Caenorhabditis elegans has two genes, unc-59 and unc-61, encoding septin-family GTPases. Mutations in the septin genes cause defects in locomotory behavior that have been previously attributed to cytokinesis failures ...
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Caenorhabditis elegans has two genes, unc-59 and unc-61, encoding septin-family GTPases. Mutations in the septin genes cause defects in locomotory behavior that have been previously attributed to cytokinesis failures in postembryonic neuroblasts. We find that mutations in either septin gene frequently cause uncoordination in newly hatched larvae in the absence of cytokinesis failures. The septins exhibit developmentally regulated expression, including expression in various neurons at times when processes are extending and synapses are forming. Motor neurons in the mutant larvae display defects in multiple aspects of axonal migration and guidance that are likely to be responsible for the locomotory behavior defects. The septins are also expressed in migrating distal. tip cells, which are leaders for gonad arm extension. Septin mutants affect morphology of the distal tip cells, as well as their migration and guidance during gonadogenesis, These results suggest that septins may be generally required for developmental migrations and pathfinding. (C) 2003 Elsevier Inc. All rights reserved.
Coordinated motor behaviors rely on a maze-like network of axonal connections between motoneurons and the body musculature. Since the time of the Renaissance, scientists have been fascinated by the question of how suc...
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Coordinated motor behaviors rely on a maze-like network of axonal connections between motoneurons and the body musculature. Since the time of the Renaissance, scientists have been fascinated by the question of how such complex, yet stereotypic, connectivity arises during embryogenesis. Here. we review the long journey of motor axons, which traverse diverse territories along predetermined routes riddled with a wealth of divergent pathway options. We conclude that motor axon migration occurs in a stepwise manner, with each step being controlled by local guidance cues, that motor axons rely on some of the same cues that also control axon migration within the CNS, and that, due to species-specific anatomical variations, the cell types providing such local cues may vary. Although studies of motor axon migration have not yet resulted in a complete understanding of the cellular and molecular mechanisms regulating this process, we have come a long way since the days of da Vinci. (C) 2003 Elsevier Inc. All rights reserved.
AIM: To determine factors influencing diagnostic yield in computed tomography (CT)-guided biopsy of lung lesions. MATERIALS AND METHODS: One hundred and ninety-five consecutive CT-guided lung biopsies were performed i...
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AIM: To determine factors influencing diagnostic yield in computed tomography (CT)-guided biopsy of lung lesions. MATERIALS AND METHODS: One hundred and ninety-five consecutive CT-guided lung biopsies were performed in 182 patients between August 1995 and September 2000 and either fine-needle aspirate samples for cytology or core biopsy samples for histology were collected. Procedures were divided into a diagnostic group (true-positive and true-negative results) and a non-diagnostic group (false-positive and false-negative results) and the factors affecting diagnostic accuracy assessed. RESULTS: One hundred and fifty-six lesions (86%) were malignant, and 26 (14%) were benign. More than one biopsy was performed for 12 lesions. One hundred and thirty-two biopsies were true-positive, 27 true-negative and 36 false-negative. No false-positive results occurred in the study. Overall diagnostic accuracy was 81.5%. Significantly more core biopsies than fine-needle aspirates were diagnostic: 93 versus 78% (p < 0.005). No difference was found in frequency of pneumothorax between these two groups. There was a difference in the average depth from the pleural surface of lesions in the diagnostic and non-diagnostic groups, but this did not attain statistical significance: 9.8 versus 17.2 mm (p = 0.054). CONCLUSION: In this study CT-guided lung biopsy core biopsy was a more accurate method of tissue sampling than fine-needle aspiration, and was not associated with an excess of complications. (C) 2003 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
The World Health Organization's International Programme on Chemical Safety (IPCS), the Organization for Economic Cooperation and Development (OECD), and the U.S. Environmental Protection Agency have developed a co...
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The World Health Organization's International Programme on Chemical Safety (IPCS), the Organization for Economic Cooperation and Development (OECD), and the U.S. Environmental Protection Agency have developed a collaborative partnership to foster integration of assessment approaches for human health and ecological risks. This paper presents the framework developed by that group. Integration provides coherent expressions of assessment results, incorporates the interdependence of humans and the environment, uses sentinel organisms, and improves the efficiency and quality of assessments relative to independent human health and ecological risk assessments. The paper describes how integration can occur within each component of risk assessment, and communicates the benefits of integration at each point. The goal of this effort is to promote the use of this internationally accepted guidance as a basis for harmonization of risk assessment.
作者：
Thies, EDavenport, RWUniv Maryland
Dept Biol Program Neurosci & Cognit Sci College Pk MD 20742 USA DESY
Max Planck Unit Struct Mol Biol D-2000 Hamburg Germany
Many external signals influence growth cone motility, pathfinding, and the formation of synapses that lead to the final map formation of the retinotectal system. Chick temporal retinal ganglion cell axons (RGCs) colla...
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Many external signals influence growth cone motility, pathfinding, and the formation of synapses that lead to the final map formation of the retinotectal system. Chick temporal retinal ganglion cell axons (RGCs) collapse and retract after encountering posterior tectal cells in vitro. During this process lateral extensions appear along the RGC axonal shaft. Lateral extensions appear as nascent interstitial axonal branches and also as defasciculating growth cones that are trailing along the pioneer axon. RGC branching controlled by repellent tectal cues has recently been shown to be the critical event in retinotectal map development. The intracellular mechanism underlying this phenomenon, however, is not understood. Inhibiting RhoA with either C3 toxin or inhibiting p160Rock kinase, an effector of RhoA, with Y27632 inhibited collapse, retraction, and the number of axons that showed lateral extensions. Lateral extension length increased significantly. Inhibiting Rac1A and cdc42 with cell permeable peptide inhibitors did not inhibit collapse of growth cones, but did inhibit axon retraction. In addition, the number of axons that showed lateral extensions and lateral extension length were significantly reduced. A dynamic cytoskeleton is necessary to react to incoming guidance information. This study addresses the problems of how growth cone motility and branching or defasciculation are affected by Rho-GTPases as extracellular signals are transmitted to the cytoskeleton. (C) 2002 Wiley Periodicals, Inc.
This study uses National Educational Longitudinal Study data to show that information about higher education, guidance, and essential preparatory actions taken by secondary students influence whether they will attend ...
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This study uses National Educational Longitudinal Study data to show that information about higher education, guidance, and essential preparatory actions taken by secondary students influence whether they will attend post-secondary educational institutions (PEIs) within 2 years of high school graduation, and, if so, what types of institutions. The conceptual framework is embedded in research on college choice and talent loss. Talent loss is described as the occurrence of promising students not reaching their full educational potential. Choice theory attempts to explain the myriad factors contributing to individuals' postsecondary destinations. We find that increased levels of information, guidance, and critical actions taken are positively and significantly associated with initial enrollment in a 4-year PET, as opposed to enrollment in a 2-year PEI (full or part time) or no enrollment. These factors explain a large part of the effect of socioeconomic status on postsecondary destination, controlling for high school achievement.
Decisional guidance is defined as how a decision support system (DSS) influences its users as they structure and execute the decision-making process. It is assumed that decisional guidance has profound effects on deci...
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Decisional guidance is defined as how a decision support system (DSS) influences its users as they structure and execute the decision-making process. It is assumed that decisional guidance has profound effects on decision making, but these effects are understudied and empirically unproven. This paper describes an empirical, laboratory-experinient-based evaluation of the effectiveness of deliberate decisional guidance and its four types. We developed and used a comprehensive model consisting of four evaluation criteria: decision quality, user satisfaction, user learning, and decision-making efficiency. On these criteria, we compared decisional guidance versus no guidance, informative versus suggestive decisional guidance, and predefined versus dynamic decisional guidance. We found that deliberate decisional guidance was more effective on all four criteria;suggestive guidance was more effective in improving decision quality and user satisfaction, and informative guidance was more effective in user learning about the problem domain, whereas dynamic guidance was more effective than predefined guidance in improving decision quality and user learning;and both suggestive guidance and dynamic guidance reduced the decision time.
The Institution of Electrical Engineers (IEE, London, UK) has recently published a professional guidance document on "EMC and Functional Safety". This issue is becoming more important as more safety-related ...
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ISBN:
(纸本)0780365690
The Institution of Electrical Engineers (IEE, London, UK) has recently published a professional guidance document on "EMC and Functional Safety". This issue is becoming more important as more safety-related functions are controlled by electronics, as the electromagnetic environment worsens, and as electronic devices become more susceptible to interference. Meeting EMC immunity standards (e.g. those under Europe's EMC directive) may well be inadequate for safety-related applications. The procedures recommended in this new guide will help compliance with safety and liability legislation for products, vehicles, systems, or large construction projects.
The European EMC Directive is being re-written. This paper describes the requirements in the latest draft where they differ from the current directive, and offers practical guidance to manufacturers to minimise advers...
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ISBN:
(纸本)0780365690
The European EMC Directive is being re-written. This paper describes the requirements in the latest draft where they differ from the current directive, and offers practical guidance to manufacturers to minimise adverse impact, and take advantage of the positive changes.
Excipients are essential components of drug products. They are also potential toxicants. Examples of known excipient-induced toxicities include renal failure and death from diethylene glycol, osmotic diarrhea caused b...
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Excipients are essential components of drug products. They are also potential toxicants. Examples of known excipient-induced toxicities include renal failure and death from diethylene glycol, osmotic diarrhea caused by ingested mannitol, hypersensitivity reactions from lanolin, and cardiotoxicity induced by propylene glycol. Proposals to test or market new drug products in the United States should adequately address the safety of the proposed exposure to the excipients in those products. The specific safety data that may be needed will vary depending upon the clinical situation, including such factors as the duration, level, and route of exposure, but may include acute, repeat-dose, reproductive, and genetic toxicity data, carcinogenicity data, and specialized toxicology information, such as sensitization or local irritation data. Many guidances exist to aid in the development of pharmaceuticals, including the International Conference on Harmonization (ICH) documents and various Food and Drug Administration/Center for Drug Evaluation and Research (FDA/CDER) pharmacology and toxicology guidances. The FDA/CDER has recently adopted a new guidance for industry, "Nonclinical Studies for Development of Pharmaceutical Excipients," which focuses on issues associated with development of safety databases that will support clinical use of excipients in drug products. The new guidance document is introduced and discussed in this article.
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