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World Journal of Gastroenterology 2006年第22期12卷 3461-3465页

作者： Scott Grier Adrian KP Lim Nayna Patel jeremy FL cobbold Howard c Thomas Isobel J cox Simon D Taylor-Robinson Liver Unit St Mary's Hospital campus Faculty of MedicineImperial College LondonLondonUnited Kingdom Department of Imaging Sciences Hammersmith Hospital campus Faculty of MedicineImperial College LondonLondonUnited Kingdom

Patients who are chronically infected with the hepatitis c virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This article examines the various assessment methods currently available from gold standard liver biopsy to serological markers and imaging. Ultrasound is one of the most widely used imaging modalities in clinical practice and is already a first-line diagnostic tool for liver disease. Microbubble ultrasound contrast agents allow higher resolution images to be obtained and functional assessments of microvascular change to be carried out. The role of these agents in quantifying the state of hepatic injury is discussed as a viable method of determining the stage and grade of liver disease in patients with hepatitis c. Although currently confined to specialist centres, the availability of microbubble contrast-enhanced ultrasound will inevitably increase in the clinical setting.

关键词： Hepatitis c Microbubble contrast agents Ultrasound

Towards real-time pilot-in-the-loop cFD simulations of helicopter/ship dynamic interface

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International Journal of Modeling, Simulation, and Scientific computing 2017年第4期8卷 64-88页

作者： Ilker Oruc Joseph F.Horn jeremy Shipman Susan Polsky Department of Aerospace Engineering The Pennsylvania State University University Park PA 16802USA cRAFT Tech PipersvillePA 18947USA NAVAIR Paxutent RiverMD 20670USA

This study presents the development of computationally efficient coupling of Navier–Stokes computational Fluid Dynamics(cFD)with a helicopter flight dynamics model with the ultimate goal of real-time simulation of airwake effects in the helicopter/ship Dynamic Interface(DI).The flight dynamics model is free to move within a computational domain,where the main rotor forces are converted to source terms in the momentum equations of the cFD solution using an actuator disk ***,the cFD solver calculates induced velocities that are fed back to the simulation and affect the aerodynamic loads in the flight *** cFD solver models the inflow,ground effect and interactional aerodynamics in the flight dynamics simulation,and these calculations can be coupled with the solution of the external flow(e.g.,ship airwake effects).The simulation framework for fully-coupled pilot-in-the-loop(PIL)flight dynamics/cFD is demonstrated for a simplified shedding *** tests were performed with 0.38 million structured grid cells running on 352 processors and showed near-real-time *** to the coupling interface are described that allow the simulation run at near-real-time execution speeds on currently available computing *** in computing hardware are expected to allow real-time simulations.

关键词： Real-time pilot-in-the-loop computational fluid dynamics(cFD) flight dynamics simulation ship airwake dynamic interface helicopter flight dynamics simulation fully-coupled helicopter/ship

Placental accommodations for transport and metabolism during intra-uterine crowding in pigs

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Journal of Animal Science and Biotechnology 2015年第2期6卷 163-176页

作者： Jeffrey L Vallet Anthony K Mc Neel jeremy R Miles Bradley A Freking U.S. Department of Agriculture Agricultural Research Service U.S. Meat Animal Research CenterState Spur 18D Clay Center NE 68933 USA

Litter size and birth weights are limited by uterine capacity, defined as the ability of the uterus to maintain the appropriate development of some number of conceptuses. Uterine capacity is the result of the combined effects of uterine, placental and embryo/fetal function. The number of living conceptuses that the uterus is capable of supporting is greater during early gestation compared to later gestation. Plots of log fetal weight versus log placental weight also indicate that fetal weights are less sensitive to reduced placental weight （and therefore reduced intrauterine space） in early gestation compared to late gestation. However, even in late gestation, mechanisms still exist that maintain fetal growth when the size of the placenta is reduced. One such mechanism is likely to be improved development of the folded placental-epithelial/maternal-epithelial bilayer. Fold depth, and therefore the maternal fetal interactive surface, increases as gestation advances and is greater in placenta from smal fetuses. On the fetal side of the placenta, the epithelial bilayer is embedded in stromal tissue. Glycosaminoglycans are major components of stroma, including hyaluronan and heparan sulfate. Hyaluronidases and heparanases are present within placental tissues, and likely play roles in modification of stromal components to facilitate fold development. Glycosaminoglycans are polymers of forms of glucose （glucosamine, glucuronic acid, iduronic acid） suggesting that glycosaminoglycan synthesis may compete with the glucose needs of the developing fetus. Pig conceptuses are fructogenic, such that a substantial portion of glucose transferred from mother to fetus is converted to fructose. Fructose is an intermediate product in the synthesis of glucosamine from glucose, and glucosamine is linked to regulation of trophoblast cell proliferation through regulation of mTOR. These findings suggest a link between glucose, fructose, glucosamine synthesis, GAG production, and placental m

关键词： Glycosaminoglycans Nutrient transport Placenta

Large-area plastic nanogap electronics enabled by adhesion lithography

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npj Flexible Electronics 2018年第1期2卷 143-152页

作者： James Semple Dimitra G.Georgiadou Gwenhivir wyatt-Moon Minho Yoon Akmaral Seitkhan Emre Yengel Stephan Rossbauer Francesca Bottacchi Martyn A.McLachlan Donal D.c.Bradley Thomas D.Anthopoulos Department of Physics&centre for Plastic Electronics Imperial College LondonPrince Consort RoadSouth KensingtonLondon SW72AZUK Division of Physical Sciences and Engineering King Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Saudi Arabia Department of Materials&centre for Plastic Electronics Imperial College LondonExhibition RoadSouth KensingtonLondon SW72AZUK Departments of Engineering Science and Physics and Division of Mathematical Physical and Life SciencesOxford University9 Parks RoadOxford OX13PDUK

Large-area manufacturing of flexible nanoscale electronics has long been sought by the printed electronics ***,the lack of a robust,reliable,high throughput and low-cost technique that is capable of delivering high-performance functional devices has hitherto hindered commercial *** we report on the extensive range of capabilities presented by adhesion lithography(a-Lith),an innovative patterning technique for the fabrication of coplanar nanogap electrodes with arbitrarily large aspect *** use this technique to fabricate a plethora of nanoscale electronic devices based on symmetric and asymmetric coplanar electrodes separated by a nanogapctional devices including self-aligned-gate transistors,radio frequency diodes and rectifying circuits,multi-colour organic light-emitting nanodiodes and multilevel non-volatile memory devices,can be fabricated in a facile manner with minimum process complexity on a range of *** compatibility of the formed nanogap electrodes with a wide range of solution processable semiconductors and substrate materials renders a-Lith highly attractive for the manufacturing of large-area nanoscale opto/electronics on arbitrary size and shape substrates.

关键词： lithography attractive electronics

chronic Hepatitis c Infection in children: current Treatment and New Therapies

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Journal of clinical and Translational Hepatology 2015年第1期3卷 36-41页

作者： Andrew Lee jeremy Rajanayagam Mona Abdel-Hady Birmingham children's Hospital Liver Unit Birmingham United Kingdom The University of Queensland School of MedicineBrisbane Australia Birmingham children's Hospital Liver Unit Birmingham United Kingdom University of Birmingham School of Infection and Immunity Birmingham United Kingdom Birmingham children's Hospital Liver Unit Birmingham United Kingdom

Viral hepatitis c is responsible for a large burden of disease *** of hepatitis c infection is currently undergoing a revolution with the development of new direct acting antivirals that offer higher cure rates and fewer side effects than other medications currently *** options for children,although well-defined and evidencebased,are limited relative to adults as there are few trials regarding the use of these newly developed agents in *** so much optimism in the development of novel therapeutic options for hepatitis c,it is timely to review and summarize the current standard of care treatment and indications for treatment of chronic hepatitis c in *** provide here an overview of recent drug developments and their potential for use in children.

关键词： Hepatitis c children Treatment Direct acting antivirals Host targeting agents

central regulation of breast cancer growth and metastasis

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Journal of cancer Metastasis and Treatment 2019年第3期4卷 90-107页

作者： jeremy c.Borniger Department of Psychiatry&Behavioral Sciences Stanford University School of MedicineP154 MSLS Building1201 Welch Rd.StanfordCA 94305USA

cancer is a systemic disease. In order to fully understand it, we must take a holistic view on how cancer interacts with its host. The brain monitors and responds to natural and aberrant signals arriving from the periphery, particularly those of metabolic or immune origin. As has been well described, a hallmark of cancer is marked disruption of metabolic and inflammatory processes. Depending on the salience and timing of these inputs, the brain responds via neural and humoral routes to alter whole-body physiology. These responses have consequences for tumor growth and metastasis, directly influencing patient quality of life and subsequent mortality. Additionally, environmental inputs such as light, diet, and stress, can promote inappropriate neural activity that benefits cancer. Here, I discuss evidence for brain-tumor interactions, with special emphasis on subcortical neuromodulator neural populations, and potential ways of harnessing this cross-talk as a novel approach for cancer treatment.

关键词： Breast cancer hypothalamus immunometabolism sympathetic nervous system neuromodulators

Adenosine A1 receptor ligands bind toα-synuclein:implications forα-synuclein misfolding andα-synucleinopathy in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 809-834页

作者： Elisabet Jakova Mohamed Taha Moutaoufik jeremy S.Lee Mohan Babu Francisco S.cayabyab Department of Surgery College of MedicineUniversity of SaskatchewanSaskatoonSKCanada Department of chemistry and Biochemistry Faculty of ScienceUniversity of ReginaReginaSKCanada Department of Biochemistry Microbiology and ImmunologyCollege of MedicineUniversity of SaskatchewanSaskatoonSKCanada.

Background:Accumulatingα-synuclein(α-syn)aggregates in neurons and glial cells are the staples of many synucleinopathy disorders,such as Parkinson’s disease(PD).Since brain adenosine becomes greatly elevated in ageing brains and chronic adenosine A1 receptor(A1R)stimulation leads to neurodegeneration,we determined whether adenosine or A1R receptor ligands mimic the action of known compounds that promoteα-syn aggregation(e.g.,the amphetamine analogue 2-aminoindan)or inhibitα-syn aggregation(e.g.,Rasagiline metabolite 1-aminoindan).In the present study,we determined whether adenosine,A1R receptor agonist N^(6)-cyclopentyladenosine(cPA)and antago-nist 8-cyclopentyl-1,3-dipropylxanthine(DPcPX)could directly interact withα-syn to modulateα-syn aggregation and neurodegeneration of dopaminergic neurons in the substantia nigra(SN).Methods:Nanopore analysis and molecular docking were used to test the binding properties of cPA and DPcPX withα-syn in ***-Dawley rats were administered with 7-day intraperitoneal injections of the A1R ligands and 1-and 2-aminoindan,and levels ofα-syn aggregation and neurodegeneration were examined in the SN pars compacta and hippocampal regions using confocal imaging and Western ***:Using nanopore analysis,we showed that the A1R agonists(cPA and adenosine)interacted with the N-terminus ofα-syn,similar to 2-aminoindan,which is expected to promote a“knot”conformation andα-syn *** contrast,the A1R antagonist DPcPX interacted with the N-and c-termini ofα-syn,similar to 1-aminoindan,which is expected to promote a“loop”conformation that preventsα-syn *** docking studies revealed that adenosine,cPA and 2-aminoindan interacted with the hydrophobic core ofα-syn N-terminus,whereas DPcPX and 1-aminoindan showed direct binding to the N-and c-terminal hydrophobic *** imaging and Western blot analyses revealed that chronic treatments with cPA alone or in combination with 2-aminoindan increasedα-syn

关键词： Alpha-synucleinopathy Adenosine A1 receptor N6-cyclopentyladenosine 8-cyclopentyl-1 3-dipropylxanthine 1-aminoindan 2-aminoindan Neuroprotection Neurodegeneration Protein misfolding

1992年兰德斯地震序列地壳变形的连续测量

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世界地震译丛 1995年第5期26卷 63-75页

作者： F.K.wyatt D.c.Agnew M.Gladwin 刘新美国家地震局地球物理研究所

我们试图解释兰德斯和约书亚特里地震序列震前、震时和震后在Pinon Flat观测站(PFO)得到的应变和倾斜的连续测量结果。这些数据显示了兰德斯主震后伴随着重大的瞬态形变,其总幅值是震时形变的百分之几和至少几天的衰减时间。与PFO观测... 详细信息

我们试图解释兰德斯和约书亚特里地震序列震前、震时和震后在Pinon Flat观测站(PFO)得到的应变和倾斜的连续测量结果。这些数据显示了兰德斯主震后伴随着重大的瞬态形变,其总幅值是震时形变的百分之几和至少几天的衰减时间。与PFO观测站的其它多种仪器的观测数据相比较,使我们可以推测该形变的可能来源。在三个长基式应变仪记录的震后瞬态值的大小几乎是相同的,这说明它或者是大尺度形变或者是靠近部分观测站的局部运动。借助覆盖该区的那些应变仪的许多其它测量结果的相似性以及更靠近震源的其它显著震后位移可以将后者大部分地排除。大尺度形变的可能机制包括:震后断层滑动、近地表岩石中与时间有关的蠕变以及水位变化引起的弹性或热的响应。头两项与PFO的观测结果很一致,但是如果震后断层滑动是源,则它的分布与震时滑动必然不相同而且可以包括那些不是地震破裂的断层。如果其它机制中的一个是主要来源,则PFO数据意味着震后滑动必须大大地小于地震的滑动,或许2％,或者更小。震前没有观测到明显的形变,即在震前数天到数分钟,没有观测到震时2×10^(-3)的形变水平。

关键词：地震地质地震序列地壳变形连续测量

Expanding plant genome-editing scope by an engineered iSpyMaccas9 system that targets A-rich PAM sequences

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Plant communications 2021年第2期2卷 78-88页

作者： Simon Sretenovic Desuo Yin Adam Levav jeremy D.Selengut Stephen M.Mount Yiping Qi Department of Plant Science and Landscape Architecture University of MarylandCollege ParkMD 20742USA Hubei Academy of Agricultural Sciences Wuhan 430064China Montgomery Blair High School Silver SpringMD 20901USA center for Bioinformatics and computational Biology University of MarylandCollege ParkMD 20742USA Department of cell Biology and Molecular Genetics University of MarylandCollege ParkMD 20742USA Institute for Bioscience and Biotechnology Research University of MarylandRockvilleMD 20850USA

The most popular cRISPR-Spcas9 systemrecognizes canonical NGG protospacer adjacent motifs(PAMs).Previously engineered Spcas9 variants,such as cas9-NG,favor G-rich PAMs in genome *** this manuscript,we describe a new plant genome-editing system based on a hybrid iSpyMaccas9 platform that allows for targeted mutagenesis,c to T base editing,and A to G base editing at A-rich *** study fills amajor technology gap in the cRISPR-cas9 system for editing NAAR PAMs in plants,which greatly expands the targeting scope of ***,our vector systems are fully compatible with Gateway cloning and will work with all existing single-guide RNA expression systems,facilitating easy adoption of the systems by *** anticipate that more tools,such as prime editing,homology-directed repair,cRISPR interference,and cRISPR activation,will be further developed based on our promising iSpyMac-cas9 platform.

关键词： plant genome editing iSpyMaccas9 PAM cytosine base editing adenine base editing

Target fabrication for the POLAR experiment on the Orion laser facility

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High Power Laser Science and Engineering 2015年第1期3卷 70-75页

作者： c.Spindloe D.wyatt D.Haddock I.East J.E.cross c.N.Danson E.Falize J.M.Foster M.Koenig G.Gregori Target Fabrication Group Central Laser Facility Rutherford Appleton Laboratory Harwell Science and Innovation Campus Atomic and Laser Physics Clarendon Laboratory University of Oxford AWE cEA-DAM-DIF Laboratoire pour l’Utilisation Des Laser Intense UMR 7605 CNRS-CEA-Ecole Polytechnique-Université Paris VI

This article describes the fabrication of a suite of laser targets by the Target Fabrication group in the central Laser Facility(cLF), STFc Rutherford Appleton Laboratory for the first academic-access experiment on the Orion laser facility(Hopps et al., Appl. Opt. 52, 3597–3601(2013)) at Atomic Weapons Establishment(AWE). This experiment, part of the POLAR project(Falize et al., Astrophys. Space Sci. 336, 81–85(2011); Busschaert et al., New J. Phys. 15, 035020(2013)),studied conditions relevant to the radiation-hydrodynamic processes occurring in a remarkable class of astrophysical star systems known as magnetic cataclysmic variables. A large number of complex fabrication technologies and research and development activities were required to field a total of 80 high-specification targets. Target design and fabrication procedures are described and initial alignment and characterization data are discussed.

关键词： astrophysics microtargets