the 'multiverse' arising in diverse cosmological scenarios involves transitions between metastable vacuum states. It was pointed out by Krauss and Dent that the transition rates decrease at very late times, leading to a dependence of the transition probability between vacua on the age of each vacuum region. I investigate the implications of this non-Markovian, age-dependent decay on the global structure of the spacetime in landscape scenarios. I show that the fractal dimension of the eternally inflating domain is precisely equal to 3, instead of being slightly below 3, which is the case in scenarios with purely Markovian, age-independent decay. I develop a complete description of a non-Markovian landscape in terms of a nonlocal master equation. Using this description I demonstrate by an explicit calculation that, under some technical assumptions about the landscape, the probabilistic predictions of our position in the landscape are essentially unchanged, regardless of the measure used to extract these predictions. I briefly discuss the physical plausibility of realizing non-Markovian vacuum decay in cosmology in view of the possible decoherence of the metastable quantum state.
Surrogate oracles, generalized dependency and simpler models
NASA Technical Reports Server (NTRS)
Wilson, Larry
Software reliability models require the sequence of interfailure times from the debugging process as input. It was previously illustrated that using data from replicated debugging could greatly improve reliability predictions. However, inexpensive replication of the debugging process requires the existence of a cheap, fast error detector. Laboratory experiments can be designed around a gold version which is used as an oracle or around an n-version error detector. Unfortunately, software developers can not be expected to have an oracle or to bear the expense of n-versions. A generic technique is being investigated for approximating replicated data by using the partially debugged software as a difference detector. It is believed that the failure rate of each fault has significant dependence on the presence or absence of other faults. Thus, in order to discuss a failure rate for a known fault, the presence or absence of each of the other known faults needs to be specified. Also, in simpler models which use shorter input sequences without sacrificing accuracy are of interest. In fact, a possible gain in performance is conjectured. To investigate these propositions, NASA computers running LIC (RTI) versions are used to generate data. This data will be used to label the debugging graph associated with each version. These labeled graphs will be used to test the utility of a surrogate oracle, to analyze the dependent nature of fault failure rates and to explore the feasibility of reliability models which use the data of only the most recent failures.
Density-dependent adjustment of inducible defenses
Tollrian, Ralph; Duggen, Sonja; Weiss, Linda C.; Laforsch, Christian; Kopp, Michael
Predation is a major factor driving evolution, and organisms have evolved adaptations increasing their survival chances. However, most defenses incur trade-offs between benefits and costs. Many organisms save costs by employing inducible defenses as responses to fluctuating predation risk. The level of defense often increases with predator densities. However, individual predation risk should not only depend on predator density but also on the density of conspecifics. If the predator has a saturating functional response one would predict a negative correlation between prey density and individual predation risk and hence defense expression. Here, we tested this hypothesis using six model systems, covering a taxonomic range from protozoa to rotifers and crustaceans. In all six systems, we found that the level of defense expression increased with predator density but decreased with prey density. In one of our systems, i.e. in Daphnia, we further show that the response to prey density is triggered by a chemical cue released by conspecifics and congeners. Our results indicate that organisms adjust the degree of defense to the acute predation risk, rather than merely to predators' densities. Our study suggests that density-dependent defense expression reflects accurate predation-risk assessment and is a general principle in many inducible-defense systems. PMID:26235428
Copper regulates cyclic-AMP-dependent lipolysis.
Krishnamoorthy, Lakshmi; Cotruvo, Joseph A; Chan, Jefferson; Kaluarachchi, Harini; Muchenditsi, Abigael; Pendyala, Venkata S; Jia, Shang; Aron, Allegra T; Ackerman, Cheri M; Wal, Mark N Vander; Guan, Timothy; Smaga, Lukas P; Farhi, Samouil L; New, Elizabeth J; Lutsenko, Svetlana; Chang, Christopher J
Cell signaling relies extensively on dynamic pools of redox-inactive metal ions such as sodium, potassium, calcium and zinc, but their redox-active transition metal counterparts such as copper and iron have been studied primarily as static enzyme cofactors. Here we report that copper is an endogenous regulator of lipolysis, the breakdown of fat, which is an essential process in maintaining body weight and energy stores. Using a mouse model of genetic copper misregulation, in combination with pharmacological alterations in copper status and imaging studies in a 3T3-L1 white adipocyte model, we found that copper regulates lipolysis at the level of the second messenger, cyclic AMP (cAMP), by altering the activity of the cAMP-degrading phosphodiesterase PDE3B. Biochemical studies of the copper-PDE3B interaction establish copper-dependent inhibition of enzyme activity and identify a key conserved cysteine residue in a PDE3-specific loop that is essential for the observed copper-dependent lipolytic phenotype. PMID:27272565
Nalbuphine hydrochloride dependence in anabolic steroid users.
Wines, J D; Gruber, A J; Pope, H G; Lukas, S E
Nalbuphine hydrochloride, a nonscheduled opioid agonist/antagonist analgesic, is currently approved for the treatment of pain. Recently, nalbuphine dependence was reported in three anabolic steroid users in Britain. To further document this phenomenon, we conducted interviews on eleven subjects who reported nalbuphine use. Eight subjects were clinically dependent on nalbuphine, and seven of the subjects who were asked about tolerance and withdrawal with nalbuphine acknowledged these symptoms. Eight subjects, who had never used drugs intravenously before, reported using nalbuphine by this route. Nalbuphine-related morbidity was extensive and included medical complications and psychiatric symptoms. Nalbuphine users also exhibited a high rate of comorbid Axis I disorders, including other substance misuse. Virtually all subjects described widespread nalbuphine use in the gymnasiums they frequented. These observations, together with the recent increase in nalbuphine-related articles in the lay press, suggest that nalbuphine may represent a new drug of abuse among athletes, especially those using anabolic steroids, and that nalbuphine's scheduling status may need to be re-evaluated. PMID:10365196
Probing dark energy through scale dependence
NASA Astrophysics Data System (ADS)
Motta, Mariele; Sawicki, Ignacy; Saltas, Ippocratis D.; Amendola, Luca; Kunz, Martin
We consider the consequences of having no prior knowledge of the true dark energy model for the interpretation of cosmological observations. The magnitude of redshift-space distortions and weak-lensing shear is determined by the metric on the geodesics of which galaxies and light propagate. We show that, given precise enough observations, we can use these data to completely reconstruct the metric on our past light cone and therefore to measure the scale and time dependence of the anisotropic stress and the evolution of the gravitational potentials in a model-independent manner. Since both dark matter and dark energy affect the visible sector only through the gravitational field they produce, they are inseparable without a model for dark energy: galaxy bias cannot be measured and therefore the distribution of dark matter determined; the peculiar velocity of dark matter can be identified with that of the galaxies only when the equivalence principle holds. Given these limitations, we show how one can nonetheless build tests for classes of dark energy models which depend on making measurements at multiple scales at a particular redshift. They are null tests on the model-independent observables, do not require modeling evolution in time, and do not require any parametrization of the free functions of these models—such as the sound speed. We show that one in principle could rule out or constrain the whole class of the most general scalar-tensor theories even without assuming the quasistatic limit.
Local frequency dependence in transcranial ultrasound transmission.
White, P J; Clement, G T; Hynynen, K
The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the necessitation of a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of insonation at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, this study examined the frequency dependence of ultrasound transmission in the range of 0.6-1.4 MHz through a series of 17 points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, it was shown that the reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. A multiple-frequency insonation with optimized frequencies over the entirety of five skull specimens was found to yield on average a temporally brief 230% increase in the transmitted intensity with an 88% decrease in time-averaged intensity transmission within the focal volume. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission. PMID:16625043
Anomalous frequency dependent diamagnetism in metal silicide
NASA Astrophysics Data System (ADS)
Dahal, Ashutosh; Gunasekera, Jagat; Harriger, Leland; Singh, David J.; Singh, Deepak K.; Leland Harriger Collaboration
Discovery of superconductivity in PbO-type FeSe has generated a lot of interest. Among the samples we synthesize with similar structure, NiSi has showed anomalous but very interesting results. Nickel silicides are important electronic materials that have been used as contacts for field effect transistors, as interconnects and in nanoelectronic devices. The magnetic properties of NiSi are not well known, however. In this presentation, we report a highly unusual magnetic phenomenon in NiSi. The ac susceptibility measurements on NiSi reveal strong frequency dependence of static and dynamic susceptibilities that are primarily diamagnetic at room temperature. The static susceptibility is found to exhibit a strong frequency dependence of the diamagnetic response below 100K, while dynamic susceptibility showed peak type feature at 10KHz frequency around 50K. Detailed neutron scattering measurements on high quality powder sample of NiSi on SPINS cold spectrometer further revealed an inelastic peak around 1.5meV, even though no magnetic order is detected. The inelastic peak dissipates above 100K, which is where the static susceptibility starts to diverge with frequency. Research is supported by U.S. Department of Energy, Office of Basic Energy Sciences under Grant No. DE-SC0014461.
Temperature dependence of optically induced cell deformations
NASA Astrophysics Data System (ADS)
Fritsch, Anatol; Kiessling, Tobias R.; Stange, Roland; Kaes, Josef A.
The mechanical properties of any material change with temperature, hence this must be true for cellular material. In biology many functions are known to undergo modulations with temperature, like myosin motor activity, mechanical properties of actin filament solutions, CO2 uptake of cultured cells or sex determination of several species. As mechanical properties of living cells are considered to play an important role in many cell functions it is surprising that only little is known on how the rheology of single cells is affected by temperature. We report the systematic temperature dependence of single cell deformations in Optical Stretcher (OS) measurements. The temperature is changed on a scale of about 20 minutes up to hours and compared to defined temperature shocks in the range of milliseconds. Thereby, a strong temperature dependence of the mechanics of single suspended cells is revealed. We conclude that the observable differences arise rather from viscosity changes of the cytosol than from structural changes of the cytoskeleton. These findings have implications for the interpretation of many rheological measurements, especially for laser based approaches in biological studies.
Multiplicity dependence of two-pion correlations
Soltz, R.A.; E802 Collaboration
Experiment E859 has measured two-pion correlations for 14.6 A{center_dot}GeV/c {sup 28}Si + Au and {sup 28}Si + Al systems as a function of total charged particle multiplicity. The data have been divided into three multiplicity regions for each system, and fits to two-dimensional Gaussian sources have been performed. The extracted source parameters R{sub l} and {tau} show little or no multiplicity dependence while the parameters R{sub t} and R show a slight dependence. Two-pion correlations were also measured for the 11.6 A{center_dot}GeV/c {sup 197}Au + Au system as part of experiment E866. The rms radius (R{sub rms}) for this system was found to be 7.03 {plus_minus} 0.53 fm, consistent with a scaling of R{sub rms} = 1.2A{sub p}{sup 1/3}, where A{sub p} is the number of projectile nucleons.
Unconscious relational encoding depends on hippocampus
Duss, Simone B.; Reber, Thomas P.; Hänggi, Jürgen; Schwab, Simon; Wiest, Roland; Müri, René M.; Brugger, Peter; Gutbrod, Klemens
Textbooks divide between human memory systems based on consciousness. Hippocampus is thought to support only conscious encoding, while neocortex supports both conscious and unconscious encoding. We tested whether processing modes, not consciousness, divide between memory systems in three neuroimaging experiments with 11 amnesic patients (mean age = 45.55 years, standard deviation = 8.74, range = 23–60) and 11 matched healthy control subjects. Examined processing modes were single item versus relational encoding with only relational encoding hypothesized to depend on hippocampus. Participants encoded and later retrieved either single words or new relations between words. Consciousness of encoding was excluded by subliminal (invisible) word presentation. Amnesic patients and controls performed equally well on the single item task activating prefrontal cortex. But only the controls succeeded on the relational task activating the hippocampus, while amnesic patients failed as a group. Hence, unconscious relational encoding, but not unconscious single item encoding, depended on hippocampus. Yet, three patients performed normally on unconscious relational encoding in spite of amnesia capitalizing on spared hippocampal tissue and connections to language cortex. This pattern of results suggests that processing modes divide between memory systems, while consciousness divides between levels of function within a memory system. PMID:25273998
The time-dependent Gutzwiller approximation
NASA Astrophysics Data System (ADS)
Fabrizio, Michele
The time-dependent Gutzwiller Approximation (t-GA) is shown to be capable of tracking the off-equilibrium evolution both of coherent quasiparticles and of incoherent Hubbard bands. The method is used to demonstrate that the sharp dynamical crossover observed by time-dependent DMFT in the quench-dynamics of a half-filled Hubbard model can be identified within the t-GA as a genuine dynamical transition separating two distinct physical phases. This result, strictly variational for lattices of infinite coordination number, is intriguing as it actually questions the occurrence of thermalization. Next, we shall present how t-GA works in a multi-band model for V2O3 that displays a first-order Mott transition. We shall show that a physically accessible excitation pathway is able to collapse the Mott gap down and drive off-equilibrium the insulator into a metastable metal phase. Work supported by the European Union, Seventh Framework Programme, under the project GO FAST, Grant Agreement No. 280555.
Nalmefene and its use in alcohol dependence.
Gual, A; Bruguera, P; López-Pelayo, H
Nalmefene is the first available drug approved in the E.U. to reduce alcohol use in alcohol-dependent patients. Reduction in alcohol use in heavy drinkers diminishes mortality risk and socio-economic burden. Nalmefene has shown efficacy at 6 months in alcohol-dependent patients with high or very high drinking risk levels in reducing total alcohol consumption (-7.6 g/day [95% confidence interval (CI): -11.6 to -3.5]; P = 0.0003), heavy drinking days (-2.00 days/month [95% CI: -3.00 to -1.00]; P ⟨ 0.00001) and other secondary outcome measures such as γ-glutamyl transferase, alanine aminotransferase, drinking risk level and Clinical Global Impression. It is generally well tolerated and has limited contraindications and interactions. As-needed dosage is a novel concept in the addictions field, which may overcome limitations of traditional regimens. In the pivotal trials, nalmefene was taken 52% of the days and compliance with the as-needed treatment regimen was good (above 80% of the days) in 68% of the nalmefene-treated patients. A new pharmacological approach combined with a brief psychosocial intervention for alcoholism is available and appears to be feasible, safe and efficacious. PMID:24918835
Authority dependence and judgments of utilitarian harm.
Piazza, Jared; Sousa, Paulo; Holbrook, Colin
Three studies tested the conditions under which people judge utilitarian harm to be authority dependent (i.e., whether its right or wrongness depends on the ruling of an authority). In Study 1, participants judged the right or wrongness of physical abuse when used as an interrogation method anticipated to yield useful information for preventing future terrorist attacks. The ruling of the military authority towards the harm was manipulated (prohibited vs. prescribed) and found to significantly influence judgments of the right or wrongness of inflicting harm. Study 2 established a boundary condition with regards to the influence of authority, which was eliminated when the utility of the harm was definitely obtained rather than forecasted. Finally, Study 3 replicated the findings of Studies 1-2 in a completely different context-an expert committee's ruling about the harming of chimpanzees for biomedical research. These results are discussed as they inform ongoing debates regarding the role of authority in moderating judgments of complex and simple harm. PMID:23747648
Climate policy and dependence on traded carbon
NASA Astrophysics Data System (ADS)
Andrew, Robbie M.; Davis, Steven J.; Peters, Glen P.
A growing number of countries regulate carbon dioxide (CO2) emissions occurring within their borders, but due to rapid growth in international trade, the products consumed in many of the same countries increasingly rely on coal, oil and gas extracted and burned in other countries where CO2 is not regulated. As a consequence, existing national and regional climate policies may be growing less effective every year. Furthermore, countries that are dependent on imported products or fossil fuels are more exposed to energy and climate policies in other countries. We show that the combined international trade in carbon (as fossil fuels and also embodied in products) increased from 12.3 GtCO2 (55% of global emissions) in 1997 to 17.6 GtCO2 (60%) in 2007 (growing at 3.7% yr-1). Within this, trade in fossil fuels was larger (10.8 GtCO2 in 2007) than trade in embodied carbon (6.9 GtCO2), but the latter grew faster (4.6% yr-1 compared with 3.1% yr-1 for fuels). Most major economies demonstrate increased dependence on traded carbon, either as exports or as imports. Because energy is increasingly embodied in internationally traded products, both as fossil fuels and as products, energy and climate policies in other countries may weaken domestic climate policy via carbon leakage and mask energy security issues.
Scale-dependent permeability of fractured andesite
NASA Astrophysics Data System (ADS)
Heap, Michael; Kennedy, Ben
Extension fractures in volcanic systems exist on all scales, from microscopic fractures to large fissures. They play a fundamental role in the movement of fluids and distribution of pore pressure, and therefore exert considerable influence over volcanic eruption recurrence. We present here laboratory permeability measurements for porous (porosity = 0.03-0.6) andesites before (i.e. intact) and after failure in tension (i.e., the samples host a throughgoing tensile fracture). The permeability of the intact andesites increases with increasing porosity, from 2 × 10-17 to 5 × 10-11 m2. Following fracture formation, the permeability of the samples (the effective permeability) falls within a narrow range regardless of their initial porosity: 2-6 × 10-11 m2. However, laboratory measurements of fractured samples likely overestimate the effective permeability due to the inherent scale-dependence of permeability. To better understand this scale-dependence, we first determined the permeability of the tensile fractures using a two-dimensional model that considers flow in parallel layers. Our calculations highlight that tensile fractures in low-porosity samples are more permeable (as high as 2.3 × 10-9 m2) than those in high-porosity samples (as low as 3.0 × 10-10 m2), a difference that can be explained by an increase in fracture tortuosity with porosity. We then use our fracture permeability data to model the effective permeability of rock with different host rock permeabilities (10-17 to 10-11 m2) populated by tensile fractures over a wide range of lengthscale. We find that the effective permeability of fractured andesite depends heavily on the initial host rock permeability and the scale of interest. At a given lengthscale, the effective permeability of high-permeability rock (10-12 to 10-11 m2) is essentially unaffected by the presence of numerous tensile fractures. By contrast, a single tensile fracture increases the effective permeability of low-permeability rock
Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus.
Ting, H H; Timimi, F K; Boles, K S; Creager, S J; Ganz, P; Creager, M A
Endothelium-dependent vasodilation is impaired in humans with diabetes mellitus. Inactivation of endothelium-derived nitric oxide by oxygen-derived free radicals contributes to abnormal vascular reactivity in experimental models of diabetes. To determine whether this observation is relevant to humans, we tested the hypothesis that the antioxidant, vitamin C, could improve endothelium-dependent vasodilation in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus. We studied 10 diabetic subjects and 10 age-matched, nondiabetic control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine (0.3-10 micrograms/min). Endothelium-independent vasodilation was measured by intraarterial infusion of nitroprusside (0.3-10 micrograms/min) and verapamil (10-300 micrograms/min). Forearm blood flow dose-response curves were determined for each drug before and during concomitant intraarterial administration of vitamin C (24 mg/min). In diabetic subjects, endothelium-dependent vasodilation to methacholine was augmented by simultaneous infusion of vitamin C (P = 0.002); in contrast, endothelium-independent vasodilation to nitroprusside and to verapamil were not affected by concomitant infusion of vitamin C (P = 0.9 and P = 0.4, respectively). In nondiabetic subjects, vitamin C administration did not alter endothelium-dependent vasodilation (P = 0.8). We conclude that endothelial dysfunction in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus can be improved by administration of the antioxidant, vitamin C. These findings support the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes. PMID:8550838
Experimental barbiturate dependence. I. Barbiturate dependence development in rats by drug-admixed food (DAF) method.
Tagashira, E; Izumi, T; Yanaura, S
A method for testing a rat's physical-dependence liability to sedaditive-hypnotic agents and for evaluating that dependence was studied by using the method. Rats received phenobarbital- or barbital-admixed food on a graded-increase dosage schedule over 30-40 days. Manifestations of CNS-suppressing action of either drug (e.g., systemic muscle relaxation, motor incoordination, staggering gait, and ptosis) persisted day and night during the drug medication. Twenty-four to 48 h after withdrawal of either drug, abstinence symptoms (e.g., muscle fasciculation, nuchal twitching, vocalization, increased irritability, ataxia, hyperthermia, and clonic-tonic and grand mal-type convulsions) were evidenced in all animals (N = 6), some of which died after convulsions. These withdrawal signs in rats were classified and found to be closely correlated with the magnitude of weight loss during the withdrawal. The calssification provides a basis for quantitatively assessing physical-dependence liability. The data obtained in the present study suggest that rats, like dogs and monkeys, are suitable experimental animals for tests in early stages of dependence liability, and that the administration of drug-admixed food is a useful method of developing dependence on both barbiturate and morphine-type drugs. PMID:418446
Grizzly bear habitat selection is scale dependent.
Ciarniello, Lana M; Boyce, Mark S; Seip, Dale R; Heard, Douglas C
The purpose of our study is to show how ecologists' interpretation of habitat selection by grizzly bears (Ursus arctos) is altered by the scale of observation and also how management questions would be best addressed using predetermined scales of analysis. Using resource selection functions (RSF) we examined how variation in the spatial extent of availability affected our interpretation of habitat selection by grizzly bears inhabiting mountain and plateau landscapes. We estimated separate models for females and males using three spatial extents: within the study area, within the home range, and within predetermined movement buffers. We employed two methods for evaluating the effects of scale on our RSF designs. First, we chose a priori six candidate models, estimated at each scale, and ranked them using Akaike Information Criteria. Using this method, results changed among scales for males but not for females. For female bears, models that included the full suite of covariates predicted habitat use best at each scale. For male bears that resided in the mountains, models based on forest successional stages ranked highest at the study-wide and home range extents, whereas models containing covariates based on terrain features ranked highest at the buffer extent. For male bears on the plateau, each scale estimated a different highest-ranked model. Second, we examined differences among model coefficients across the three scales for one candidate model. We found that both the magnitude and direction of coefficients were dependent upon the scale examined; results varied between landscapes, scales, and sexes. Greenness, reflecting lush green vegetation, was a strong predictor of the presence of female bears in both landscapes and males that resided in the mountains. Male bears on the plateau were the only animals to select areas that exposed them to a high risk of mortality by humans. Our results show that grizzly bear habitat selection is scale dependent. Further, the
38 CFR 3.5 - Dependency and indemnity compensation.
Code of Federal Regulations, 2011 CFR
... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Dependency and indemnity compensation. 3.5 Section 3.5 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.5 Dependency and indemnity compensation. (a) Dependency...
38 CFR 3.5 - Dependency and indemnity compensation.
Code of Federal Regulations, 2013 CFR
... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Dependency and indemnity compensation. 3.5 Section 3.5 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.5 Dependency and indemnity compensation. (a) Dependency...
38 CFR 3.5 - Dependency and indemnity compensation.
Code of Federal Regulations, 2010 CFR
... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Dependency and indemnity compensation. 3.5 Section 3.5 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.5 Dependency and indemnity compensation. (a) Dependency...
Bayesian Network Models for Local Dependence among Observable Outcome Variables
ERIC Educational Resources Information Center
Almond, Russell G.; Mulder, Joris; Hemat, Lisa A.; Yan, Duanli
Bayesian network models offer a large degree of flexibility for modeling dependence among observables (item outcome variables) from the same task, which may be dependent. This article explores four design patterns for modeling locally dependent observations: (a) no context--ignores dependence among observables; (b) compensatory context--introduces…
Indicators of Welfare Dependence. Annual Report to Congress, 2001.
ERIC Educational Resources Information Center
Department of Health and Human Services, Washington, DC.
This fourth annual report addresses the extent to which U.S. families depend on income from welfare programs, providing updated data on measures of welfare recipiency, dependency, and predictors of welfare dependence developed for previous reports. It highlights benefits under Aid to Families with Dependent Children (AFDC), now Temporary…
Local Dependence in an Operational CAT: Diagnosis and Implications
ERIC Educational Resources Information Center
Pommerich, Mary; Segall, Daniel O.
The accuracy of CAT scores can be negatively affected by local dependence if the CAT utilizes parameters that are misspecified due to the presence of local dependence and/or fails to control for local dependence in responses during the administration stage. This article evaluates the existence and effect of local dependence in a test of…
Neonatal Narcotic Dependence. Report Series 29, No. 1.
ERIC Educational Resources Information Center
National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.
This brief report suggests that it is evident that many uncertainties still remain with regard to neonatal narcotic dependence. Discussion centers on the precise causes and symptoms of neonatal narcotic dependence, the most efficacious treatment procedures, the relative severity of heroin dependence as compared with methadone dependence in the…
View-Dependent Streamline Deformation and Exploration.
Tong, Xin; Edwards, John; Chen, Chun-Ming; Shen, Han-Wei; Johnson, Chris R; Wong, Pak Chung
Occlusion presents a major challenge in visualizing 3D flow and tensor fields using streamlines. Displaying too many streamlines creates a dense visualization filled with occluded structures, but displaying too few streams risks losing important features. We propose a new streamline exploration approach by visually manipulating the cluttered streamlines by pulling visible layers apart and revealing the hidden structures underneath. This paper presents a customized view-dependent deformation algorithm and an interactive visualization tool to minimize visual clutter in 3D vector and tensor fields. The algorithm is able to maintain the overall integrity of the fields and expose previously hidden structures. Our system supports both mouse and direct-touch interactions to manipulate the viewing perspectives and visualize the streamlines in depth. By using a lens metaphor of different shapes to select the transition zone of the targeted area interactively, the users can move their focus and examine the vector or tensor field freely. PMID:26600061
Repeated Sprints: An Independent Not Dependent Variable.
Taylor, Jonathan M; Macpherson, Tom W; Spears, Iain R; Weston, Matthew
The ability to repeatedly perform sprints has traditionally been viewed as a key performance measure in team sports, and the relationship between repeated-sprint ability (RSA) and performance has been explored extensively. However, when reviewing the repeated-sprint profile of team-sports match play it appears that the occurrence of repeated-sprint bouts is sparse, indicating that RSA is not as important to performance as commonly believed. Repeated sprints are, however, a potent and time-efficient training strategy, effective in developing acceleration, speed, explosive leg power, aerobic power, and high-intensity-running performance--all of which are crucial to team-sport performance. As such, we propose that repeated-sprint exercise in team sports should be viewed as an independent variable (eg, a means of developing fitness) as opposed to a dependent variable (eg, a means of assessing fitness/performance). PMID:27197118
Stimuli dependent impedance of conductive magnetorheological elastomers
NASA Astrophysics Data System (ADS)
Wang, Yu; Xuan, Shouhu; Dong, Bo; Xu, Feng; Gong, Xinglong
The structure dependent impedance of conductive magnetorheological elastomers (MREs) under different loads and magnetic fields has been studied in this work. By increasing the weight fraction of iron particles, the conductivity of the MREs increased. Dynamic mechanical measurements and synchrotron radiation x-ray computed tomography (SR-CT) were used and they provided reasons for the electrical properties changing significantly under pressure and magnetic field stimulation. The high sensitivity of MREs to external stimuli renders them suitable for application in force or magnetic field sensors. The equivalent circuit model was proposed to analyze the impedance response of MREs and it fits the experimental results very well. Each circuit component reflected the change of the inner interface under different conditions, thus relative changes in the microstructure could be distinguished. This method could be used not only to detect the structural changes in the MRE but also to provide a great deal of valuable information for the further understanding of the MR mechanism.
SPOTing Acetyl-Lysine Dependent Interactions
Picaud, Sarah; Filippakopoulos, Panagis
Post translational modifications have been recognized as chemical signals that create docking sites for evolutionary conserved effector modules, allowing for signal integration within large networks of interactions. Lysine acetylation in particular has attracted attention as a regulatory modification, affecting chromatin structure and linking to transcriptional activation. Advances in peptide array technologies have facilitated the study of acetyl-lysine-containing linear motifs interacting with the evolutionary conserved bromodomain module, which specifically recognizes and binds to acetylated sequences in histones and other proteins. Here we summarize recent work employing SPOT peptide technology to identify acetyl-lysine dependent interactions and document the protocols adapted in our lab, as well as our efforts to characterize such bromodomain-histone interactions. Our results highlight the versatility of SPOT methods and establish an affordable tool for rapid access to potential protein/modified-peptide interactions involving lysine acetylation.
Frequency dependent squeezed light at audio frequencies
NASA Astrophysics Data System (ADS)
Miller, John
Following successful implementation in the previous generation of instruments, squeezed states of light represent a proven technology for the reduction of quantum noise in ground-based interferometric gravitational-wave detectors. As a result of lower noise and increased circulating power, the current generation of detectors places one further demand on this technique - that the orientation of the squeezed ellipse be rotated as function of frequency. This extension allows previously negligible quantum radiation pressure noise to be mitigated in addition to quantum shot noise. I will present the results of an experiment which performs the appropriate rotation by reflecting the squeezed state from a detuned high-finesse optical cavity, demonstrating frequency dependent squeezing at audio frequencies for the first time and paving the way for broadband quantum noise reduction in Advanced LIGO. Further, I will indicate how a realistic implementation of this approach will impact Advanced LIGO both alone and in combination with other potential upgrades.
Temperature-Dependent Photoluminescence of Graphene Oxide
NASA Astrophysics Data System (ADS)
Jadhav, S. T.; Rajoba, S. J.; Patil, S. A.; Han, S. H.; Jadhav, L. D.
Graphene oxide thin films have been deposited by spray pyrolysis using graphene oxide powder prepared by modified Hummers method. These thin films were characterized by different physico-chemical techniques. The x-ray diffraction studies revealed the structural properties of GO (graphene oxide) while the Raman spectrum showed the presence of D and G and two-dimensional bands. The D/G intensity ratio for spray-deposited GO film is 1.10. The x-ray photoelectron spectroscopy showed 67% and 33% atomic percentages of carbon and oxygen, respectively. The ratio of O1s/C1s was found to be 0.49. The temperature-dependent photoluminescence of GO thin film and GO solution showed a blue emission.
Habitable zone dependence on stellar parameter uncertainties
Kane, Stephen R.
An important property of exoplanetary systems is the extent of the Habitable Zone (HZ), defined as that region where water can exist in a liquid state on the surface of a planet with sufficient atmospheric pressure. Both ground- and space-based observations have revealed a plethora of confirmed exoplanets and exoplanetary candidates, most notably from the Kepler mission using the transit detection technique. Many of these detected planets lie within the predicted HZ of their host star. However, as is the case with the derived properties of the planets themselves, the HZ boundaries depend on how well we understand the host star. Here we quantify the uncertainties of HZ boundaries on the parameter uncertainties of the host star. We examine the distribution of stellar parameter uncertainties from confirmed exoplanet hosts and Kepler candidate hosts and translate these into HZ boundary uncertainties. We apply this to several known systems with an HZ planet to determine the uncertainty in their HZ status.
Coulomb blockade of spin-dependent shuttling
NASA Astrophysics Data System (ADS)
Park, Hee Chul; Kadigrobov, Anatoli M.; Shekhter, Robert I.; Jonson, M.
We show that nanomechanical shuttling of single electrons may enable qualitatively new functionality if spin-polarized electrons are injected into a nanoelectromechanical single-electron tunneling (NEM-SET) device. This is due to the combined effects of spin-dependent electron tunneling and Coulomb blockade of tunneling, which are phenomena that occur in certain magnetic NEM-SET devices. Two effects are predicted to occur in such structures. The first is a reentrant shuttle instability, by which we mean the sequential appearance, disappearance and again the appearance of a shuttle instability as the driving voltage is increased (or the mechanical dissipation is diminished). The second effect is an enhanced spin polarization of the nanomechanically assisted current flow.
Temporal, latitude and altitude absorbed dose dependences
NASA Astrophysics Data System (ADS)
Stozhkov, Y.; Svirzhevsky, N.; Bazilevskaya, G.
The regular balloon measurements in the Earth's atmosphere are carried on at the Lebedev Physical Institute since 1957. The regular balloon flights have been made at the high latitude stations (near Murmansk - northern hemisphere and Mi ny -r Antarctica) and at the middle latitude (Moscow). Based on these long-term measurements as well as on the latitude data obtained in the several Soviet Antarctic expeditions the calculations of absorbed doses were fulfilled for altitudes of 10, 15, 20 and 30 km. The absorbed dose dependences on the geomagnetic cutoff rigidities and the phase of the 11-year solar cycle were found. The evaluation of the solar proton events and energetic electron precipitation contributions to the absorbed dose enhancements was made.
Driving and insulin-dependent diabetes.
Frier, B M; Matthews, D M; Steel, J M; Duncan, L J
A survey of 250 patients with insulin-dependent diabetes (IDD) holding a full motor vehicle driving licence revealed that 107 (42.8%) had not declared IDD on their application for a driving licence. 70 of these (28% of entire group) claimed that they were unaware of the statutory requirements. There was no difference in the declaration-rate between men and women. 159 patients (66%) declared IDD for their motor insurance. 86 patients (34.4%) had had severe or frequent hypoglycaemia in the preceding six months, during which they had been driving regularly. 34 patients (13.6%) admitted involvement in a driving accident since commencing treatment with insulin, and 13 of these patients were aware that hypoglycaemia had been an important causal factor. The prevalence of diabetic retinopathy and cataracts was considerable, but few patients (2.4%) had severe impairment of vision in both eyes. PMID:6104046
Methionine dependency of cultured human lymphocytes.
Hall, C A; Begley, J A; Chu, R C
Human peripheral blood lymphocytes stimulated with phytohemagglutinin and a lymphocyte model consisting of the RPMI 6410 cell, a human virus-transformed B cell, required added methionine (Met) for growth of the cultures. This failure to meet all needs for Met via endogenous synthesis, which is characteristic of oncogenic transformation, occurred even in the presence of adequate homocysteine, methylfolate (5-CH3-H4PteGlu) and cobalamin (Cbl)-dependent methionine synthetase activity. Folinic acid (5-CHO-H4PteGlu), which provides available folate independently of Cbl, improved growth only slightly in the absence of Met. Free Cbl at 222 nM, an amount great enough to alter other intracellular events, failed to increase growth in the absence of Met, but 0.22 nM Cbl bound to transcobalamin II did, however, enhance growth. PMID:3703873
Selective fishing induces density-dependent growth.
Svedäng, Henrik; Hornborg, Sara
Over the last decades, views on fisheries management have oscillated between alarm and trust in management progress. The predominant policy for remedying the world fishing crisis aims at maximum sustainable yield (MSY) by adjusting gear selectivity and fishing effort. Here we report a case study on how striving for higher yields from the Eastern Baltic cod stock by increasing selectivity has become exceedingly detrimental for its productivity. Although there is a successive increase in numbers of undersized fish, growth potential is severely reduced, and fishing mortality in fishable size has increased. Once density-dependent growth is introduced, the process is self-enforcing as long as the recruitment remains stable. Our findings suggest that policies focusing on maximum yield while targeting greater sizes are risky and should instead prioritize catch rates over yield. Disregarding the underlying population structure may jeopardize stock productivity, with dire consequences for the fishing industry and ecosystem structure and function. PMID:24920387
NAD + -dependent Formate Dehydrogenase from Plants
Alekseeva, A.A.; Savin, S.S.; Tishkov, V.I.
NAD+-dependent formate dehydrogenase (FDH, EC 126.96.36.199) widely occurs in nature. FDH consists of two identical subunits and contains neither prosthetic groups nor metal ions. This type of FDH was found in different microorganisms (including pathogenic ones), such as bacteria, yeasts, fungi, and plants. As opposed to microbiological FDHs functioning in cytoplasm, plant FDHs localize in mitochondria. Formate dehydrogenase activity was first discovered as early as in 1921 in plant; however, until the past decade FDHs from plants had been considerably less studied than the enzymes from microorganisms. This review summarizes the recent results on studying the physiological role, properties, structure, and protein engineering of plant formate dehydrogenases. PMID:22649703
Amplitude dependence of the tune shift
Gelfand, N.M.
Recent studies in the Tevatron have measured the tune shift as a function of the displacement from a closed orbit. The measured values of tune shift were found to be much smaller than one would expect from the measured distribution of the normal octupole moments in the Tevatron. Tracking studies performed to see if, and under what conditions, the observed results could be obtained are reported. The effect of linear coupling is taken into consideration, and is found to significantly reduce the coefficient of the tune shift. The dependence of the tune shift on the initial coordinate of a particle in the presence of a distribution of octupole moments is calculated. The ''smear'' is calculated as a function of linear coupling. (LEW)
View-Dependent Streamline Deformation and Exploration
Tong, Xin; Edwards, John; Chen, Chun-Ming; Shen, Han-Wei; Johnson, Chris R.; Wong, Pak Chung
Occlusion presents a major challenge in visualizing 3D flow and tensor fields using streamlines. Displaying too many streamlines creates a dense visualization filled with occluded structures, but displaying too few streams risks losing important features. We propose a new streamline exploration approach by visually manipulating the cluttered streamlines by pulling visible layers apart and revealing the hidden structures underneath. This paper presents a customized view-dependent deformation algorithm and an interactive visualization tool to minimize visual clutter in 3D vector and tensor fields. The algorithm is able to maintain the overall integrity of the fields and expose previously hidden structures. Our system supports both mouse and direct-touch interactions to manipulate the viewing perspectives and visualize the streamlines in depth. By using a lens metaphor of different shapes to select the transition zone of the targeted area interactively, the users can move their focus and examine the vector or tensor field freely. PMID:26600061
The contact area dependent interfacial thermal conductance
Liu, Chenhan; Wei, Zhiyong; Bi, Kedong; Yang, Juekuan; Chen, Yunfei; Wang, Jian
The effects of the contact area on the interfacial thermal conductance σ are investigated using the atomic Green's function method. Different from the prediction of the heat diffusion transport model, we obtain an interesting result that the interfacial thermal conductance per unit area Λ is positively dependent on the contact area as the area varies from a few atoms to several square nanometers. Through calculating the phonon transmission function, it is uncovered that the phonon transmission per unit area increases with the increased contact area. This is attributed to that each atom has more neighboring atoms in the counterpart of the interface with the increased contact area, which provides more channels for phonon transport.
Operations automation using temporal dependency networks
NASA Technical Reports Server (NTRS)
Cooper, Lynne P.
Precalibration activities for the Deep Space Network are time- and work force-intensive. Significant gains in availability and efficiency could be realized by intelligently incorporating automation techniques. An approach is presented to automation based on the use of Temporal Dependency Networks (TDNs). A TDN represents an activity by breaking it down into its component pieces and formalizing the precedence and other constraints associated with lower level activities. The representations are described which are used to implement a TDN and the underlying system architecture needed to support its use. The commercial applications of this technique are numerous. It has potential for application in any system which requires real-time, system-level control, and accurate monitoring of health, status, and configuration in an asynchronous environment.
Temperature-dependent reflectivity of silicon carbide
NASA Technical Reports Server (NTRS)
Ng, Daniel
The spectral reflectivity of a commercial silicon carbide (SiC) ceramic surface was measured at wavelengths from 2.5 to 14.5 microns and at temperatures ranging from 358 to 520 K using a NASA-developed multiwavelength pyrometer. The SiC surface reflectivity was low at the short wavelengths, decreasing to almost zero at 10 microns, then increasing rapidly to a maximum at approximately 12.5 microns, and decreasing gradually thereafter. The reflectivity maximum increased in magnitude with increasing surface temperature. The wavelength and temperature dependence can be explained in terms of the classical dispersion theory of crystals and the Lorentz electron theory. Electronic transitions between the donor state and the conduction band states were responsible for the dispersion. The concentration of the donor state in SiC was determined to be approximately 4 x 10 exp 18 and its ionization energy was determined to be approximately 71 meV.
Image Compression in Signal-Dependent Noise
NASA Astrophysics Data System (ADS)
Shahnaz, Rubeena; Walkup, John F.; Krile, Thomas F.
The performance of an image compression scheme is affected by the presence of noise, and the achievable compression may be reduced significantly. We investigated the effects of specific signal-dependent-noise (SDN) sources, such as film-grain and speckle noise, on image compression, using JPEG (Joint Photographic Experts Group) standard image compression. For the improvement of compression ratios noisy images are preprocessed for noise suppression before compression is applied. Two approaches are employed for noise suppression. In one approach an estimator designed specifically for the SDN model is used. In an alternate approach, the noise is first transformed into signal-independent noise (SIN) and then an estimator designed for SIN is employed. The performances of these two schemes are compared. The compression results achieved for noiseless, noisy, and restored images are also presented.
Face adaptation depends on seeing the face.
Moradi, Farshad; Koch, Christof; Shimojo, Shinsuke
Retinal input that is suppressed from visual awareness can nevertheless produce measurable aftereffects, revealing neural processes that do not directly result in a conscious percept. We here report that the face identity-specific aftereffect requires a visible face; it is effectively cancelled by binocular suppression or by inattentional blindness of the inducing face. Conversely, the same suppression does not interfere with the orientation-specific aftereffect. Thus, the competition between incompatible or interfering visual inputs to reach awareness is resolved before those aspects of information that are exploited in face identification are processed. We also found that the face aftereffect remained intact when the visual distracters in the inattention experiment were replaced with auditory distracters. Thus, cross-modal or cognitive interference that does not affect the visibility of the face does not interfere with the face aftereffect. We conclude that adaptation to face identity depends on seeing the face. PMID:15629711
Salivary lysozyme in smoking alcohol dependent persons.
Waszkiewicz, Napoleon; Zalewska-Szajda, Beata; Zalewska, Anna; Waszkiewicz, Magdalena; Szajda, Slawomir Dariusz; Repka, Bernadeta; Szulc, Agata; Kepka, Alina; Minarowska, Alina; Ladny, Jerzy Robert; Zwierz, Krzysztof
The purpose of this study was to evaluate the effect of chronic alcohol intoxication and smoking on the concentration and output of salivary lysozyme. Thirty seven men participated in the study, including 17 male smoking alcohol-dependent patients after chronic alcohol intoxication (AS), and 20 control non-smoking male social drinkers (CNS) with no history of alcohol abuse or smoking. The level of lysozyme was assessed by the radial immunodiffusion method. Significantly lower lysozyme output in the AS group compared to the CNS group was found. Moreover, gingival index was significantly higher in AS than in the CNS group. It appeared that the reduced salivary lysozyme output was more likely the result of ethanol action than smoking. In conclusion, persons addicted to alcohol and nicotine have a poorer periodontal status than non-smoking social drinkers, which may partially be due to the diminished protective effects of lysozyme present in the saliva. PMID:23264227
Pharmacological inhibitors of cyclin-dependent kinases.
Knockaert, Marie; Greengard, Paul; Meijer, Laurent
Cyclin-dependent kinases (CDKs) regulate the cell division cycle, apoptosis, transcription and differentiation in addition to functions in the nervous system. Deregulation of CDKs in various diseases has stimulated an intensive search for selective pharmacological inhibitors of these kinases. More than 50 inhibitors have been identified, among which >20 have been co-crystallized with CDK2. These inhibitors all target the ATP-binding pocket of the catalytic site of the kinase. The actual selectivity of most known CDK inhibitors, and thus the underlying mechanism of their cellular effects, is poorly known. Pharmacological inhibitors of CDKs are currently being evaluated for therapeutic use against cancer, alopecia, neurodegenerative disorders (e.g. Alzheimer's disease, amyotrophic lateral sclerosis and stroke), cardiovascular disorders (e.g. atherosclerosis and restenosis), glomerulonephritis, viral infections (e.g. HCMV, HIV and HSV) and parasitic protozoa (Plasmodium sp. and Leishmania sp.). PMID:12237154
On the shape dependence of Entanglement Entropy
NASA Astrophysics Data System (ADS)
Carmi, Dean
We study the shape dependence of entanglement entropy (EE) by deforming symmetric entangling surfaces. We show that entangling surfaces with a rotational or translational symmetry extremize (locally) the EE with respect to shape deformations that break some of the symmetry (i.e. the 1st order correction vanishes). This result applies to EE and Renyi entropy for any QFT in any dimension. Using Solodukhin's formula in 4 d and holography in any d, we calculate the 2nd order correction to the universal EE for CFTs and simple symmetric entangling surfaces. For several entangling surfaces we find that the 2nd order correction is positive for any perturbation, and thus the corresponding symmetric entangling surface is a local minimum. Some of the results are extended to free massive fields and to 4d Renyi entropy.
Load-dependent regulation of neuromuscular system
NASA Technical Reports Server (NTRS)
Ohira, Yoshinobu; Kawano, Fuminori; Stevens, James L.; Wang, Xiao D.; Ishihara, Akihiko
Roles of gravitational loading, sarcomere length, and/or tension development on the electromyogram (EMG) of soleus and afferent neurogram recorded at the L5 segmental level of spinal cord were investigated during parabolic flight of a jet airplane or hindlimb suspension in conscious rats. Both EMG and neurogram levels were increased when the gravity levels were elevated from 1-G to 2-G during the parabolic flight. They were decreased when the hindlimbs were unloaded by exposure to actual microgravity or by suspension. These phenomena were related to passive shortening of muscle fibers and/or sarcomeres. Unloading-related decrease in sarcomere length was greater at the central rather than the proximal and distal regions of fibers. These activities and tension development were not detected when the mean sarcomere length was less than 2.03 micrometers. It is suggested that load-dependent regulation of neuromuscular system is related to the tension development which is influenced by sarcomere length.
Transverse-mode dependence of femtosecond filamentation.
Song, Zhenming; Zhang, Zhigang; Nakajima, Takashi
We theoretically investigate the transverse-mode dependence of femtosecond filamentation in Ar gas. Three different transverse modes, Bessel, Gaussian, and Laguerre modes, are considered for incident laser pulses. By solving the extended nonlinear Schrödinger equation coupled with the electron density equation, we find that the lengths of the filament and the plasma channel induced by the Bessel incident beam is much longer than the other transverse modes with the same peak intensity, pulse duration, and beam diameter. Moreover we find that the temporal profile of the pulse with the Bessel incident mode is nearly undistorted during the propagation. Since the pulse energy that the Bessel beam can carry is more than one order of magnitude larger than the other modes for the same peak intensity, pulse duration, and beam diameter, the Bessel beam can be a very powerful tool in ultrafast nonlinear optics involving propagation in a Kerr medium. PMID:19654624
Colloid particle size-dependent dispersivity
NASA Astrophysics Data System (ADS)
Chrysikopoulos, C. V.; Katzourakis, V. E.
Laboratory and field studies have demonstrated that dispersion coefficients evaluated by fitting advection-dispersion transport models to nonreactive tracer breakthrough curves do not adequately describe colloid transport under the same flow field conditions. Here an extensive laboratory study was undertaken to assess whether the dispersivity, which traditionally has been considered to be a property of the porous medium, is dependent on colloid particle size and interstitial velocity. A total of 49 colloid transport experiments were performed in columns packed with glass beads under chemically unfavorable colloid attachment conditions. Nine different colloid diameters, and various flow velocities were examined. The breakthrough curves were successfully simulated with a mathematical model describing colloid transport in homogeneous, water saturated porous media. The results demonstrated that the dispersivity is positively correlated with colloid particle size, and increases with increasing velocity.
The potential dependence of porous silicon electroluminescence
Riley, D.J.; Peter, L.M.; Wielgosz, R.I.
The observation of visible luminescence from porous silicon has resulted in strong interest in this material. It has been demonstrated that the electrochemical reduction of persulfate ions at a porous silicon electrode/electrolyte interface may lead to intense luminescence (electroluminescence). Further, it has been found that the intensity and wavelength of the electroluminescence is potential dependent, this phenomenon is termed {open_quotes}potential tuning{close_quotes}. This paper is concerned with the elucidation of the mechanism of electroluminescence potential tuning. It will be shown that the process is related to the particle size distribution and the dynamics of electron transfer between the bulk silicon substrate, the surface silicon nanocrystals and the electrolyte. Further, the results of combined in-situ FTIR and electroluminescence studies will be reported. The influence of surface chemistry on the electroluminescence will be discussed with reference to the proposed {open_quotes}tuning{close_quotes} mechanism.
Pseudospectral time-dependent density functional theory
NASA Astrophysics Data System (ADS)
Ko, Chaehyuk; Malick, David K.; Braden, Dale A.; Friesner, Richard A.; Martínez, Todd J.
Time-dependent density functional theory (TDDFT) is implemented within the Tamm-Dancoff approximation (TDA) using a pseudospectral approach to evaluate two-electron repulsion integrals. The pseudospectral approximation uses a split representation with both spectral basis functions and a physical space grid to achieve a reduction in the scaling behavior of electronic structure methods. We demonstrate here that exceptionally sparse grids may be used in the excitation energy calculation, following earlier work employing the pseudospectral approximation for determining correlation energies in wavefunction-based methods with similar conclusions. The pseudospectral TDA-TDDFT method is shown to be up to ten times faster than a conventional algorithm for hybrid functionals without sacrificing chemical accuracy.
Age-dependent dysregulation of innate immunity
Shaw, Albert C.; Goldstein, Daniel R.; Montgomery, Ruth R.
Preface As we age, the innate immune system becomes dysregulated and is characterized by persistent inflammatory responses that involve multiple immune and non-immune cell types, and that vary depending on the cell activation state and tissue context. This ageing-associated basal inflammation, particularly in humans, is thought to be induced by factors including the reactivation of latent viral infections and the release of endogenous damage-associated ligands of pattern recognition receptors (PRRs). Innate immune cell functions, such as cell migration and PRR signalling, that are required to respond to pathogens or vaccines are also impaired in aged individuals. This immune dysregulation may affect conditions associated with chronic inflammation, such as atherosclerosis and Alzheimer's disease. PMID:24157572
Perceptions of benzodiazepine dependence among women age 65 and older.
Canham, Sarah L; Gallo, Joseph; Simoni-Wastila, Linda
A phenomenological study explored whether older women who are chronic benzodiazepine users identified themselves as dependent, how dependence was perceived, and how meanings and understandings shaped experiences of benzodiazepine use. Self-reported benzodiazepine dependence was associated with being unable to reduce use or a desire to discontinue use and reliance on benzodiazepines to remain comfortable and able to handle daily life. Themes included: (a) benzodiazepine dependence is similar to dependence to diabetes or blood pressure medications; (b) dependence is distinctive from addiction/abuse; (c) addiction/abuse is perceived as worse than dependence; and (d) concerns of addiction/abuse result in low-dose benzodiazepine use. PMID:24918963
Perceptions of Benzodiazepine Dependence Among Women Age 65 and Older
Canham, Sarah L.; Gallo, Joseph; Simoni-Wastila, Linda
A phenomenological study explored whether older women who are chronic benzodiazepine users identified themselves as dependent, how dependence was perceived, and how meanings and understandings shaped experiences of benzodiazepine use. Self-reported benzodiazepine dependence was associated with being unable to reduce use or a desire to discontinue use and reliance on benzodiazepines to remain comfortable and able to handle daily life. Themes included: 1) benzodiazepine dependence is similar to dependence to diabetes or blood pressure medications; 2) dependence is distinctive from addiction/abuse; 3) addiction/abuse is perceived as worse than dependence; and 4) concerns of addiction/abuse result in low-dose benzodiazepine use. PMID:24918963
Modafinil for the Treatment of Methamphetamine Dependence
Anderson, Ann L.; Li, Shou-Hua; Biswas, Kousick; McSherry, Frances; Holmes, Tyson; Iturriaga, Erin; Kahn, Roberta; Chiang, Nora; Beresford, Thomas; Campbell, Jan; Haning, William; Mawhinney, Joseph; McCann, Michael; Rawson, Richard; Stock, Christopher; Weis, Dennis; Yu, Elmer; Elkashef, Ahmed M.
Aim Modafinil was tested for efficacy in decreasing use in methamphetamine-dependent participants, compared to placebo. Methods This was a randomized, double-blind, placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Eight outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, who all had a DSM-IV diagnosis of methamphetamine dependence; 68 participants to placebo, 72 to modafinil 200mg, and 70 to modafinil 400mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments, urine drug screens, and group psychotherapy. The primary outcome measure was a methamphetamine non-use week, which required all the week's qualitative urine drug screens to be negative for methamphetamine. Results Regression analysis showed no significant difference between either modafinil group (200 or 400mg) and placebo in change in weekly percentage having a methamphetamine non-use week over the 12-week treatment period (p=0.53). Similarly, a number of secondary outcomes did not show significant effects of modafinil. However, an ad-hoc analysis of medication compliance, by urinalysis for modafinil and its metabolite, did find a significant difference in maximum duration of abstinence (23 days vs. 10 days, p=0.003), between those having the top quartile of compliance (>85% urines modafinil +, N=36), and the lower three quartiles of modafinil 200 and 400mg groups (N=106). Conclusions Although these data suggest that modafinil, plus group behavioral therapy, was not effective for decreasing methamphetamine use, the study is probably inconclusive because of inadequate compliance with taking medication. PMID:21840138
Motor skill depends on knowledge of facts
Stanley, Jason; Krakauer, John W.
Those in 20th century philosophy, psychology, and neuroscience who have discussed the nature of skilled action have, for the most part, accepted the view that being skilled at an activity is independent of knowing facts about that activity, i.e., that skill is independent of knowledge of facts. In this paper we question this view of motor skill. We begin by situating the notion of skill in historical and philosophical context. We use the discussion to explain and motivate the view that motor skill depends upon knowledge of facts. This conclusion seemingly contradicts well-known results in cognitive science. It is natural, on the face of it, to take the case of H.M., the seminal case in cognitive neuroscience that led to the discovery of different memory systems, as providing powerful evidence for the independence of knowledge and skill acquisition. After all, H.M. seems to show that motor learning is retained even when previous knowledge about the activity has been lost. Improvements in skill generally require increased precision of selected actions, which we call motor acuity. Motor acuity may indeed not require propositional knowledge and has direct parallels with perceptual acuity. We argue, however, that reflection on the specifics of H.M.'s case, as well as other research on the nature of skill, indicates that learning to become skilled at a motor task, for example tennis, depends also on knowledge-based selection of the right actions. Thus skilled activity requires both acuity and knowledge, with both increasing with practice. The moral of our discussion ranges beyond debates about motor skill; we argue that it undermines any attempt to draw a distinction between practical and theoretical activities. While we will reject the independence of skill and knowledge, our discussion leaves open several different possible relations between knowledge and skill. Deciding between them is a task to be resolved by future research. PMID:24009571
Thermal cracking and amplitude dependent attenuation
Johnston, D.H.; Toksoez, M.N.
The role of crack and grain boundary contacts in determining seismic wave attenuation in rock is investigated by examining Q as a function of thermal cycling (cracking) and wave strain amplitude. Q values are obtained using a longitudinal resonant bar technique in the 10- to 20-kHz range for maximum strain amplitudes varying from roughly 10/sup -8/ to 10/sup -5/. The samples studied include the Berea and Navajo sandstones, Plexiglas, Westerly granite, Solenhofen limestone, and Frederick diabase, the latter two relatively crack free in their virgin state. Measurements were made at room temperature and pressure in air. Q values for both sandstones are constant at low strains (<10/sup -6/) but decrease rapidly with amplitude at higher strains. There is no hysteresis of Q with amplitude. Q values for Plexiglas show no indication of amplitude dependent behavior. The granite, limestone, and diabase are thermally cycled at both fast and slow heating rates in order to induce cracking. Samples slowly cycled at 400/sup 0/C show a marked increase in Q that cannot be entirely explained by outgassing of volatiles. Cycling may also widen thin cracks and grain boundaries, reducing contact areas. Samples heated beyond 400/sup 0/C, or rapidly heated, result in generally decreasing Q values. The amplitude dependence of Q is found to be coupled to the effects of thermal cycling. For rock slowly cycled 400)C or less, the transition from low-amplitude contant Q to high-amplitude variable Q behavior decreases to lower amplitudes as a function of maximum temperature. Above 400/sup 0/C, and possibly in th rapidly heated samples also, the transition moves to higher amplitudes.
Solvent viscosity dependence for enzymatic reactions
NASA Astrophysics Data System (ADS)
Sitnitsky, A. E.
A mechanism for relationship of solvent viscosity with reaction rate constant at enzyme action is suggested. It is based on fluctuations of electric field in enzyme active site produced by thermally equilibrium rocking (crankshaft motion) of the rigid plane (in which the dipole moment ≈3.6 D lies) of a favourably located and oriented peptide group (or may be a few of them). Thus the rocking of the plane leads to fluctuations of the electric field of the dipole moment. These fluctuations can interact with the reaction coordinate because the latter in its turn has transition dipole moment due to separation of charges at movement of the reacting system along it. The rocking of the plane of the peptide group is sensitive to the microviscosity of its environment in protein interior and the latter is a function of the solvent viscosity. Thus we obtain an additional factor of interrelationship for these characteristics with the reaction rate constant. We argue that due to the properties of the crankshaft motion the frequency spectrum of the electric field fluctuations has a sharp resonance peak at some frequency and the corresponding Fourier mode can be approximated as oscillations. We employ a known result from the theory of thermally activated escape with periodic driving to obtain the reaction rate constant and argue that it yields reliable description of the pre-exponent where the dependence on solvent viscosity manifests itself. The suggested mechanism is shown to grasp the main feature of this dependence known from the experiment and satisfactorily yields the upper limit of the fractional index of a power in it.