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Emerging function of mTORC2 as a core regulator in glioblastoma: metabolic reprogramming and drug resistance

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Cancer Biology & Medicine 2014年第4期11卷 255-263页

作者： Si-Han Wu Jun-Feng Bi Timothy Cloughesy webster K.Cavenee Paul S.Mischel Ludwig Institute for Cancer Research University of California Neuro-Oncology Program University of California

Glioblastoma （GBM） is one of the most lethal human cancers. Genomic analyses define the molecular architecture of GBM and highlight a central function for mechanistic target of rapamycin （roTOR） signaling, roTOR kinase exists in two multi- protein complexes, namely, mTORC 1 and mTORC2. These complexes differ in terms of function, regulation and rapamycin sensitivity, mTORC 1 is well established as a cancer drug target, whereas the functions of mTORC2 in cancer, including GBM, remains poorly understood. This study reviews the recent findings that demonstrate a central function ofmTORC2 in regulating tumor growth, metabolic reprogramming, and targeted therapy resistance in GBM, which makes mTORCZ as a critical GBM drug target.

关键词： Glioblastoma mTOR metabolic reprogramming mTORC2 Warburg effect PI3K

Rare presentation of Brunner's gland adenoma:another differentiation in patients with recurrent "idiopathic" pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2012年第1期11卷 107-110页

作者： Soumil Vyas James RA Skipworth Dimitrios Lytras Claire Smyth Anthony Mee Adrian Hatfield Charles Imber George webster Department of Hepatobiliary & Pancreatic Surgery University College London Hospital NHS Trust Department of Gastroenterology University College London Hospital NHS Trust Department of Gastroenterology Royal Berkshire Hospital NHS Trust

BACKGROUND:Brunner's gland adenoma (BGA) is an unusual benign neoplasm arising from Brunner's glands in the *** symptomatic it presents either with duodenal obstruction or ***,pancreatitis secondary to ampullary obstruction from a BGA is very ***:A 23-year-old female presented with recurrent episodes of 'idiopathic' *** was extensively investigated and was found to have a large polypoid BGA,intermittently obstructing the *** created a ball-valve effect causing secondary intermittent obstruction of the pancreatic duct resulting in *** condition was cured surgically,through transduodenal excision of the *** reviewed the surgical literature pertaining to these unusual and similar causes of obstructive pancreatitis,not related to ***:BGA of the duodenum is a rare cause of *** investigations should be carried out in all cases of unexplained pancreatitis before classifying the condition as 'idiopathic'.Discovery of a lesion of this nature gives an opportunity to provide a permanent surgical ***:BGA adds an unusual etiology for *** patients with pancreatitis should undergo extensive investigations before being termed 'idiopathic'.Surgical excision of the BGA provides a definitive curative treatment for the adenoma and pancreatitis.

关键词： ampullary polyp Brunner's gland adenoma pancreatitis excision

Decontamination of mobile phones and electronic devices for health care professionals using a chlorhexidine/carbomer 940■gel

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Frontiers of Chemical Science and Engineering 2019年第1期13卷 192-198页

作者： Rafael Muniz de Oliveira Nereida Mello da Rosa Gioppo Jancineide Oliveirade Carvalho Francilio Carvalho Oliveira Thomas Jay webster Fernanda Roberta Marciano Anderson Oliveira Lobo University Hospital of the West of Parana State University of West of Parana Cascavel PR Brazil University Center for Health. Humanities and Technology of Piaui (UNINOVAFAPI). Piaui Brazil Science and Technology Institute Brasil University Itaquera SP Brazil Nanomedicine Laboratory Department of Chemical Engineering Northeastern University MA 02115 USA Materials Science and Engineering graduation program Technology Center Federal University of Piaui. PI Brazil

Though they reduce microorganism growth, current hospital disinfectants also damage many of today’s modern electronic devices such as tablets and smartphones. Herein, the efficacy of a new chlorhexidine digluconate gel (CDG) was tested as a disinfectant for mobile and electronic devices in a clinical environment. Specifically, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus were used to infect the screen of eight smartphones. The CDG was prepared at concentrations of 2%, 4% and 6%, and tested on paper disks infected with these bacteria before being tested on the smartphones. The devices were disinfected with the CDG gel (4%) at two times: immediately and after 5 min of the bacterial contamination. In all cases, the CDG gel eliminated 100% of gram-positive and gram-negative microorganisms compared to the control (without any agent). In addition, the gel did not damage the smartphones. Therefore, our study suggests that the CDG gel may be applied to disinfect a wide range of electronic devices for health care professionals in the hospital environment.

关键词： smartphones disinfection clinical environment chlorhexidine bacteria

CAR-T cells: Early successes in blood cancer and challenges in solid tumors

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Acta Pharmaceutica Sinica B 2021年第5期11卷 1129-1147页

作者： Hassan Dana Ghanbar Mahmoodi Chalbatani Seyed Amir Jalali Hamid Reza Mirzaei Stephan A.Grupp Eloah Rabello Suarez Catarina Raposo Thomas J.webster Cancer Research Center Cancer Institute of IranTehran University of Medical SciencesTehran 13145-158Iran Department of Medical Immunology School of MedicineTehran University of Medical SciencesTehran ***Iron Department of Immunology School of MedicineShahid Beheshti University of Medical SciencesTehran ***Iran Division of Oncology Department of Pediatricsthe Children's Hospital of PhiladelphiaPhiladelphiaPA 19104USA Center for Natural and Human Sciences Federal University of ABCSanto AndreSP 09210-580Brazil Faculty of Pharmaceutical Sciences State University of Campinas(UNICAMP)CampinasSP 13083-87JBrazil Department of Chemical Engineering Northeastern UniversityBostonMA 02115USA

New approaches to cancer immunotherapy have been developed, showing the ability to harness the immune system to treat and eliminate cancer. For many solid tumors, therapy with checkpoint inhibitors has shown promise. For hematologic malignancies, adoptive and engineered cell therapies are being widely developed, using cells such as T lymphocytes, as well as natural killer(NK) cells, dendritic cells, and potentially others. Among these adoptive cell therapies, the most active and advanced therapy involves chimeric antigen receptor(CAR)-T cells, which are T cells in which a chimeric antigen receptor is used to redirect specificity and allow T cell recognition, activation and killing of cancers, such as leukemia and lymphoma. Two autologous CAR-T products have been approved by several health authorities,starting with the U.S. Food and Drug Administration(FDA) in 2017. These products have shown powerful, inducing, long-lasting effects against B cell cancers in many cases. In distinction to the results seen in hematologic malignancies, the field of using CAR-T products against solid tumors is in its infancy. Targeting solid tumors and trafficking CAR-T cells into an immunosuppressive microenvironment are both significant challenges. The goal of this review is to summarize some of the most recent aspects of CAR-T cell design and manufacturing that have led to successes in hematological malignancies, allowing the reader to appreciate the barriers that must be overcome to extend CAR-T therapies to solid tumors successfully.

关键词： Immunotherapy T cell therapy Chimeric antigen receptor(CAR) Genetic engineering

Searching the literature

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Searching the literature

A novel near-infrared light responsive 4D printed nanoarchitecture with dynamically and remotely controllable transformation

2008年中华医学会全国麻醉学术年会

作者： N webster Academic Unit of Anaesthesia & Intensive Care University of Aberdeen

DIY literature searching Evidence-based medicine means that clinicians search the published literature to find answers to their clinical questions Research requires a comprehensive search of the literature There are millions of published reports,journal articles,correspondence and studies available to clinicians and researchers Choosing the best resource to search is an important decision

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Nano Research 2019年第6期12卷 1381-1388页

作者： Haitao Cui Shida Miao Timothy Esworthy Se-jun Lee Xuan Zhou Sung Yun Hann Thomas J.webster Brent T.Harris Lijie Grace Zhang Department of Mechanical and Aerospace Engineering The George Washington UniversityWashingtonDC 20052USA Department of Chemical Engineering Northeastern UniversityBostonMA 02115USA Department of Neurology and Pathology Georgetown UniversityWashingtonDC 20007USA Departments of Electrical and Computer Engineering The George Washington UniversityWashingtonDC 20052USA Department of Biomedical Engineering The George Washington UniversityWashingtonDC 20052USA Department of Medicine The George Washington UniversityWashingtonDC 20052USA

Four-dimensional (4D) printing is an emerging and highly innovative additive manufacturing process by which to fabricate pre-designed,self-assembly structures with the ability to transform over ***,one of the critical challenges of 4D printing is the lack of advanced 4D printing systems that not only meet all the essential requirements of shape change but also possess smart,dynamic capabilities to spatiotemporally and instantly control the shape-transformation ***,we present a facile 4D printing platform which incorporates nanomaterials into the conventional stimuli-responsive polymer,allowing the 4D printed object to achieve a dynamic and remote controlled,on-time and position shape transformation.A proof-of-concept 4D printed brain model was created using near-infrared light (NIR) responsive nanocomposite to evaluate the capacity for controllable 4D transformation,and the feasibility of photothermal stimulation for modulating neural stem cell *** novel 4D printing strategy can not only be used to create dynamic 3D patterned biological structures that can spatiotemporally control their shapes or behaviors of transformation under a human benign stimulus (NIR),but can also provide a potential method for building complex self-morphing objects for widespread applications.

关键词： near-infrared light responsive four-dimensional (4D) printing dynamically and remotely controllable graphene brain neural stem cell

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基本气流对热带波动传播影响的数值试验

气象科学研究院院刊 1989年第2期 113-123页

作者：董敏 P.J.webster 气象科学研究院气候研究所宾夕法尼亚州立大学

本文研究了在各种定常基本状态下大气对位于热带及中纬度地区的定常强迫源的响应。进一步证实了东风基本气流将限制热带扰动向中高纬度的传播,从而也抑制了两半球的相互作用;西风基本气流则有利于热带波动向中纬度传播,有利于中纬度扰... 详细信息

本文研究了在各种定常基本状态下大气对位于热带及中纬度地区的定常强迫源的响应。进一步证实了东风基本气流将限制热带扰动向中高纬度的传播,从而也抑制了两半球的相互作用;西风基本气流则有利于热带波动向中纬度传播,有利于中纬度扰动通过热带向另一半球传播。赤道地区基本气流随经度的变化对罗斯贝波的传播也有重大影响,波动能量将在基本气流辐合的地区累积并向中纬度发射。因此赤道西风辐合最大的地区就是热带与中纬度相互作用以及两半球相互作用最明显的地区。应用实测风场作基本气流所进行的实验表明,冬季与夏季热带波动的传播特征,两半球相互作用的状况均有明显差异。

关键词：基本气流数值试验赤道地区罗斯贝波东风带中高纬度赤道西风中纬度地区辐合区定常波

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复句研究与修辞结构理论

外语教学与研究 1999年第4期31卷 16-22,78页

作者：徐赳赳 JonathanJ.webster 中国社会科学院语言研究所香港城市大学

本文概述和比较汉语复句研究与西方修辞结构理论的异同。两者均研究大于小句的书面语言片断及小句之间的语义关系，但在理论和方法上，前者不够系统，分析方法较简单，后者理论较为完整，有相应的一套分析方法；前者注重形式标记（如... 详细信息

本文概述和比较汉语复句研究与西方修辞结构理论的异同。两者均研究大于小句的书面语言片断及小句之间的语义关系，但在理论和方法上，前者不够系统，分析方法较简单，后者理论较为完整，有相应的一套分析方法；前者注重形式标记（如关联词），后者注重功能，并根据功能划分各种关系。

关键词：复句修辞结构理论(RST) 标记

An application of system identification in the two-degree-freedom VIV experiments

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Journal of Marine Science and Application 2009年第2期8卷 99-104页

作者：康庄 William C.webster 哈尔滨工程大学深海工程技术研究中心黑龙江哈尔滨150001 美国加利福尼亚大学伯克利分校

Experiments on the two-degree-freedom vortex-induced vibration （VIV） of a flexibly-mounted, rigid, smooth cylinder were performed at MIT. The research reported here is an analysis of the cylinder＇s trajectories. System identification methods were used to derive a best Fourier representation for these motions and to parse these motions into symmetric and asymmetric behaviors. It was postulated that the asymmetric behavior was due to distortions caused by the free surface and bottom used at the test facility, and that the symmetric behavior is representative of deepwater VIV. Further application of systems identification methods was used to associate the symmetric behavior and test conditions to a traditional vortex street model. These models were analyzed for their ability to predict details of VIV trajectories.

关键词： system identification two-degree-freedom vortex-induced vibration (VIV)