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High affinity soluble ILT2 receptor:a potent inhibitor of CD8^(+)T cell activation

Protein & Cell 2010年第12期1卷 1118-1127页

作者： Ruth K.moysey Yi Li Samantha J.Paston Emma E.Baston malkit S.Sami Brian J.Cameron Jessie Gavarret Penio Todorov Annelise Vuidepot Steven m.Dunn Nicholas J.Pumphrey Katherine J.Adams Fang Yuan rebecca E.Dennis Deborah H.Sutton Andy D.Johnson Joanna E.Brewer rebecca Ashfield Nikolai m.Lissin Bent K.Jakobsen Immunocore Limited 57c Milton ParkAbingdonOxonOX144RXUK Current address:Oxford Nanopore Technologies UK Current address:Geneva merck Serono S.A. Switzerland Current address:Adaptimmune Limited UK

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin superfamily receptor ILT2(synonyms:LIR1,mIR7,CD85j),we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex(mHC)class I *** in a dimeric form,either by chemical cross-linking with bivalent polyethylene glycol(PEG)derivatives or as a genetic fusion with human IgG Fc-fragment,the mutants exhibited a further increase in ligand-binding strength due to the avidity effect,with resident half-times(t1/2)on the surface of mHC I-positive cells of many *** novel compounds antagonized the interaction of CD8 co-receptor with mHC I in vitro without affecting the peptide-specific binding of T-cell receptors(TCRs).In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8^(+)cytotoxic T lymphocytes(CTLs)in the presence of their target cells,with subnanomolar potency and in a dose-dependent *** a selective inhibitor of CD8^(+)CTL responses,the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.

关键词： CD8^(+)T cells cellular activation autoimmunity cell surface molecules binding affinity phage display

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桡骨头骨折以及植入物重建后的运动学与稳定性(下)

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中华骨科杂志 2009年第1期29卷 90-92页

作者： James A.Johnson Daphne m.Beingessner Karen D.Gordon Cynthia E.Dunning rebecca A.Stacpoole Graham J.W.King 加拿大西安大略大学内科与牙科学院外科加拿大西安大略大学机械与材料工程系约瑟夫保健院约瑟夫保健院手与上肢中心约瑟夫保健院生物工程实验室

二、桡骨头切除的影响对于mason Ⅲ型骨折,特别是不伴韧带损伤时,如何进行外科治疗还没有得到彻底解决。桡骨头切除对肘部运动及稳定的影响已有大量研究。可以明确的是,桡骨头的缺失将导致肘部的外翻稳定性降低,是仅次于mCL的一个重要... 详细信息

二、桡骨头切除的影响对于mason Ⅲ型骨折,特别是不伴韧带损伤时,如何进行外科治疗还没有得到彻底解决。桡骨头切除对肘部运动及稳定的影响已有大量研究。可以明确的是,桡骨头的缺失将导致肘部的外翻稳定性降低,是仅次于mCL的一个重要约束。我们的内翻-外翻松弛测试显示,桡骨头的缺失导致松弛显著增加。然而,相对于mCL,桡骨头的作用要低得多,对最大内翻-外翻松弛起24%的作用(先切除桡骨头)。

关键词：桡骨头骨折植入物重建

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How old is too old? In vivo engraftment of human peripheral blood stem cells cryopreserved for up to 18 years-implications for clinical transplantation and stability programs

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World Journal of Stem Cells 2020年第5期12卷 359-367页

作者： John Underwood mahvish Rahim Carijo West rebecca Britton Elaine Skipworth Vicki Graves Steven Sexton Hillary Harris Dave Schwering Anthony Sinn Karen E Pollok Kent A Robertson W Scott Goebel Kerry m Hege Departments of Internal medicine and Pediatrics Indiana University School of MedicineIndianapolisIN 46202United States Department of Pediatrics Division of Pediatric Hematology/OncologyIndiana University School of MedicineIndianapolisIN 46202United States Cellular Therapy Laboratory Indiana University HealthIndianapolisIN 46202United States Department of Pediatrics Herman B Wells Center for Pediatric ResearchIn Vivo Therapeutics Core and Angio Biocore Shared Resource Facilities for the Indiana University Simon Cancer CenterIndiana University School of MedicineIndianapolisIN 46202United States

BACKGROUND Peripheral blood stem cells(PBSC)are commonly cryopreserved awaiting clinical use for hematopoietic stem cell *** term cryopreservation is commonly defined as five years or longer,and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully *** programs,stem cell banks,and regulatory and accrediting agencies interested in product stability would benefit from such ***,we assessed recovery and colony forming ability of PBSC following long-term cryopreservation as well as their ability to engraft in NOD/SCID/IL-2 Rγnull(NSG)*** To investigate the in vivo engraftment potential of long-term cryopreserved PBSC *** PBSC units which were collected and frozen using validated clinical protocols were obtained for research use from the Cellular Therapy Laboratory at Indiana University *** units were thawed in the Cellular Therapy Laboratory using clinical standards of practice,and the pre-freeze and post-thaw characteristics of the units were *** function was assessed using standard colony-forming ***34-selected cells were transplanted into immunodeficient mice to assess stem cell *** Ten PBSC units with mean of 17 years in cryopreservation(range 13.6-18.3 years)demonstrated a mean total cell recovery of 88%±12%(range 68%-110%)and post-thaw viability of 69%±17%(range 34%-86%).BFU-E growth was shown in 9 of 10 units and CFU-Gm growth in 7 of 10 units *** mice were transplanted with CD34-selected cells from four randomly chosen PBSC *** mice demonstrated long-term engraftment at 12 wk with mean34%±24%human CD45+cells,and differentiation with presence of human CD19+,CD3+and CD33+*** bone marrow from all mice demonstrated growth of erythroid and myeloid *** We demonstrated engraftment of clinically-collected and thawed PBSC following cryopreservation up to 18 years in NSG mice,sign

关键词： Colony-forming units assay Cryopreservation Hematopoietic stem cells Hematopoietic stem cell transplantation In vitro techniques Peripheral blood stem cell Viability Transplant Long-term storage

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Shoot-Specific Down-Regulation of Protein Farnesyltransferase （α-Subunit） for Yield Protection against Drought in Canola

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molecular Plant 2009年第1期2卷 191-200页

作者： Yang Wang michelle Beaith maryse Chalifoux Jifeng Ying Tina Uchacz Carlene Sarvas rebecca Griffiths monika Kuzma Jiangxin Wan Yafan Huang Performance Plants Inc. 700 Gardiners Road Kingston Ontario Canada K7M 3X9

Canola （Brassica napus L.） is one of the most important oilseed crops in the world and its seed yield and quality are significantly affected by drought stress. As an innate and adaptive response to water deficit, land plants avoid potential damage by rapid biosynthesis of the phytohormone abscisic acid （ABA）, which triggers stomatal closure to reduce transpirational water loss. The ABA-mediated stomatal response is a dosage-dependent process; thus, one genetic engineering approach for achieving drought avoidance could be to sensitize the guard cell＇s responsiveness to this hormone. Recent genetic studies have pinpointed protein farnesyltransferase as a key negative regulator controlling ABA sensitivity in the guard cells. We have previously shown that down-regulation of the gene encoding Arabidopsis β-subunit of farnesyltransferase （ERA1） enhances the plant＇s sensitivity to ABA and drought tolerance. Although the β-subunit of famesyltransferase （AtFTA） is also implicated in ABA sensing, the effectiveness of using such a gene target for improving drought tolerance in a crop plant has not been validated. Here, we report the identification and characterization of the promoter of Arabidopsis hydroxypyruvate reductase （AtHPR1）, which expresses specifically in the shoot and not in non-photosynthetic tissues such as root. The promoter region of AtHPR1 contains the core motif of the well characterized dehydration-responsive cis-acting element and we have confirmed thatAtHPR1 expression is inducible by drought stress. Conditional and specific down-regulation of FTA in canola using the AtHPR1 promoter driving an RNAi construct resulted in yield protection against drought stress in the field. Using this molecular strategy, we have made significant progress in engineering drought tolerance in this important crop species.

关键词： ABA signaling protein farnesylation conditional promoter drought stomatal response seed yield field trial.

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Coronary Artery Bypass Surgery for Patients Presenting with Ventricular Arrhythmias: Propensity matched Early and Late Outcome

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World Journal of Cardiovascular Surgery 2018年第2期8卷 40-50页

作者： Ahmed m. Habib Azar Hussain martin jarvis Alexander Cale michael Cowen Dumbor Ngaage mubarak Chaudhry mahmoud Loubani Cardiothoracic Surgery Castle Hill Hospital Cottingham UK Cardiothoracic Surgery Ain Shams University Hospitals Cairo Egypt

Objectives: Patients with ischemic ventricular arrhythmia (IVA) in the form of fibrillation or tachycardia represent a surgical challenge. Evidence in the literature suggests that ventricular arrhythmia threatens survival even after cardiac surgery. We aim to review the results of our patients presenting with IVA with regard to short and long term outcome following cardiac surgery. methods: This was a retrospective study of data entered prospectively into our cardiac surgical database between January 1999 and September 2015. A total of 9609 patients underwent Cardiac Surgery which included 54 patients after surviving IVA. The short- and long-term outcomes were compared to a propensity matched group. Actuarial survival was calculated using Kaplan meier analysis. Results: The 54 study group patients were propensity matched on a 1:2 basis with a control group of non-IVA (n = 108). The baseline preoperative characteristics and risk factors were similar between the 2 groups and all cases underwent CABG only. Univariate analysis showed pacing postoperatively (33.3 vs 66.7%;p = 0.001) and postoperative ventricular arrhythmia (10 vs 22.2%;p = 0.039) to be significantly higher in the IVA group. Cox-multivariate analysis showed postoperative ventricular arrhythmia in either group (Hazard ratio = 1.5) to be the only significant factor to impact mortality (p 0.001). Long term survival was not significantly different between the two groups (10.4;CI: 9.08 - 11.75 vs 9.3;CI: 7.61 - 11.01 yrs, p = 0.3). Conclusion: Cardiac surgery on patients presenting with IVA can be performed safely yielding short and long term results equivalent to non-IVA cases. These patients should not be denied surgery with consideration of good long term outcome.

关键词： Ischemic Ventricular Arrhythmia (IVA) Ventricular Fibrillation (VF) Implantable Cardioverter (ICD) Coronary Artery Disease (CAD)

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Identification of anticancer drugs to radiosensitise BRAF-wild-type and mutant colorectal cancer

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Cancer Biology & medicine 2019年第2期16卷 234-246页

作者： rebecca Carter Azadeh Cheraghchi-Bashi Adam Westhorpe Sheng Yu Yasmin Shanneik Elena Seraia Djamila Ouaret Yasuhiro Inoue Catherine Koch Jenny Wilding Daniel Ebner Anderson J. Ryan Francesca m. Buffa Ricky A. Sharma NIHR University College London Hospitals Biomedical Research Centre/ UCL Cancer Institute University College London London WC1E 6DD UK NIHR Oxford Biomedical Research Centre Department of Oncology University of Oxford Oxford 0X1 2JD UK Computational Biology and Integrative Genomics University of Oxford Oxford 0X1 2JD UK NDm Research Building Nuffield Department of Medicine University of Oxford Oxford 0X1 2JD UK Weatherall Institute of molecular medicine John Radcliffe Hospital University of Oxford Oxford 0X1 2JD UK mie University Graduate School of Medicine Department of Gastrointestinal and Pediatric Surgery Division of Reparative Medicine Institute of Life Sciences Edobashi 2-174 Tsu Japan Departme nt of Biology Massachusetts In stitute of Tech no logy Cambridge Massachusetts 02142 USA Target Discovery Institute National Phenotypic Screening Centre Nuffield Department of Medicine University of OxfordOxford 0X1 2JD UK CRUK & mRC Oxford Institute for Radiation Oncology University of Oxford Oxford 0X1 2JD UK

Objective: Patients with BRAF-mutant colorectal cancer(CRC) have a poor prognosis. molecular status is not currently used to select which drug to use in combination with radiotherapy. Our aim was to identify drugs that radiosensitise CRC cells with known BRAF ***: We screened 298 oncological drugs with and without ionising radiation in colorectal cancer cells isogenic for BRAF. Hits from rank product analysis were validated in a 16-cell line panel of human CRC cell lines, using clonogenic survival assays and xenograft models in ***: most consistently identified hits were drugs targeting cell growth/proliferation or DNA damage repair. The most effective class of drugs that radiosensitised wild-type and mutant cell lines was PARP inhibitors. In clonogenic survival assays, talazoparib produced a radiation enhancement ratio of 1.9 in DLD1(BRAF-wildtype) cells and 1.8 in RKO(BRAF V600 E) cells. In DLD1 xenografts, talazoparib significantly increased the inhibitory effect of radiation on tumour growth(P ≤ 0.01).Conclusions: Our method for screening large drug libraries for radiosensitisation has identified PARP inhibitors as promising radiosensitisers of colorectal cancer cells with wild-type and mutant BRAF backgrounds.

关键词： Radiosensitizer colorectal cancer PARP inhibitor radiotherapy

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The role of Pacific water in the dramatic retreat of arctic sea ice during summer 2007

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Chinese Journal of Polar Science 2008年第2期19卷 93-107页

作者： mike Steele rebecca Woodgate Polar Science Center Applied Physics LaboratoryCollege of Ocean and Fishery SciencesUniversity of WashingtonSeattleWA 98105

A model study is conducted to examine the role of Pacific water in the dramatic retreat of arctic sea ice during summer 2007. The model generally agrees with the observations in showing considerable seasonal and interannual variability of the Pacific water inflow at Bering Strait in response to changes in atmospheric circulation. During summer 2007 anomalously strong southerly winds over the PaCific sector of the Arctic Ocean strengthen the ocean circulation and bring more Pacific water into the Arctic than the recent （2000-2006） average. The simulated summer （3 months ） 2007 mean Pacific water inflow at Bering Strait is 1.2 Sv, which is the highest in the past three decades of the simulation and is 20% higher than the recent average. Particularly, the Pacific water inflow in September 2007 is about 0.5 Sv or 50% above the 2000-2006 average. The strengthened warm Pacific water inflow carries an additional 1.0 x 1020 Joules of heat into the Arctic, enough to melt an additional 0.5 m of ice over the whole Chukchi Sea. In the model the extra summer oceanic heat brought in by the Pacific water mainly stays in the Chukchi and Beaufort region, contributing to the warming of surface waters in that region. The heat is in constant contact with the ice cover in the region in July through September. Thus the Pacific water plays a role in ice melting in the Chukchi and Beaufort region all summer long in 2007, likely contributing to up to O. 5 m per month additional ice melting in some area of that region.

关键词： Pacific water Arctic sea ice.

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Analysis for stress environment in the alveolar sac model

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Journal of Biomedical Science and Engineering 2013年第9期6卷 901-907页

作者： Ramana m. Pidaparti matthew Burnette rebecca L. Heise Angela Reynolds Department of Applied mathematics Virginia Commonwealth University Richmond USA Department of Biomedical Engineering Virginia Commonwealth University Richmond USA Department of mechanical and Nuclear Engineering Virginia Commonwealth University Richmond USA

Better understanding of alveolar mechanics is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. The objective of this study was to investigate the alveolar mechanics for two different alveolar sac models, one based on actual geometry and the other an idealized spherical geometry using coupled fluid-solid computational analysis. Both the models were analyzed through coupled fluid-solid analysis to estimate the parameters such as pressures/ velocities and displacements/stresses under mechanical ventilation conditions. The results obtained from the fluid analysis indicate that both the alveolar geometries give similar results for pressures and velocities. However, the results obtained from coupled fluid-solid analysis indicate that the actual alveolar geometry results in smaller displacements in comparison to a spherical alveolar model. This trend is also true for stress/strain between the two models. The results presented indicate that alveolar geometry greatly affects the pressure/velocities as well as displacements and stresses/strains.

关键词： Alveolar Sac Stress Analysis modeling

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Evaluation of Pedestrian–Train Fatalities in the State of maryland: A 5‑Year Retrospective Study

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Journal of Forensic Science and medicine 2020年第4期6卷 135-139页

作者： Elvira Carias Claire Hammerschmidt Taylor Hall Xiang Zhang rebecca Phipps Ling Li Office of the Chief medical Examiner State of MarylandBaltimoreMarylandUSA master of Science in Forensic medicine Program Graduate Schoolat University of Maryland BaltimoreBaltimoreMarylandUSA

Few studies have been done on the incidences of train-related pedestrian fatalities throughout the United States,with no previous studies reported in the State of maryland.A retrospective study was conducted at the statewide medical examiner’s office in maryland to evaluate the characteristics of train-related pedestrian fatalities from 2014 to *** aim of the study was to analyze circumstances of deaths through the medicolegal death investigation and postmortem examination findings,including toxicological study,to help identify epidemiological characteristics of pedestrian–train‑related fatalities.A total of 48 pedestrian-train deaths were *** the 48 cases identified,21 deaths(43.75%)were determined to be accident,20 deaths(41.67%)were suicide,and 7 deaths(14.58%)whose manner of death could not be *** the 21 accidental victims,17 were male and 4 were female(m:F ratio=4.3:1),11(52.38%)were white,6(28.57%)African American,and 4 Hispanic(19.05%),with age ranging from 16 to 58 years(mean age=35).Of the 20 suicide victims,17 were males and 3 females(m:F ratio=5.7:1),16(80%)were white,2(10%)African American,and 2(10%)Hispanic,with age ranging from 22 to 60 years(mean age=40).The majority of accidents occurred during weekday evening rush hours between 4:00 pm and 7:00 pm,while the suicides showed no specific time *** specific peak for seasons of year was found in suicides or *** toxicological studies showed that 52.38%(11/21 cases)of accidental victims were positive for alcohol and 30%(6/20 cases)of suicide victims were positive for *** of death could not be determined in 7 cases because of unclear circumstances of *** death scene investigation and complete postmortem examination,including comprehensive toxicological testing,is very important in all train-related pedestrian *** the manner of death can directly affect the outcome of civil ligation and dispersal of insurance ***

关键词： Pedestrian train accident suicide forensic investigation

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滑槽淬火系统的推荐设计

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金属热处理 1998年第1期23卷 31-34页

作者： G E Totten,G m Webster(Union Crbide Corporation,Tarrytown,NY ) R R Blackwood,L m.jarvis(Tenaxol Inc,milwaukee,WL) T Narumi(Nagase Chemspec Ltd,Tokyo,Japan)

目前，聚合物淬火剂（ｑｕｅｎｃｈａｎｔ）在各类热处理中的应用日益增加，其中包括某些具备滑槽（ｃｈｕｔｅ）淬火装置的连续炉系统。滑槽淬火的成功运用依赖于淬火剂的使用量和搅拌的均匀性。本文提供了一系列推荐的设计指导原则及... 详细信息

目前，聚合物淬火剂（ｑｕｅｎｃｈａｎｔ）在各类热处理中的应用日益增加，其中包括某些具备滑槽（ｃｈｕｔｅ）淬火装置的连续炉系统。滑槽淬火的成功运用依赖于淬火剂的使用量和搅拌的均匀性。本文提供了一系列推荐的设计指导原则及一些已成功运用的滑槽淬火装置的示意图例。

关键词： PAG 聚合物淬火剂淬火均匀性滑槽淬火系统

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