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The p75 neurotrophin receptor:at the crossroad of neural repair and death

Neural Regeneration Research 2015年第5期10卷 721-725页

作者： Rick B.Meeker Kimberly S.williams Department of Neurology University of North Carolina Curriculum in Neurobiology University of North Carolina

The strong repair and pro-survival functions of neurotrophins at their primary receptors, TrkA, TrkB and TrkC, have made them attractive candidates for treatment of nervous system injury and disease. However, difficulties with the clinical implementation of neurotrophin therapies have prompted the search for treatments that are stable, easier to deliver and allow more precise regula- tion of neurotrophin actions. Recently, the p75 neurotrophin receptor （p75wrR） has emerged as a potential target for pharmacological control of neurotrophin activity, supported in part by stud- ies demonstrating 1） regulation of neural plasticity in the mature nervous system, 2） promotion of adult neurogenesis and 3） increased expression in neurons, macrophages, microglia, astro- cytes and/or Schwann cells in response to injury and neurodegenerative diseases. Although the receptor has no intrinsic catalytic activity it interacts with and modulates the function of TrkA, TrkB, and TrkC, as well as sortilin and the Nogo receptor. This provides substantial cellular and molecular diversity for regulation of neuron survival, neurogenesis, immune responses and pro- cesses that support neural function. Upregulation of the p75^NTR under pathological conditions places the receptor in a key position to control numerous processes necessary for nervous system recovery. Support for this possibility has come from recent studies showing that small, non-pep- tide p75^NTR ligands can selectively modify pro-survival and repair functions. While a great deal remains to be discovered about the wide ranging functions of the p75^NTR, studies summarized in this review highlight the immense potential for development of novel neuroprotective and neu- rorestorative therapies.

关键词： injury plasticity neurodegenerative disease brain therapy neuron microglia neuralprogenitor

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Convenient synthesis of nucleoside 5'-(α-P-thio)triphosphates and phosphorothioate nucleic acids(DNA and RNA)

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Science China Chemistry 2012年第1期55卷 80-89页

作者： CATON-williams Julianne FIAZ Bilal HOXHAJ Rudiona SMITH Matthew Department of Chemistry Georgia State University

Modified deoxy-and ribo-nucleoside triphosphates are chemically synthesized in multiple steps due to the protection and deprotection of the nucleoside *** conveniently synthesize the S-modified triphosphates for enzymatically preparing phosphorothioate DNAs and RNAs(PS-DNA and PS-RNA) as potential therapeutics,herein we report a one-pot strategy to synthesize the deoxy-and ribo-nucleoside 5'-(α-P-thio)triphosphates(dNTPαS and NTPαS) without protecting any nucleoside *** facile synthesis is achieved by treating the nucleosides with a mild phosphitylating reagent,reacting selectively with the 5'-hydroxyl group of each unprotected nucleoside,followed by sulfurization and hydrolysis to afford the crude dNTPαS and NTPαS analogs(mixtures of Sp and Rp diastereomers).We also demonstrated that after just simple precipitation(without HPLC and ion-exchange purification),the quality of the synthesized dNTPαS and NTPαS analogs is excellent for direct DNA polymerization and RNA transcription,*** Klenow DNA polymerase and T7 RNA polymerase accept the Sp diastereomers of dNTPαS and NTPαS analogs,respectively,while the Rp diastereomers are neither substrates nor inhibitors,the diastereomerically-pure PS-DNAs and PS-RNAs can be conveniently synthesized enzymatically.

关键词： sulfur modification S-derivatized nucleic acid nucleoside triphosphates nucleoside phosphorothioates phosphorothioate DNA and RNA diastereomers DNA and RNA polymerases

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XMT enabled prediction of structure and permeability of flocculated structures and sediments

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2005年第12期6卷 1367-1373页

作者： williams R.A. SELOMULYA C. JIA X. Institute of Particle Science ＆ Engineering School of Process Environmental ＆ Materials Engineering University of Leeds Leeds LS2 9JT UK ARC Centre for Functional Nanomaterials School of Chemical Engineering ＆ Industrial Chemistry University of New South Wales Sydney NSW 2052 Australia

3D visualisations of the microstructure of flocculated particulates and sediments using optical confocal laser mi- croscopy and high resolution X-ray microtomography (XMT) methods are described. Data obtained from in-situ measurements should enable direct computation of the properties of solids assembly (shape, size, contact area) and their permeability to fluids. A specific application relating to the formation of silica aggregates is described from which the behaviour of sediments containing these materials can be predicted on the basis of a bench-top test and the use of a Lattice Boltzman simulation. It is proposed that the method can potentially be used to predict trends such as the filtration behaviour of porous structures under different states of compression. This offers a significant benefit in assisting the formulation design of flocculated materials pertinent to a number of industrial sectors wishing to design optimal filtration or relevant operations.

关键词： Fluid flow Imaging Microstructure Porous media Visualization Tomography

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Characterization of the gas pulse frequency,amplitude and velocity in non-steady dense phase pneumatic conveying of powders

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Particuology 2008年第5期6卷 301-306页

作者： Kenneth C.williams Mark G.Jones Ahmed A.Cenna Centre for Bulk Solids and Particulate Technologies School of EngineeringUniversity of Newcastle

Current modelling techniques for the prediction of conveying line pressure drop in low velocity dense phase pneumatic conveying are largely based on steady state analyses. Work in this area has been on-going for many years with only marginal improvements in the accuracy of prediction being achieved. Experimental and theoretical investigations undertaken by the authors suggest that the flow mechanisms involved in dense phase conveying are dominated by transient effects rather than those of steady state and are possibly the principal reasons for the limited improvement in accuracy. This paper reports on investigations on the pressure fluctuation behaviour in dense phase pneumatic conveying of powders. The pressure behaviour of the gas flow in the top section of the pipeline was found to exhibit pulsatile oscillations. In particular, the pulse velocity showed variation in magnitude while the frequency of the oscillations rarely exceeded 5 Hz. A wavelet analysis using the Daubechie 4 wavelet found that the amplitude of the oscillations increased along the pipeline. Furthermore, there was significant variation in gas pulse amplitude for different types of particulate material.

关键词： Pneumatic conveying Powders Dense phase Pulsatile flow Transient flow

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East African topography and volcanism explained by a single,migrating plume

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Geoscience Frontiers 2020年第5期11卷 1669-1680页

作者： Rakib Hassan Simon E.williams Michael Gurnis Dietmar Muller School of Geosciences Room 412Madsen Building F09 Eastern AvenueThe University of SydneyNSW2006Australia Seismological Laboratory California Institute of TechnologyPasadenaCA91125USA Now at Geoscience Australia GPO Box 378CanberraACT2601Australia State Key Laboratory of Continental Dynamics Department of GeologyNorthwest UniversityXi’an 710069China

Anomalous topographic swells and Cenozoic volcanism in east Africa have been associated with mantle *** models involving one or more fixed plumes beneath the northeastward migrating African plate have been suggested to explain the space-time distribution of magmatism in east *** devise paleogeographically constrained global models of mantle convection and,based on the evolution of flow in the deepest lower mantle,show that the Afar plume migrated southward throughout its *** models suggest that the mobile Afar plume provides a dynamically consistent explanation for the spatial extent of the southward propagation of the east African rift system(EARS),which is difficult to explain by the northeastward migration of Africa over one or more fixed plumes alone,over the last≈45 *** further show that the age-progression of volcanism associated with the southward propagation of EARS is consistent with the apparent surface hotspot motion that results from southward motion of the modelled Afar plume beneath the northeastward migrating African *** models suggest that the Afar plume became weaker as it migrated southwards,consistent with trends observed in the geochemical record.

关键词： Numerical mantle flow models Deep mantle flow LLSVP morphology Plume dynamics Plume motion Dynamic topography

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Structure and mechanics of native and decellularized porcine cranial dura mater

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再生工程(英文) 2023年第2期4卷 205-213页

作者： Ashma Sharma Jun Liao Lakiesha N.williams J.Crayton Pruitt Family Department of Biomedical Engineering University of FloridaGainesvilleFL 32611United States Department of Bioengineering University of Texas at ArlingtonArlingtonTX 76010United States

The dura mater is the outermost layer of meninges and consists of a dense elastic membrane that keeps cere-brospinal fluid inside the *** most cranial surgical interventions,the dura mater is incised and needs to be repaired with a graft *** assessed decellularized porcine dura mater as a novel graft material by quantifying the mechanical and structural properties of the dura *** dura mater was decellular-ized using the Sodium Dodecyl Sulfate(SDS)technique and subjected to uniaxial tensile testing,micro indentation testing,histological analysis,and Transmission Electron Microscopy(TEM).For native dura,we found the tensile modulus in the linear region(15%-25%strain)to be 19.31±1.23 MPa,with an initial tensile modulus(0%-3.5%strain range)of 451±0.30 kPa,and the failure stress as 4.61±1.50 MPa at 35%*** decellularized dura,the tensile modulus in the linear region was 10.81±0.88 MPa,the initial tensile modulus was 226±22 kPa,and the failure stress was 4.55±1.05 MPa at 55%*** effective compressive modulus was 7 to 19 kPa and 19-57 kPa for the native dura and the decellularized dura,*** histological and TEM observations showed that the orientation of fibers within the dura was maintained after *** short,our study demonstrated that decellularized porcine dura was able to maintain its overall morphological/structural integrity and preserve the native dura’s mechanical behavior,which provides a solid foundation for its use as a functional grafting material.

关键词： Cranial dura Decellularization Mechanical properties

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Experimental evidence that soil heterogeneity enhances plant diversity during community assembly

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Journal of Plant Ecology 2014年第5期7卷 461-469页

作者： Brandon M.williams Gregory R.Houseman Department of Biological Sciences Wichita State University1845 FairmountWichitaKS 67260USA

Aims Environmental heterogeneity is a primary mechanism explain-ing species coexistence and extant patterns of *** strong theoretical support and ample observational evidence,few experimental studies in plant communities have been able to demonstrate a causal link between environmental heterogene-ity and plant *** lack of experimental evidence sug-gests that either fine-scale heterogeneity has weak effects on plant diversity or previous experiments have been unable to effectively manipulate ***,we utilize a unique soil manipu-lation to test whether fine-scale soil heterogeneity will increase plant richness through species sorting among experimental patch *** This experiment was conducted in the tallgrass prairie region of south-central Kansas,*** utilized the inherent variation found in the vertical soil profile,which varied in both biotic and abiotic characteristics,and redistributed these strata into either homoge-neous or heterogeneous spatial arrangements in 2.4×2.4 m *** the soil manipulation,34 native prairie species were sown into all *** conducted annual censuses at peak biomass to quantify species composition and plant density by species within the experimental *** Findings After 2 years,species richness was significantly higher in heteroge-neous relative to homogeneous plots and this pattern was independ-ent of total plant *** the heterogeneous plots,13 species had higher establishment in a specific patch type representing one of the three soil ***,no species had greater estab-lishment in the mixed stratum,which comprised the homogene-ous plots,relative to the heterogeneous *** species sorting patterns suggest that fine-scale heterogeneity creates opportunities for plant establishment due to niche differences,which translates into increased plant diversity at the plot *** richness was more strongly related to plant density among patch

关键词： environmental heterogeneity species richness species sorting community assembly niche theory neutral theory

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Crustacean parasites associated with hermit crabs from the western Mediterranean Sea,with first documentation of egg predation by the burrowing barnacle Trypetesa lampas(Cirripedia:Acrothoracica:Trypetesidae)

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Integrative Zoology 2011年第1期6卷 13-27页

作者： Jason D.williams Alejandra GALLARDO Angela E.MURPHY Department of Biology Hofstra UniversityHempsteadNYUSA

Parasitic isopods(family Bopyridae)and burrowing barnacles(family Trypetesidae)infesting hermit crabs were investigated from shallow subtidal collections made along the southeastern coast of Spain in 2009.A total of 713 specimens of Clibanarius erythropus(Latreille,1818)and 82 Calcinus tubularis(L.,1767)were *** shells and worm tubes inhabited by hermit crabs were collected by hand while snorkeling and were cracked to determine host species,size,sex and presence of *** species of bopyrid isopods were found on ***:the branchial parasite Bopyrissa fraiseii(Carayon,1943)and the abdominal parasite Parathelges cardonae Codreanu and Codreanu in Codreanu,*** all *** examined,Bopyrissa fraiseii was found on 0.6%of hermit crabs and *** was found on 0.3%.A redescription of *** is provided and the species is documented with light and scanning electron microscopy for the first *** Calcinus tubularis harbored parasitic isopods,but one specimen was parasitized by an unidentified rhizocephalan barnacle of the genus Septosaccus(1.2%).The burrowing barnacle Trypetesa lampas(Hancock,1849)was found associated with both hermit crab species and evidence of predation on host eggs by this barnacle is shown for the first *** lampas was found in 4.2%of the shells *** present study expands our knowledge of the parasite fauna of hermit crabs from the Mediterranean Sea and indicates that additional research is needed to determine the impact of trypetesid egg predators on hermit crab populations.

关键词： Bopyridae egg predator Isopoda parasitism Rhizocephala

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Integrated soil, water and agronomic management effects on crop productivity and selected soil properties in Western Ethiopia

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International Soil and Water Conservation Research 2018年第4期6卷 305-316页

作者： Teklu Erkossa Timothy O.williams Fanuel Laekemariam International Water Management Institute P.O.Box 5689C/o ILRI Addis CampusAddis AbabaEthiopia Wolita University Ethiopia

Land degradation is a major challenge limiting crop production in Ethiopia. Integrated soil and water conservation is widely applied as a means to reverse the trend and increase productivity. This study investigated the effects of such integrated approaches at two sites, Jeldu and Diga, inWestern Ethiopia. A split plot design with physical soil and water conservation in the main plots and agronomic practices in the sub plots was employed. Maize (Zea mays L.) followed by groundnut (Arachis hypogaea L.) at Diga, and wheat (Triticum aestivum) followed by faba bean (Vicia faba L.) were the test crops. Surface soils were sampled before sowing and after the crop harvest, and analyzed for selected parameters. Soil moisture content during the growing period was also monitored. The use of soil bund increased soil moisture content, and significantly (P < 0.05) increased days to flowering and maturity, kernel weight and harvest index, grain yield of the test crops, with the exception of maize. The improved agronomic practices (intercropping, fertilization and row planting) significantly (P < 0.05) increased grain yield of all the test crops. The effect of the treatments on soil parameters may require longer time to be evident. Although the increase in crop yield due to soil bund and the improved agronomic practices is eminent, economic analysis is necessary before recommending the widespread use of the improved options.

关键词： Land degradation Soil bund Inter-cropping Improved crop varieties Crop-livestock systems

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Seismic Performance Assessment of a Conventional Multi-storey Building

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International Journal of Disaster Risk Science 2017年第3期8卷 237-245页

作者： Giuseppe Marcantonio Del Gobbo Martin S.williams Anthony Blakeborough Department of Engineering Science University of OxfordOxford OX1 3PJUK

Recent earthquakes have revealed that conventional seismic design philosophy allows for large levels of nonstructural damage. Nonstructural earthquake damage results in extensive repair costs and lengthy functional disruptions, as nonstructural systems comprise the majority of building investment and are essential to building operations. A better understanding of the expected overall seismic performance of code-compliant buildings is needed. This study investigates the seismic performance of a conventional building. A 16-storey steel office building was designed using a modern seismic structural code(Eurocode 8). This study is the first to assess in detail the substantial earthquake repair costs expected in a modern Eurocode concentric braced frame structure, considering nonstructural systems with the FEMA P-58 procedure. The breakdown of total repair costs by engineering demand parameter and by fragility group is novel. The seismic performance assessment indicated that substantial earthquake repair costs are expected. Limitations of the Eurocode nonstructural damage methodology were revealed in a novel manner using FEMA P-58, as the prescribed drift limits did not minimize nonstructural repair costs. These findings demonstrate the need for design procedures that improve nonstructural seismic performance. The study results provide a benchmark on which to evaluate retrofit alternatives for existing buildings and design options for new structures.

关键词： Eurocode 8 FEMA P-58 Nonstructural systems Seismic performance assessment

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