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Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2015年第4期6卷 213-222页

作者： Kunwar shailubhai Vaseem Palejwala Krishna Priya Arjunan sayali saykhedkar Bradley Nefsky John A Foss stephen Comiskey gary s jacob scott E Plevy R and D Center Synergy Pharmaceuticals Inc. Baruch Blumberg Institute PA Biotechnology Center synergy Pharmaceuticals Inc. Departments of Medicine Microbiology and Immunology University of North Carolina School of Medicine

AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine ***: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. sulfasalazine or 5-amino salicylic acid(5-AsA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(Dss) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBs) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase ***: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both Dss and TNBs-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P sease activity index(P s by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-AsA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUsION: This is the first-ever s

关键词： Guanylate cyclase-C Inflammatory bowel disease Uro

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Upper limb bilateral symmetric training with robotic assistance and clinical outcomes for stroke A pilot study

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International Journal of Intelligent Computing and Cybernetics 2016年第1期9卷 83-104页

作者： Matt simkins Nancy Byl Hyunchul Kim gary Abrams jacob Rosen Mechanical and Mechatronic Engineering and sustainable Manufacture California State UniversityChicoCaliforniaUSA Department of Physical Therapy and Rehabilitation science University of CaliforniaSan FranciscoCaliforniaUSA Apple Inc. Santa ClaraCaliforniaUSA Department of Neurology University of CaliforniaSan FranciscoCaliforniaUSA Department of Computer Engineering University of CaliforniaSanta CruzCaliforniaUSA

Purpose–The purpose of this paper is to evaluate the physiotherapeutic benefits of bilateral symmetric training(BsT)for stroke survivors affected by ***/methodology/approach–Other studies have investigated symmetric physiotherapy.A key difficulty in previous work is in maintaining mirror-imaged trajectories between the affected and less-affected *** obstacle was overcome in this work by using a two-armed robotic exoskeleton to enforce *** total,15 subjects,W6 months post stroke were,randomly assigned to bilateral symmetric robotic training,unilateral robotic training,and standard physical ***–After 12 training sessions(90 minutes/session),the bilateral training group had the greatest intensity of movement *** also had the greatest improvement in range of motion at the *** unilateral training group showed the greatest reduction in *** limitations/implications–The rationale for symmetric physiotherapy is that it might promote connections from the undamaged brain *** robot generated copious amounts of detailed kinematic *** though these data provided insights into the human to machine interface using different training modalities,it proved difficult to draw neurological *** is recommended that future research along these lines should include measures of neurophysiological change and/or changes in neurological *** implications–This research suggests that the advantage of bilateral symmetric movement over other modalities is slight,and that robotic training has comparable results with standard *** BsTis used,care is potentially needed toavoid exacerbation of ***,this research includes a novel quantitative approach for evaluating robotic ***/value–This study is of value to therapeutic researchers interested in new physiotherapy techniques,roboticists interested in developing rehabilitation devices,or for rehabilitatio

关键词： Robotics Virtual reality Data mining Real-time systems stroke survivors Physical therapy stroke Bilateral symmetric

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Experimental and finite element analysis on determining the fatigue life of pb-free solder joint(sn-0.5Cu-3Bi-1Ag)used in electronic packages under harmonic loads

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International Journal of Modeling, simulation, and scientific Computing 2020年第3期11卷 60-67页

作者： Jayesh s jacob Elias Department of Mechanical Engineering school of Engineering Cochin University of Science and Technology KochiKerala-682022India

Electronic packages that are used these days are exposed to different types of vibration loadings in their usage *** vibration exposure can be categorized as harmonic and random *** reliability assessment of modern electronic systems is considered,vibration loading has an important role to *** of the biggest challenges facing today is the accurate and rapid assessment of fatigue life under the vibration *** solder joints were made of lead-tin *** to many environment legislations and rules,lead is prohibited as an ingredient in the solder *** reason for the prohibition of the usage of the lead is that it poisons the *** this study,sn-0.5Cu-3Bi-1Ag is used as the lead-free solder *** life prediction of electronic package containing sAC405 is conducted with the aid of vibration testing and Finite element analysis under harmonic vibration loading.A specially designed Plastic Ball Grid Array Package(PBGA)component is mounted on Printed Circuit Board(PCB).It is taken as a test vehicle for the vibration *** test vehicle is excited by a sinusoidal *** frequency of this excitation equals the fundamental frequency of the test vehicle and it is continued till the component *** the solder balls are very small for direct measurement,Finite Element analysis(FEA)is used for noting down the *** stress versus failures cycles(s-N)curve is made by relating both the stresses on the solder balls obtained and the number of failure cycles from vibration *** fatigue life of the component can be estimated from the generated s-N *** is analyzed that the methodology is effective in predicting the component’s ***,the reliability of electronic package can be improved.

关键词： PCB lead free solder joint FEA PBGA s-N curve

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Management of symptomatic ureteric stumps laparoscopically

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Asian Journal of Andrology 2001年第2期3卷 147-150页

作者： A.M.Khan s.jacob Department of surgery King George Hospital Ilford Essex IG1 2HL UKDepartment of Surgery King George Hospital Ilford Essex IG1 2HL UK

Aim: To study the advantage of excision of the distal symptomatic ureteric stumps with the retroperitoneal laparo-scopic approach. Methods: Four patients who had failed to settle their symptoms with the initial conservative man-agement were included in the study. All underwent excision of the distal symptomatic ureteric stumps with the retroperi-toneal laparoscopic approach and then received prophylactic antibiotics. Results: We have achieved better resultsthan those reported in the literature in terms of operating time (mean 1 h 45 min), blood loss ( stopera-tive recovery (within 12 h) and hospital stay ( sion; Retroperitoneal laparoscopic excision is asafe, simple and effective method in the management of symptomatic ureteric stumps.

关键词： ureter laparoscopy retroperitoneal space

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A balancing act between IFITM3 and IRF3

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Cellular & Molecular Immunology 2018年第10期15卷 873-874页

作者： Temet M McMichael Mahesh Chemudupati jacob s Yount Department of Microbial Infection and Immunity Center for Microbial Interface BiologyThe Ohio State UniversityColumbusOH 43210USA

Interferon(IFN)-induced transmembrane protein 3(IFITM3)is a potent antiviral factor capable of restricting numerous virus infections.1 Viruses inhibited by IFITM3 generally enter cells via endocytosis,and are trafficked to IFITM3-positive intracellular membrane compartments.1,2 IFITM3-positive compartments are acidic and stain positive for a variety of endosomal,lysosomal and autophagosomal markers.2,3 Although the membrane fusion of many endocytic viruses,such as influenza virus,is triggered by acidic pH,fusion is blocked in the presence of IFITM3,and virions are degraded2,4,5(Figure 1).It has been proposed that IFITM3 alters membrane properties,including rigidity and curvature,to inhibit virus membrane fusion.5 The molecular mechanism underlying these IFITM3-induced membrane alterations is not well characterized,and whether IFITM3 has other cellular functions is also not known.

关键词： IFITM3 inhibited alterations

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Water yield and biomass production for on a eucalypt-dominated Mediterranean catchment under different climate scenarios

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Journal of Forestry Research 2023年第5期34卷 1263-1278页

作者： Joao Rocha Ana Quintela Dalila serpa Jan jacob Keizer sérgio Fabres RAIZ-Forest and Paper Research Institute Quinta de S.FranciscoRua JoséEstevao(EN 230-1)3800–783 EixoAveiroPortugal Department of Environment and Planning Centre of Environmental and Marine Studies(CESAM)University of AveiroCampus Universitário de Santiago3810–193 AveiroPortugal

Worldwide,forests are vital in the regulation of the water cycle regulation and in water balance *** of ecohydrological responses of production forests is essential to support management strategies,especially where water is already *** climatological patterns are expected to impact thermopluviometric regimes,water cycle components,hydrological responses,and plant physiology,evapotranspiration rates,crop productivity and land management *** work(1)assessed the impacts of different predicted climate conditions on water yield;(2)inferred the impacts of climate change on biomass production on eucalypt-to-eucalypt succes *** this end,the widely accepted soil and Water Assessment Tool(sWAT)was run with the RCA,HIRHAM5 and RACMO climate models for two emission scenarios(RCP 4.5 and8.5).Three 12-year periods were considered to simulate tree growth under coppice *** results revealed an overall reduction in streamflow and water yield in the catchment in line with the projected reduction in total annual ***,HIRHAM5 and RACMO models forecast a slight shift in seasonal streamflow of up to 2 months(for2024-2048)in line with the projected increase in precipitation from May to *** biomass production,the extreme climate model(RCA)and severe emis sion scenario(RCP 8.5)predicted a decrease up to 46%.However,in the less extreme and more-correlated(with actual catchment climate conditions)climate models(RACMO and HIRHAM5)and in the less extreme emission scenario(RCP 4.5),biomass production increased(up to 20%),and the growth cycle was slightly *** was proven to be a valuable tool to assess climate change impacts on a eucalypt-dominated catchment and is a suitable decision-support tool for forest managers.

关键词： Climate scenarios Forested catchments Forest ecohydrological modelling Eucalypt biomass production sWAT model

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sulfurized-polyacrylonitrile in lithium-sulfur batteries:Interactions between undercoordinated carbons and polymer structure under low lithiation

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Journal of Energy Chemistry 2022年第3期31卷 587-596,I0016页

作者： samuel Bertolini Timo jacob Institute of Electrochemistry Ulm UniversityAlbert-Einstein-Allee 4789081 UlmGermany Helmholtz-Institute Ulm(HIU) Electrochemical Energy StorageHelmholtzstr.1189081 UlmGermany Karlsruhe Institute of Technology(KIT) P.O.Box 364076021 KarlsruheGermany

Lithium-sulfur battery(LsB)represents an important candidate to be used in energy storage applications,due to its high specific ***-polyacrylonitrile(sPAN)is a candidate as a host material in LsB to replace graphite,due to its ability to chemisorb polysulfides(Pss).The sulfur chains attached to the polymer can reversibly form Li2s,and sPAN indicates to have a good cyclability and better performance than graphite,thus,sPAN acts partially as an active and also as a host *** this study,we investigated the capacity of the solvent or the sPAN to lose a hydrogen atom from the backbone,to predict possible anodic reactions between solvent and host *** simulation suggests that the photophilic salts may preferentially react with the solvent,and possibly building a cathode electrolyte interphase(CEI).We observed that an undercoordinated carbon(C_(uc))can be thermodynamically created,due to *** Cuccan react with the solvent on the polymer backbone through different mechanisms,however,the simulations indicated that the reaction should be affected by the interaction between the solvent and C_(uc),according to sPAN’s ***,C_(uc)reacts with long sulfur chains attached to sPAN,capturing sulfur and forming a C-s bond.A sulfur chain from one sPAN can connect to another polymer backbone,however,this process is affected by lithiation and ***,this work also investigates the formation of interconnected sPAN structures and the multiple C_(uc)effects.

关键词： Density functional theory Ab initio molecular dynamics Lithium-sulfur batteries sulfurized-polyacrylonitrile

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Mixed mode properties of CNT reinforced composites using Arcan test rig

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Frontiers of structural and Civil Engineering 2015年第4期9卷 397-404页

作者： jacob MUTHU DsT-NRF Centre of Excellence in strong Materials and RP/Composite Facility School of Mechanical Industrial and AeronauticalEngineering University of the Witwatersrand Johannesburg South Africa

Composite materials reinforced with carbon nanotubes were mechanical tested using Arcan test rig under Mode-I, Mode-II and mixed mode loading conditions to obtain their fracture properties. The butterfly composite specimens were fabricated with 0.02, 0.05 and 0.1 wt % CNTs. The polyester/CNT composite was fabricated using VRTM (Vacuum Resin Transfer Molding) where the CNTs were first functionalised to reach an optimum properties. Arcan test rig was designed and fabricated to work with the shimadzu testing machine. The results show that the functionalised CNTs have improved the fracture behavior by acting as bridge between the cracked face. In addition, the fracture properties were not improved for the higher weight fraction of 0.1 wt% CNTs.

关键词： CNT composites Arcan test rig stress intensity factor

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The Mathematical Theory of Multifocal Lenses(Dedicated to Professor Haim Brezis on the occasion of his 70th birthday)

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Chinese Annals of Mathematics,series B 2017年第2期38卷 647-660页

作者： jacob RUBINsTEIN department of mathematics TechnionHaifa 32000Israel

This paper presents the fundamental optical concepts of designing multifocal ophthalmic lenses and the mathematical methods associated with them. In particular, it is shown that the design methodology is heavily based on differential geometric ideas such as Willmore surfaces. A key role is played by Hamilton's eikonal functions. It is shown that these functions capture all the information on the local blur and distortion created by the lenses. Along the way, formulas for computing the eikonal functions are derived. Finally,the author lists a few intriguing mathematical problems and novel concepts in optics as future projects.

关键词： Optical design, Differential geometry, Eikonal functions,Multifocal lenses

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Hydration lubrication

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Friction 2013年第1期1卷 1-23页

作者： jacob KLEIN Department of Materials&Interfaces Weizmann Institute of ScienceRehovot76100Israel

The hydration lubrication paradigm,whereby hydration layers are both strongly held by the charges they surround,and so can support large pressures without being squeezed out,and at the same time remain very rapidly relaxing and so have a fluid response to shear,provides a framework for understanding,controlling,and designing very efficient boundary lubrication systems in aqueous and biological *** review discusses the properties of confined water,which-unlike organic solvents-retains its fluidity down to molecularly thin *** then describes lubrication by hydrated ions trapped between charged surfaces,and by other hydrated boundary species including charged and zwitterionic polymer brushes,surfactant monolayers,liposomes,and biological macromolecules implicated in synovial joint ***,challenges and prospects for future development of this new boundary lubrication approach are considered.

关键词： hydration lubrication biolubrication boundary lubrication liposomes polymer brushes hydration repulsion hydration layers

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