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perspectives on the clinical development of mmunotherapy in prostate cancer

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Asian Journal of Andrology 2018年第3期20卷 253-259页

作者： Lisa M Cordes james L Gulley Ravi A Madan Clinical Center National Institutes of Health Bethesda MD 20892 USA Genitourinary Malignancies Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

Despite impressive survival benefits with immunotherapy in patients with various solid tumors, the full potential of these agents in prostate cancer has yet to be realized. SipuleuceI-T demonstrated a survival benefit in this population, indicating that prostate cancer is an immunoresponsive disease; however, these results have not been matched by other agents. A large trial with ipilimumab in prostate cancer failed to meet its primary objective, and small trials with pD-1/pD-L1 inhibitors did not yield a significant improvement in overall response. However, several late-stage clinical trials are underway with other vaccines in prostate cancer. Reports of clinical benefit with immunotherapies, particularly when used in combination or a select population, have provided the framework to develop sound clinical trials. Understanding immunogenic modulation, antigen spread, biomarkers, and DNA-repair defects will also help mold future strategies. Through rational patient selection and evidence-based combination approaches, patients with prostate cancer may soon derive durable survival benefits with immunotherapies.

关键词： checkpoint inhibitor immunotherapy prostate cancer therapeutic vaccine

Rock inhibitor may compromise human induced pluripotent stem cells for cardiac differentiation in 3D

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Bioactive Materials 2022年第3期7卷 508-522页

作者： Bin Jiang Wenquan Ou james G.Shamul Hao Chen Sarah Van Belleghem Samantha Stewart Zhenguo Liu John p.Fisher Xiaoming He Fischell Department of Bioengineering University of MarylandCollege ParkMD20742United States Division of Cardiovascular Medicine University of Missouri School of MedicineColumbiaMO65212United States Marlene and Stewart Greenebaum Comprehensive Cancer Center University of MarylandBaltimoreMD21201United States

Cardiomyocytes differentiated from human induced pluripotent stem cells(ipSCs)are valuable for the understanding/treatment of the deadly heart diseases and their drug ***,the very much needed homogeneous 3D cardiac differentiation of human ipSCs is still ***,it is discovered surprisingly that Rock inhibitor(RI),used ubiquitously to improve the survival/yield of human ipSCs,induces early gastrulation-like change to human ipSCs in 3D culture and may cause their heterogeneous differentiation into all the three germ layers(i.e.,ectoderm,mesoderm,and endoderm)at the commonly used concentration(10μM).This greatly compromises the capacity of human ipSCs for homogeneous 3D cardiac *** reducing the RI to 1μM for 3D culture,the human ipSCs retain high pluripotency/quality in inner cell mass-like solid 3D ***,the beating efficiency of 3D cardiac differentiation can be improved to more than 95%in~7 days(compared to less than~50%in 14 days for the 10μM RI condition).Furthermore,the outset beating time(OBT)of all resultant cardiac spheroids(CSs)is synchronized within only 1 day and they form a synchronously beating 3D construct after 5-day culture in gelatin methacrylol(GelMA)hydrogel,showing high homogeneity(in terms of the OBT)in functional maturity of the ***,the resultant cardiomyocytes are of high quality with key functional ultrastructures and highly responsive to cardiac *** discoveries may greatly facilitate the utilization of human ipSCs for understanding and treating heart diseases.

关键词： Episomal ipSC Cardiomyocyte Spheroid GelMA

Eating, Cooking, and Shanghai＇s =Less-than- Manly MenD： The Social Consequences of Food Rationing and Economic Reforms

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Frontiers of History in China 2013年第2期8卷 259-293页

作者： james Z. Gao Department of History University of Maryland College Park MD 20742 USA

This study examines some social consequences of food rationing and economic reforms in Shanghai by considering the notion of ＂Shanghai little men＂（a broader translation of which is ＂Shanghai less-than-manly men＂）. Male Shanghainese are notorious for doing household labor and being obedient to their wives, which has earned them the nickname Shanghai little men. This study indicates that their grocery shopping and cooking were first inspired by fundamental changes in food distribution and the power structure during the 1950s and 1960s. It treats Shanghai little men as both a special group and a symbol of certain changes in gender roles at home and the redefining of gender norms in the larger society. It examines the shifting discourse concerning Shanghai little men in the era of economic reforms and analyzes a recent popular discourse about ＂seeking real men＂ and ＂being real women.＂ Finally, it deconstructs the current cultural nostalgia for traditional gender-defined divisions of labor, reflecting a parallel developmen--the ＂transnational business masculinity＂ that one sees in China.

关键词： little men economic reforms food rationing household labor,masculinity femininity gender practice Shanghainese

Noncovalent reversible binding-enabled facile fabrication of leak-free pDMS microfluidic devices without plasma treatment for convenient cell loading and retrieval

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Bioactive Materials 2022年第10期7卷 346-358页

作者： Bin Jiang Alisa White Wenquan Ou Sarah Van Belleghem Samantha Stewart james G.Shamul Shaik O.Rahaman John p.Fisher Xiaoming He Fischell Department of Bioengineering University of MarylandCollege ParkMD20742USA Department of Nutrition and Food Science University of MarylandCollege ParkMD20742USA Marlene and Stewart Greenebaum Comprehensive Cancer Center University of MarylandBaltimoreMD21201USA

The conventional approach for fabricating polydimethylsiloxane(pDMS)microfluidic devices is a lengthy and inconvenient procedure and may require a clean-room microfabrication facility often not readily ***,living cells can’t survive the oxygen-plasma and high-temperature-baking treatments required for covalent bonding to assemble multiple pDMS parts into a leak-free device,and it is difficult to disassemble the devices because of the irreversible covalent *** a result,seeding/loading cells into and retrieving cells from the devices are ***,we discovered that decreasing the curing agent for crosslinking the pDMS prepolymer increases the noncovalent binding energy of the resultant pDMS surfaces without plasma or any other *** enables convenient fabrication of leak-free microfluidic devices by noncovalent binding for various biomedical applications that require high pressure/flow rates and/or long-term cell culture,by simply hand-pressing the pDMS parts without plasma or any other treatment to bind/*** this method,multiple types of cells can be conveniently loaded into specific areas of the pDMS parts before assembly and due to the reversible nature of the noncovalent bonding,the assembled device can be easily disassembled by hand peeling for retrieving *** with 3D printers that are widely available for making masters to eliminate the need of photolithography,this facile yet rigorous fabrication approach is much faster and more convenient for making pDMS microfluidic devices than the conventional oxygen plasma-baking-based irreversible covalent bonding method.

关键词： Binding energy 3D printing Soft lithography Microfluidics polydimethylsiloxane

Self-reaction of initial active groups in coal

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International Journal of Mining Science and Technology 2012年第2期22卷 169-175页

作者： Qi Xuyao Wang Deming james A Milke Zhong Xiaoxing State Key Laboratory of Coal Resources and Mine Safety School of Safety EngineeringChina University of Mining&TechnologyXuzhou 221008China Department of Fire protection Engineering University of Maryland.College ParkMD 20742USA

For further understanding of self-heating of coal, we tested the reactions of seven different ranks of coal under inert atmosphere. In the test, 50-gram of coal sample ranged from 0.18 mm to 0.38 mm was put into a special designed copper reaction vessel and let pure nitrogen to flow into the coal sample from the bottom at a rate of 100 mL/min. The programmed temperature enclosure was run at a programmed rate of 0.8 ~C/min. The concentration of the carbon oxides and the coal temperature were tested. The results show that the coal reactions under inert atmosphere can generate CO and C02. The reactions under inert atmosphere are affected by coal ranks, initial pore structure of coal and sulfur content. For low ranks of coal, the productions of carbon oxides are piecewise. The coal temperature is lower than the surrounding temperature throughout the reactions under inert atmosphere, but it rises quickly and reaches a crossing point temperature in the later stage under dry-air atmosphere. Based on the analysis, it indicates the self-reaction of initial active groups exists in the self-heating of coal besides the reactions in the two parallel reactions model. Spontaneous combustion of coal is due to both the oxidation heat accumulation and the chain reaction. A new reaction model of self-heating of coal was orooosed.

关键词： CoalSelf-heatingInitial active groupsSelf-reactionInert atmosphereCarbon oxides

Work conjugate strain of virial stress

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International Journal of Smart and Nano Materials 2016年第1期7卷 39-51页

作者： Leyu Wang Jiaoyan Li james D.Lee Center for Collision Safety and Analysis College of ScienceGeorge Mason UniversityFairfaxVAUSA School of Engineering Brown UniversityProvidenceRIUSA Department of Mechanical and Aerospace Engineering The George Washington UniversityWashingtonDCUSA

Certain stress tensor and strain tensor form a conjugate pair if there exists a scalar valued strain energy function such that the stress tensor is equal to the derivative of strain energy function with respect to the strain *** stress is widely accepted as the stress measurement in molecular dynamics(md).However,its conjugate strain is not yet *** atomic logarithmic strain is proposed and numerically verified as the conjugate strain of virial stress at 0 K *** strain energy is calculated by virial stress and the proposed atomic logarithmic strain equals to the interatomic potential energy *** conclusion is numerically verified with(1)Coulomb-Buckingham potential,Lenard-Jones potential,or arbitrary nonlinear pair potential and(2)randomly generated atomic configurations and deformation *** are given in determining the stress–strain relation for magnesium oxide with md *** result shows that the atomic logarithmic strain is identical to engineer-ing strain when deformation is small.

关键词： Thermodynamic pair conjugacy virial stress atomic logarithmic strain molecular dynamics interatomic potential strain energy magnesium oxide

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充血性心力衰竭患者生命的最后六个月

世界医学杂志 2001年第10期5卷 55-63页

作者： james W Levenson,md 李明洲等

目的：明确充血性心力衰竭患者生命最后6个月经历的特点。设计：前瞻性队列研究的回顾性分析。承担者：不同地区的5所医学院的三级医疗中心。参加者：共1404例诊断为充血性心力衰竭并急剧恶化的患者入选本研究。这些患者是参加明白疾病... 详细信息

目的：明确充血性心力衰竭患者生命最后6个月经历的特点。设计：前瞻性队列研究的回顾性分析。承担者：不同地区的5所医学院的三级医疗中心。参加者：共1404例诊断为充血性心力衰竭并急剧恶化的患者入选本研究。这些患者是参加明白疾病的预后以及选择治疗可致的不良后果（Study to Understand prognose and preference for Outcomes and Risks of Treatment,SUppORT）这一临床研究的病人。其中539例患者在登记住院后一年内死亡。方法：在SUppORT研究的各个不同时间，采访患者或其监护人，收集材料并制成简表。为描述走向死亡的进程，我们设计了在时间上倒序的观察窗口。此时间观察窗口始于患者死亡的日期，止于纳入SUppORT研究的日期或死亡前6个月。所有收集资料的时间观察窗口都由患者提供每一结局信息。我们描述每一种结局的时间分布频度并检验其趋势。结局的测定：各时间观察窗口测定的结局包括：住院天数（占纳入后整个生存天数）的百分比、基于模型的预期存活6个月的可能性、功能状态、躯体及情绪方面的严重症状（包括疼痛、抑郁和焦虎）、患者治疗的选择、患者疾病对家庭经济的影响。结果：随着死亡的临近，患者的预后变得更差，疾病更加严重。住院患者生理评分的中位值从死亡前6个月至3个月之间的33分升高到死亡前3天内的44分。但直到死亡前3天内，基于模型的预计存活6个月存活率的中位数仍为54%。随着死亡的临近，受损功能的数目、抑郁评分的中位数及诉严重疼痛或呼吸困难的患者数增加。41%的监护人诉患者在死亡前3天内严重疼痛，63%诉患者严重气促。患者自我评估的生活质量基本没有变化。在死亡前各阶段，29%-58%的患者报告生活质量“好”至“优”。随着死亡的临近，患者越来越不情愿接受心肺复苏，死亡前6个月至3个月不情愿复苏的患者为33%，而到死亡前1个月至3天上升为47%（p<0.05）。随着死亡的临近，住院患者中写下书面遗嘱不情愿复苏的患者也增多。患者疾病对其家庭经济有显著的影响。在患者死亡时，23%的患者家庭花掉了绝大部分或全部积蓄。结论：在充血性心力衰竭的最后6个月，随着死亡的临近，疾病变得更重，患者功能丧失及出现某些症状更频繁，不情愿接受复苏患者更为普遍。但生活质量无明显下降。许多患者基于模型的6个月预后的中位数仍较好，且生活质量“好”至“优”。此结果反射出在充血性心力衰竭患者生命的最后几个月病况具有不可预测性。

关键词：充血性心力衰竭预后

Review of barriers and interventions to promote treatment engagement for pediatric attention deficit hyperactivity disorder care

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World Journal of psychiatry 2021年第12期11卷 1206-1227页

作者： Raman Baweja Cesar A Soutullo james G Waxmonsky Department of psychiatry and Behavioral Health Penn State College of MedicineHersheyPA 17033United States Louis A.Faillace MD Department of Psychiatry and Behavioral SciencesThe University of Texas Health Science Center at HoustonHoustonTX 77054United States

Attention deficit hyperactivity disorder(ADHD)is a common and impairing behavioral health disorder,impacting over 5%of children *** are multiple evidence-based pharmacological and psychosocial treatments for ADHD,and greater service utilization is associated with improved acute and long-term ***,long-term outcomes are suboptimal as multimodal treatments are often not accessed and most care ends *** narrative review discusses barriers to engagement for children and adolescents with ADHD and their families as well as interventions to overcome these *** face a variety of structural and attitudinal barriers,ranging from cost and access to stigma and low self-efficacy to successfully implement *** are multiple interventions that may enhance engagement with ADHD care including psychoeducation,integration of behavioral services in general medical settings,telehealth as well as specific adaptations to existing ADHD treatments,such as the use of motivational interviewing or shared decision *** of behavioral health into general medical settings and telehealth have been found in controlled studies to increase access by reducing both structural and attitudinal *** motivational interviewing,shared decision making and other engagement interventions to evidence-based ADHD treatments has been found to reduce attitudinal barriers that translates into improved participation and satisfaction while enhancing ***,little is known about how to promote extended engagement with ADHD services even though a chronic care model for ADHD is recommended.

关键词： Attention deficit hyperactivity disorder Treatment engagement Barriers Interventions Children Adolescents

Crossing point temperature of coal

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Mining Science and Technology 2011年第2期21卷 255-260页

作者： Qi xuyao Deming Wang james A. Milke Xiaoxing Zhong State Key Laboratory of Coal Resources and Safe Mining Faculty of Safety Engineering China University of Mining ＆ Technology Xuzhou 221008 China Department of Fire protection Enguneering University of Maryland College Park MD20742 USA

A further understanding of the self-heating of coal was obtained by investigating the crossing point temperature（CpT） of different ranks of *** tests were carried out using a self-designed experimental system for coal self-heating.50 g（±0.01 g） of coal particles ranging from 0.18 mm to 0.38 mm in size were put into a pure copper reaction vessel attached to the center of a temperature programmed *** temperature program increased the temperature at a rate of 0.8℃/*** air was permitted to flow into the coal reaction vessel at different *** surrounding temperature and the coal temperature were monitored by a temperature *** results indicate that CpT is affected by coal rank,moisture,sulfur, and the experimental *** ranked coals show higher CpT values.A high moisture content causes a delay phenomenon during the self-heating of the *** at 40℃decreases the effects of *** reactivity of sulfur components in the coal is low under dry and low-temperature conditions. These components form a film that covers the coal surface and slightly inhibits the self-heating of the coal. The flow rate of dry air,and the heating rate of the surroundings,also affect the self-heating of the *** most appropriate experimental conditions for coal samples of a given weight and particle size were determined through contrastive *** on this analysis we propose that CpTs be determined under the same,or nearly the same conditions,for evaluation of the spontaneous combustion of coal.

关键词： Coal Spontaneous combustion Crossing point temperature Moisture Sulfur Coal rank