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Characterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporation

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Research 2019年第1期2019卷 1005-1018页

作者： J.W.Ivey E.M.Wasson N.Alinezhadbalalami A.Kanitkar W.Debinski Z.Sheng R.V.Davalos S.S.Verbridge School of Biomedical Engineering and Sciences Virginia Tech-Wake Forest UniversityBlacksburgVA 24061USA Department of Mechanical Engineering Virginia TechBlacksburgVA 24061USA Brain Tumor Center of Excellence Comprehensive Cancer CenterWake Forest Baptist Medical CenterWinston-SalemNC 27157USA Virginia Tech Carilion Research Institute RoanokeVA 24061USA Department of Internal Medicine Virginia Tech Carilion School of MedicineRoanokeVA 24016USA Faculty of Health Science Virginia TechBlacksburgVA 24061USA

High-frequency irreversible electroporation(H-FIRE)is a technique that uses pulsed electric felds that have been shown to ablate malignant *** order to evaluate the clinical potential of H-FIRE to treat glioblastoma(GBM),a primary brain tumor,we have studied the efects of high-frequency waveforms on therapy-resistant glioma stem-like cell(GSC)*** demonstrate that patient-derived GSCs are more susceptible to H-FIRE damage than primary normal *** selectivity presents an opportunity for a degree of malignant cell targeting as bulk tumor cells and tumor stem cells are seen to exhibit similar lethal electric feld thresholds,signifcantly lower than that of healthy ***,neural stem cell(NSC)populations also exhibit a similar sensitivity to these *** observation may suggest that diferent considerations be taken when applying these therapies in younger versus older patients,where the importance of preserving NSC populations may impose diferent restrictions on *** also demonstrate variability in threshold among the three patient-derived GSC lines studied,suggesting the need for personalized cell-specifc characterization in the development of potential clinical *** work may provide further useful insights regarding this patient-dependent variability observed that could inform targeted and personalized treatment.

关键词： clinical younger irreversible

Unlocking antitumor immunity with adenosine receptorblockers

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Cancer Drug Resistance 2023年第4期6卷 748-767页

作者： Victoria A.Remley Joel Linden Todd W.Bauer Julien Dimastromatteo Department of Surgery University of VirginiaCharlottesvilleVA 22903USA Adovate CharlottesvilleVA 22901USA University of Virginia Comprehensive Cancer Center CharlottesvilleVA 22903USA

Tumors survive by creating a tumor microenvironment(TME)that suppresses antitumor *** TME suppresses the immune system by limiting antigen presentation,inhibiting lymphocyte and natural killer(NK)cell activation,and facilitating T cell *** inhibitors like anti-PD-1 and anti-CTLA4 are immunostimulatory antibodies,and their blockade extends the survival of some but not all cancer *** adenosine triphosphate(ATP)is abundant in inflamed tumors,and its metabolite,adenosine(ADO),is a driver of immunosuppression mediated by adenosine A2A receptors(A2AR)and adenosine A2B receptors(A2BR)found on tumor-associated lymphoid and myeloid *** review will focus on adenosine as a key checkpoint inhibitor-like immunosuppressive player in the TME and how reducing adenosine production or blocking A2AR and A2BR enhances antitumor immunity.

关键词： Immunotherapy adenosine adenosine receptors adenosine A2A receptors(A2AR) adenosine A2B receptors(A2BR) tumor cells immune cells tumor microenvironment

Pediatric ocular nanomedicines：Challenges and opportunities

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Chinese Chemical Letters 2017年第9期28卷 1817-1821页

作者： Natasha D.Sheybani Hu Yang Department of Biomedical Engineering Virginia Commonwealth University Richmond VA 23284. United States Department of Chemical & Life Science Engineering. Virginia Commonwealth University Richmond VA 23219. United States Department of Pharmaceutics Virginia Commonwealth University Richmond VA 23298. United States Massey Cancer Center. Virginia Commonwealth University Richmond VA 23298. United States

The eye is a highly complex,yet readily accessible organ within the human *** such,the eye is an appealing candidate target for a vast array of drug *** advances in ocular drug therapy research,the focus on pediatric ocular drug delivery continues to be highly underrepresented due to the limited number of degenerative ocular diseases with childhood *** this review,we explore more deeply the reasons underlying the disparity between ocular therapies available for children and for adults by highlighting diseases that most commonly afflict children（with focus on the anterior eye） and existing prognoses,recent developments in ocular drug delivery systems and nanomedicines for children,and barriers to use for pediatric patients

关键词： Pediatric Ocular drug delivery Nanomedicine Drug administration Compliance

Redefining the possibility of digital Earth and geosciences with spatial cloud computing

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International Journal of Digital Earth 2013年第4期6卷 297-312页

作者： Chaowei Yang Yan Xu Douglas Nebert Center of Intelligent Spatial Computing for Water/Energy Sciences George Mason UniversityFairfaxVAUSA Microsoft Research RedmondWAUSA Federal Geographic Data Committee RestonVAUSA

Global challenges(such as economy and natural hazards)and technology advancements have triggered international leaders and organizations to rethink geosciences and Digital Earth in the new *** next generation visions pose grand challenges for infrastructure,especially computing *** gradual establishment of cloud computing as a primary infrastructure provides new capabilities to meet the *** paper reviews research conducted using cloud computing to address geoscience and Digital Earth needs within the context of an integrated Earth *** also introduce the five papers selected through a rigorous review process as exemplar research in using cloud capabilities to address the *** literature and research demonstrate that spatial cloud computing provides unprecedented new capabilities to enable Digital Earth and geosciences in the twenty-first century in several aspects:(1)virtually unlimited computing power for addressing big data storage,sharing,processing,and knowledge discovering challenges,(2)elastic,flexible,and easy-to-use computing infrastructure to facilitate the building of the next generation geospatial cyberin-frastructure,CyberGIS,CloudGIS,and Digital Earth,(3)seamless integration environment that enables mashing up observation,data,models,problems,and citizens,(4)research opportunities triggered by global challenges that may lead to breakthroughs in relevant fields including infrastructure building,GIScience,computer science,and geosciences,and(5)collaboration supported by cloud computing and across science domains,agencies,countries to collectively address global challenges from policy,management,system engineering,acquisition,and operation aspects.

关键词： EarthCube CloudGIS eScience Earthscience interoperability

Enzalutamide:a new indication for nonmetastatic castration-resistant prostate cancer

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Asian Journal of Andrology 2019年第2期21卷 107-108页

作者： Logan P Rhea Brinda Gupta Jeanny B Aragon-Ching Department of Medicine Inova Fairfax Medical CenterFairfaxVA 22042USA Department of Medicine Virginia Common wealth UniversityRichmondVA 23219USA GU Medical Oncology Inova Schar Cancer InstituteFairfaxVA 22031USA

PROSPER is an international Phase III trial demonstrating the beneficial role of enzalutamide,an androgen receptor antagonist,in prolonging metastasisfree survival in men with nonmetastatic castration-resistant prostate *** trial showed that the median metastasis-free survival was 21.9 months longer for those treated with enzalutamide(36.6 months)compared to those treated with placebo(14.7 months).Enzalutamide also showed prolonged time to PSA progression,PSA response,and time to initiating additional antineoplastic therapy although overall survival is not yet *** is the second antiandrogen(next to apalutamide)that has gained the United States Food and Drug Administration(US FDA)label indication for use in the setting of nonmetastatic castration-resistant prostate cancer.

关键词： PROSPER beneficial role nonmetastatic castration-resistant prostate cancer

A technical survey on tire-road friction estimation

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Friction 2017年第2期5卷 123-146页

作者： Seyedmeysam KHALEGHIAN Anahita EMAMI Saied TAHERI Center for Tire Research(CenTiRe) Department of Mechanical Engineering Virginia Tech Blacksburg VA 24061 United States Department of Biomedical Engineering and Mechanics Virginia Tech Blacksburg VA 24061 United States

Lack of driver's knowledge about the abrupt changes in pavement's friction and poor performance of the vehicle's stability,traction,and ABS controllers on the low friction surfaces are the most important factors affecting car *** to its direct relation to vehicle stability,accurate estimation of tire-road friction is of interest to all vehicle and tire *** studies have been conducted in this field and researchers have used different tools and have proposed different *** literature survey introduces different approaches,which have been widely used to estimate the friction or other related parameters,and covers the recent literature that contains these *** emphasize of this review paper is on the algorithms and studies,which are more popular and have been repeated several *** focus has been divided into two main groups:experiment-based and model-based *** of these main groups has several sub-categories,which are explained in the next few *** summary tables are provided in which the overall feature of each approach is reviewed that gives the reader the general picture of different algorithms,which are widely used in friction estimation studies.

关键词： tire-road friction friction estimation model-based approach experiment-based approach

Integrin binding peptides facilitate growth and interconnected vascular-like network formation of rat primary cortical vascular endothelial cells in vitro

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Neural Regeneration Research 2023年第5期18卷 1052-1056页

作者： Ram Kuwar Xuejun Wen Ning Zhang Dong Sun Department of Anatomy and Neurobiology Medical College of Virginia CampusVirginia Commonwealth UniversityRichmondVAUSA Department of Chemical and Life Science Engineering College of EngineeringVirginia Commonwealth UniversityRichmondVAUSA Department of Biomedical Engineering College of EngineeringVirginia Commonwealth UniversityRichmondVAUSA

Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells. Brain microvascular endothelial cells were isolated from rat brain on post-natal day 7. Cells were cultured in a custom-designed integrin array system containing short synthetic peptides binding to 16 types of integrins commonly expressed on cells in vertebrates. After 7 days of culture, the brain microvascular endothelial cells were processed for immunostaining with markers for endothelial cells including von Willibrand factor and platelet endothelial cell adhesion molecule. 5-Bromo-2′-dexoyuridine was added to the culture at 48 hours prior to fixation to assess cell proliferation. Among 16 integrins tested, we found that α5β1, αvβ5 and αvβ8 greatly promoted proliferation of endothelial cells in culture. To investigate the effect of integrin-binding peptides in promoting neovascularization and angiogenesis, the binding peptides to the above three types of integrins were immobilized to our custom-designed hydrogel in three-dimensional(3 D) culture of brain microvascular endothelial cells with the addition of vascular endothelial growth factor. Following a 7-day 3 D culture, the culture was fixed and processed for double labeling of phalloidin with von Willibrand factor or platelet endothelial cell adhesion molecule and assessed under confocal microscopy. In the 3 D culture in hydrogels conjugated with the integrin-binding peptide, brain microvascular endothelial c

关键词： 3D culture angiogenesis brain microvascular endothelial cells hydrogel integrins platelet endothelial cell adhesion molecule(PECAM-1) vascular endothelial growth factor(VEGF) vascularization

Adventures Beyond Amdahl's Law:How Power-Performance Measurement and Modeling at Scale Drive Server and Supercomputer Design

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Journal of Computer Science & Technology 2023年第1期38卷 80-86页

作者： Kirk W.Cameron Computer Science Virginia TechWashington D.C.VA 24061U.S.A.

Amdahl’s Law painted a bleak picture for large-scale *** implication was that parallelism was limited and therefore so was potential *** Amdahl’s contribution was seminal and important,it drove others vested in parallel processing to define more clearly why large-scale systems are critical to our future and how they fundamentally provide opportunities for speedup beyond Amdahl’s *** the early 2000s,much like Amdahl,we predicted dire consequences for large-scale systems due to power *** our early work was often dismissed,the implications were clear to some:power would ultimately limit *** this retrospective,we discuss how power-performance measurement and modeling at scale led to contributions that have driven server and supercomputer design for more than a *** the influence of these techniques is now indisputable,we discuss their connections,limits and additional research directions necessary to continue the performance gains our industry is accustomed to.

关键词： Amdahl’s Law speedup power-aware computing power modeling performance modeling performance prediction power measurement

Transgenic technologies for the study of epididymal function

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Asian Journal of Andrology 2000年第1期2卷 33-38页

作者： R.JohnLye BarryT.Hinton Department of Cell Biology University of Virginia Health System School of Medicine Charlotesville VA 22908 USADepartment of Cell Biology University of Virginia Health System School of Medicine Charlotesville VA 22908 USA

Sperm mature and acquire the capacity for fertilization during their transit through the epididymis, however little isknown of the molecular events that comprise sperm maturation. Recent advances in transgenic mouse technology holdpromise for illumination of this process. Most of the existing infertile, transgenic mouse lines seem to have defects inepithelial structure or sperm transport rather than direct defects in the maturation of sperm. Temporally and spatially re-stricted targeted disruptions of epididymal specific genes should provide great insight into the epididymal contribution tosperm maturation. (Asian J Androl 2000; 2: 33 - 38 )

关键词： epididymis sperm maturation transgenic organisms fertility