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The anatomy, function, and development of mammalian Aβ low-threshold mechanoreceptors

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Frontiers in Biology 2013年第4期8卷 408-420页

作者： michael s. FLEMING Wenqin LUO Department of Neuroscience University of Pennsylvania Perelman School of Medicine Philadelphia PA 19014 USA

t Touch sensation is critical for our social and environmental interactions. In mammals, most discriminative light touch sensation is mediated by the Aβ low-threshold mechanoreceptors. Cell bodies of Aβ low-threshold mechanoreceptors are located in the dorsal root ganglia and trigeminal ganglia, which extend a central projection innervating the spinal cord and brain stem and a peripheral projection innervating the specialized mechanosensory end organs. These specialized mechanosensory end organs include Meissner＇s corpuscles, Pacinian corpuscles, lanceolate endings, Merkel cells, and Ruffini corpuscles. The morphologies and physiological properties of these mechanosensory end organs and their innervating neurons have been investigated for over a century. In addition, recent advances in mouse genetics have enabled the identification of molecular mechanisms underlying the development of Aβ low- threshold mechanoreceptors, which highlight the crucial roles of neurotrophic factor signaling and transcription factor activity in this process. Here, we will review the anatomy, physiological properties, and development of mammalian low- threshold Aβ mechanoreceptors.

关键词： mechanoreceptor Meissner's corpuscle Pacinian corpuscle lanceolate ending Merkel cell Ruffini corpuscle dorsal root ganglion

strategies for scalable symbolic execution-driven test generation for programs

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science China(Information sciences) 2011年第9期54卷 1797-1812页

作者： KRIsHNAMOORTHY saparya HsIAO michael s. LINGAPPAN Loganathan Intel Corporation Department of Electrical and Computer Engineering Virginia Polytechnic Institute and State University

With the advent of advanced program analysis and constraint solving techniques,several test generation tools use variants of symbolic *** techniques have been shown to be very effective in path-based test generation;however,they fail to scale to large programs due to the exponential number of paths to be *** this paper,we focus on tackling this path explosion problem and propose search strategies to achieve quick branch coverage under symbolic execution,while exploring only a fraction of paths in the *** present a reachability-guided strategy that makes use of the reachability graph of the program to explore unvisited portions of the program and a conflict-driven backtracking strategy that utilizes conflict analysis to perform nonchronological *** present experimental evidence that these strategies can significantly reduce the search space and improve the speed of test generation for programs.

关键词： test generation software testing symbolic execution path explosion conflict analysis

Agricultural pesticide use and food safety:California's model

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Journal of Integrative Agriculture 2015年第11期14卷 2340-2357页

作者： Minghua Zhang michael R Zeiss shu Geng Department of Land Air and Water ResourcesUniversity of California California Department of Pesticide Regulation sino-Us Joint Food safety Research Center Northwest A&F University Department of Plant sciences University of California

Pesticides have been an essential part of agriculture to protect crops and livestock from pest infestations and yield reduction for many decades. Despite their usefulness, pesticides could pose potential risks to food safety and the environment as well as human health. This paper reviews the positive benefits of agricultural pesticide use as well as some potential negative impacts on the environment and food safety. In addition, using the case of California, we discuss the need for both residue monitoring and effective pest management to promote food safety. Twenty years＇ pesticide residue data from California＇s pesticide residue monitoring program were analyzed. Results showed that more than 95% of food samples were in compliance with Us pesticide residue standards （tolerances）. However, certain commodities from certain sources had high percentages of residues above tolerance levels. Even when residues above tolerance levels were detected, most were at levels well below 1 mg kg^-1, and most posed negligible acute health risk. However, a few detected residues had the potential to cause health effects. Therefore, establishing an effective food residue monitoring program is important to ensure food quality throughout the marketplace.

关键词： food safety food security pesticide use residue monitoring environmental impacts IPM tolerances maximum residue limits (MRLs)

Advanced Computational Methods of Rapid and Rigorous 3-D Inversion of Airborne Electromagnetic Data

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Communications in Computational Physics 2008年第1期3卷 160-179页

作者： Leif H.Cox michael s.Zhdanov Department of Geophysical Engineering Montana Tech of the University of Montana1300W Park StreetButteMT 59701-8997USA Department of Geology and Geophysics University of Utah135 S.1460 E.Rm 719Salt Lake CityUT 84112USA.

We develop a new computational method for modeling and inverting frequency domain airborne electromagnetic(EM)*** method is based on the contraction integral equation method for forward EM modeling and on inversion using the localized quasi-linear(LQL)approximation followed by the rigorous inversion,if *** LQL inversion serves to provide a fast image of the *** results are checked by a rigorous update of the domain electric field,allowing a more accurate calculation of the predicted *** the accuracy is poorer than desired,rigorous inversion follows,using the resulting conductivity distribution and electric field from LQL as a starting *** rigorous inversion iteratively solves the field and domain equations,converting the non-linear inversion into a series of linear *** test this method on synthetic and field *** results of the inversion are very encouraging with respect to both the speed and the accuracy of the algorithm,showing this is a useful tool for airborne EM interpretation.

关键词： Computational geophysics airborne electromagnetics inversion 3-D LQL rigorous

Increased susceptibility of aging gastric mucosa to injury:The mechanisms and clinical implications

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World Journal of Gastroenterology 2014年第16期20卷 4467-4482页

作者： Andrzej s Tarnawski Amrita Ahluwalia michael K Jones University of California Irvine and the Veterans Administration Long Beach Healthcare system 5901 E. 7~(th) StreetLong BeachCA 90822-5201United States

This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-“aging gastropathy”-has prominent structural and functional abnormalities vs young gastric mucosa. some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NsAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged

关键词： Aging gastric mucosa Injury Phosphatase and tensin homologue deleted on chromosome ten-PTEN survivin Apoptosis Hypoxia

Mouse models of colorectal cancer: Past, present and future perspectives

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World Journal of Gastroenterology 2020年第13期26卷 1394-1426页

作者： Florian Bürtin Christina s Mullins michael Linnebacher Department of General VisceralVascular and Transplantation SurgeryUniversity Medical Center RostockUniversity of RostockRostock 18057Germany Department of Thoracic surgery University Medical Center RostockUniversity of RostockRostock 18057Germany Molecular Oncology and Immunotherapy Department of GeneralVisceralVascular and Transplantation SurgeryUniversity Medical Center RostockRostock 18057Germany

Colorectal cancer(CRC)is the third most common diagnosed malignancy among both sexes in the United states as well as in the European *** the incidence and mortality rates in western,high developed countries are declining,reflecting the success of screening programs and improved treatment regimen,a rise of the overall global CRC burden can be observed due to lifestyle changes paralleling an increasing human development *** a growing insight into the biology of CRC and many therapeutic improvements in the recent decades,preclinical in vivo models are still indispensable for the development of new treatment *** the development of carcinogen-induced rodent models for CRC more than 80 years ago,a plethora of animal models has been established to study colon cancer *** tenuous invasiveness and metastatic behavior,these models are useful for chemoprevention studies and to evaluate colitis-related *** engineered mouse models(GEMM)mirror the pathogenesis of sporadic as well as inherited CRC depending on the specific molecular pathways activated or *** the vast majority of CRC GEMM lack invasiveness,metastasis and tumor heterogeneity,they still have proven useful for examination of the tumor microenvironment as well as systemic immune responses;thus,supporting development of new therapeutic *** of metastatic disease by orthotopic injection of CRC cell lines is possible,but the so generated models lack genetic diversity and the number of suited cell lines is very ***-derived xenografts,in contrast,maintain the pathological and molecular characteristics of the individual patient's CRC after subcutaneous implantation into immunodeficient mice and are therefore most reliable for preclinical drug development–even in comparison to GEMM or cell line-based ***,subcutaneous patient-derived xenograft models are less suitable for studying most aspects of the tumor micr

关键词： Colorectal cancer Mouse models Patient-derived xenografts Carcinogen-induced models Genetically engineered mouse models Preclinical drug development

Inflammatory bowel disease imaging:current practice andfuture directions

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World Journal of Gastroenterology 2016年第3期22卷 917-932页

作者： Aoife Kilcoyne Jess L Kaplan michael s Gee Department of Radiology Massachusetts General HospitalBostonMA 02214United States Department of Pediatrics Massachusetts General HospitalBostonMA 02214United States

The purpose of this paper is to evaluate the role of imaging in inflammatory bowel disease(IBD), including detection of extraluminal complications and extraintestinal manifestations of IBD, assessment of disease activity and treatment response, and discrimination of inflammatory from fibrotic strictures. IBD is a chronic idiopathic disease affecting the gastrointestinal tract that is comprised of two separate, but related intestinal disorders; Crohn's disease and ulcerative colitis. The paper discusses, in detail the pros and cons of the different IBD imaging modalities that need to be considered in order to optimize the imaging and clinical evaluation of patients with IBD. Historically, IBD evaluation of the bowel has included imaging to assess the portions of the small bowel that are inaccessible to optical endoscopic visualization. This traditionally was performed using barium fluoroscopic techniques; however, cross-sectional imaging techniques(computed tomography and magnetic resonance imaging) are being increasingly utilized for IBD evaluation because they can simultaneously assess mural and extramural IBD manifestations. Recent advances in imaging technology, that continue to improve the ability of imaging to noninvasively follow disease activity and treatment response, are also discussed. This review article summarizes the current imaging approach in inflammatory bowel disease as well as the role of emerging imaging modalities.

关键词： Imaging inflammatory bowel disease Crohn's disease ulcerative colitis computed tomography magnetic resonance imaging

Large-scale Electromagnetic Modeling for Multiple Inhomogeneous Domains

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Communications in Computational Physics 2009年第7期6卷 269-289页

作者： Masashi Endo Martin Cuma michael s.Zhdanov Department of Geology and Geophysics University of Utah135S 1460ERm 719Salt Lake CityUT 84112USA

We develop a new formulation of the integral equation(IE)method for three-dimensional(3D)electromagnetic(EM)field computation in large-scale models with multiple inhomogeneous *** problem arises in many practical applications including modeling the EM fields within the complex geoelectrical structures in geophysical *** geophysical applications,it is difficult to describe an earth structure using the horizontally layered background conductivity model,which is required for the efficient implementation of the conventional IE *** a result,a large domain of interest with anomalous conductivity distribution needs to be discretized,which complicates the *** new method allows us to consider multiple inhomogeneous domains,where the conductivity distribution is different from that of the background,and to use independent discretizations for different *** reduces dramatically the computational resources required for largescale *** addition,using this method,we can analyze the response of each domain separately without an inappropriate use of the superposition principle for the EM field *** method was carefully tested for the modeling the marine controlled-source electromagnetic(MCsEM)fields for complex geoelectric structures with multiple inhomogeneous domains,such as a seafloor with the rough bathymetry,salt domes,and *** have also used this technique to investigate the return induction effects from regional geoelectrical structures,e.g.,seafloor bathymetry and salt domes,which can distort the EM response from the geophysical exploration target.

关键词： Large-scale EM modeling multiple inhomogeneous domains marine CsEM

A whiter shade of male： Color background matching as a function of size and sex in the yellow shore crab Hemigrapsus oregonensis （Dana, 1851）

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Current Zoology 2015年第4期61卷 729-738页

作者： Gregory C. JENsEN michael s. EGNOTOVICH school of Aquatic and Fishery sciences Box 355020 University of Washington Seattle WA 98195 USA

Juveniles of the shore crab Hemigrapsus oregonensis are highly variable in color, ranging from the typical yellowish- green of adults to pure white and myriad patterns of white mottling and other disruptive markings, but large individuals with white coloration appear to be very rare. Using image analysis to quantify the relative ＂whiteness＂ of beaches, we sampled crabs from nine locations in Washington state that varied widely in their amount of shell fragments and other light-colored material. The total proportion of white individuals in the different locations was strongly correlated to the proportion of white material on the beaches, but there was a striking difference between sexes. Although white specimens of both sexes declined significantly at sizes above 10 mm carapace width, white females generally persisted throughout the entire female size range on lighter-colored beaches while white males larger than 10 mm were virtually absent from all of the sampled populations. Pure white males held on dark backgrounds in captivity remained white, as they lack the dark chromatophores in their hypoderrnis needed to change color; off-white males became darker and in some cases lightened up again when transferred back to a white background. Behavioral differences between the sexes may result in differential mortality of white individuals by visual predators [Current Zoology 61 （4） 729-738, 2015 ].

关键词： Camouflage Color Polymorphism Disruptive patterns Crabs