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Publications (343)937.84 Total impact
Article: Multi-gradient echo MR thermometry for monitoring of the near-field area during MR-guided high intensity focused ultrasound heating[Show abstract] [Hide abstract]
ABSTRACT: The multi-gradient echo MR thermometry (MGE MRT) method is proposed to use at the interface of the muscle and fat layers found in the abdominal wall, to monitor MR-HIFU heating. As MGE MRT uses fat as a reference, it is field-drift corrected. Relative temperature maps were reconstructed by subtracting absolute temperature maps. Because the absolute temperature maps are reconstructed of individual scans, MGE MRT provides the flexibility of interleaved mapping of temperature changes between two arbitrary time points. The method's performance was assessed in an ex vivo water bath experiment. An ex vivo HIFU experiment was performed to show the method's ability to monitor heating of consecutive HIFU sonications and to estimate cooling time constants, in the presence of field drift. The interleaved use between scans of a clinical protocol was demonstrated in vivo in a patient during a clinical uterine fibroid treatment. The relative temperature measurements were accurate (mean absolute error 0.3 °C) and provided excellent visualization of the heating of consecutive HIFU sonications. Maps were reconstructed of estimated cooling time constants and mean ROI values could be well explained by the applied heating pattern. Heating upon HIFU sonication and subsequent cooling could be observed in the in vivo demonstration.Physics in Medicine and Biology 09/2015; 60(19):7729-7746. DOI:10.1088/0031-9155/60/19/7729 · 2.76 Impact Factor
Article: Intercostal high intensity focused ultrasound for liver ablation: The influence of beam shaping on sonication efficacy and near-field risks[Show abstract] [Hide abstract]
ABSTRACT: Purpose: One of the major issues in high intensity focused ultrasound ablation of abdominal lesions is obstruction of the ultrasound beam by the thoracic cage. Beam shaping strategies have been shown by several authors to increase focal point intensity while limiting rib exposure. However, as rib obstruction leaves only part of the aperture available for energy transmission, conserving total emitted acoustic power, the intensity in the near-field tissues inherently increases after beam shaping. Despite of effective rib sparing, those tissues are therefore subjected to increased risk of thermal damage. In this study, for a number of clinically representative intercostal sonication geometries, modeling clinically available hardware, the effect of beam shaping on both the exposure of the ribs and near-field to acoustic energy was evaluated and the implications for the volumetric ablation rate were addressed.Medical Physics 08/2015; 42(8):4685. DOI:10.1118/1.4925056 · 2.64 Impact Factor
Article: Recruitment of endocytosis in sonopermeabilization-mediated drug delivery: A real-time study[Show abstract] [Hide abstract]
ABSTRACT: Microbubbles (MBs) in combination with ultrasound (US) can enhance cell membrane permeability, and have the potential to facilitate the cellular uptake of hydrophilic molecules. However, the exact mechanism behind US- and MB-mediated intracellular delivery still remains to be fully understood. Among the proposed mechanisms are formation of transient pores and endocytosis stimulation. In our study, we investigated whether endocytosis is involved in US- and MB-mediated delivery of small molecules. Dynamic fluorescence microscopy was used to investigate the effects of endocytosis inhibitors on the pharmacokinetic parameters of US- and MB-mediated uptake of SYTOX Green, a 600 Da hydrophilic model drug. C6 rat glioma cells, together with SonoVue(®) MBs, were exposed to 1.4 MHz US waves at 0.2 MPa peak-negative pressure. Collection of the signal intensity in each individual nucleus was monitored during and after US exposure by a fibered confocal fluorescence microscope designed for real-time imaging. Exposed to US waves, C6 cells pretreated with chlorpromazine, an inhibitor of clathrin-mediated endocytosis, showed up to a 2.5-fold significant increase of the uptake time constant, and a 1.1-fold increase with genistein, an inhibitor of caveolae-mediated endocytosis. Both inhibitors slowed down the US-mediated uptake of SYTOX Green. With C6 cells and our experimental settings, these quantitative data indicate that endocytosis plays a role in sonopermeabilization-mediated delivery of small molecules with a more predominant contribution of clathrin-mediated endocytosis.Physical Biology 07/2015; 12(4):046010. DOI:10.1088/1478-3975/12/4/046010 · 2.54 Impact Factor
Article: A framework for the correction of slow physiological drifts during MR-guided HIFU therapies: Proof of concept[Show abstract] [Hide abstract]
ABSTRACT: Purpose: While respiratory motion compensation for magnetic resonance (MR)-guided high intensity focused ultrasound (HIFU) interventions has been extensively studied, the influence of slow physiological motion due to, for example, peristaltic activity, has so far been largely neglected. During lengthy interventions, the magnitude of the latter can exceed acceptable therapeutic margins. The goal of the present study is to exploit the episodic workflow of these therapies to implement a motion correction strategy for slow varying drifts of the target area and organs at risk over the entire duration of the intervention.Medical Physics 07/2015; 42(7):4137. DOI:10.1118/1.4922403 · 2.64 Impact Factor
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ABSTRACT: The combination of microbubbles and ultrasound has emerged as a promising method for local drug delivery. Microbubbles can be locally activated by a targeted ultrasound beam, which can result in several bio-effects. For drug delivery, microbubble-assisted ultrasound is used to increase vascular- and plasma membrane permeability for facilitating drug extravasation and the cellular uptake of drugs in the treated region, respectively. In the case of drug-loaded microbubbles, these two mechanisms can be combined with local release of the drug following destruction of the microbubble. The use of microbubble-assisted ultrasound to deliver chemotherapeutic agents is also referred to as sonochemotherapy. In this review, the basic principles of sonochemotherapy are discussed, including aspects such as the type of (drug-loaded) microbubbles used, the routes of administration used in vivo, ultrasound devices and parameters, treatment schedules and safety issues. Finally, the clinical translation of sonochemotherapy is discussed, including the first clinical study using sonochemotherapy.Frontiers in Pharmacology 07/2015; 6:138. DOI:10.3389/fphar.2015.00138 · 3.80 Impact Factor
Article: MRI methods for the evaluation of high intensity focused ultrasound tumor treatment: Current status and future needs[Show abstract] [Hide abstract]
ABSTRACT: Thermal ablation with high intensity focused ultrasound (HIFU) is an emerging noninvasive technique for the treatment of solid tumors. HIFU treatment of malignant tumors requires accurate treatment planning, monitoring and evaluation, which can be facilitated by performing the procedure in an MR-guided HIFU system. The MR-based evaluation of HIFU treatment is most often restricted to contrast-enhanced T1 -weighted imaging, while it has been shown that the non-perfused volume may not reflect the extent of nonviable tumor tissue after HIFU treatment. There are multiple studies in which more advanced MRI methods were assessed for their suitability for the evaluation of HIFU treatment. While several of these methods seem promising regarding their sensitivity to HIFU-induced tissue changes, there is still ample room for improvement of MRI protocols for HIFU treatment evaluation. In this review article, we describe the major acute and delayed effects of HIFU treatment. For each effect, the MRI methods that have been-or could be-used to detect the associated tissue changes are described. In addition, the potential value of multiparametric MRI for the evaluation of HIFU treatment is discussed. The review ends with a discussion on future directions for the MRI-based evaluation of HIFU treatment. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.Magnetic Resonance in Medicine 06/2015; DOI:10.1002/mrm.25758 · 3.57 Impact Factor
Article: Spatiotemporal control of gene expression in bone-marrow derived cells of the tumor microenvironment induced by MRI guided focused ultrasound[Show abstract] [Hide abstract]
ABSTRACT: The tumor microenvironment is an interesting target for anticancer therapies but modifying this compartment is challenging. Here, we demonstrate the feasibility of a gene therapy strategy that combined targeting to bone marrow-derived tumor microenvironment using genetically modified bone-marrow derived cells and control of transgene expression by local hyperthermia through a thermo-inducible promoter. Chimera were obtained by engraftment of bone marrow from transgenic mice expressing reporter genes under transcriptional control of heat shock promoter and inoculated sub-cutaneously with tumors cells. Heat shocks were applied at the tumor site using a water bath or magnetic resonance guided high intensity focused ultrasound device. Reporter gene expression was followed by bioluminescence and fluorescence imaging and immunohistochemistry. Bone marrow-derived cells expressing reporter genes were identified to be mainly tumor-associated macrophages. We thus provide the proof of concept for a gene therapy strategy that allows for spatiotemporal control of transgenes expression by macrophages targeted to the tumor microenvironment.Oncotarget 06/2015; 6(27). DOI:10.18632/oncotarget.4288 · 6.36 Impact Factor
Article: Influence of water and fat heterogeneity on fat-referenced MR thermometry: Influence of Water/Fat Heterogeneity on Fat-Referenced MR Thermometry[Show abstract] [Hide abstract]
ABSTRACT: To investigate the effect of the aqueous and fatty tissue magnetic susceptibility distribution on absolute and relative temperature measurements as obtained directly from the water/fat (w/f) frequency difference. Absolute thermometry was investigated using spherical phantoms filled with pork and margarine, which were scanned in three orthogonal orientations. To evaluate relative fat referencing, multigradient echo scans were acquired before and after heating pork tissue via high-intensity focused ultrasound (HIFU). Simulations were performed to estimate the errors that can be expected in human breast tissue. The sphere experiment showed susceptibility-related errors of 8.4°C and 0.2°C for pork and margarine, respectively. For relative fat referencing measurements, fat showed pronounced phase changes of opposite polarity to aqueous tissue. The apparent mean temperature for a numerical breast model assumed to be 37°C was 47.2 ± 21.6°C. Simulations of relative fat referencing for a HIFU sonication (ΔT = 29.7°C) yielded a maximum temperature error of 6.6°C compared with 2.5°C without fat referencing. Variations in the observed frequency difference between water and fat are largely due to variations in the w/f spatial distribution. This effect may lead to considerable errors in absolute MR thermometry. Additionally, fat referencing may exacerbate rather than correct for proton resonance frequency shift-temperature measurement errors. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.Magnetic Resonance in Medicine 05/2015; DOI:10.1002/mrm.25727 · 3.57 Impact Factor
Article: Real-time estimation and characterization of physiological organ deformations for MR-guided interventional therapies
Article: Correction of Photobleaching for the Assessment of Pharmacokinetic Parameters using Dynamic Fluorescence Microscopy
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ABSTRACT: High-intensity focused ultrasound allows for minimally invasive, highly localized cancer therapies that can complement surgical procedures or chemotherapy. For high-intensity focused ultrasound interventions in the upper abdomen, the thoracic cage obstructs and aberrates the ultrasonic beam, causing undesired heating of healthy tissue. When a phased array therapeutic transducer is used, such complications can be minimized by applying an apodization law based on analysis of beam path obstructions. In this work, a rib detection method based on cavitation-enhanced ultrasonic reflections is introduced and validated on a porcine tissue sample containing ribs. Apodization laws obtained for different transducer positions were approximately 90% similar to those obtained using image analysis. Additionally, the proposed method provides information on attenuation between transducer elements and the focus. This principle was confirmed experimentally on a polymer phantom. The proposed methods could, in principle, be implemented in real time for determination of the optimal shot position in intercostal high-intensity focused ultrasound therapy. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.Ultrasound in medicine & biology 04/2015; 41(6). DOI:10.1016/j.ultrasmedbio.2015.01.024 · 2.21 Impact Factor
Article: Performance analysis of a dedicated breast MR-HIFU system for tumor ablation in breast cancer patients[Show abstract] [Hide abstract]
ABSTRACT: MR-guided HIFU ablation is a promising technique for the non-invasive treatment of breast cancer. A phase I study was performed to assess the safety and treatment accuracy and precision of MR-HIFU ablation in breast cancer patients (n=10) using a newly developed MR-HIFU platform dedicated to applications in the breast. In this paper a technical analysis of the performance of the dedicated breast MR-HIFU system during breast tumors ablation is described. The main points of investigation were the spatial targeting accuracy and precision of the system and the performance of real-time respiration-corrected MR thermometry.The mean targeting accuracy was in the range of 2.4-2.6 mm, whereas the mean targeting precision was in the range of 1.5-1.8 mm. To correct for respiration-induced magnetic field fluctuations during MR temperature mapping a look-up-table (LUT)-based correction method was used. An optimized procedural sedation protocol in combination with the LUT-based correction method allowed for precise MR thermometry during the ablation procedure (temperature standard deviation <3 °C). No unwanted heating in the near field (i.e. skin) nor in the far field (pectoral muscle) was detected.The newly developed dedicated breast MR-HIFU system allows for safe, accurate and precise ablation of breast tumors.Physics in Medicine and Biology 03/2015; 60(14). DOI:10.1088/0031-9155/60/14/5527 · 2.76 Impact Factor
Article: Development of a tumor tissue-mimicking model with endothelial cell layer and collagen gel for evaluating drug penetration[Show abstract] [Hide abstract]
ABSTRACT: The endothelial cells of vessels, the interstitial matrix and the distance between the tumor cells and vessels, are the major penetration barriers for intravenously administered anticancer drugs in reaching tumor cells after intravenous injection. The availability of a tumor tissue-mimicking model that includes both the endothelial cell layer and the extracellular matrix would be beneficial to assess drug penetration in early stages of drug development. Here, we propose a novel in vitro model for studying the above mentioned barriers. Human umbilical vein endothelial cells were cultured as a single layer on a collagen type-I coated permeable cell culture insert. After culturing for five days, the insert was superimposed on collagen type-I gel containing cancer cells. The system was evaluated for assessing penetration-enhancement by ultrasound triggered microbubble cavitation. Our model allowed visualization of the penetration distance of a model drug (fluorescein isothiocyanate-Dextran 500,000-conjugated, FD500) from the endothelial cell layer into the cancer cell containing collagen matrix upon different sonication treatments. Initial results showed that the model allows the visualization of drug penetration and that the endothelial cell layer is affecting this. The presented in vitro model aims to mimic vessels and stromal tissue in cancer, and thus can aid in the assessment of drug penetration in the case of tumor-targeted drug delivery, and in the reduction and refinement of animal studies. Copyright © 2015. Published by Elsevier B.V.International Journal of Pharmaceutics 01/2015; 482(1-2). DOI:10.1016/j.ijpharm.2015.01.039 · 3.65 Impact Factor
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ABSTRACT: Ultrasound (US) induced cavitation can be used to enhance the intracellular delivery of drugs by transiently increasing the cell membrane permeability. The duration of this increased permeability, termed temporal window, has not been fully elucidated. In this study, the temporal window was investigated systematically using an endothelial- and two breast cancer cell lines. Model drug uptake was measured as a function of time after sonication, in the presence of SonoVue™ microbubbles, in HUVEC, MDA-MB-468 and 4T1 cells. In addition, US pressure amplitude was varied in MDA-MB-468 cells to investigate its effect on the temporal window. Cell membrane permeability of HUVEC and MDA-MB-468 cells returned to control level within 1-2h post-sonication, while 4T1 cells needed over 3h. US pressure affected the number of cells with increased membrane permeability, as well as the temporal window in MDA-MB-468 cells. This study shows that the duration of increased membrane permeability differed between the cell lines and US pressures used here. However, all were consistently in the order of 1-3h after sonication. Copyright © 2014. Published by Elsevier B.V.International Journal of Pharmaceutics 12/2014; 482(1-2). DOI:10.1016/j.ijpharm.2014.12.013 · 3.65 Impact Factor
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ABSTRACT: Dynamic MR-imaging can provide functional and positional information in real-time, which can be conveniently used on-line to control a cancer therapy, e.g. using High Intensity Focused Ultrasound or Radio Therapy. However, a precise realtime correction for motion is fundamental in abdominal organs to ensure an optimal treatment dose associated with a limited toxicity in nearby organs at risk. This paper proposes a real-time direct PCA-based technique which offers a robust approach for motion estimation of abdominal organs and allows correcting motion related artifacts. The PCA was used to detect spatio-temporal coherences of the periodic organ motion in a learning step. During the interventional procedure, physiological contributions were characterized quantitatively using a small set of parameters. A coarse-to-fine resolution scheme is proposed to improve the stability of the algorithm and afford a predictable constant latency of 80 ms. The technique was evaluated on 12 free-breathing volunteers and provided an improved real-time description of motion related to both breathing and cardiac cycles. A reduced learning step of 10 s was sufficient without any need for patient-specific control parameters, rendering the method suitable for clinical use.IEEE Transactions on Medical Imaging 11/2014; 34(4). DOI:10.1109/TMI.2014.2371995 · 3.39 Impact Factor
Article: Rapid Dynamic Temperature/T1/T2* Assessment: A Method With Potential For Monitoring Drug Delivery[Show abstract] [Hide abstract]
ABSTRACT: Local drug delivery by hyperthermia-induced drug release from thermosensitive liposomes (TSLs) may reduce the systemic toxicity of chemotherapy, whilst maintaining or increasing its efficacy. Relaxivity contrast agents can be co-encapsulated with the drug to allow the visualization of the presence of liposomes, by means of R2 *, as well as the co-release of the contrast agent and the drug, by means of R1, on heating. Here, the mathematical method used to extract both R2 * and R1 from a fast dynamic multi-echo spoiled gradient echo (ME-SPGR) is presented and analyzed. Finally, this method is used to monitor such release events. R2 * was obtained from a fit to the ME-SPGR data. Absolute R1 was calculated from the signal magnitude changes corrected for the apparent proton density changes and a baseline Look-Locker R1 map. The method was used to monitor nearly homogeneous water bath heating and local focused ultrasound heating of muscle tissue, and to visualize the release of a gadolinium chelate from TSLs in vitro. R2 *, R1 and temperature maps were measured with a 5-s temporal resolution. Both R2 *and R1 measured were found to change with temperature. The dynamic R1 measurements after heating agreed with the Look-Locker R1 values if changes in equilibrium magnetization with temperature were considered. Release of gadolinium from TSLs was detected by an R1 increase near the phase transition temperature, as well as a shallow R2 * increase. Simultaneous temperature, R2 * and R1 mapping is feasible in real time and has the potential for use in image-guided drug delivery studies. Copyright © 2014 John Wiley & Sons, Ltd.NMR in Biomedicine 11/2014; 27(11). DOI:10.1002/nbm.3182 · 3.04 Impact Factor
Conference Paper: Volumetric MR-guided high-intensity focused ultrasound with direct skin cooling for the treatment of symptomatic uterine fibroids: proof of concept studyFocused Ultrasound Symposium, Washington DC; 10/2014
Article: Feasibility of volumetric MRI-guided high intensity focused ultrasound (MR-HIFU) for painful bone metastases[Show abstract] [Hide abstract]
ABSTRACT: Background Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has recently emerged as an effective treatment option for painful bone metastases. We describe here the first experience with volumetric MR-HIFU for palliative treatment of painful bone metastases and evaluate the technique on three levels: technical feasibility, safety, and initial effectiveness. Methods In this observational cohort study, 11 consecutive patients (7 male and 4 female; median age, 60 years; age range, 53–86 years) underwent 13 treatments for 12 bone metastases. All patients exhibited persistent metastatic bone pain refractory to the standard of care. Patients were asked to rate their worst pain on an 11-point pain scale before treatment, 3 days after treatment, and 1 month after treatment. Complications were monitored. All data were prospectively recorded in the context of routine clinical care. Response was defined as a ≥2-point decrease in pain at the treated site without increase in analgesic intake. Baseline pain scores were compared to pain scores at 3 days and 1 month using the Wilcoxon signed-rank test. For reporting, the STROBE guidelines were followed. Results No treatment-related major adverse events were observed. At 3 days after volumetric MR-HIFU ablation, pain scores decreased significantly (p = 0.045) and response was observed in a 6/11 (55%) patients. At 1-month follow-up, which was available for nine patients, pain scores decreased significantly compared to baseline (p = 0.028) and 6/9 patients obtained pain response (overall response rate 67% (95% confidence interval (CI) 35%–88%)). Conclusions This is the first study reporting on the volumetric MR-HIFU ablation for painful bone metastases. No major treatment-related adverse events were observed during follow-up. The results of our study showed that volumetric MR-HIFU ablation for painful bone metastases is technically feasible and can induce pain relief in patients with metastatic bone pain refractory to the standard of care. Future research should be aimed at standardization of the treatment procedures and treatment of larger numbers of patients to assess treatment effectiveness and comparison to the standard of care.10/2014; 2(1):16. DOI:10.1186/2050-5736-2-16
Article: In Vivo T-2-Based MR Thermometry in Adipose Tissue Layers for High-Intensity Focused Ultrasound Near-Field Monitoring[Show abstract] [Hide abstract]
ABSTRACT: During MR-guided high-intensity focused ultrasound (HIFU) therapy, ultrasound absorption in the near field represents a safety risk and limits efficient energy deposition at the target. In this study, we investigated the feasibility of using T2 mapping to monitor the temperature change in subcutaneous adipose tissue layers. The T2 temperature dependence and reversibility was determined for fresh adipose porcine samples. The accuracy was evaluated by comparing T2 -based temperature measurements with probe readings in an ex vivo HIFU experiment. The in vivo feasibility of T2 -based thermometry was studied during HIFU ablations in the liver in pigs and of uterine fibroids in human patients. T2 changed linearly and reversibly with temperature with an average coefficient of 5.2 ± 0.1 ms/°C. For the ex vivo HIFU experiment, the difference between the T2 -based temperature change and the probe temperature was <0.9°C. All in vivo experiments showed temperature-related T2 changes in the near field directly after sonications. As expected, considerable intersubject variations in the cooling times were measured in the in vivo porcine experiments. The reversibility and linearity of the T2 -temperature dependence of adipose tissue allows for the monitoring of the temperature in the subcutaneous adipose tissue layers. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.Magnetic Resonance in Medicine 10/2014; 72(4). DOI:10.1002/mrm.25025 · 3.57 Impact Factor
Top Journals
University Medical Center Utrecht
Utrecht, Utrecht, Netherlands
- Division of Imaging
Netherlands Institute for Space Research, UtrechtUtrecht, Utrecht, Netherlands
University of BordeauxBurdeos, Aquitaine, France
French National Centre for Scientific ResearchLutetia Parisorum, Île-de-France, France
Université Victor Segalen Bordeaux 2
Burdeos, Aquitaine, France
- Centre de Résonance Magnétique des Systèmes Biologiques
Georgetown University
Rockville, MD, United States
- Department of Pharmacology
NCI-FrederickФредерик, Maryland, United States
Centre Hospitalier Universitaire de BordeauxBurdeos, Aquitaine, France
Aarhus University Hospital
Århus, Central Jutland, Denmark
- Institute of Clinical Medicine
University of ToursTours, Centre, France
National Institutes of Health
Maryland, United States
- Laboratory of Research Technologies
National Institute of Mental Health (NIMH)
Bethesda, MD, United States
- Clinical Brain Disorders Branch
Johns Hopkins University
Baltimore, Maryland, United States
- Department of Radiology
College of Saint ElizabethWashington, Washington, D.C., United States
Royal College of Surgeons of EnglandLondinium, England, United Kingdom
Wageningen University
Wageningen, Provincie Gelderland, Netherlands
- Laboratory of Biochemistry
University of California, Davis
Davis, California, United States
- Department of Pediatrics


text: Recently sayed at the Rialto to go to a concert in Melbourne. Easy walking distance to the Road Laver Arena. Very polite staff who remember your name every time they greet you - even the door staff! The evening meal was fabulous, the breakfast was wonderful, the room was up to the standard that you would expect, the rooms were very quiet, cleanliness was outstanding. Love the ambiance and the history of the Rialto.

subset: commoncrawl


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Shifts in Attitude Kill Off Suburban Gay Bars
PHILADELPHIA - David Ralston came out in the early 1990s the only way he knew how: He went to a gay bar.
Not just any gay bar, but one in the suburbs, far from his Northeast Philadelphia home and the eyes of anyone in his large Irish Catholic family.
"I would still feel funny going into gay bars in Philadelphia," Ralston, now 46, recalled. "I would wonder who's watching me going in and out? Who's going to tell my mother?"
So he drove to Gatsby's in Cherry Hill, just one of a wide variety of gay bars tucked discreetly in the suburbs at the time. There was the Lark in Bridgeport, for instance, and the CR Bar was in Upper Darby. New Hope had three.
No more.
Suburban gay bars have all but disappeared. New Hope supports only one gay bar now, the Raven.
The decline reflects major shifts in American attitudes - among both gay and straight people - and the emergence of online sites for dating and hooking up.
It also illuminates the obsolete business model of the traditional gay bar. Simply having a gay clientele is not enough and has not been for a long time.
"Those were our ghetto bars," Mark Segal, publisher of the Philadelphia Gay News, said of some of the windowless places in the suburbs. "We were stuck there. Today we're not stuck. Our dollars are welcomed everywhere."
He added: "There was a time when a gay couple could only go to the gay bars in New Hope. Can you imagine today a couple not feeling comfortable going to almost any bar there?"
In 2007, Entrepreneur magazine listed gay bars - along with newspapers and record stores - among 10 businesses facing extinction in 10 years. "The very best of them will endure; the rest won't," the magazine wrote.
In 2011, Slate magazine noted a 12.5 percent decrease in the number of gay bars nationwide since 2005.
Brett Bumgarner, who is writing his dissertation on how gay men meet, said gay bars are perceived less as singles places now, their original purpose replaced by cellphone applications such as Grindr that signal users when another interested gay man is nearby.
"A lot of people I know have talked about feeling uncomfortable because someone 40 years their senior is aggressively flirting with them," said Bumgarner, 28, who studies at the University of Pennsylvania. "I think that's what has attracted people to non-gay bars now."
Younger people in particular - both gay and straight - are more interested in mixed settings. Straight bars, for instance, are offering gay nights.
Suburban gay bars also have had to compete with Philadelphia, an increasingly safer and younger city with a thriving "Gayborhood" that allows folks to bar hop.
"It's very difficult for the suburban bar to compete with the city," said Malcolm Lazin, executive director of the Equality Forum. "When you go to a smaller bar (in the suburbs), it's probably less interesting, less upscale, has fewer people and the same people."
Bob Skiba, director of the LGBT (lesbian, gay, bisexual and transgender) archive at the William Way Center in Philadelphia, said gay bars date to the 19th century in Philadelphia. They proliferated with speakeasies in the 1920s. Their numbers rose again after World War II when an entertainment district sprouted along 13th Street and Locust.


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Police: Speed leads to chargeNovember 29,2013Police: Speed
leads to charge
WEATHERSFIELD A White River Junction woman is facing charges after allegedly driving too fast during a storm Wednesday night.
Vermont State Police Trooper Timothy Gould said 19-year-old Makenzie Baker was driving at a high rate of speed during inclement weather and poor road conditions when he pulled her over as she drove south on Interstate 91.
Baker was taken to the Springfield Police Department where she was charged with negligent operation of a vehicle. She was released with a citation to appear Jan. 21 in White River Junction criminal court.MORE IN This Just In
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Woman cited
after crash
POULTNEY — A Poultney woman was cited and released ... Full StoryBENNINGTON A Massachusetts man is facing a felony charge after police said he was driving in a... Full Story
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Tampa Country Bars & Clubs
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The Dallas Bull was named Tampa's most popular nightclub by the Tampa Bay Times and upholds their reputation by housing 20,000 unique visitors each month...
18 Over | Billiards Pool | College | Country | Dance
Located in the heart of Ybor City on 7th Ave, Coyote Ugly Tampa is a country and rock saloon featuring lady bartenders dancing on the bar, cold beer and...
Biker | Country | Happy Hour | Rock
Country Western Club located in North West Tampa featuring a 3,000-foot dance floor and two main bar areas for plenty of partying space to bring out a big...
Country | Dance
The Parrot offers great food, cold beer and liquor drinks all day every day. Daily Lunch Specials, Happy Hour and Shot Specials and always a good friendly...
American | Carryout | 18 Over | Billiards Pool | College
The Chelsea has closed permanently.
18 Over | Adult Entertainment | Billiards Pool | College | Country
Uncle Mike's is located inside the Harley Davidson Dealership on HIghway 60 in Brandon. Outdoor dining with waterview. Great location to have private parties...
American | Barbecue | Breakfast | Carryout | Catering
Southern Ground Saloon is a country bar in North Tampa located on Nebraska Ave between Fletcher and Bearss Avenue. They take pride in offering true southern...
A saloon-style bar in SoHo featuring an awesome country environment, great drinks, live entertainment, and much more. Now serving FULL LIQUOR.
College | Country | Live Music | Neighborhood and Dive | Rock
At Whiskey Dicks...We make em stiff! Live music, professional bartenders, hot women serving beer, and did we mention live music every night? Sundays- Bikes-Blues-n-BBQ...
Biker | Billiards Pool | College | Comedy | Country
YOUR NEIGHBORHOOD PUB!!Now open Mon - Fri: 3pm to 3am Sat - Sun: 12pm to 3am. Join us for Happy Hour 3pm-7pm Monday-Friday 2-for-1 Drafts and Well drinks.Poker...
18 Over | Adult Entertainment | Biker | Billiards Pool | Brewery
18 Over | Biker | Billiards Pool | Brewery | Cigar
A great combination of food, drink, music and atmosphere is here. Keep checking in for updates, menus, hours and entertainment schedules. SEE YOU SOON!!!!!
American | Barbecue | Carryout | Catering | Mexican
The End Zone Bar and Grill, South Tampa Sports Bar with lots of beer specials and a daily happy hour.
18 Over | Biker | Billiards Pool | College | Country
Fun, Local Plant City Bar offering live music. Become a regular here!
Biker | Country | Live Music | Neighborhood and Dive | Rock
Quail Hollow is a hidden gem in Wesley Chapel, it's a must see to believe! Amazing food, golf, 2 vegas style pools, VIP cabanas, private parties and the...
American | Catering | Biker | Cigar | College


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Taylor Swift
Sponsored By
Taylor Swift Donates $50K to Backup Dancer's Family MemberTaylor Swift has once again used her fame and fortune for the greater good.
Watch Taylor Swift and Haim Play Back-Up for Nelly's 'Hot In Herre'Needless to say, it got really hot in therre.
Taylor Swift Denies Mansion & Marriage Rumors
Watch: Taylor Swift Brings Kelsea Ballerini On StageTaylor Swift and Kelsea Ballerini sing "Love Me Like You Mean It"
Watch Taylor Swift Have an Epic Dance Party with 7-Year-Old SuperfanThey look like they're having a really good time.
Watch Taylor Swift & Dierks Bentley Perform 'Every Mile A Memory'Dierk's lucky boots didn't stay retired long.
Taylor Swift, Ryan Adams Talk '1989' Covers Album"They're not just cover songs, they're re-imaginings of my songs.
Why Taylor Swift Owes Eric Church Big TimeChurch's Country Music Hall of Fame exhibit features a piece you might not be expecting.
Listen to Ryan Adam's Cover of Taylor Swift's 'Bad Blood,' Full '1989' Album Arrives MondayThe album drops Monday, September 21.
Watch Taylor Swift and The Band Perry Perform 'If I Die Young'"I still am such a huge fan of country music, and, in my opinion, the people I'm about to bring out are some of best musicians."
Taylor Swift's Emmy Brings Her Halfway to 'EGOT'Now she just needs and Oscar and a Tony.
Inspirational T Swift and CornIf you were able to catch Taylor over the weekend and loved the message that she shared about self worth, you're going to enjoy this. If you love Corn, you're going to enjoy this. If you like Taylor Swift AND Corn, you're really going to like this.


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Groton - Joe C. Quaratella Jr. cut the hair of a young man Wednesday who graduates from officer training school on Friday but can't move to his next training program because his paperwork's tied up.
Quaratella, owner of Nautilus Barber Shop near the Naval Submarine Base in Groton, met people who tried to shop at the commissary on the base, but found the grocery closed.
"The government has had three years to settle this," Quaratella said.
Nearly 1,300 people arrived to work Tuesday at the sub base and the Connecticut National Guard facilities, only to find they had to wrap things up and leave.
They left not knowing when they'd be back after the federal government shut down for the first time in 17 years.
The Republican-controlled House of Representatives passed a continuing resolution to extend the current spending rates for six weeks but also to delay the Affordable Care Act, which Senate leaders would not agree to.
The government closed at midnight Monday.
Ed Ettinger of Mystic, interviewed Wednesday in the barber shop, said he had tickets to fly to Annapolis, Md., though he wasn't sure what he'd end up doing.
"I am heading to the now non-existent Navy-Air Force game this weekend," he said. It was unclear whether the game would go on as planned.
He said there was plenty of blame to go around among federal officials.
"I'm quite upset because I feel the Republicans are being held as the villains but the other side won't compromise," he said.
Sean Bosselman was among three members without at least one of their jobs. Bosselman, interviewed outside Groton Head Start, said he bagged groceries at the commissary until Friday. Bosselman's brother, who works full-time at the commissary and at Lawrence + Memorial Hospital, has three young children and is out of one job.
Sean Bosselman also said his father, who works in supplies on the base, is temporarily not working.
"Honestly, I don't even know what happened," Sean Bosselman said. "They're not really saying much." As for the close of the commissary, he added, "Stop & Shop is going to be loaded."
Alysha Uhler of Norwich, who works at the Groton Stop & Shop, said Wednesday the store was busier than usual.
"Yesterday we had lines down the aisles," she said. Employees were hustling to keep up with the demand, she said.
At the barber shop, Quaratella cut hair while commenting on the lack of federal wisdom. He's run the shop more than 50 years and cut the hair of Clarence B. Sharp, the former mayor for whom Groton's highway is named. Quaratella's also seen his share of U.S. presidents.
"This president couldn't run the Poquonnock Bridge Fire Department," he said, referring to the local fire district near bankruptcy.
Customer Steve Skrabacz, who works for Electric Boat and lives in New London, said the federal government standoff has become like a game of chicken.
"Like who's going to flinch first," he said. "It's a shame, but that's how it works, I suppose."
Animal advocates monitor cruetly case of former Mystic, Niantic dog trainer
Chief Ackley's future separates the New London mayoral candidates
Doctors Without Borders: 19 dead, including 3 children in Kunduz hospital bombing
Russia declares partial victory in bombing campaign in Syria
Electric Boat employees offer free tutoring to local students
Nearly a dozen arrested in prostitution, narcotics sting in Groton
Stonington High School bans grinding and other 'inappropriate dancing'
Former Hartford police officer plans to remove vessel from Crescent Beach
'Soup kitchen' could run out of operating funds by the end of the year
Newtown families' suit against gun maker sent to state court


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Clemson v Syracuse
- ACC Football Championship
- American Football - Sport
- Atlantic Coast Conference
- Carrier Dome
- Clemson Tigers
- Clemson University
- Dome
- Horizontal
- Lining Up
- NCAA College Conference Team
- NCAA College Football
- New York State
- Reception - American Football
- Sport
- Stadium
- Syracuse - New York
- Syracuse Orange
- Tajh Boyd
- Waist Up
Tajh Boyd of Clemson Tigers lines up a first down reception in the... News PhotoACC Football Championship,American Football - Sport,Atlantic Coast Conference,Carrier Dome,Clemson Tigers,Clemson University,Dome,Horizontal,Lining Up,NCAA College Conference Team,NCAA College Football,New York State,Reception - American Football,Sport,Stadium,Syracuse - New York,Syracuse Orange,Tajh Boyd,USA,Waist UpPhotographer Brett CarlsenCollection: Getty Images Sport 2013 Getty ImagesSYRACUSE, NY - OCTOBER 5: Tajh Boyd #10 of Clemson Tigers lines up a first down reception in the first quarter against Syracuse Orange on October 5, 2013 at the Carrier Dome in Syracuse, New York. Clemson defeated Syracuse 49-14. (Photo by Brett Carlsen/Getty Images)


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To enable more efficient administration in setting up a Horizon 2020 proposal, a consortium has agreed to make use of cloud server software, where all partners could easily keep in contact with each other and share information.
However, one of the SMEs involved in these negotiations was concerned about the disclosure of information to the partners through the cloud without any prior agreement between the partners. At the same time, however, the period for the preparation of the proposal was of six months duration and therefore the SME was concerned about finding an easy and quick solution, to avoid losing time that should be used for the preparation of the proposal.
In this case study you can see how this consortium easily overcame confidentiality concerns and was able to reach an optimal solution for all partners involved.
Comment on this article in our Linkedin group
This summer issue of the European IPR Helpdesk Bulletin firstly presents an easy-to-use map of different free-of-charge initiatives available to assist SMEs with intellectual property related matters. Thinking on the growing relevance of designs in business, the Bulletin features an article on industrial design protection in the EU and the use of its grace period. An interview with a European agro/food biotech company underlines the relevance of IP in the biotechnology sector.
Regarding the research sector, this issue offers an interesting article on the DESCA 2020, a model consortium agreement tailored to be used in Horizon 2020. Two pieces featured by OHIM show the importance of IP enforcement via the outcomes of the first International IP Enforcement Summit and how the OHIM Academy plays a role in helping stakeholders throughout the EU.
The Innovaccess IP cost tool, a free-of-charge tool allowing the calculation of the costs related to different IP titles, the patent quiz and the Information Package on IP in Horizon 2020 complete this substantial fourteenth Bulletin issue.
DIGITALEUROPE members have published a new consortium agreement model for Horizon 2020 projects: MCARD-2020.
This new model is similar to the Integrated Project Consortium Agreement (IPCA) developed by DIGITALEUROPE for the Seventh Framework Programme.
According to DIGITALEUROPE "as with the IPCA, consortia in any scientific field, not just in the ICT domain, are free to adapt and use the MCARD-2020. The objective is to encourage the participation of partners from academia, small businesses as well as established companies in H2020 projects."
For further details and to read MCARD-2020, please click here.
DESCA, the most widespread model Consortium Agreement in the 7th Framework Programme, has been updated for Horizon 2020.
DESCA is a simple and comprehensive model, stripped of all unnecessary complexity in both content and language. The modular structure of DESCA, with various options and alternative modules and clauses, provides maximum flexibility.
Elucidation notes with concrete examples and detailed explanations about the various options and clauses are provided throughout the model. These notes will help research managers (who typically do not have legal training) and first-time FP participants to make informed choices about the best wording to protect their interests.
Initiated by key Horizon2020 stakeholder groups, and co-developed with the FP community, this initiative seeks to balance the interests of all participant categories: large and small firms, universities, public research institutes and RTOs, in the spirit of the Responsible Partnering Initiative. The DESCA Core Group is represented by ANRT, EUA, Eurochambres, EARTO, KoWi, LERU, VTT, ZENIT and coordinated by Fraunhofer and the Helmholtz Association.
For further information, please click here.


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Are you Jae-Chul Jung?Claim your profile
Publications (76)136.67 Total impact
Article: Anti-Inflammatory Activities of Licorice Extract and Its Active Compounds, Glycyrrhizic Acid, Liquiritin and Liquiritigenin, in BV2 Cells and Mice Liver[Show abstract] [Hide abstract]
ABSTRACT: This study provides the scientific basis for the anti-inflammatory effects of licorice extract in a t-BHP (tert-butyl hydrogen peroxide)-induced liver damage model and the effects of its ingredients, glycyrrhizic acid (GA), liquiritin (LQ) and liquiritigenin (LG), in a lipopolysaccharide (LPS)-stimulated microglial cell model. The GA, LQ and LG inhibited the LPS-stimulated elevation of pro-inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and interleukin (IL)-6 in BV2 (mouse brain microglia) cells. Furthermore, licorice extract inhibited the expression levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in the livers of t-BHP-treated mice models. This result suggested that mechanistic-based evidence substantiating the traditional claims of licorice extract and its three bioactive components can be applied for the treatment of inflammation-related disorders, such as oxidative liver damage and inflammation diseases.Molecules 07/2015; 20(7):13041-54. DOI:10.3390/molecules200713041 · 2.42 Impact Factor
Article: Benzylideneacetophenone derivatives attenuate IFN-γ-induced IP-10/CXCL10 production in orbital fibroblasts of patients with thyroid-associated ophthalmopathy through STAT-1 inhibition[Show abstract] [Hide abstract]
ABSTRACT: The aim of the present study was to identify a new candidate anti-inflammatory compound for use in the active stage of thyroid-associated ophthalmopathy (TAO). Benzylideneacetophenone compound JC3 [(2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one] was synthesized based on a structural modification of yakuchinone B, a constituent of the seeds of Alpinia oxyphylla, which belongs to the ginger family (Zingiberaceae), has been widely used in folk medicine as an anti-inflammatory phytochemical. Orbital fibroblasts were primarily cultured from patients with TAO, and the potential of JC3 to suppress the interferon (IFN)-γ-induced protein (IP)-10/CXCL10 production in these cells was determined. IFN-γ strongly increased the level of IP-10/CXCL10 in orbital fibroblasts from patients with TAO. JC3 exerted a significant inhibitory effect on the IFN-γ-induced increase in IP-10/CXCL10 in a dose-dependent manner; its potency was greater than that of an identical concentration of yakuchinone B with no toxicity to cells at the concentration range used. Moreover, the constructed dimer and trimer polystructures of JC3, showed greater potency than JC3 in suppressing the IFN-γ-induced production of IP-10/CXCL10. JC3 significantly attenuated the IP-10/CXCL10 mRNA expression induced by IFN-γ, and a gel-shift assay showed that JC3 suppressed IFN-γ-induced DNA binding of signal transducer and activator of transcription-1 (STAT-1) in TAO orbital fibroblasts. Our results provide initial evidence that the JC3 compound reduces the levels of IP-10/CXCL10 protein and mRNA induced by IFN-γ in orbital fibroblasts of TAO patients. Therefore, JC3 might be considered as a future candidate for therapeutic application in TAO that exerts its effects by modulating the pathogenic mechanisms in orbital fibroblasts.Experimental and Molecular Medicine 06/2014; 46(6):e100. DOI:10.1038/emm.2014.26 · 3.45 Impact Factor
Article: Xanthigen Attenuates High-fat Diet-induced Obesity through Down-regulation of PPAR gamma and Activation of the AMPK Pathway[Show abstract] [Hide abstract]
ABSTRACT: Xanthigen, a mixture of brown seaweed and pomegranate seed extracts, has weight loss properties and lipid-lowering effects in mice and humans. This study elucidated the Xanthigen mechanism of an anti-obesity activity in high-fat diet (HFD)-fed mice. Xanthigen decreased expression of peroxisome proliferator-activated receptor γ (PPARγ) in the adipose tissue of HFD-fed mice. The serum leptin level and the adipose tissue leptin expression in mice fed HFD plus Xanthigen were significantly decreased, compared to HFD-fed mice. Phosphorylation of AMPactivated protein kinase (AMPK) α and β and acetyl-CoA carboxylase (ACC) in the adipose tissue of HFD plus Xanthigen-fed mice was elevated, and HMG-CoA reductase (HMGCR) expression was decreased. Xanthigen may have an anti-obesity activity by down-regulation of PPARγ and activation of the AMPK pathway.Food science and biotechnology 06/2014; 23(3):931-935. DOI:10.1007/s10068-014-0125-1 · 0.65 Impact Factor
Article: Synthesis, biological evaluation, hydration site thermodynamics, and chemical reactivity analysis of α-keto substituted peptidomimetics for the inhibition of Plasmodium falciparum[Show abstract] [Hide abstract]
ABSTRACT: A new series of peptidomimetic pseudo-prolyl-homophenylalanylketones were designed, synthesized and evaluated for inhibition of the Plasmodium falciparum cysteine proteases falcipain-2 (FP-2) and falcipain-3 (FP-3). In addition, the parasite killing activity of these compounds in human blood-cultured P. falciparum was examined. Of twenty-two (22) compounds synthesized, one peptidomimetic comprising a homophenylalanine-based α-hydroxyketone linked Cbz-protected hydroxyproline (39) showed the most potency (IC50 80nM against FP-2 and 60nM against FP-3). In silico analysis of these peptidomimetic analogs offered important protein-ligand structural insights including the role, by WaterMap, of water molecules in the active sites of these protease isoforms. The pseudo-dipeptide 39 and related compounds may serve as a promising direction forward in the design of competitive inhibitors of falcipains for the effective treatment of malaria.Bioorganic & medicinal chemistry letters 01/2014; 24(5). DOI:10.1016/j.bmcl.2014.01.062 · 2.42 Impact Factor
Article: Fructus Sophorae Enhances the Production of Prostaglandin E2 and Tumor Necrosis Factor-α through Activation of MAPKs and PI3K/AKT Signaling Pathways in Murine Macrophages[Show abstract] [Hide abstract]
ABSTRACT: Fructus Sophorae, the dried ripe fruit of Styphnolobium japonicum (L.), is an herbal ingredient used in traditional Oriental medicine. This study was carried out to investigate the effects of Fructus Sophorae extracts (FSE) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the production of prostaglandin () and tumor necrotic () were evaluated. Our data revealed that FSE increased the macrophage activation and the production of and , which was consistently correlated with upregulation of cyclooxygenase-2 (COX-2) and expression at both transcriptional and translational levels. On comparative cytokine protein array, FSE significantly increased several cytokines, which was associated with phosphorylation of mitogen- activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK), and Akt in RAW 264.7 cells. However, each inhibitor of these molecules attenuated the FSE-induced production. These results indicate that FSE activated macrophages through the activation of MAPKs and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways in RAW 264.7 macrophages. These findings suggest that FSE may provide a promising source of an immunoenhancing agent.11/2013; 23(11). DOI:10.5352/JLS.2013.23.11.1397
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ABSTRACT: Echinacea purpurea has been shown to have anti-diabetic activities; for example, it activates peroxisome proliferator-activated receptor γ (PPARγ) and increases insulin-stimulated glucose uptake. Adipogenesis has been used to study the insulin signaling pathway and to screen anti-diabetic compounds. The present study was conducted to investigate the effects of an ethanol extract of E. purpurea (EEEP) and its constituents on the insulin-induced adipocyte differentiation of 3T3-L1 preadipocytes. When adipocyte differentiation was induced with insulin plus 3-isobutyl-1-methylxanthine and dexamethasone, the accumulation of lipid droplets and the cellular triglyceride content were significantly increased by EEEP. The expressions of PPARγ and C/EBPα in adipocytes treated with EEEP were gradually increased as compared with control cells. Fat accumulation and triglyceride content of adipocytes treated with dodeca-2(E),4(E)-dienoic acid isobutylamide were significantly increased as compared with control cells. The expressions of PPARγ and C/EBPα in adipocytes treated with dodeca-2(E),4(E)-dienoic acid isobutylamide were significantly higher than in control cells. These results suggest EEEP promotes the adipogenesis that is partially induced by insulin and that dodeca-2(E),4(E)-dienoic acid isobutylamide appears to be responsible for EEEP-enhanced adipocyte differentiation.Archives of Pharmacal Research 10/2013; 37(6). DOI:10.1007/s12272-013-0251-y · 2.05 Impact Factor
Article: A simple synthesis of trans-3,4,5-trimethoxycinnamamides and evaluation of their biologic activity[Show abstract] [Hide abstract]
ABSTRACT: A simple synthesis and biologic evaluation of trans-3,4,5-trimethoxycinnamamides 10a–e and 11 as novel antinarcotic agents is described. The synthetic key strategies involve condensation reaction and coupling reaction to generate trans-3,4,5-trimethoxycinnamamides 10a–e and 11. They were evaluated for free radical scavenging, inhibitory action for neurotoxicity in cultured neurons, and antinarcotic activity in mice. It was found that compounds 10a, 10d, and 10e displayed significant inhibitory action of the glutamate-induced neurotoxicity and 10a–e and 11 showed high antinarcotic activity in mice.Medicinal Chemistry Research 10/2013; 22(10). DOI:10.1007/s00044-012-0415-1 · 1.40 Impact Factor
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ABSTRACT: To determine the biological activity of Rhodiola rosea, the protein expression of iNOS and proinflammatory cytokines was measured after the activation of murine microglial BV2 cells by LPS under the exposure of constituents of Rhodiola rosea: crude extract, rosin, rosarin, and salidroside (each 1-50 μ g/mL). The LPS-induced expression of iNOS and cytokines in BV2 cells was suppressed by the constituents of Rhodiola rosea in a concentration-dependent manner. Also the expression of the proinflammatory factors iNOS, IL-1 β , and TNF- α in the kidney and prefrontal cortex of brain in mice was suppressed by the oral administration of Rhodiola rosea crude extract (500 mg/kg). To determine the neuroprotective effect of constituents of Rhodiola rosea, neuronal cells were activated by L-glutamate, and neurotoxicity was analyzed. The L-glutamate-induced neurotoxicity was suppressed by the treatment with rosin but not by rosarin. The level of phosphorylated MAPK, pJNK, and pp38 was increased by L-glutamate treatment but decreased by the treatment with rosin and salidroside. These results indicate that Rhodiola rosea may have therapeutic potential for the treatment of inflammation and neurodegenerative disease.Evidence-based Complementary and Alternative Medicine 04/2013; 2013:514049. DOI:10.1155/2013/514049 · 1.88 Impact Factor
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ABSTRACT: The function and the role of glucosylceramide have not been well studied in the central nervous system. This study was aimed to investigate the possible roles of glucosylceramide in memory function in aged mice. Glucosylceramide (50 mg/kg, p.o.) showed memory enhancing activity after 3-month treatment in the aged mice (C56BL/6, 18-20 months old) through Y-maze, novel objective test, and Morris water maze test. Long-term treatment of glucosylceramide decreased the expression of iNOS and COX-2 in the brain of aged mice. The LPS-induced mRNA level of iNOS, COX-2, IL-1 β , and TNF- α was reduced by the acute treatment with glucosylceramide in adult mice. These results suggest that glucosylceramide plays an important role in anti-inflammatory and memory enhancement, and it could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer's disease.Evidence-based Complementary and Alternative Medicine 04/2013; 2013:824120. DOI:10.1155/2013/824120 · 1.88 Impact Factor
Article: Total Synthesis of Flocoumafen via Knoevenagel Condensation and Intramolecular Ring Cyclization: General Access to Natural Products[Show abstract] [Hide abstract]
ABSTRACT: The total synthesis and structure determination of cis- and trans-flocoumafen was described. The key synthetic steps involve Knoevenagel condensation with p-methoxybenzaldehyde, in situ decarboxylation and intramolecular ring cyclization to construct the tetralone skeleton. Stereospecific reduction of the O-alkylated ketone 13 afforded good yield of precusor alcohol 5. Final coupling of alcohol 5 with 4-hydroxy-coumarin yielded flocoumafen (1). Separation and structure determination of cis- and trans-flocoumafen through 2D NMR analyses-assisted computer simulation techniques for the evaluation of anticoagulant activities are reported for the first time. This method is useful for generating the core tetralone skeleton of 4-hydroxycoumarin derivatives and provides a generalized access to various warfarin type anticoagulants.Molecules 12/2012; 17(2):2091-102. DOI:10.3390/molecules17022091 · 2.42 Impact Factor
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ABSTRACT: Simple synthesis of modafinil derivatives and their biological activity are described. The key synthetic strategies involve substitution and coupling reactions. We determined the anti-inflammatory effects of modafinil derivatives in cultured BV2 cells by measuring the inhibition of nitrite production and expression of iNOS and COX-2 after LPS stimulation. It was found that for sulfide analogues introduction of aliphatic groups on the amide part (compounds 11a - d ) resulted in lower anti-inflammatory activity compared with cyclic or aromatic moieties (compounds 1 1e - k ). However, for the sulfoxide analogues, introduction of aliphatic moieties (compounds 1 2a - d ) showed higher anti-inflammatory activity than cyclic or aromatic fragments (compounds 1 2e - k ) in BV-2 microglia cells.Molecules 12/2012; 17(9):10446-58. DOI:10.3390/molecules170910446 · 2.42 Impact Factor
Article: Synthesis and Evaluation of a Series of 3,4,5-Trimethoxycinnamic Acid Derivatives as Potential Antinarcotic Agents[Show abstract] [Hide abstract]
ABSTRACT: A series of 3,4,5-trimethoxycinnamic acid (TMCA) derivatives was prepared and evaluated for antinarcotic effects on morphine dependence in mice and binding affinities on serotonergic receptors. The key synthetic strategies involve generation of ketones 6-7, esters 9-12 through condensation reaction, and amides 13-19 via coupling reaction using HOBt/EDCI system in high yield. We found that the naloxone-induced morphine withdrawal syndrome was significantly suppressed by new synthetic TMCA derivatives (20 mg/kg/day). Most of TMCA derivatives were found to have high affinity to 5-HT(1A) receptor. The naloxone-induced morphine withdrawal syndrome was attenuated by (+)8-OH-DPAT (0.1 mg/kg/day, i.p.), a 5-HT(1A) receptor agonist. In cortical neuronal cells, (+)8-OH-DPAT (1 uM) produced an elevation of the pERK 1/2 expression, and the elevated pERK levels were inhibited by WAY 100635, a 5-HT(1A) receptor-specific antagonist. Interestingly, the pERK levels were increased by the TMCA derivatives and the derivatives-mediated changes in pERK levels were blocked by the WAY 100635. These results suggested that new synthetic TMCA derivatives have a potential antinarcotic effect through acting as a 5-HT(1A) receptor agonist in mice. © 2012 John Wiley & Sons A/S.Chemical Biology & Drug Design 11/2012; 81(3). DOI:10.1111/cbdd.12087 · 2.49 Impact Factor
Article: Anti-Inflammatory Effect of Triterpene Saponins Isolated from Blue Cohosh (Caulophyllum thalictroides)[Show abstract] [Hide abstract]
ABSTRACT: Blue cohosh has been used as a medicinal herb in eastern North America. It was commonly used as traditional medicines for the treatment of menopausal symptoms, rheumatic pain, and as anti-inflammatory remedy. Particularly, extract of blue cohosh roots has been used as anti-inflammatory antipyretic in traditional medicines. In the present study, we investigated the effects of blue cohosh components on the suppressive expression of iNOS or proinflammatory cytokines after the activation of microglia with lipopolysaccharide (LPS). The expression of iNOS, TNF-α, IL-1β, and IL-6 was determined by western blotting or gene expression. Blue cohosh treatment suppressed the elevation of LPS-induced iNOS expression in a concentration-dependent manner in microglia cells. Blue cohosh constituents also suppressed the expression of TNF-α, IL-1β, and IL-6. In addition, blue cohosh extract suppressed the expression of COX-2, iNOS, and proinflammatory cytokines in adrenal glands of mice. These results demonstrate that constituents of blue cohosh exert anti-inflammatory effects through the inhibition of expression of iNOS and proinflammatory cytokines. Therefore, blue cohosh may have therapeutic potential for the treatment of inflammation-related diseases.Evidence-based Complementary and Alternative Medicine 09/2012; 2012:798192. DOI:10.1155/2012/798192 · 1.88 Impact Factor
Article: Statement of retraction: "Larvicidal activity of 4-hydroxycoumarin derivatives against Aedes aegypti". Pharmaceutical Biology 2011 49:2, 190-3.Pharmaceutical Biology 09/2012; 50(9):1199. DOI:10.3109/13880209.2012.712023 · 1.24 Impact Factor
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ABSTRACT: Modafinil has been used as a psychostimulant for the treatment of narcolepsy. However, its primary mechanism of action remains elusive. Therefore, we examined the effects of modafinil on K(Ca)3.1 channels and vascular smooth muscle contraction. K(Ca)3.1 currents and channel activity were measured using a voltage-clamp technique and inside-out patches in mouse embryonic fibroblast cell line, NIH-3T3 fibroblasts. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration was measured, and the phosphorylation of K(Ca)3.1 channel protein was examined using western blotting in NIH-3T3 fibroblasts and/or primary cultured mouse aortic smooth muscle cells (SMCs). Muscle contractions were recorded from mouse aorta and rat pulmonary artery by using a myograph developed in-house. Modafinil was found to inhibit K(Ca)3.1 currents in a concentration-dependent manner, and the half-maximal inhibition (IC(50)) of modafinil for the current inhibition was 6.8 ± 0.7 nM. The protein kinase A (PKA) activator forskolin also inhibited K(Ca)3.1 currents. The inhibitory effects of modafinil and forskolin on K(Ca)3.1 currents were blocked by the PKA inhibitors PKI(14-22) or H-89. In addition, modafinil relaxed blood vessels (mouse aorta and rat pulmonary artery) in a concentration-dependent manner. Modafinil increased cAMP concentrations in NIH-3T3 fibroblasts or primary cultured mouse aortic SMCs and phosphorylated K(Ca)3.1 channel protein in NIH-3T3 fibroblasts. However, open probability and single-channel current amplitudes of K(Ca)3.1 channels were not changed by modafinil. From these results, we conclude that modafinil inhibits K(Ca)3.1 channels and vascular smooth muscle contraction by cAMP-dependent phosphorylation, suggesting that modafinil can be used as a cAMP-dependent K(Ca)3.1 channel blocker and vasodilator.Pharmacological Research 03/2012; 66(1):51-9. DOI:10.1016/j.phrs.2012.02.009 · 4.41 Impact Factor
Article: Convenient Synthesis and Biological Evaluation of Modafinil Derivatives: Benzhydrylsulfanyl and Benzhydrylsulfinyl [1,2,3]triazol-4-yl-methyl Esters[Show abstract] [Hide abstract]
ABSTRACT: Simple synthesis and biological activities of modafinil derivatives are described. The key reactions include condensation of acid and propargyl alcohol, subsequent 1,3-dipolar cycloaddition reaction of alkynes and (3-azido-propyl)cyclohexane or (4-azido-butyl)benzene in the presence of sodium ascorbate and CuSO₄·5H₂O in excellent yield. They were then evaluated for the suppression of LPS-induced NO generation in vitro. It was found that all compounds showed moderate effects for suppression of LPS-induced NO generation.Molecules 12/2011; 16(12):10409-19. DOI:10.3390/molecules161210409 · 2.42 Impact Factor
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ABSTRACT: The function and the role phytoceramide (PCER) and phytosphingosine (PSO) in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS) showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o.) recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer's disease.Molecules 12/2011; 16(11):9090-100. DOI:10.3390/molecules16119090 · 2.42 Impact Factor
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ABSTRACT: A simple and efficient seven steps synthesis of brodifacoum and difethialone from phenylacetyl chloride is described. The key synthetic strategies involve Friedel-Crafts acylation, intramolecular ring cyclization and condensation reaction in the presence of Brønsted-Lowry acids. It was found that brodifacoum showed favorable inhibiting activities on LPS-stimulated nitrite production in BV-2 microglia cells. Brodifacoum exhibited superior anti-inflammatory effects than difethialone. We expect that an efficient linear synthesis of 4-hydroxycoumarin derivatives and key fragments that are useful agents for the modulation of inflammation as well as inhibition of coagulation will be of practical use.Molecules 12/2011; 17(1):240-7. DOI:10.3390/molecules17010240 · 2.42 Impact Factor
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ABSTRACT: Here, we describe the practical synthesis and biological properties of bergenin and its structural analogs. Synthetic bergenin compounds were prepared by acylation of bergenin. These compounds were then evaluated for suppression of lipopolysaccharide-induced nitric oxide (NO) generation in cultured cells and anti-narcotic effects on morphine-dependent mice. We found that bergenin derivatives showed potent anti-inflammatory activity (suppression of NO generation) at concentrations ranging from 20 to 30 μmin vitro, and bergenin derivatives (10-20 mg/kg) exhibited significant anti-narcotic effects on morphine dependence in mice. These results suggest the potential utility of bergenin and its analogs as anti-narcotic agents and the design of more potent anti-inflammatory compounds.Chemical Biology & Drug Design 07/2011; 78(4):725-9. DOI:10.1111/j.1747-0285.2011.01194.x · 2.49 Impact Factor
Top Journals
Seegene Institute of Life SciencesSŏul, Seoul, South Korea
Ewha Womans University
Sŏul, Seoul, South Korea
- • School of Medicine
- • Medical Research Institute
University of Mississippi
Mississippi, United States
- Department of Medicinal Chemistry
Yonsei University
Seoul, Seoul, South Korea
- Division of Biological Science and Technology
Rexgene Biotech. Ltd.Sŏul, Seoul, South Korea
Chungbuk National University
Chinsen, North Chungcheong, South Korea
- Department of Chemistry


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A very difficult weapon to screenshot on a tiny lalafell, when my character is almost 2 meters tall.
But here is the High Allagan Staff :
Unsheated :
sheated :
High Allagan Grimoire of Healing :
And last but not least my hairstyle and color change!
Bonus shot on my White Mage with glasses (crappy quality screenshot sadly, but fraps jpg will be fraps jpg.) :
finally got to downing titan ex ... never had the chance or never was interested in it and we tried ifrit ex got it to last phase to around 15% and wiped mostly because of random people ...
So annoying getting used to KB/M controls again. Oh well... Will only play like 2-3 weeks tops.
Thyrus Zenith:
Only plays Magic DPS Classes, Healers and Machinist/Engineers.
Playing MMO: FFXIV (Balmung)
Waiting On: FFXV, KH3, Tree of Savior, RE:FFVII · Saving For: New Computer


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This one is for you, Eiichi Ito...STORM ON!
Greenland Storm Rolls performed in the beautiful waters of Queensland's Great Sandy Straits
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Warner Bros. Pushing Ahead With "Justice League Dark"
Comic Books
Comic Books, TV
The Buy Pile
The Mission
Shelf Life
The Buy Pile
Comics Should be Good
Robot 6
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I'm not generally a fan of photo covers, but who can resist DC's Comic-Con International-exclusive cover for Batman '66 #1, which uses action figures from the new Mattel line — let's hear it for cross-promotion! — to recreate one of the great recurring gags of the classic TV series: the "window cameos." Alas, the collection doesn't include 6-inch versions Sammy Davis Jr., Suzy Knickerbocker or Werner Klemperer to make the homage complete.
It's just one of four convention-exclusive covers announced this morning on the DC Comics website:
Each of the Comic-Con exclusives is priced at $10. Comic-Con International will be held July 18-21 in San Diego. Continue Reading »
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Just as the topic says... After some file search, Activision appears to not even included a controller.ini file anywhere either... I have a Logitech dual action controller, which works in all my other games such as Fifa 13 so i know its not the controller or that windows doesn't even see it.. I'd be interested to know if anyone else has had this issue, but basically after plugging in the USB controller, loading the game up, when you go to the controls menu in the options, the gamepad is not selectable as a controller... and which in tern, prevents you being able to do coop with friends or family... considering this game is $50 !!!!!!!! that is totally un-acceptable....
NO PC Controller Support for PC Version
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embrace diversity in computing
MBRACE is committed to developing student-centered support services to attract a diverse group of students into computing to serve the growing demand for computing talent in our society.
There are so many incredible things happening in computing in today's world! Even within the Monterey Bay region there are astronauts programming satellites to go into space, there are marine biologists using computers to track and study data about sea life, and there are countless companies and organizations figuring out better ways to transmit information, build newer phones and computers, and keep personal data secure.
With all of this at your fingertips, why not consider becoming a part of it? Whether you're a high school student just starting to think about your goals after graduation or you're a current college student trying to figure out your next steps, mbrace will do our best to connect you with the computing information and services you need.
Go ahead. Explore your options.


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Are you Touko Inao?Claim your profile
Publications (8)32.88 Total impact
Article: The HSP70 and Autophagy Inhibitor Pifithrin-mu Enhances the Antitumor Effects of TRAIL on Human Pancreatic Cancer[Show abstract] [Hide abstract]
ABSTRACT: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and agonistic death receptor-specific antibodies can induce apoptosis in cancer cells with little cytotoxicity to normal cells. To improve TRAIL-induced antitumor effects, we tested its effectiveness in combination with pifithrin-μ, which has the potential to inhibit HSP70 function and autophagy, both of which participate in TRAIL resistance in cancer cells. Among the four human pancreatic cancer cell lines tested, MiaPaca-2, Panc-1, and BxPC-3 cells showed varying sensitivities to TRAIL. In MiaPaca-2 and Panc-1 cells, knockdown of HSP70 or Beclin-1, the latter an autophagy-related molecule, by RNA interference augmented TRAIL-induced antitumor effects, decreasing cell viability and increasing apoptosis. Based on these findings, we next determined whether the TRAIL-induced antitumor effects could be augmented by its combination with pifithrin-μ. The combination of TRAIL plus pifithrin-μ significantly decreased the viability and colony-forming ability of MiaPaca-2 and Panc-1 cells compared to cells treated with either agent alone. When applied alone, pifithrin-μ increased Annexin V+ cells in both caspase-dependent and caspase-independent manners. It also promoted TRAIL-induced apoptosis and arrested cancer cell growth. Furthermore, pifithrin-μ antagonized TRAIL-associated NF-κB activation in cancer cells. In a xenograft mouse model, combination therapy significantly inhibited MiaPaca-2 tumor growth compared to treatment with either agent alone. The results of this study suggest protective roles for HSP70 and autophagy in TRAIL resistance in pancreatic cancer cells and suggest that pifithrin-μ is a promising agent for use in therapies intended to enhance the antitumor effects of TRAIL.Molecular Cancer Therapeutics 01/2013; 12(4). DOI:10.1158/1535-7163.MCT-12-0954 · 5.68 Impact Factor
Article: Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo[Show abstract] [Hide abstract]
ABSTRACT: Several chemotherapeutic drugs have immune-modulating effects. For example, cyclophosphamide (CP) and gemcitabine (GEM) diminish immunosuppression by regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), respectively. Here, we show that intermittent (metronomic) chemotherapy with low-dose CP plus GEM can induce anti-tumor T cell immunity in CT26 colon carcinoma-bearing mice. Although no significant growth suppression was observed by injections of CP (100 mg/kg) at 8-day intervals or those of CP (50 mg/kg) at 4-day intervals, CP injection (100 mg/kg) increased the frequency of tumor peptide-specific T lymphocytes in draining lymph nodes, which was abolished by two injections of CP (50 mg/kg) at a 4-day interval. Alternatively, injection of GEM (50 mg/kg) was superior to that of GEM (100 mg/kg) in suppressing tumor growth in vivo, despite the smaller dose. When CT26-bearing mice were treated with low-dose (50 mg/kg) CP plus (50 mg/kg) GEM at 8-day intervals, tumor growth was suppressed without impairing T cell function; the effect was mainly T cell dependent. The metronomic combination chemotherapy cured one-third of CT26-bearing mice that acquired tumor-specific T cell immunity. The combination therapy decreased Foxp3 and arginase-1 mRNA levels but increased IFN-γ mRNA expression in tumor tissues. The percentages of tumor-infiltrating CD45(+) cells, especially Gr-1(high) CD11b(+) MDSCs, were decreased. These results indicate that metronomic chemotherapy with low-dose CP plus GEM is a promising protocol to mitigate totally Treg- and MDSC-mediated immunosuppression and elicit anti-tumor T cell immunity in vivo.Cancer Immunology and Immunotherapy 08/2012; 62(2). DOI:10.1007/s00262-012-1343-0 · 3.94 Impact Factor
Article: Antitumor effects of cytoplasmic delivery of an innate adjuvant receptor ligand, poly(I:C), on human breast cancer[Show abstract] [Hide abstract]
ABSTRACT: Innate adjuvant receptors are expressed in immune cells and some types of cancers. If antitumor therapies targeting these receptors are established, it is likely that they will be therapeutically beneficial because antitumor effects and immune-cell activation can be induced simultaneously. In this study, we tested this possibility of using an innate adjuvant receptor ligand, polyinosinic-polycytidylic acid [poly(I:C)], to treat human breast cancer cell lines. Three breast cancer cell lines (MCF-7, MDA-MB-231, and BT-549) were used in this study. Poly(I:C) was transfected into these cancer cells to stimulate melanoma differentiation-associated gene (MDA) 5, which is a cytoplasmic adjuvant receptor. Poly(I:C) transfection significantly reduced the viability of all cell lines in a manner partially dependent on MDA5. Flow cytometeric analyses and immunoblot assays revealed that the antitumor effect depended on both caspase-dependent apoptosis and c-Myc- and cyclinD1-dependent growth arrest. Interestingly, poly(I:C) transfection was accompanied by autophagy, which is thought to protect cancer cells from apoptosis after poly(I:C) transfection. In a xenograft mouse model, local transfection of poly(I:C) significantly inhibited the growth of xenografted MDA-MB-231 cells. Our findings indicate that cytoplasmic delivery of poly(I:C) can induce apoptosis and growth arrest of human breast cancer cells, and that therapy-associated autophagy prevents apoptosis. The results of this study suggest that the innate adjuvant receptors are promising targets and that their ligands could serve as antitumor reagents, which have the potential to simultaneously induce antitumor effects and activate immune cells.Breast Cancer Research and Treatment 12/2011; 134(1):89-100. DOI:10.1007/s10549-011-1930-3 · 3.94 Impact Factor
Article: Cytokeratin 20 (CK20) and apomucin 1 (MUC1) expression in ampullary carcinoma: Correlation with tumor progression and prognosis[Show abstract] [Hide abstract]
ABSTRACT: We assessed the expression of cytokeratin (CK) and apomucin (MUC) in ampullary carcinoma (AC) to develop a system for the classification of ACs on the basis of their clinical significance. We studied the expressions of CK7, CK20, MUC1, MUC2, MUC5AC, and MUC6 in 43 patients with ACs. Clinical data were obtained retrospectively by examining surgically resected ACs of the patients. We classified the cases into 3 groups: tumors expressing CK20 and lacking MUC1 (intestinal type [I-type], 26%), tumors expressing MUC1 and lacking CK20 (pancreatobiliary type [PB-type], 35%), and those expressing or lacking both CK20 and MUC1 (other type [O-type], 39%). Eight (73%) of 11 I-type carcinomas, 3 (20%) of 15 PB-type carcinomas, and 4 (24%) of 17 O-type carcinomas were classified as pT1. The number of I-type carcinomas in the early tumor stages was significantly higher than the number of PB- and O-type carcinomas (p = 0.014 and p = 0.018, respectively). The 5-year survival rates for pT1, pT2, and pT3 tumors were 76%, 33%, and 22%, respectively (p < 0.001). Rates of MUC5AC and MUC6 coexpression for I-type, PB-type, and O-type tumors were 18%, 13%, and 53%, respectively. There was a significant correlation between MUC5AC and MUC6 coexpression and O-type characteristics (p = 0.031). The five-year survival rates for O-type ACs with and without MUC5AC and MUC6 coexpression were 71% and 17%, respectively (p = 0.048). The immunohistochemical subtypes based on CK and MUC expression correlated with tumor progression. Gastric MUC5AC and MUC6 coexpression correlated with better prognosis for O-type ACs.Diagnostic Pathology 11/2010; 5(1):75. DOI:10.1186/1746-1596-5-75 · 2.60 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Intraductal papillary mucinous neoplasm (IPMN) is reported to complicate malignancies disease in 30% of cases and complicate invasive ductal carcinoma of the pancreas too, but is rare in multiple cancers. We report a patient with IPMN accompanied by triple cancers. The 60-year-old woman had been followed for IPMN for 7 years, during which time she underwent a hysterectomy due to uterine corpus cancer at age 56 and bilateral breast-preserving surgery due to bilateral breast cancer at age 60. During radiation therapy after breast cancer surgery, a tumor was found in the pancreas body in abdominal computed tomography. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed the main pancreas duct to be occluded at the body and at the tail to be delated. Cytology of the pancreatic juice was class IV. We diagnosed pancreatic cancer with IPMN and conducted subtotal distal pancreatectomy, without resecting the IPMN, which was considered benign. Physicians should look for malignant disease in patients with IPMN because cancer complications may adversely affect their prognosis.Nippon Shokaki Geka Gakkai zasshi 06/2008; 41(6):653-657. DOI:10.5833/jjgs.41.653
Article: S1783 New Classification of Cytokeratin 20 (CK20) and Apomucin 1 (MUC1) Expression in Ampullary Carcinoma:Its Relationship with Tumor Progression and PrognosisGastroenterology 04/2008; 134(4). DOI:10.1016/S0016-5085(08)61250-0 · 16.72 Impact Factor
- Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 01/2007; 68(4):993-997. DOI:10.3919/jjsa.68.993
Article: A Case of Spontaneous Rupture of Hepatocellular Carcinoma of the Left Caudate Lobe (Spiegel's Lobe) with StalkNippon Shokaki Geka Gakkai zasshi 01/2007; 40(9):1599-1604. DOI:10.5833/jjgs.40.1599
Top Journals
Shimane University
Matsu, Shimane, Japan
- • Department of Surgery
- • Department of Immunology
- • Department of Digestive and General Surgery


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Im Putting my cat to sleep today. He has Been sick for 2 months and this just breaks my heart. I have had him for 10 years. I had to put my rescue cat to sleep 2 months ago. Sometimes I wonder if it's my fault bc all my attention was on my LO and not on my fur babies. This blows
Sad day
Posted 01/26/2013
Comments (10)
Posted 01/26/2013
So sorry. It's not your fault. Our fur babies naturally get less attention when our LO's come along. I'm sure that's not why ur kitties got sick. Hugs!
Me(30) DH(30)
Addelyn born 1/13/10 at 3:09 am
AJ born 9/13/12 8:31 am
Posted 01/26/2013
So sorry :( I can't even imagine what you're going through. My cousin lost both her fur babies with a month between them. She was really upset but she said it gets a little better each day. Don't blame yourself, your kitty had a good long life and I know you gave it nothing but love! Will the vet take a stamp of a paw for you so you can put it in a picture frame with your cat?
Posted 01/26/2013
Don't blame yourself. She was very lucky to have you and have a place to live. Alot of animals are not that fortunate. You gave her many good years. I'm so sorry that you have to go through this. I couldn't even imagine. *hugs*
Megs2884 · Original Poster
Posted 01/26/2013
Thanks. Yes, they will give us a paw print. I also did a paw impression using salt dough last night.
Posted 01/26/2013
I'm so sorry. Big humongous hugs...one of my dogs passed while I was still pregnant and it was excruciating. I'm sure you gave your fur babies a wonderful life and loved them very much.
Posted 01/26/2013
:(. I'm so sorry. It's not your fault. My poor kitty's don't get any attention anymore either. I feel terrible about it, but we really don't have a choice. Our lo's NEED all of our attention. T&P to you and your family.
First Time Mom - Married the love of my life 10/3/2009
**Anxiously awaiting the arrival of our little girl 9/13/2012**
Posted 01/26/2013
Im so sorry. I had to put down my kitty this past summer. It was horrible. But he's better now, was in so much pain.
Hugs mama.
Hugs mama.
Posted 01/26/2013
I'm so sorry!! I have cried some nights just thinking about how I need to spend more time with my 2 dogs, my 1st kids!!
I took my dog (my first baby) to the dr yesterday and the vet asked me why I hadn't brought her in sooner ;(( I felt bad but having a LO takes most of my attention now.
I took my dog (my first baby) to the dr yesterday and the vet asked me why I hadn't brought her in sooner ;(( I felt bad but having a LO takes most of my attention now.
Megs2884 · Original Poster
Posted 01/27/2013
Thank you all for your kind words. Today is a little better. Miss my little guy but he is in a better place.
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The Painted Desert
Day 272 - Today we went back to the Visitor Center where they were hosting a two day celebration of re-enactors portraying Civil War soldier from both the North and the South doing battle. Complete with canon fire - boy those things are loud - I may now be a candidate for hearing aids after those blasts! It was fun to see the men and women enjoying their roles. They go all over the United States doing these types of shows for schools, festivals ...
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Sherwin-WilliamsRead MoreWarm facial towels, aromatherapy oils, and heat therapy are a few of the supplemental services the therapists at VidaTherapy Massage Center use to relax clients. They stir these add-ons into an array of Swedish, deep-tissue, and sports massages to further pamper clients. After a massage, clients' blood circulates better, sleep comes easier, their headaches can vanish, and the digital self-destruct timer on their back stops counting down.3510 N Oakland AveShorewood, WI US
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Mattress Firm WisconsinRead MoreAt more than 1,000 Mattress Firm locations around the country, shoppers sink into plush mattresses, recline on firm beds, and belly-flop onto pillow tops. Knowledgeable staffers can help customers create an ideal bedtime environment by dispensing advice based on sleep preferences and illuminating the difference between the many kinds of mattresses. And to the delight of their customers, much of Mattress Firm's bedding wears the label of a premium brand, such as Sealy, Serta, Simmons Beautyrest, or Stearns & Foster.400 W Silver Spring DrGlendale, WI US
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Posts Tagged 'synchronised swimmers'
gokil .. 10 ribu PELAJAR di CHINA peragakan KUNGFU secara serentak !!!
13 Juni 2012 1 komentar
Synchronised swimmers, eat your heart out: Thousands of students take part in a stunning display of kung fu choreography at the Tagou martial arts school in China
Display of discipline: The event was held to mark China's annual Cultural Heritage Day which promotes the protection of the country's rich history
Wouldn't want to take these guys on: Students at the Tagou martial arts school can also take courses in wrestling, kick-boxing and 'free fight'
Standing up for their history: Cultural Heritage day was established by the government six years ago and is held on the second Saturday of June


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As part of our project at Blue Ridge to write and record new Christmas music, student Shannon Enloe composed the lyrics for "A Winter of Love". I enjoyed trying some new chord progressions. I am hoping that the sheet music will soon be available!
"A Winter of Love" by Shannon Enloe and Wade Richards
{ 2 comments… read them below or add one }


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Camilla Parker Bowles: Unassuming Duchess or Leader of a Crazed British Children's Cult?
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Our new "How to Study the Bible" series starts soon! Sign up today.
were six in number (Num. 35). 1. On the west of Jordan were (1) Kadesh, in Naphtali; (2) Shechem, in Mount Ephraim; (3) Hebron, in Judah. 2. On the east of Jordan were, (1) Golan, in Bashan; (2) Ramoth-Gilead, in Gad; and (3) Bezer, in Reuben. (See under each of these names.)


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About Regina Williams
My name is Regina Williams. Photography has been a passion of mine for many years. I love working with families, children, seniors, pets, expectant mothers and brides. I will customize packages to fit any budget. I enjoy traveling to various areas of Virginia be it for a portraiture shoot or to capture the many wonderful points of interest that Virginia has to offer. Currently I reside in East Virginia where my experiences have been with families, children, seniors, pets, expectant mothers , brides and wildlife in multiple locations from local parks to the beautiful beaches.
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