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PubMed2000

Nonlinear dimensionality reduction by locally linear embedding.

Many areas of science depend on exploratory data analysis and visualization. The need to analyze large amounts of multivariate data raises the fundamental problem of dimensionality reduction: how to discover compact representations of high-dimensional data. Here, we introduce locally linear embedding (LLE), an unsupervised learning algorithm that computes low-dimensional, neighborhood-preserving embeddings of high-dimensional inputs. Unlike clustering methods for local dimensionality reduction, LLE maps its inputs into a single global coordinate system of lower dimensionality, and its optimizations do not involve local minima. By exploiting the local symmetries of linear reconstructions, LLE is able to learn the global structure of nonlinear manifolds, such as those generated by images of faces or documents of text.

Algorithms↗
PubMedDate not supplied

Cancer policy framework for: public health assessment of carcinogens in the environment.

Cancer remains at the forefront of public health concerns in the United States and throughout the world. Over the past 20 years a wide range of federal agencies and other organizations have been involved in developing policy statements, classification strategies, and assessment methods to address carcinogenesis and health risks. Each of these documents was developed in response to issues confronted by those organizations in pursuing their mission, often as a direct function of legislative mandates. In pursuing its mandated responsibilities, the Agency for Toxic Substances and Disease Registry (ATSDR) must address public health concerns associated with exposure to carcinogens in the context of all available relevant information. This information includes both technical data as well as science policy positions adopted by the range of organizations with programs germane to the assessment and/or regulation of carcinogens. Because of distinct differences in perspective, practice, and policy dictated by the mandated activities of these organizations and the rapidly evolving understanding of carcinogenesis, apparently divergent positions may be reflected in their conclusions. The differences outlined above, coupled with requests from the public, other agencies, and the private sector for a statement reflecting the Agency's position on science and science policy issues related to cancer, prompted the development of this policy. This document is intended to serve as a framework to guide the Agency in its programs and actions regarding carcinogens and to harmonize such efforts with those of other federal agencies and relevant organizations. This framework reflects an assessment of current practice within the Agency and defines the appropriate roles of conclusions derived by other groups, professional judgment, and emerging scientific principles in ATSDR's public health assessments of exposures to carcinogens. This Cancer Policy Framework is not intended to encompass the development of operational guidelines per se, although the Agency recognizes the utility of such efforts. A central theme of this Cancer Policy Framework is the use of risk analysis as an organizing construct based on sound biomedical and other scientific judgment to define plausible exposure ranges of concern rather than single numerical conclusions that may convey an artificial sense of precision. The development and use of innovative tools for exposure and dose response assessment (with particular emphasis on molecular epidemiology) are also endorsed.

Carcinogens, Environmental↗
PubMed1996

Role of Radiation Therapy and Fluoropyrimidines in the Treatment of Gastrointestinal Malignancies.

BACKGROUND: The use of combined chemotherapy and radiation for gastrointestinal malignancies has several theoretical advantages, and clinical trials to determine the type and extent of clinical benefits have been performed. METHODS: The basic science and clinical trial data evaluating such combinations are reviewed, with an emphasis on the interactions between fluoropyrimidines and radiation. RESULTS: Improved outcomes from chemoradiotherapy have been demonstrated in patients with selected stages of anal, esophageal, rectal, and pancreatic cancer. CONCLUSIONS: Despite these positive results, further work is needed to demonstrate even more effective and less toxic treatment regimens.

Journal Article↗
PubMed2003

Chemoprevention of melanoma: an unexplored strategy.

The incidence and mortality of melanoma has continued to increase steeply-faster than most other preventable cancers in the United States. Current sun protection strategies have yet to reduce this increased incidence and mortality. Chemoprevention, defined as the use of natural or synthetic agents to delay, reverse, suppress, or prevent premalignant molecular or histologic lesions from progressing to invasive cancer, has become an important area in cancer research. Melanoma, with its associated risk factors and its known precursors or premalignant lesions, should lend itself well to chemoprevention. Prerequisites for this research should include determination of the molecular mechanisms of ultraviolet (UV) melanomagenesis; use of animal models to test candidate prevention agents; use of molecular and histologic markers as surrogate end point markers; collection of epidemiological, basic science, or in vitro data on potential chemoprevention candidate drugs; and selection of a high-risk patient population in which to carry out clinical chemoprevention trials. Preliminary data available in all these areas are reviewed. Possible mechanisms and molecular targets for the chemoprevention of UV-induced melanoma are discussed. This recent information should stimulate research in the chemoprevention of melanoma.

Animals↗
PubMed1997

Jean-Martin Charcot and Silas Weir Mitchell.

Although Charcot and Mitchell only met once or possibly twice in Paris (1873 and 1875), they interacted in multiple ways to influence one another's research and the development of nineteenth century neurology. Charcot strongly relied on, and openly credited, Mitchell's important contributions on the fragility of bones in locomotor ataxia when he postulated his own historic concepts on neuropathic arthropathies (Charcot joints). Mitchell likewise referred to Charcot in his texts and manuscripts, although his comments were not always complementary. Most notably, Mitchell publicly criticized Charcot for wrongfully claiming precedence over Americans (i.e., Mitchell himself) in the development of isolation therapy. The two men shared many specific neurologic interests, especially the effects of trauma and disorders affecting women, including hysteria. In the development of clinical neurology as a new scientific field, Charcot and Mitchell were both strong empiricists who distrusted theory but believed that clinical medicine, and specifically neurology, required continued infusion of new data from the laboratory sciences. Both men were exemplary teachers, Mitchell primarily a preceptor and supervisor of doctors outside the university system and Charcot the first European professor of clinical neurology and head of the celebrated School of the Salpêtrière.

France↗
PubMed2001

Charting the map of life.

Scientists expect that mapping the human genome will lead to a host of innovations in biology and research. For example, it may become possible to use DNA microarrays to accurately diagnose cancer and infectious disease subtypes and to predict clinical outcomes. Scientists might also use the genome to look at the interactions of the environment, genetic makeup, and toxic exposures, including the ability of certain beneficial genes to detoxify the body and resist disease. But despite the great potential of the field of genomics, scientists caution that public expectations need to be tempered by reality. People are as much a product of their environment as they are of their genes, say experts, and to suggest that genetics is the sole determinant that defines humans as individuals stretches the science beyond the current data.

Animals↗
PubMed2001

Nonpeptide endothelin antagonists in clinical development.

Endothelins (ET-1, ET-2 and ET-3) are 21-amino-acid peptides with two disulfide bonds that belong to the sarafotoxin family. ET-1, ET-2 and ET-3 are produced endogenously from preproendothelin to give big endothelins, which are cleaved by endothelin-converting enzyme (ECE) to yield the active protein. Endothelin has been shown to play important physiological and pathological roles by interacting with its G-protein-coupled receptors. There are two cloned ET receptors: the ET(A) receptor, which is selective for ET-1, and the ET(B) receptor, which binds ET-1, ET-2 and ET-3 with similar affinities. Since the discovery of endothelin, and especially since the availability of peptide ET antagonists such as BQ-123 and BQ-788, and nonpeptide compounds such as bosentan, considerable effort has been spent on better understanding the role of endothelin and its receptor antagonists. As a result, endothelin has been implicated in a variety of serious diseases, such as congestive heart failure, hypertension, pulmonary hypertension and prostate cancer. Research in pharmaceutical and biotechnology laboratories has generated many endothelin antagonists with either sulfonamide or triaryl carboxylic acid scaffolds, and a number of ET(A)-selective or nonselective ET(A)/ET(B) endothelin antagonists have entered clinical trials. This article will review the small-molecule ET(A)-selective and nonselective ET(A)/ET(B) antagonists that are under clinical evaluation, and highlight a member of this group of compounds, sitaxsentan. A summary of the medicinal chemistry that led to the identification of sitaxsentan will be presented, followed by selected animal and human clinical trial data. (c) 2001 Prous Science. All rights reserved.

Journal Article↗
PubMed2006

[Study of animal viruses in yeast].

Yeast is often considered to be a model eukaryotic organism, in a manner analogous to E. coli as a model prokaryotic organism. Yeast has been extensively characterized and the genomes completely sequenced. Despite the small genome size, yeast displays most of features of higher eukaryotes. The facts that most of cellular machinery is conserved among different eukaryotes and that the powerful technologies of genetics and molecular biology are available have made yeast model eukaryotic cells in biological and biomedical sciences including virology. Cumulative data indicate that yeast can be a host for animal viruses. I briefly describe yeast gene expression and review viral replication in yeast. Great discovery include complete replication of animal viruses and production of virus-like particle vaccines in yeast. Current studies on yeast focus on identification of host factors and machinery used for viral replication. The studies are based on traditional yeast genetics and genome-wide identification using a complete set of yeast deletion strains.

Animals↗
PubMed2002

Using the human patient simulator to educate students of veterinary medicine.

INTRODUCTION: The human patient simulator has proved to be an effective educational device for teaching physicians and paramedical personnel. METHODOLOGY: To determine whether veterinary medicine students would benefit from similar educational sessions, 90 students each took a turn being the patient's clinician as real-life scenarios were played out on the simulator. The students induced and maintained anesthesia on their patient and monitored vital signs. Several critical events were presented for the students to diagnose and treat as they occurred. All students submitted a written evaluation of the course upon completion. The last 40 students were randomly divided into two groups of 20 students each. The students in Group I experienced the simulator before their clerkship examination, and those in Group II took the examination before their simulator experience. RESULTS: The students rapidly gained confidence in treating their simulated patient. This carried over to the clinical setting, where they appeared to be more confident when anesthetizing live patients. The simulator experience brought together much of the previous didactic material that they had been exposed to so they could appreciate its clinical relevance. The overwhelming response to the simulator experience was positive. The students in Group I had a significantly higher score on the clerkship examination dealing with concepts reviewed by simulation than those in Group II, who engaged in self-study instead of the simulation exercise (p < 0.001). CONCLUSION: We conclude that the human patient simulator was a valuable learning tool for students of veterinary medicine. It was exciting for the students to work with, made them deal with "real-life" scenarios, permitted them to learn without subjecting live patients to complications, enabled them to retrace their steps when their therapy did not correct the simulated patient's problems, and facilitated correlation of their basic science knowledge with clinical data, thus accelerating their ability to handle complex clinical problems in healthy and diseased patients.

Humans↗
PubMedDate not supplied

Student assistance program: a new approach for student success in addressing behavioral health and life events.

College health centers, whether large or small, often find it challenging to provide counseling and supportive services for all students (including remotely located students) 24 hours a day, 7 days a week. Student assistance programs (SAPs) are services provided to students through a contractual arrangement to the university or college as a part of student services. The goal is to address psychosocial concerns that may interfere with academic performance within the realm of short-term counseling. These services range from traditional behavioral health concerns about stress and depressive reactions to how to find child care with foreign-speaking services. In this article, the authors describe a method to provide such short-term counseling to a 2,200-student health-science campus. They present data from 1 year of service as well as the benefits and limitations.

Counseling↗
PubMed1999

Preclinical evaluation of prototype products.

Preclinical evaluation of medical devices (prototype products) offers the opportunity to investigate and study the intended use of device materials. Preclinical evaluation programs are designed to determine the efficacy, safety, and biocompatibility of biomaterials, prostheses, and medical devices. The purpose of safety testing is to determine if a material presents potential harm to the human; it evaluates the interaction of the material with the in vivo environment and determines the effect of the host on the implant. Preclinical evaluation is the determination of the ability of the prototype product to perform with appropriate host response in a specific application, considered from the perspective of human clinical use. Therefore, preclinical data should include materials science and engineering, biology, biochemistry, medicine, host reactions and their evaluation, the testing of biomaterials, and the degradation of materials in a biological environment.

Animals↗
PubMed2006

The use of digital video recorders (DVRs) for capturing digital video files for use in both The Observer and Ethovision.

Before switching a laboratory from analog to digital, for the recording of video files for use in Noldus software such as Ethovision and The Observer, researchers need to proceed with caution. There are obvious advantages in moving to digital recording for behavioral work, including increased storage capacity; no requirement to purchase video tapes; immediate search by date, time, or event; digital images are of higher quality; ability to view study sites remotely by Internet connection; and "smart" features, such as motion detection. But before you throw away your time-lapse video recorders, time code generators, and video multiplexors, there are some important cautions to take account of. Some research groups have bought digital surveillance systems on the assumption that they work with Ethovision and The Observer, only to be disappointed. The vast majority of systems depend on proprietary compression software that must then be converted to work properly in Ethovision or The Observer.

Animals↗
PubMed1999

The PC tachistoscope has 240 pages.

Myors (1998) showed how to combine familiar video page switching with bit-plane layering in video mode 0dh to increase the capacity of the PC tachistoscope from 8 to 32 pages. The present article shows how to combine video page switching with color page switching to implement a 240-page tachistoscope, thus producing an almost eightfold increase in the capacity of the PC tachistoscope. The main limitation of this technique is that the images cannot all be located in the same position on the screen. Complete source code in C is included.

Cognitive Science↗