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Novel immunotherapy approaches for metastatic urothelial and renal cell carcinoma

Asian journal of Urology 2016年第4期3卷 268-277页

作者： Zhiying Shao Andrew Z.Wang daniel j.george Tian Zhang Department of Medical Oncology The Affiliated Hospital of Xuzhou Medical UniversityJiangsu Center for the Collaboration and Innovation of Cancer BiotherapyCancer InstituteXuzhou Medical UniversityXuzhouJiangsuChina Department of Radiation Oncology Lineberger Comprehensive Cancer CenterUniversity of North Carolina-Chapel HillChapel HillNCUSA Division of Medical Oncology Department of MedicineDivision of UrologyDepartment of SurgeryDuke Cancer InstituteDuke University Medical CenterDurhamNCUSA Division of Medical Oncology Department of MedicineDuke Cancer InstituteDuke University Medical CenterDurhamNCUSA

The treatment of metastatic renal cell carcinoma(RCC)and urothelial carcinoma(UC)remains a major *** research has implicated the immune system in tumor surveillance of both malignancies,leading to the application of immunotherapy agents for both *** them,the most promising agents are the checkpoint blockade drugs,such as antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),programmed death receptor 1(PD-1),and PD-1 ligand(PD-L1).In normal physiology,these immune checkpoints act as inhibitory signals to fine-tune the duration and strength of immune reactions,which is pivotal for maintaining ***,tumor cells also utilize immune checkpoint pathways to evade anti-tumor immune response,leading to disease progression and ***,there has been intense preclinical and clinical effort focused on the application of checkpoint inhibitors in metastatic RCC and *** date,nivolumab(anti-PD-1)and atezolizumab(anti-PD-L1)have been approved for the treatment of metastatic RCC and UC,*** these successes,challenges remain in how to further improve response rates to immunotherapy and how to select patients that will benefit from this *** this report,we review existing data and research on immunotherapy in metastatic RCC and UC.

关键词： Immune checkpoint inhibitors Nivolumab Atezolizumab Pembrolizumab Renal cell carcinoma Urothelial carcinoma

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The promise of immunotherapy in genitourinary malignancies

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Precision Clinical Medicine 2018年第3期1卷 97-101页

作者： Tian Zhang Andrew j.Armstrong daniel j.george jiaoti Huang Duke Cancer Institute Duke University School of MedicineDurhamNC27514

A broad understanding of the tumor immune landscape has led to a revolution of immune checkpoint inhibitors in the treatment of multiple cancer *** genitourinary malignancies,immune checkpoint inhibitors have improved outcomes for patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma;however,these treatments have not yet proven broadly beneficial for patients with metastatic prostate *** prospective trials are ongoing to further improve outcomes with immunotherapy combinations and for biomarker development to predict benefit from immune checkpoint *** perspective article highlights our current immunotherapy approaches in each of the genitourinary malignancies and the ongoing clinical trials that may inform our future treatments in renal,urothelial,and prostate cancers.

关键词： immune checkpoint inhibition urothelial carcinoma renal cell carcinoma prostate cancer

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Understanding Performance for Two 802.11 Competing Flows

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journal of Computer Science & Technology 2008年第3期23卷 365-376页

作者： Michael j.Feeley Brendan Cully Sharath j.george Department of Computer Science University of British ColumbiaVanconverCanada

It is well known that 802.11 suffers from both inefficiency and unfairness in the face of competition and interference. This paper provides a detailed analysis of the impact of topology and traffic type on network performance when two flows compete with each other for airspace. We consider both TCP and UDP flows and a comprehensive set of node topologies. We vary these topologies to consider all combinations of the following four node-to-node interactions：（1） nodes unable to read or sense each other, （2） nodes able to sense each other but not able to read each other＇s packets and nodes able to communicate with （3） weak and with （4） strong signal. We evaluate all possible cases through simulation and show that the cases can be reduced to 9 UDP and 10 TCP 802.11g models with similar efficiency/fairness characteristics. We also validate our simulation results with extensive experiments conducted in a laboratory testbed. These more detailed models improve on previous work such as hidden-/exposed-terminal categorization and are thus better suited as a basis for adaptive techniques to improve performance in 802.11 multi-hop WLAN or Mesh Networks.

关键词： 802.11 wireless unfairness two-flow competition network topology

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Determination of selected semi-volatile organic compounds in water using automated online solid-phase extraction with large-volume injection/gas chromatography/mass spectrometry

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Frontiers of Environmental Science & Engineering 2011年第3期5卷 417-425页

作者： Yongtao LI Christina L.MCCARTY Ed j.george Drinking Water Quality Laboratory Underwriters Laboratories Inc.South BendIN 46617USA Chemical Analysis Bruker DaltonicsFremontCA 94538USA

A rapid,sensitive,and cost-effective analyticalmethod was developed for the analysis of selected semivolatileorganic compounds in *** method used anautomated online solid-phase extraction technique coupledwith programmed-temperature vaporization large-volumeinjection gas chromatography/mass *** samples were extracted by using a fully automatedmobile rack system based on x-y-z robotic techniquesusing syringes and disposable 96-well extraction *** method was validated for the analysis of 30 semivolatileanalytes in drinking water,groundwater,andsurface *** a sample volume of 10 mL,the linearcalibrations ranged from 0.01 or 0.05 to 2.5μg·L^(-1),and themethod detection limits were less than 0.1μg·L^(-1).For thereagent water samples fortified at 1.0μg·L^(-1)and2.0μg·L^(-1),the obtained mean absolute recoveries were70%-130%with relative standard deviations of less than20%for most *** the drinking water,groundwater,and surface water samples fortified at 1.0μg·L^(-1),theobtained mean absolute recoveries were 50%-130%withrelative standard deviations of less than 20%for *** new method demonstrated three advantages:1)no manipulation except the fortification of surrogatestandards prior to extraction;2)significant cost reductionassociated with sample collection,shipping,storage,andpreparation;and 3)reduced exposure to hazardous solventsand other *** a result,this new automatedmethod can be used as an effective approach for screeningand/or compliance monitoring of selected semi-volatileorganic compounds in water.

关键词： automated solid-phase extraction programmed-temperature vaporization large-volume injection gas chromatography/mass spectrometry semi-volatile organic compounds water analysis

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan george jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Carbon nanotube and conducting polymer composites for supercapacitors

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Progress in Natural Science:Materials International 2008年第7期18卷 777-788页

作者： daniel jewell george Z. Chen School of Chemical and Environmental and Mining Engineering University of Nottingham University ParkNottingham NG7 2RD UK

Composites of carbon nanotubes and conducting polymers can be prepared via chemical synthesis, electrochemical deposition on pre- formed carbon nanotube electrodes, or by electrochemical co-deposition. The composites combine the large pseudocapacitance of the conducting polymers with the fast charging/discharging double-layer capacitance and excellent mechanical properties of the carbon nanotubes. The electrochemically co-deposited composites are the most homogeneous and show an unusual interaction between the polymer and nanotubes, giving rise to a strengthened electron delocalisation and conjugation along the polymer chains. As a result they exhibit excellent electrochemical charge storage properties and fast charge/discharge switching, making them promising electrode mate- rials for high power supercapacitors.

关键词： Supercapacitor Carbon nanotube Conducting polymer

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台式计算机化是一个连续的过程

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计算机工程与应用 1991年第5期27卷 110-120页

作者： M.Zmuidzinas R.Kling j.george 祁伟国家教委信息中心

本文首次对工作小组计算机化的连续过程进行纵向的、定量的分析。我们认为计算机化应被定义成连续的过程,而不象通常认为的静态过程。我们还认为计算机化也不象许多技术杂志上所描述的那种动态的变化。把计算机化看作是连续过程也隐含... 详细信息

本文首次对工作小组计算机化的连续过程进行纵向的、定量的分析。我们认为计算机化应被定义成连续的过程,而不象通常认为的静态过程。我们还认为计算机化也不象许多技术杂志上所描述的那种动态的变化。把计算机化看作是连续过程也隐含了在计算机化的小组中工作是如何变化的、以及我们如何研究工作的变化。为获取动态的信息和区分稳定和偶然的因素,在配置设备之后的较长时间内观察工作的变化并进行重复的观察是需要的。我们将介绍我们的研究成果,这些成果是对二年来在39个工作小组中,计算机化所起的作用的调查基础上取得的。在1999和1989年中,我们通过调查和访问收集了有关的数据。我们把计算机化过程分为四个要素:设备、基础条件、计算的社会组织和控制方式。对每个要素我们将提供有关的数据。在88到89年间,技术因素变得更复杂了(例如:设备种类,配备及使用的广度),社会因素(如:计算的基础条件)没有多大的变化。工作变化的初步分析表明,工作小组的工作更繁忙了。

关键词：计算机化连续过程计算机应用

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Predicting the synthesizability of crystalline inorganic materials from the data of known material compositions

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npj Computational Materials 2023年第1期9卷 733-743页

作者： Evan R.Antoniuk Gowoon Cheon george Wang daniel Bernstein William Cai Evan j.Reed Materials Science Division Physical and Life Sciences DirectorateLawrence Livermore National LaboratoryLivermoreCAUSA Department of Chemistry Stanford UniversityStanfordCAUSA Department of Applied Physics Stanford UniversityStanfordCAUSA Google Research Mountain ViewCAUSA Department of Physics Stanford UniversityStanfordCAUSA Department of Mathematics Stanford UniversityStanfordCAUSA Department of Computer Science Stanford UniversityStanfordCAUSA Department of Materials Science and Engineering Stanford UniversityStanfordCAUSA

Reliably identifying synthesizable inorganic crystalline materials is an unsolved challenge required for realizing autonomous materials *** this work,we develop a deep learning synthesizability model(SynthNN)that leverages the entire space of synthesized inorganic chemical *** reformulating material discovery as a synthesizability classification task,SynthNN identifies synthesizable materials with 7×higher precision than with DFT-calculated formation *** a head-to-head material discovery comparison against 20 expert material scientists,SynthNN outperforms all experts,achieves 1.5×higher precision and completes the task five orders of magnitude faster than the best human ***,without any prior chemical knowledge,our experiments indicate that SynthNN learns the chemical principles of charge-balancing,chemical family relationships and ionicity,and utilizes these principles to generate synthesizability *** development of SynthNN will allow for synthesizability constraints to be seamlessly integrated into computational material screening workflows to increase their reliability for identifying synthetically accessible materials.

关键词： inorganic crystalline utilize

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c-Met signaling in the development of tumorigenesis and chemoresistance: Potential applications in pancreatic cancer

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World journal of Gastroenterology 2014年第26期20卷 8458-8470页

作者： daniel Delitto Eva Vertes-george Steven j Hughes Kevin E Behrns jose G Trevino Department of Surgery University of Florida-Gainesville Department of Pathology University of Florida-Gainesville

Pancreatic ductal adenocarcinoma is the 4th leading cause of cancer deaths in the United States. The majority of patients are candidates only for palliative chemotherapy, which has proven largely ineffective in halting tumor progression. One proposed mechanism of chemoresistance involves signaling via the mesenchymal-epithelial transition factor protein (MET), a previously established pathway critical to cell proliferation and migration. Here, we review the literature to characterize the role of MET in the development of tumorigenesis, metastasis and chemoresistance, highlighting the potential of MET as a therapeutic target in pancreatic cancer. In this review, we characterize the role of c-Met in the development of tumorigenesis, metastasis and chemoresistance, highlighting the potential of c-Met as a therapeutic target in pancreatic cancer.

关键词： Pancreatic adenocarcinoma c-Met Chemoresistance Receptor tyrosine kinase

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Visualizing temperature-dependent phase stability in high

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npj Computational Materials 2021年第1期7卷 1375-1383页

作者： daniel Evans jiadong Chen george Bokas Wei Chen Geoffroy Hautier Wenhao Sun Department of Materials Science and Engineering University of MichiganAnn ArborMIUSA Institute of Condensed Matter and Nanosciences(IMCN) UCLouvainLouvain-La-NeuveBelgium Thayer School of Engineering Dartmouth CollegeHanoverNHUSA

High entropy alloys(HEAs)contain near equimolar amounts of five or more elements and are a compelling space for materials *** the design of HEAs,great emphasis is placed on identifying thermodynamic conditions for single-phase and multi-phase stability regions,but this process is hindered by the difficulty of navigating stability relationships in high-component *** phase diagrams use barycentric coordinates to represent composition axes,which require(N–1)spatial dimensions to represent an N-component system,meaning that HEA systems with N>4 components cannot be readily ***,we propose forgoing barycentric composition axes in favor of two energy axes:a formation-energy axis and a‘reaction energy’*** Inverse Hull Webs offer an information-dense 2D representation that successfully captures complex phase stability relationships in N≥5 component *** use our proposed diagrams to visualize the transition of HEA solid-solutions from high-temperature stability to metastability upon quenching,and identify important thermodynamic features that are correlated with the persistence or decomposition of metastable HEAs.

关键词： stability phase thermodynamic

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