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targeting trkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen alvin Huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

tropomyosin receptor kinase B(trkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic trkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with trkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss trkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of trkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with trkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated trkB.t1 *** trkB agonists and antibodies that activate trkB are being intensively investigated,they cannot distinguish the multiple human trkB splicing isoforms or cell type-specific *** trkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost trkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity trkB

A review of strategies to overcome immune resistance in the treatment of advanced prostate cancer

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Cancer Drug Resistance 2023年第3期6卷 656-673页

作者： Kenneth Sooi Robert Walsh Nesaretnam Kumarakulasinghe alvin Wong Natalie Ngoi Department of Haematology-Oncology National University Cancer InstituteSingapore 119228Singapore

Immunotherapy has become integral in cancer therapeutics over the past two decades and is now part of standard-of-care treatment in multiple cancer types. While various biomarkers and pathway alterations such as dMMR, CDK12, and AR-V7 have been identified in advanced prostate cancer to predict immunotherapy responsiveness, the vast majority of prostate cancer remain intrinsically immune-resistant, as evidenced by low response rates to anti-PD(L)1 monotherapy. Since regulatory approval of the vaccine therapy sipuleucel-t in the biomarker-unselected population, there has not been much success with immunotherapy treatment in advanced prostate cancer. Researchers have looked at various strategies to overcome immune resistance, including the identification of more biomarkers and the combination of immunotherapy with existing effective prostate cancer treatments. On the horizon, novel drugs using bispecific t-cell engager (BitE) and chimeric antigen receptors (CAR) technology are being explored and have shown promising early efficacy in this disease. Here we discuss the features of the tumour microenvironment that predispose to immune resistance and rational strategies to enhance antitumour responsiveness in advanced prostate cancer.

关键词： Prostate cancer immunotherapy immune checkpoint inhibitor immune resistance tumour microenvironment

Auxo: an architecture-centric framework supporting the online tuning of software adaptivity

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Science China(Information Sciences) 2015年第9期58卷 31-45页

作者： WANG HuaiMin DING Bo SHI DianXi CAO JianNong alvin t.S.Chan National Key Laboratory of Parallel and Distributed Processing College of ComputerNational University of Defense Technology Department of Computing Hong Kong Polytechnic University

Adaptivity is the capacity of software to adjust itself to changes in its environment. A common approach to achieving adaptivity is to introduce dedicated code during software development stage. However,since those code fragments are designed a priori, self-adaptive software cannot handle situations adequately when the contextual changes go beyond those that are originally anticipated. In this case, the original builtin adaptivity should be tuned. For example, new code should be added to provide the capacity to sense the unexpected environment or to replace outdated adaptation decision logic. the technical challenges in this process, especially that of tuning software adaptivity at runtime, cannot be understated. In this paper,we propose an architecture-centric application framework for self-adaptive software named Auxo. Similar to existing work, our framework supports the development and running of self-adaptive software. Furthermore,our framework supports the tuning of software adaptivity without requiring the running self-adaptive software to be terminated. In short, the architecture style that we are introducing can encapsulate not only general functional logic but also the concerns in the self-adaptation loop(such as sensing, decision, and execution)as architecture elements. As a result, a third party, potentially the operator or an augmented software entity equipped with explicit domain knowledge, is able to dynamically and flexibly adjust the self-adaptation concerns through modifying the runtime software architecture. to truly exercise, validate, and evaluate our approach,we describe a self-adaptive application that was deployed on the framework, and conducted several experiments involving self-adaptation and the online tuning of software adaptivity.

关键词： software architecture self-adaptive software architecture style application framework software adaptation

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

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世界胃肠病学杂志:英文版 2023年第33期29卷 4942-4961页

作者： Joyce Wing Yan Mak alvin Wing Hin Law Kimmy Wan tung Law Rita Ho Carmen Ka Man Cheung Man Fai Law Department of Medicine and therapeutics Prince of Wales HospitalHong Kong 852China West Island School Hong Kong 852China Department of Medicine North District HospitalHong Kong 852China

Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is *** reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing therapy for hematological malignancies and those receiving stem cell *** with inactive and even resolved HBV infection still have persistence of HBV genomes in the *** expression of these silent genomes is controlled by the immune *** or ablation of immune cells,most importantly B cells,may lead to reactivation of seemingly resolved HBV ***,all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core *** found to be positive for HBsAg should be given prophylactic antiviral *** patients with resolved HBV infection,there are two *** first is pre-emptive therapy guided by serial HBV DNA monitoring,and treatment with antiviral therapy as soon as HBV DNA becomes *** second approach is prophy-lactic antiviral therapy,particularly for patients receiving high-risk therapy,especially anti-CD20 monoclonal antibody or hematopoietic stem cell *** and tenofovir are the preferred antiviral *** new effective therapies for hematological malignancies have been introduced in the past decade,for example,chimeric antigen receptor(CAR)-t cell therapy,novel monoclonal antibodies,bispecific antibody drug conjugates,and small molecule inhibitors,which may be associated with HBV *** there is limited evidence to guide the optimal preventive measures,we recommend antivi-ral prophylaxis in HBsAg-positive patients receiving novel treatments,including Bruton’s tyrosine kinase inhibitors,B-cell lymphoma 2 inhibitors,and CAR-t cell *** studies are needed to determine the risk o

关键词： Hepatitis B Hematologic neoplasms Chimeric antigen receptor-t cell therapy Monoclonal antibodies Bruton’s tyrosine kinase inhibitors Antiviral agents

the Definitive Guide to How Computers Do Math: Featuring the Virtual DIY Calculator 1st edition

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2005年

作者： Clive “MAX” Maxfield alvin Brown

ISBN: (数字)9780471741978

ISBN: (纸本)9780471732785

the Basics of Computer Arithmetic Made Enjoyable and Accessible-with a Special Program Included for Hands-on Learning "the combination of this book and its associated virtual computer is fantastic! Experience over the last fifty years has shown me that there's only one way to truly understand how computers work; and that is to learn one computer and its instruction set-no matter how simple or primitive-from the ground up. Once you fully comprehend how that simple computer functions, you can easily extrapolate to more complex machines."-Fred Hudson, retired engineer/scientist "this book-along with the virtual DIY Calculator-is an incredibly useful teaching and learning tool. the interesting trivia nuggets keep you turning the pages to see what's next. Students will have so much fun reading the text and performing the labs that they won't even realize they are learning."-Michael Haghighi, Chairperson of the Business and Computer Information Systems Division, Calhoun Community College, Alabama "At last, a book that presents an innovative approach to the teaching of computer architecture. Written with authority and verve, witty, superbly illustrated, and enhanced with many laboratory exercises, this book is a must for students and teachers alike."-Dr. Albert Koelmans, Lecturer in Computer Engineering, University of Newcastle upon tyne, UK, and the 2003 recipient of the EASIt-Eng. Gold Award for Innovative teaching in Computer Engineering Packed with nuggets of information and tidbits of trivia, How Computers Do Math provides an incredibly fun and interesting introduction to the way in which computers perform their magic in general and math in particular. the accompanying CD-ROM contains a virtual computer/calculator called the DIY Calculator, and the book's step-by-step interactive laboratories guide you in the creation of a simple program to run on your DIY Calculator. How Computers Do Math can be enjoyed by non-technical individuals; students of computer science, elec

关键词： Computer science

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tHEAtER : 5th ed.

Season of the year influences infection rates following total hip arthroplasty

2005年

作者： EDWIN WILSON alvin GOLDFARB.

Includes bibliographical references (p. b-b-11) and index.

ISBN: (数字)0072872187

ISBN: (纸本)9780072872187

Includes bibliographical references (p. b-b-11) and index.

关键词： theater.

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World Journal of Orthopedics 2017年第12期8卷 895-901页

作者： Samuel Rosas alvin C Ong Leonard t Buller Karim G Sabeh tsun yee Law Martin W Roche Victor H Hernandez Department of Orthopedic Surgery Wake Forest School of Medicine Holy Cross Orthopedic Institute Orthopedic Surgery Thomas Jefferson University Hospital Department of Orthopedics Surgery University of Miami Department of Orthopaedic Surgery Holy Cross Hospital

AIM to research the influence of season of the year on periprosthetic joint *** We conducted a retrospective review of the entire Medicare files from 2005 to 2014. Seasons were classified as spring, summer, fall or winter. Regional variations were accounted for by dividing patients into four geographic regions as per the United States Census Bureau(Northeast, Midwest, West and South). Acute postoperative infection and deep periprosthetic infections within 90 d after surgery were tracked. RESULtS In all regions, winter had the highest incidence of periprosthetic infections(mean 0.98%, SD 0.1%) and was significantly higher than other seasons in the Midwest, South and West(P t not the Northeast(P = 0.358). Acute postoperative infection rates were more frequent in the summer and were significantly affected by season of the year in the *** Season of the year is a risk factor for periprosthetic joint infection following total hip arthroplasty(tHA). Understanding the influence of season on outcomes following tHA is essential when risk-stratifying patients to optimize outcomes and reduce episode of care costs.

关键词： Hip arthroplasty Healthcare Infection Outcomes Season

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组合测试故障定位的关系树模型

计算机学报 2014年第12期37卷 2505-2518页

作者：钮鑫涛聂长海 CHAN alvin 南京大学计算机软件新技术国家重点实验室南京210023 香港理工大学电子计算学系

组合测试是一种重要的软件测试方法,该方法通常采用覆盖表作为测试用例集,适用于检测系统中由特定配置组合引发的故障.覆盖表中的一条引发系统故障的测试用例含有多个配置组合,如何确定其中哪个或哪几个配置组合引发系统故障有助于系统... 详细信息

组合测试是一种重要的软件测试方法,该方法通常采用覆盖表作为测试用例集,适用于检测系统中由特定配置组合引发的故障.覆盖表中的一条引发系统故障的测试用例含有多个配置组合,如何确定其中哪个或哪几个配置组合引发系统故障有助于系统开发人员检测出故障原因并做出改进.目前已有一些研究尝试解决上述问题,然而这些方法都没有对待定元组关系进行深入的研究与分析,因此定位过程代价很大并且定位结果也并不完整.文中构建了一个待定元组关系树(tuple Relationship tree,tRt)来描述所有待定元组的关系,利用tRt可以减少生成附加测试用例的数量,并且由于tRt给出全部待定元组的清晰视图,可以避免漏掉分析可能的待定元组,特别是有重叠部分的故障元组.基于tRt,我们提出了4种选择策略来辅助故障定位.系统的实验表明:其中的路径方法可以以较高的效率得到一个比已有方法更加完整的故障定位结果.

关键词：组合测试故障定位待定元组关系树有重叠部分元组选择策略软件测试

testicular fine-needle aspiration for the assessmen＇ of intratesticular hormone concentrations

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Asian Journal of Andrology 2016年第1期18卷 21-24页

作者： Ada P Lee Mara Y Roth Jean-Jacques Nya-Ngatchou Kat Lin thomas J Walsh Stephanie t Page alvin M Matsumoto William J Bremner John K Amory Bradley D Anawalt Department of Medicine University of California San Francisco San Francisco CA USA Department of Medicine and Center for Research in Reproduction and Contraception University of Washington Seattle WA USA Department of Obstetrics and Gynecology University of Washington Seattle WA USA Department of Urology University of Washington Seattle WA USA Department of Medicine Geriatric Research Education and Clinical Center VA Puget Sound Health Care System Seattle WA USA.

Measurement of intratesticular sex steroid concentrations in men informs both the development of male hormonal contraceptives and the understanding of male infertility. Given the challenges of using invasive techniques to measure testicular hormone physiology, our group has used a minimally-invasive fine-needle aspiration technique to measure intratesticular hormones in normal healthy men. Herein, we present a post-hoc analysis of the safety and efficacy of testicular fine-needle aspiration （FNA） completed as part of six clinical trials. From 2001 through 2011, a total of 404 procedures were conducted among 163 research volunteers, 85.9% of which were successful in obtaining sufficient fluid for the measurement of intratesticular steroid concentrations. Pain was the most common side effect, with 36.8% of procedures associated with moderate procedural pain and 4.7% with severe procedural pain. Postprocedural pain was uncommon and abated within a few days. Mild local bruising occurred with 14.9% of procedures. two serious adverse events （0.5%） required surgical intervention. the risk of an adverse event was not associated with age, body mass index, testicular size, or the volume of fluid aspirated. testicular FNA to obtain fluid for measurement of intratesticular steroid concentrations frequently causes mild to moderate procedural pain, but serious adverse events occur rarely. testicular FNA has been instrumental for defining human intratesticular hormone physiology and is a minimally-invasive, safe, effective method for obtaining fluid for research on testicular physiology and pathology.

关键词： male contraception physiology reproductive and urinary testis