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Semiautomatic image analysis for grain counting in in situ hybridization experiments

NeuroImage 1994年第3期1卷 163-172页

作者： Mize, R. Ranney Thouron, Carol Lucas, Louis Harlan, Richard Department of Anatomy Neurosci. Ctr. Comp. Imaging Lab. Louisiana State Univ. Medical Center New Orleans LA 70112 United States Department of Anatomy Neuroscience Training Program Tulane University Medical Center New Orleans LA 70112 United States

We have developed a computer image analysis procedure for counting autoradiographic grains in in situ hybridization experiments. The procedure automatically estimates the number of autoradiographic grains over cells and measures cell number and size so that grain density per unit cell area can be calculated. Advantages include the clear separation of grains and cells, using chromatic and spatial filters to enhance the image;the use of gray level operators to extract cells from grains;and the use of binary operators for separating apposed or partially overlapping cells and grains. Comparison of manual and automated grain counts revealed a significant correlation between human and computer estimations of grain number. However, the automatic grain counting techniques consistently underestimated the number of grains when grain density was high. Measures of the fractional area occupied by grains normalized by the average area of a single grain were a better estimate at high grain densities. The procedure can be modified easily to operate on most image analyzers. © 1994 Academic Press. All rights reserved.

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How does gamma-interferon mediate resistance to Listefia monocytogenes?

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Trends in Microbiology 1994年第6期2卷 206-208页

作者： Metcalf, Dianne R. Campbell, Priscilla A. Medical Scientist Training Program University of Colorado Health Sciences Center Denver CO 80262 4200 East 9th Avenue United States Divn of Basic Immunology National Jewish Center for Immunology and Respiratory Medicine Denver CO 80206 1400 Jackson Street United States

Gamma-interferon (IFN-γ) seems to be required for resistance to Listeria monocytogenes in vivo, but acts early in infection, before apparent T cell involvement. The early role of IFN-γ is unknown, but might include enhancing antigen presentation, inducing secretion of tumor necrosis factor α and helping early precursor macrophages to express nonspecific listericidal activity. © 1994.

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COIL OPTIMIZATION FOR MRI BY CONJUGATE-GRADIENT DESCENT

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MAGNETIC RESONANCE IN MEDICINE 1991年第1期21卷 39-48页

作者： WONG, EC JESMANOWICZ, A HYDE, JS Biophysics Section Department of Radiology Medical College of Wisconsin Milwaukee Wisconsin 53226 Candidate for the combined MD and PhD degrees in the Medical Scientist Training Program at the Medical College of Wisconsin.

A flexible iterative algorithm is presented for optimizing gradient and radio frequency coils for MRI. It is based on a model using discrete current elements and direct Biot-Savart calculation of the fields. An error function is defined over a region of interest (ROI) and is minimized by conjugate gradient descent. The choice of error function allows optimization of the field uniformity, the inductance, and the efficiency of the coil in any combination. Neither the coil nor the ROI is restricted to any particular geometry. A 40- turn cylindrical z-gradient coil of radius a and length 4a, designed for a ROI of radius 0.7a and length 2a has an average error in the gradient fields generated of 0.85%, an inductance of 0.014a mH/cm, and an efficiency of 6.65a⁻² Gem/A. A 16-turn birdcage-like RF coil of radius 5 cm, designed for a ROI of radius 4 cm has an average error of 0.79%. ? 1991 Academic Press, Inc.

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HA-996 (1-hydroxy-3-aminopyrrolidone-2) selectively reduces N-methyl-d-aspartate (NMDA)-mediated brain damage

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neuroscience Letters 1989年第1-2期104卷 167-170页

作者： McDonald, John W. Uckele, John Silverstein, Faye S. Johnston, Michael V. Neuroscience and Medical Scientist Training Program University of Michigan Medical School Ann Arbor MI United States Department of Pediatrics University of Michigan Medical School Ann Arbor MI United States Department of Neurology University of Michigan Medical School Ann Arbor MI United States Department of Neurology The Johns Hopkins University School of Medicine the Kennedy Institute Baltimore MD United States Department of Pediatrics The Johns Hopkins University School of Medicine the Kennedy Institute Baltimore MD United States

The neuroprotective effects of the strychnine-insensitive glycine receptor antagonist, HA-966, against N-methyl-d-aspartate (NMDA)- and quisqualate (QA)-mediated brain injury were determined in perinatal rats. Postnatal day (PND) 7 rats received intrastriatal injections of NMDA (25 nmol) or QA (100 nmol) and then were administered intraperitoneal (i.p.) injections of varying doses of HA-966 or vehicle 15 min later. Animals were sacrificed 5 days later and the degree of brain injury was calculated by comparison of the weights of injected and contralateral cerebral hemispheres. HA-966 selectively reduced the degree of NMDA-mediated brain injury in a dose-dependent manner. However, HA-966 did not attenuate QA-mediated brain injury. © 1989.

关键词： MK-801 N-Methyl-d-aspartate Neuroprotection Neurotoxicity Phencyclidine Rat brain Strychnine-insensitive glycine receptor

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Organizational Characteristics, Occupational Stress, and Depression in Rural Emergency medical Technicians

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The Journal of Rural Health 1988年第2期4卷 73-83页

作者： Revicki, Dennis A. Whitley, Theodore W. Landis, Sandra S. Allison, E Jackson DENNIS A. REVICKI Ph.D. is a Research Scientist in the Medical Technology Assessment Program of the Human Main Research Centers at Battelle Memo rial Institute and Adjunct Assistant Professor in the Department of Family Medicine at the University of Maryland. For the past six years he has been involved in studies of occupational stress in the health professions. His current research is concerned with the measurement of quality of life and the cost4Ectiveness of medical technology. THEODORE W. WHITLEY Ph.D. is Director of the Division of Research in the Department of Emergency Medicine at the East Carolina University School of Medicine. Dr. Whitley is currently involved in surveying several groups of emergency health care providers to idenufy sources of Occupational satisfaction and stress. E. JACKSON ALLISON JR M.D. M.P.H. is Professor and Chairman of the Department of Emergency Medicine at the East Carolina University School of Medicine. Dr. Allison is a member of the Board of Directors of the American College of Emergency Physicians and is Chairman-Elect cf the Residency Review Committe for Emergency Medicine. He has been actively involved in the improvement of prehospital care in eastern North Carolina for the past seven years. SAMLRA S. LANDIS R.N. MICN is Coordinator of the Division of Emergency Medical Sewices in the Department of Emergency Medicine at the East Cam lina University School of Medicine. Ms. Iandis has been instrumental in developing advanced life support training programs in eastern North Carolina during the past eight years. She is currently responsible for conducting initial training and continuing education programs for prehospital care providers at advanced levels.

A model of organizational characteristics, occupational stress and mental health in emergency medical technicians (EMTs) is developed and tested. Supervisor behavior and work group support are used as predictors of negative role perception. Negative role perception is specified as intervening between the organizational variables and occupational stress. Occupational stress is hypothesized to directly influence depression. Data collected from 250 EMTs is used in a structural equation analysis to estimate model parameters. The sample is mostly male (74%), white (94%), and married (68%). Results suggest that there is a direct relationship between perceived occupational stress and increased depression. Role perception is a critical intervening variable between supervisor behavior, work group support, and occupational stress. The findings suggest that EMTs are more satisfied when supervisory practices result in an environment which encourages open expression and group problem solving. This work environment leads to more supportive relationships among squad members, reduced role ambiguity, and decreased occupational stress and depression. Copyright © 1988, Wiley Blackwell. All rights reserved

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THIAMINE IN NEURAL MEMBRANES ENZYMIC HYDROLYSIS OF THIAMINE DIPHOSPHATE

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JOURNAL OF NEUROCHEMISTRY 1972年第4期19卷 1039-+页

作者： BARCHI, RL BRAUN, PE Department of Biochemistry University of Pennsylvania Philadelphia Pa. 19104. Trainee of the Medical Scientist Training Program.

Abstract— The membrane-associated diphosphatase from rat brain which catalyses the hydrolysis of thiamine diphosphate and nucleoside diphosphate is described. The parallel sub-cellular distribution of thiamine diphosphatase and nucleoside diphosphatase activity and the equal inhibition of both activities by adenosine methylenediphosphonate, a non-hydrolysable structural analogue of ADP, suggests that a single enzyme is involved. The divalent cation requirement and basic kinetic properties of this enzyme have been determined. This nucleoside diphosphatase is not activated by ATP.

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Decoding the Therapeutic Target SVEP1: Harnessing Molecular Trait GWASs to Unravel Mechanisms of Human Disease

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Organizational Psychology and Organizational Behavior 1000年第1期12卷 131-148页

作者： Jared S. Elenbaas Paul C. Lee Ved Patel Nathan O. Stitziel 2Medical Scientist Training Program Washington University School of Medicine Saint Louis Missouri USA 1Center for Cardiovascular Research Division of Cardiology Department of Medicine Washington University School of Medicine Saint Louis Missouri USA email: nstitziel@wustl.edu 3Department of Genetics Washington University School of Medicine Saint Louis Missouri USA

Although human genetics has substantial potential to illuminate novel disease pathways and facilitate drug development, identifying causal variants and deciphering their mechanisms remain challenging. We believe these challenges can be addressed, in part, by creatively repurposing the results of molecular trait genome-wide association studies (GWASs). In this review, we introduce techniques related to molecular GWASs and unconventionally apply them to understanding SVEP1, a human coronary artery disease risk locus. Our analyses highlight SVEP1’s causal link to cardiometabolic disease and glaucoma, as well as the surprising discovery of SVEP1 as the first known physiologic ligand for PEAR1, a critical receptor governing platelet reactivity. We further employ these techniques to dissect the interactions between SVEP1, PEAR1, and the Ang/Tie pathway, with therapeutic implications for a constellation of diseases. This review underscores the potential of molecular GWASs to guide drug discovery and unravel the complexities of human health and disease by demonstrating an integrative approach that grounds mechanistic research in human biology.

关键词： SVEP1 PEAR1 Ang/Tie genetics GWAS disease mechanisms

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Computational Methods for Single-Cell Proteomics

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Biomedical Data Science 1000年第1期6卷 47-71页

作者： Sophia M. Guldberg Trine Line Hauge Okholm Elizabeth E. McCarthy Matthew H. Spitzer 3Gladstone-UCSF Institute for Genomic Immunology San Francisco California USA 2Biomedical Sciences Graduate Program University of California San Francisco California USA 1Department of Otolaryngology–Head and Neck Surgery and Department of Microbiology and Immunology University of California San Francisco California USA email: matthew.spitzer@ucsf.edu 4Helen Diller Family Comprehensive Cancer Center University of California San Francisco California USA 5Institute for Human Genetics Division of Rheumatology Department of Medicine Medical Scientist Training Program and Biological and Medical Informatics Graduate Program University of California San Francisco California USA 6Parker Institute for Cancer Immunotherapy San Francisco California USA 7Chan Zuckerberg Biohub San Francisco California USA

Advances in single-cell proteomics technologies have resulted in high-dimensional datasets comprising millions of cells that are capable of answering key questions about biology and disease. The advent of these technologies has prompted the development of computational tools to process and visualize the complex data. In this review, we outline the steps of single-cell and spatial proteomics analysis pipelines. In addition to describing available methods, we highlight benchmarking studies that have identified advantages and pitfalls of the currently available computational toolkits. As these technologies continue to advance, robust analysis tools should be developed in tandem to take full advantage of the potential biological insights provided by these data.

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The Hippo Pathway in Liver Homeostasis and Pathophysiology

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Pathology: Mechanisms of Disease 1000年第1期16卷 299-322页

作者： Jordan H. Driskill Duojia Pan 2Medical Scientist Training Program University of Texas Southwestern Medical Center Dallas Texas 75390 USA 1Department of Physiology Howard Hughes Medical Institute University of Texas Southwestern Medical Center Dallas Texas 75390 USA email: Jordan.Driskill@UTSouthwestern.eduDuojia.Pan@UTSouthwestern.edu

Studies of the regenerative capacity of the liver have converged on the Hippo pathway, a serine/threonine kinase cascade discovered in Drosophila and conserved from unicellular organisms to mammals. Genetic studies of mouse and rat livers have revealed that the Hippo pathway is a key regulator of liver size, regeneration, development, metabolism, and homeostasis and that perturbations in the Hippo pathway can lead to the development of common liver diseases, such as fatty liver disease and liver cancer. In turn, pharmacological targeting of the Hippo pathway may be utilized to boost regeneration and to prevent the development and progression of liver diseases. We review current insights provided by the Hippo pathway into liver pathophysiology. Furthermore, we present a path forward for future studies to understand how newly identified components of the Hippo pathway may control liver physiology and how the Hippo pathway is regulated in the liver.

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An Expanding Role for Nonvisual Opsins in Extraocular Light Sensing Physiology

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Vision Science 1000年第1期9卷 245-267页

作者： Mutahar Andrabi Brian A. Upton Richard A. Lang Shruti Vemaraju 2Science of Light Center Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA 1The Visual Systems Group Abrahamson Pediatric Eye Institute Division of Pediatric Ophthalmology Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA email: richard.lang@***shruti.vemaraju@*** 3Molecular and Developmental Biology Graduate Program College of Medicine University of Cincinnati Cincinnati Ohio USA 4Medical Scientist Training Program College of Medicine University of Cincinnati Cincinnati Ohio USA 5Division of Developmental Biology Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA 6Department of Ophthalmology College of Medicine University of Cincinnati Cincinnati Ohio USA

We live on a planet that is bathed in daily and seasonal sunlight cycles. In this context, terrestrial life forms have evolved mechanisms that directly harness light energy (plants) or decode light information for adaptive advantage. In animals, the main light sensors are a family of G protein–coupled receptors called opsins. Opsin function is best described for the visual sense. However, most animals also use opsins for extraocular light sensing for seasonal behavior and camouflage. While it has long been believed that mammals do not have an extraocular light sensing capacity, recent evidence suggests otherwise. Notably, encephalopsin (OPN3) and neuropsin (OPN5) are both known to mediate extraocular light sensing in mice. Examples of this mediation include photoentrainment of circadian clocks in skin (by OPN5) and acute light-dependent regulation of metabolic pathways (by OPN3 and OPN5). This review summarizes current findings in the expanding field of extraocular photoreception and their relevance for human physiology.

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