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Advances in newly developing therapy for chronic hepatitis C virus infection

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Frontiers of Medicine 2014年第2期8卷 166-174页

作者： paul j. Pockros Division of Gastro/Hepatology Scripps Clinic 10666 N Torrey Pines Road N203 La Jolla CA 92067 USA

Chronic hepatitis C virus （HCV） infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral （DAA） agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN ＋ RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

关键词： direct-acting antiviral (DAA) nucleotide polymerase inhibitors protease inhibitors

Three-dimensional simulation of liquid inj.ction,film formation and transport,in fluidized beds

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Particuology 2009年第5期7卷 337-346页

作者： paul Zhao Peter j. O'Rourke Dale Snider CPFD Software LLCAlbuquerqueNM 87111USA CFD d'OR Software and Consulting LLCLos AlamosNM 87544USA

Liquid inj.ction, and film formation and transport in dense-phase gas-solids fluidized beds are numerically simulated in three dimensions using a collisional exchange model that is based on the mechanism that collisions cause transfer of liquid mass, momentum, and energy between particles. In the model, each of the particles is represented by a solid core and a liquid film surrounding the core. The model is incorporated in the framework of the commercial code Barracuda developed by CPFD Software. The commercial software is an advanced CFD-based computational tool where the particles are treated as discrete entities, calculated by the MP-PIC method, and tracked using the Lagrangian method. Details of the collisional liquid transfer model have been previously presented in O＇Rourke, Zhao, and Snider （2009）; this paper presents new capabilities and proof-testing of the collision model and a new method to better quantify the penetration length. Example calculations of a fluidized bed without liquid inj.ction show the expected effect of collisions on the reduction of granular temperature （fluctuational kinetic energy） of the bed. When applied to liquid inj.ction into a dense-phase fluidized bed under different conditions, the model predicts liquid penetration lengths comparable to the experiments. In addition, the simulation reveals for the first time the dynamic mixing of the liquid droplets with the bed particles and the transient distribution of the droplets inside the bed.

关键词： MP-PIC Liquid inj.ction Fluidized bed Particle collisions CPFD j.t penetration

Assessing mixing characteristics of particle-mixing and granulation devices

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Particuology 2008年第6期6卷 419-444页

作者： paul W. Cleary matthew D. Sinnott CSIRO Mathematical and Information Sciences

The mixing of particulates such as powders is an important process in many industries including pharmaceuticals, plastics, household products （such as detergents） and food processing. The quality of products depends on the degree of mixing of their constituent materials which in turn depends on both geometric design and operating conditions. Unfortunately, due to lack of understanding of the interaction between mixer geometry and the granular material, limited progress has been made in optimizing mixer design. The discrete element method （DEM） is a computational technique that allows particle systems to be simulated and mixing to be predicted. Simulation is an effective way of acquiring information on the performance of different mixers that is difficult and/or expensive to obtain using traditional experimental approaches. Here we demonstrate how DEM can be used to unravel flow dynamics and assess mixing in several different types of devices. These devices used for mixing and/or granulation of particulates, are classified broadly as gravity controlled, bladed and high shear. We also explore the role of particle shape in mixing performance and use DEM to test whether Froude number scaling is suitable for predicting scale performance of rotating mixers.

关键词： Discrete element modelling Mixing Mixers Blenders Granulation Scale up Particle shape

Improving rice photosynthesis and yield through trehalose 6-phosphate signaling

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Molecular Plant 2022年第4期15卷 586-588页

作者： matthew j.paul j.vier A.Miret Cara A.Griffiths Plant Science Rothamsted ResearchAL52JQ HarpendenHertfordshireUK

THE T6P-SnRK1 SIGNALING PATHWAY IN PLANTS,The biosynthetic route for the synthesis of trehalose in plants is through a low-flux pathway that leads to the accumulation of micromolar amounts of trehalose 6-phosphate(T6P)and trehalose when sucrose is available.T6P accumulates in proportion to sucrose(Lunn et al.,2006)as an indispensable regulator of carbohydrate utilization(Schluepmann et al.,2003).At least some of the indispensability of T6P and its profound and widespread effects on plant growth and development can be explained through T6P inhibition of the SNF1-related protein kinase SnRK1(Zhang et al.,2009),a central regulator of plant responses to carbon and energy status.

关键词： molar synthesis explained

Cell Wall Microstructure Analysis Implicates Hemicellulose Polysaccharides in Cell Adhesion in Tomato Fruit Pericarp Parenchyma

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Molecular Plant 2009年第5期2卷 910-921页

作者： j.se j. Ordaz-Ortiz Susan E. Marcus j. paul Knox Centre for Plant Sciences Faculty of Biological Sciences University of Leeds Leeds LS2 9JT United Kingdom

Methods developed to isolate intact cells from both unripe and ripe tomato fruit pericarp parenchyma have allowed the cell biological analysis of polysaccharide epitopes at the surface of separated cells. The LM7 pectic homogalacturonan epitope is a marker of the j.nctions of adhesion planes and intercellular spaces in parenchyma systems. The LM7 epitope persistently marked the former edge of adhesion planes at the surface of cells separated from unripe and ripened tomato fruit and also from fruits with the Cnr mutation. The LM 11 xylan epitope was associated, in sections, with cell walls lining intercellular space but the epitope was not detected at the surface of isolated cells, being lost during cell isolation. The LM15 xyloglucan epitope was present at the surface of cells isolated from unripe fruit in a pattern reflecting the former edge of cell adhesion planes/intercellular space but with gaps and apparent breaks. An equivalent pattern of LM15 epitope occurrence was revealed at the surface of cells isolated by pectate lyase action but was not present in cells isolated from ripe fruit or from Cnr fruit. In contrast to wild-type cells, the LM5 galactan and LM21 mannan epitopes occurred predominantly in positions reflecting intercellular space in Cnr, suggesting a concerted alteration in cell wall microstructure in response to this mutation. Galactanase and mannanase, along with pectic homogalacturonan-degrading enzymes, were capable of releasing cells from unripe fruit parenchyma. These observations indicate that hemicellulose polymers are present in architectural contexts reflecting cell adhesion and that several cell wall polysaccharide classes are likely to contribute to cell adhesion/cell separation in tomato fruit pericarp parenchyma.

关键词： Cell walls fruit development tomato cell adhesion cell separation polysaccharide.

Flow hydrodynamics in embankment breach

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j.urnal of Hydrodynamics 2015年第6期27卷 835-844页

作者： ZHAO Gensheng VISSER paul j. REN Yankai UIj.TEWAAL Wim S.j. Department of Hydraulic Engineering Delft University of Technology Flanders Hydraulics Research Flemish Government Department of Mobility and Public Works

Breaching flow occurs during the breach development of the embankment, dike, earthen dam, landslide barrier, etc. and plays an import role in the breaching erosion as the driving force. According to the previous research, the breaching process can be classified into initiation phase, breach widening phase and breach deepening phase. Based on the breaching development classifications, the breaching flow can be seen as a special compound weir flow when the breach channel is in the relatively equilibrium condition. There were five physical flow models were designed in the hypothesis of rectangular shape and trapezoidal shape for the breach channel cross sections to study the breaching flow characteristics. The distributions of water level and velocity were measured and analysed in the breaching flows in overtopping condition and emerged condition. There were two helicoidal flows above the breach channel slopes and triangular hydraulic j.mp in the downstream of the breach channel in the overtopping condition and emerged condition. The hydraulic energy loss was calculated according to the breaching velocity and water level distribution in the upstream and downstream of the model. It is found that the test results of the breach flow physical model can be valuable to bring insight of the breaching process of embankment and make contributions to the validations and verifications of breach numerical models.

关键词： embankment breach physical model breaching flow helicoidal flow hydraulic j.mp

Role of proteasome inhibition in sensitized transplant candidates

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Chinese Medical j.urnal 2011年第5期124卷 771-774页

作者： matthew j. Everly j.son j. Everly paul I. Terasaki One Lambda Inc Research 2 Division Los Angeles CA 90064 USA

Obj.ctive To review this efficacy and safety of bortezomib, a proteasome inhibitor, in the setting of the sensitized transplant candidate. Data sources The data used in this review were from articles published （PubMed） between 2000 to 2010. Additionally abstracts from medical meetings related to transplant were also used. Study selection Articles were selected if they were trial results or case studies for the use of bortezomib in the sensitized patient *** The early data using bortezomib as a part of desensitization regimens has shown success. Although one cycle （4 doses） of bortezomib seems to have affect on many patients, it also seems likely that to provide complete desensitization multiple cycles will be required. Regarding safety, bortezomib has been shown to have minimal side effects. The most common side effects reported are those of thrombocytopenia and anemia. These side effects are dose related and self limiting upon discontinuation of the *** Bortezomib with plasmapheresis is a promising new alternative to desensitization protocols that use either high dose intravenous immune globulin （IVIG） or low dose IVIG and plasmapheresis. The efficacy on antibody reduction looks to be batter that that of the IVIG based regimens without significant addition toxicity. The results of ongoing prospective trials are positive and their complete results are greatly anticipated.

关键词： proteasome inhibition bortezomib desensitization plasma cell alloantibodies human leukocyte antigen transplantation

Sexual/aggressive behavior of wild yak(Bos mutus Prej.valsky1883) during the rut: influence of female choice

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Chinese Science Bulletin 2014年第22期59卷 2756-2763页

作者： paul j. Buzzard Donghua Xu Huan Li China Exploration & Research Society

Wild yaks(Bos mutus)ranged across the Tibetan Plateau in large herds before being forced to remote areas of the ***,little has been published about their behavioral *** present the first extensive study on wild yak behavior during the *** gathered data on activity budgets,aggressive/sexual behaviors,and the behavior of bulls inside and outside mixed groups during 11 days in 2010 and 9 days in *** ate less and were more social during the rut than during *** ate less than females and socialized more during the *** observed yaks for 234.25 h and recorded 2,078 aggressive/sexual *** bulls inspected and tended cows showing off their profiles during lateral displays,the most common type of indirect *** bulls inside mixed sex groups rested less and socialized more than bulls *** initiated intense intra-sexual competition and led at least 25 bulls on *** then incited fight frenzies of numerous bulls from inside and outside the groups before copulations,and fights could be *** discuss female choice selecting for large size and fighting ability in males,the similarity of yak and bison(genus Bison)behavior,and conservation implications.

关键词：攻击行为野牦牛发情期女性战斗能力青藏高原行为生态学社会化

Temporal and spatial variations of carbon isotope signature reveal substantial contribution of bracts and internode assimilates to grain filling of j.ponica rice

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The Crop j.urnal 2021年第2期9卷 271-281页

作者： Mengj.ao j.ang Hongfa Xu Nianfu Yang Ganghua Li Yanfeng Ding matthew j.paul Zhenghui Liu College of Agriculture Nanjing Agricultural UniversityNanjing 210095JiangsuChina Collaborative Innovation Center for Modern Crop Production Nanjing Agricultural UniversityNanjing 210095JiangsuChina Plant Science Rothamsted ResearchHarpendenHertfordshire AL52JQUK

Carbon isotope composition(δ^(13)C)of a plant organ is an inherent signature reflecting its physiological property,and thus is used as an integrative index in crop *** is also a non-intrusive method for quantifying the relative contribution of different source organs to grain filling in *** the samples collected from two-year field and pot experiments with two nitrogen(N)fertilization treatments,we investigated the temporal and spatial variations of δ^(13)C in source organs of leaf,sheath,internode,and bracts,and in sink organ *** nature of δ^(13)C was uncovered,with an order of leaf(−27.84‰)

关键词： j.ponica rice Carbon isotope composition(δ^(13)C) Temporal and spatial variations Source and sink relation Grain yield formation