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The rising cost of health care publications. Why science is becoming a luxury purchase.
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Learning and development in neural networks--the importance of prior experience.
Infants can discriminate between familiar and unfamiliar grammatical patterns expressed in a vocabulary that is distinct from that used earlier during familiarization (Cognition 70(2) (1999) 109; Science 283 (1999) 77). Various models have captured the data, although each required that discrimination be distinct, in terms of the computational process, from familiarization. This article describes a simple recurrent network (SRN), equipped only with the assumption that it should predict what comes next, which models the data without distinguishing between familiarization and discrimination. To accomplish this, the SRN requires pre-training on a range of sequences instantiating different structures and different vocabulary items to those used subsequently during familiarization and test. Pre-training enables the network to avoid replacing structure acquired during familiarization with structure experienced at test. An equivalent enabling condition may underpin infants' resistance to catastrophic interference between the different structures and vocabulary items to which they are exposed.
A neural network based virtual high throughput screening test for the prediction of CNS activity.
A virtual high throughput screening test to identify potentially CNS-active drugs has been developed. Discrimination was based on the knowledge available in databases containing CNS-active (Cipsline from Prous Science) and inactive compounds (Chemical Directory from Sigma-Aldrich). Molecular structures were represented using 2D Unit y fingerprints and a feedforward neural network was trained to classify molecules regarding their CNS activity. The parameterized network was validated by reclassification of the training set elements, by the classification of a test set preselected from the Prous database, and also by the prediction of activity for known CNS drugs not used in the training set but available in the Medchem database (Daylight). These tests revealed that our neural net recognized at least 89% of CNS-active compounds and would be suitable for use in our virtual screening protocol.
Information system linking a medical school with practitioners and hospitals.
A recently established medical information network uses computers and telephone lines to link rural Georgia medical practitioners, Georgia hospitals, and the Mercer University School of Medicine (MUSM) in Macon, Georgia. This network, the Georgia Interactive Network for Medical Information (GaIN), provides a service and educational support system for its members. The GaIN model embodies many of the educational and information management principles endorsed by two reports by the Association of American Medical Colleges: the 1984 report of the Project Panel on the General Professional Education of the Physician and a 1982 project report called "Academic Information in the Academic Health Sciences Center." The design, services, utilization patterns, and results of the GaIN project and implications for the network's future are described. Use of the GaIN has made MUSM students more at ease with computers, has connected MUSM with remote teaching sites and rural practices, and has served as a catalyst for Georgia physicians' investigation of computer applications to support health care delivery in the state.
Use of a moderated international Internet information exchange in the study of male reproduction.
It is clear that modern information technology is having a profound impact on the way researchers and clinicians exchange information. Use of the Internet is one example of how such change can be translated into scientific progress and improved patient care. Androlog, a moderated international information exchange, has proven to be very useful in the transfer of information pertaining to the study and treatment of male reproductive disorders. Allowing instantaneous dispersal of messages to members in 27 countries, this system has become a valuable source of scientific information, as well as an excellent forum for the discussion of a broad range of clinical and laboratory topics. Moderated-user groups such as Androlog are highly applicable to many other areas of urology. Establishment of such an information exchange requires only a modest investment in computer hardware and software and moderators who are willing to perform the necessary tasks of system administration and message review. Given the unique advantages provided by this method of communication, there is little doubt that systems such as Androlog will flourish in the future, providing a valuable tool in the advance of medical science.
White matter and behavioral neurology.
Although the study of higher brain function has traditionally focused on the cortical gray matter, recent years have witnessed the recognition that white matter also makes an important contribution to cognition and emotion. White matter comprises nearly half the brain volume and plays a key role in development, aging, and many neurologic and psychiatric disorders across the life span. More than 100 disorders exist in which white matter neuropathology is the primary or a prominent feature. A variety of neurobehavioral syndromes may result from these disorders; the concept of white matter dementia has been introduced as characteristic of many patients with white matter involvement, and a wide range of focal neurobehavioral syndromes and psychiatric disorders can also be related to dysfunction of myelinated tracts. Understanding the neurobehavioral aspects of white matter disorders is important for clinical diagnosis, treatment, prognosis, and research on brain-behavior relationships. Central to these investigations is the use of modern neuroimaging techniques, which have already provided substantial information on the characterization of white matter and its disorders, and which promise to advance our knowledge further with continued innovation. Diffusion tensor imaging is an exciting method that will assist with the identification of critical white matter tracts in the brain, and the localization of specific lesions that can be correlated with neurobehavioral syndromes. A behavioral neurology of white matter is thus emerging in which clinical observation combined with sophisticated neuroimaging will enable elucidation of the role of white matter connectivity in the distributed neural networks subserving higher brain function.
New measures for new roles: defining and measuring the current practices of health sciences librarians.
The roles of academic health sciences librarians are continually evolving as librarians initiate new programs and services in response to developments in computer technology and user demands. However, statistics currently collected by libraries do not accurately reflect or measure these new roles. It is essential for librarians to document, measure, and evaluate these new activities to continue to meet the needs of users and to ensure the viability of their professional role. To determine what new measures should be compiled, the authors examined current statistics, user demands, professional literature, and current activities of librarians as reported in abstracts of poster sessions at Medical Library Association annual meetings. Three new categories of services to be measured are proposed. The first, consultation, groups activities such as quality filtering and individual point-of-need instruction. The second, outreach, includes activities such as working as liaisons, participating in grand rounds or morning report, and providing continuing education. The third area, Web authoring, encompasses activities such as designing Web pages, creating online tutorials, and developing new products. Adding these three measures to those already being collected will provide a more accurate and complete depiction of the services offered by academic health sciences librarians.
Idiotypic network mimicry and antibody catalysis: lessons for the elicitation of efficient anti-idiotypic protease antibodies.
An important challenge in the field of catalytic antibodies is the generation of antibodies with designed sequence-specific protease activities. Such catalysts would not only be recruited for diverse applications in basic biological science, but could also offer new approaches in biotechnology and medicine. We have previously used the "internal image" property of the idiotypic network to elicit antibodies with efficient esterase and amidase activities. In the present report, we present preliminary results for the production of anti-idiotypic antibodies mimicking subtilisin. A monoclonal inhibitory antibody of subtilisin was characterized and used to elicit anti-idiotypic antibodies. Some of these antibodies exhibit not only an amidase activity against synthetic substrates, but are also able to cleave a protein, bovine serum albumin (BSA).
[Epigenetics: gene and epigene networks in ontogeny and phylogeny].
An attempt was made to systematize theoretical and experimental epigenetic data in the framework of genetics as a science on laws of preservation, coding, transfer, and transformation of heritable information in the living systems. The structure of the total hereditary memory is discussed in context of the theory of epigenes, hereditary units of the next to genes level of complexity. In epigenes as cells of functional hereditary memory, part of the hereditary information is stored, coded, and transmitted to the progeny irrespective of the primary structure of the genomic DNA molecules. The principles of the structure and the general laws of functioning of cellular governing gene networks are presented. The ontogenetic and phylogenetic role of epigene networks as the second level of the hereditary system is considered. Arguments for inheritance of somatic epimutations are presented, as well as the results of in silico and in vivo experiments showing the possibility of an epigenetic mechanism of primary biochemical divergent determination (autodetermination). A network hypothesis on material carriers of the common heterotary memory is formulated.
The brain and the immune system: a psychosomatic network.
The central nervous system (CNS) and the immune system, communicating through the neuroendocrine system, are closely involved in the individual's adaptation to the environment. The data from basic science research and clinical observations are overviewed, and more recent studies are summarized. As changes in immune function may mediate the effects of psychosocial factors in psychosomatic disorders, it is important for all biopsychosocially oriented physicians to understand the network that connects the central nervous and immune systems.
Movies for teaching science. The first public database of scientific films and images for educational use went online this year.
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Application of stable isotopes and mass isotopomer distribution analysis to the study of intermediary metabolism of nutrients.
Genomic investigations in animals have begun to reveal the metabolic and physiological functions of genes and protein products. However, a thorough understanding of the genomic roadmaps will require investigative approaches that yield qualitative and quantitative information on the activities, fluxes, and connectivity of pathways involved in nutrient use in farm animals; that is, the metabolic phenotype. Recently, the commercial availability of stable isotope (13C, 15N, 2H)-labeled compounds and highly accurate mass spectrometers has made it possible to probe the details of metabolic pathways involved in macronutrient use. For years, the biological sciences have exploited uniformly 13C-labeled substrates (e.g., glucose, amino acids, nucleic acids) and 13C-mass isotopomer distribution (MID) in their metabolic investigations, whereas their use in the animal sciences is very limited. When [U-13C] substrates are fed, infused, or added to cell incubations, the 13C-skeletons distribute throughout metabolic networks. 13C-Mass isotopomer distribution in intermediates and end products of the pathways provides a signature of the fluxes and activities of pathway enzymes traveled by the precursor molecule. This paper highlights aspects of animal nutrition and metabolism in which [U-13C] substrates and MID can be applied to investigations of amino acid, carbohydrate, and fat metabolism. We will focus on [U-13C] glucose as a tracer in chickens, fish, sheep, and cell cultures to investigate the interconnectivity of the pathways of macronutrient and nucleic acid metabolism, and provide demonstration of the central position of the Krebs cycle in preserving metabolic flexibility via anaplerotic and cataplerotic sequences. Exploitation of this approach in animal sciences offers endless opportunities to provide missing details of the biochemical networks of nutrient use that may prove to be strictly under genomic control.
Health information multitype library reference referral networking: panacea for the '90s.
Librarians are exploring new approaches to information sharing to cope with a rapidly changing environment dominated by budget cuts, information explosion, and globalization of the economy, science, and culture. In 1990, the University of Illinois at Chicago Library of the Health Sciences (UIC LHS) initiated a pilot project aimed at establishing an effective balance between state-of-the-art information technology and traditional library methods and promoting cooperation among health information professionals by establishing the Health Information Referral Network (HIRN) in the state of Illinois. HIRN's background and development, Internet home page, and networking techniques reviewed in this paper are applicable to multitype libraries and information centers interested in improving information use and the referral process.
The cannabinoid system and cytokine network.
Many advances have been made in the last few years concerning our understanding of the receptors and ligands composing the cannabinoid system. Likewise, the science surrounding cytokine biology has advanced enabling us to measure these proteins more precisely as well as understand and interpret the meaning of changes in their levels. Scientists wishing to study the health consequences of smoking marijuana as well as understand the possible role of endogenous cannabimimetic ligands in immune regulation have continued to study the influence of these substances on the regulation and development of the cytokine network. Research has shown that two major cannabinoid receptor subtypes exist and that subtype 1 (CB1) is expressed primarily in the brain whereas subtype 2 (CB2) is expressed primarily in the periphery. A variety of ligands for these receptors based on the cannabinoid structure have been synthesized and studied as well as low affinity compounds, noncannabinoid ligands, and endogenous ligands derived from fatty acid eicosanoids. Highly selective receptor antagonists have also been introduced and studied. Synthetic, low affinity ligands such as (+)-HU-211 and DMH-11C have been shown to cause anti-inflammatory effects possibly through inhibiting the production and action of TNF-alpha and other acute phase cytokines. In addition, suppression of TNF and other cytokines such as GM-CSF, IL-6, IFNgamma, and IL-12 has also been seen following exposure to high affinity and psychoactive ligands such as marijuana and THC. However, some of these ligands have also been shown to increase rather than decrease interleukins such as IL-1, IL-4, IL-10, and IL-6, cytokines such as TNF-alpha, and chemokines such as IL-8, MIP-1, and RANTES. The endogenous ligand, anandamide, has been shown in culture to either suppress the proliferation response to prolactin or enhance the response to cytokines such as IL-3 and IL-6. This eicosanoid has also been shown to increase the production of interleukins and other cytokines. Cannabinoid receptors have been shown to be involved in some but not all of these effects. It is clear that psychoactive and nonpsychoactive compounds have demonstrated effects in vivo and in vitro on the production and function of a variety of cytokines. Depending upon the model system, these effects are often conflicting, and the involvement of cannabinoid receptors is unclear. However, enough evidence exists to suggest that the cannabinoid system significantly impacts the functioning of the cytokine network, and this association may provide clues to the mechanisms of certain immune diseases and form the basis for new immunotherapies.
Reconstructing phylogenetic networks using maximum parsimony.
Phylogenies - the evolutionary histories of groups of organisms - are one of the most widely used tools throughout the life sciences, as well as objects of research within systematics, evolutionary biology, epidemiology, etc. Almost every tool devised to date to reconstruct phylogenies produces trees; yet it is widely understood and accepted that trees oversimplify the evolutionary histories of many groups of organims, most prominently bacteria (because of horizontal gene transfer) and plants (because of hybrid speciation). Various methods and criteria have been introduced for phylogenetic tree reconstruction. Parsimony is one of the most widely used and studied criteria, and various accurate and efficient heuristics for reconstructing trees based on parsimony have been devised. Jotun Hein suggested a straightforward extension of the parsimony criterion to phylogenetic networks. In this paper we formalize this concept, and provide the first experimental study of the quality of parsimony as a criterion for constructing and evaluating phylogenetic networks. Our results show that, when extended to phylogenetic networks, the parsimony criterion produces promising results. In a great majority of the cases in our experiments, the parsimony criterion accurately predicts the numbers and placements of non-tree events.
Formative years of the Urodynamics Society: reminiscences.
This paper traces the roots and foundations of the Urodynamics Society as a scientific urologic research society back to the postwar information explosion of the 1950s and 1960s. It describes the then-separate islands of science and urologic practice which gradually became amalgamated through interdisciplinary and crossprofessional collaborations and networks, aided by generous government subsidies and wise university policies.
Novel approaches to the analysis of the Maillard reaction of proteins.
The Maillard reaction comprises a complex network of reactions which has proven to be of great importance in both food science and medicine. The majority of methods developed for studying the Maillard reaction in food have focused on model systems containing amino acids and monosaccharides. In this study, a number of electrophoretic techniques, including two-dimensional gel electrophoresis and capillary electrophoresis, are presented. These have been developed specifically for the analysis of the Maillard reaction of food proteins, and are giving important insights into this complex process.