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PubMed1998

Databases in genomic research.

Genome-related databases have already become an invaluable part of the scientific landscape. The role played by these databases will only increase as the volume and complexity of relevant biology data rapidly expand. We are far enough into the genome project and into the development of these databases to assess their attributes and to reexamine some of the conceptual organizations and approaches they are taking. It is clear that there are needs for both highly detailed and simplified database views, the latter being especially needed to make expert domain data more accessible to nonspecialists.

Animals↗
PubMed1977

Characterization of bacterial growth by means of flow microfluorometry.

By means of flow microfluorometry, the protein and nucleic acid contents of individual bacterial cells may be measured at the rate of several thousand cells per second. Accumulation of such information over a few minutes yields the composition distribution of the microbial population. These distributions have been determined at different times during batch growth of Bactillus subtilis, and the results indicate that the variance of cell composition decreases as the population passes through the exponential into the stationary phase. The relative abundance of endospores and vegetative cells as well as the protein distributions of these subpopulations may be readily determined from flow microfluorometry data. Experimental access to such details of microbial population dynamics should foster improved understanding of cell growth, spore germination, and spore formation kinetics.

Bacillus subtilis↗
PubMed1982

Intellectual property: the control of scientific information.

Control of scientific information is increasingly at the center of legal and administrative disputes, raising questions of sovereignty and secrecy, of proprietary rights over research. Disputes originate from efforts to extend the right of access to data at an early stage of research, from demands for information that threaten confidentiality, from proprietary interests in competitive areas of research, and from government restrictions on the free exchange of scientific ideas. They reflect policy changes with respect to information disclosure, university-industry collaboration, patent rights, and national security. A review of diverse situations that have led to disputes and of efforts to negotiate principles for controlling intellectual property suggests the problems of establishing such principles in the context of the changing role of science.

Confidentiality↗
PubMed2005

Cell signaling: from beginning to end.

The Connections Maps database and the graphical Web interface at Science's STKE for accessing the data represent an emerging Web-based tool through which researchers in cell signaling can share their knowledge with the scientific community. This tool provides a mechanism by which researchers, students, and clinicians can transform information about interactions between biomolecules into knowledge about a cellular process. In 2005, new Pathways were added to the Connections Maps database and several of the existing Pathways were updated.

Cooperative Behavior↗
PubMed2002

The crystal structure of Zn(II)-free Treponema pallidum TroA, a periplasmic metal-binding protein, reveals a closed conformation.

We previously demonstrated that Treponema pallidum TroA is a periplasmic metal-binding protein (MBP) with a distinctive alpha-helical backbone. To better understand the mechanisms of metal binding and release by TroA, we determined the crystal structure of the apoprotein at a resolution of 2.5 A and compared it to that of the Zn(II)-bound form (Protein Data Bank accession code 1toa). apo-TroA shows a conformation even more closed than that of its Zn(II)-bound counterpart due to a 4 degrees tilt of the C-terminal domain (residues 190 through 308) about an axis parallel to the poorly flexible backbone helix. This domain tilting pushes two loops (residues 248 through 253 and 277 through 286) towards the metal-binding site by more than 1 A, resulting in an unfavorable interaction of I251 with D66. To avoid this contact, D66 shifts towards H68, one of the four Zn(II)-coordinating residues. The approach of this negative charge coincides with the flipping of the imidazole side chain of H68, resulting in the formation of a new hydrogen bond. The conformational change of H68, along with a slight rearrangement of D279, a C-terminal domain Zn(II)-coordinating residue, distorts the metal-binding site geometry, presumably causing the release of the bound metal ion. Ligand binding and release by TroA, and presumably by other members of the MBP cluster, differs from the "Venus flytrap" mechanism utilized by bacterial nonmetal solute-binding receptors.

ATP-Binding Cassette Transporters↗
PubMed2004

cis-Acting determinants of heterochromatin formation on Drosophila melanogaster chromosome four.

The heterochromatic domains of Drosophila melanogaster (pericentric heterochromatin, telomeres, and the fourth chromosome) are characterized by histone hypoacetylation, high levels of histone H3 methylated on lysine 9 (H3-mK9), and association with heterochromatin protein 1 (HP1). While the specific interaction of HP1 with both H3-mK9 and histone methyltransferases suggests a mechanism for the maintenance of heterochromatin, it leaves open the question of how heterochromatin formation is targeted to specific domains. Expression characteristics of reporter transgenes inserted at different sites in the fourth chromosome define a minimum of three euchromatic and three heterochromatic domains, interspersed. Here we searched for cis-acting DNA sequence determinants that specify heterochromatic domains. Genetic screens for a switch in phenotype demonstrate that local deletions or duplications of 5 to 80 kb of DNA flanking a transposon reporter can lead to the loss or acquisition of variegation, pointing to short-range cis-acting determinants for silencing. This silencing is dependent on HP1. A switch in transgene expression correlates with a switch in chromatin structure, judged by nuclease accessibility. Mapping data implicate the 1360 transposon as a target for heterochromatin formation. We propose that heterochromatin formation is initiated at dispersed repetitive elements along the fourth chromosome and spreads for approximately 10 kb or until encountering competition from a euchromatic determinant.

Animals↗
PubMed2005

Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A.

Aurora-A, a mitotic serine/threonine kinase with oncogene characteristics, has recently drawn intense attention because of its association with the development of human cancers and its relationship with mitotic progression. Using the gene expression profiles of Aurora-A as a template to search for and compare transcriptome expression profiles in publicly accessible microarray data sets, we identified HURP (encodes hepatoma upregulated protein) as one of the best Aurora-A-correlated genes. Empirical validation indicates that HURP has several characteristics in common with Aurora-A. These two genes have similar expression patterns in hepatocellular carcinoma, liver regeneration after partial hepatectomy, and cell cycle progression and across a variety of tissues and cell lines. Moreover, Aurora-A phosphorylated HURP in vitro and in vivo. Ectopic expression of either the catalytically inactive form of Aurora-A or the HURP-4P mutant, in which the Aurora-A phosphorylation sites were replaced with Ala, resulted in HURP instability and complex disassembly. In addition, HURP-wild-type stable transfectants were capable of growing in low-serum environments whereas HURP-4P grew poorly under low-serum conditions and failed to proliferate. These studies together support the view that the ability to integrate evidence derived from microarray studies into biochemical analyses may ultimately augment our predictive power when analyzing the potential role of poorly characterized proteins. While this combined approach was simply an initial attempt to answer a range of complex biological questions, our findings do suggest that HURP is a potential oncogenic target of Aurora-A.

Amino Acid Sequence↗
PubMed1997

Smart cards--the key to trustworthy health information systems.

Some 20 years after they were first developed, "smart cards" are set to play a crucial part in healthcare systems. Last year about a billion were supplied, mainly for use in the financial sector, but their special features make them of particular strategic importance for the health sector, where they offer a ready made solution to some key problems of security and confidentiality. This article outlines what smart cards are and why they are so important in managing health information. I discuss some of the unique features of smart cards that are of special importance in the development of secure and trustworthy health information systems. Smart cards would enable individuals' identities to be authenticated and communications to be secured and would provide the mechanisms for implementing strong security, differential access to data, and definitive audit trails. Patient cards can also with complete security carry personal details, data on current health problems and medications, emergency care data, and pointers to where medical records for the patient can be found. Provider cards can in addition carry authorisations and information on computer set up.

Computer Security↗
PubMed2002

Assessing community child passenger safety efforts in three Northwest Tribes.

OBJECTIVE: To identify strengths and weaknesses in community based child passenger safety programs by developing a scoring instrument and conducting observations of child restraint use in three Native American communities. SETTING: The three communities are autonomous Tribal reservations in the Pacific Northwest. Their per capita incomes and rates of unemployment are comparable. METHODS: In each community, 100 children under 5 years old were observed for car seat use. A six item community assessment tool (100 points maximum) awarded points for such items as the type (primary or secondary) and enforcement of child restraint laws; availability of car seats from distribution programs; extent of educational programs; and access to data on vehicle injuries. RESULTS: For children from birth to 4 years, the car seat use rate ranged from 12%-21%. Rates for infants (71%-80%) far exceeded rates for 1-4 year old children (5%-14%). Community scores ranged from 0 to 31.5 points. There was no correlation between scores and observed car seat use. One reason was the total lack of enforcement of restraint laws. CONCLUSIONS: A community assessment tool can highlight weaknesses in child passenger efforts. Linking such a tool with an objective measure of impact can be applied to other injury problems, such as fire safety or domestic violence. The very process of creating and implementing a community assessment can enhance agency collaboration and publicize evidence based "best practices" for injury prevention. Further study is needed to address methodologic issues and to examine crash and medical data in relation to community child passenger safety scores.

Accidents, Traffic↗
PubMed2003

Differential ranking of causes of fatal versus non-fatal injuries among US children.

OBJECTIVE: Leading causes of fatal and non-fatal injury among US children aged <15 years were compared. METHOD: A descriptive study was conducted using nationally representative data on injury related deaths (National Vital Statistics System) and on non-fatal injury related emergency department visits (IEDV; National Electronic Injury Surveillance System-All Injury Program). Data were accessed using a publicly available web based system. RESULTS: Annually, an estimated 7100000 pediatric IEDV and 7400 injury deaths occurred. The overall non-fatal to fatal ratio (NF:F) was 966 IEDV:1 death. Among deaths, the leading causes were motor vehicle traffic occupants (n = 1700; NF:F = 150:1), suffocations (n = 1037; NF:F = 14:1), and drownings (n = 971, NF:F = 6:1). Among non-fatal injuries, falls (estimated 2400000) and struck by/against (estimated 1800000) were the most common causes, but substantially less lethal (NF:F = 19000:1 and 15000:1, respectively). CONCLUSIONS: The leading causes of pediatric fatal and non-fatal injuries differed substantially. This study indicates the need for consideration of common causes of non-fatal injury, especially falls.

Accidental Falls↗
PubMedDate not supplied

From data to knowledge through concept-oriented terminologies: experience with the Medical Entities Dictionary.

Knowledge representation involves enumeration of conceptual symbols and arrangement of these symbols into some meaningful structure. Medical knowledge representation has traditionally focused more on the structure than the symbols. Several significant efforts are under way, at local, national, and international levels, to address the representation of the symbols though the creation of high-quality terminologies that are themselves knowledge based. This paper reviews these efforts, including the Medical Entities Dictionary (MED) in use at Columbia University and the New York Presbyterian Hospital. A decade's experience with the MED is summarized to serve as a proof-of-concept that knowledge-based terminologies can support the use of coded patient data for a variety of knowledge-based activities, including the improved understanding of patient data, the access of information sources relevant to specific patient care problems, the application of expert systems directly to the care of patients, and the discovery of new medical knowledge. The terminological knowledge in the MED has also been used successfully to support clinical application development and maintenance, including that of the MED itself. On the basis of this experience, current efforts to create standard knowledge-based terminologies appear to be justified.

Artificial Intelligence↗
PubMed2001

Human genetics on the web.

Use of the World Wide Web ("the web") and our knowledge of human genetics are both currently expanding rapidly. By allowing swift, universal, and free access to data, the web has already played an important role in human genetics research. It has also begun to change the way that information is shared in clinical genetics and, to a lesser degree, affect how education in human genetics occurs. There are scores of web sites helpful to those interested in either research or clinical aspects of human genetics. The web and related communication technologies should continue to play increasingly important roles in human genetics.

Databases, Genetic↗
PubMed1989

Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy. A population-based study in Olmsted County, Minnesota, 1975-1984.

Using the records linkage system of the Mayo Clinic and of the Rochester Epidemiology Project, which accesses diagnostic data on the entire population of Olmsted County, Minnesota, we identified 45 new cases of idiopathic dilated cardiomyopathy (DCM) and 19 new cases of hypertrophic cardiomyopathy (HCM) among county residents for the years 1975-1984. Overall age- and sex-adjusted incidence rates were 6.0/100,000 and 2.5/100,000 person-years, respectively. The incidence of DCM doubled from 3.9/100,000 in the first 5 years to 7.9/100,000 person-years in the last 5 years of study. The corresponding change for HCM was from 1.4 to 3.6/100,000 person-years. Age- and sex-adjusted prevalence rates as of January 1, 1985, for DCM and HCM were 36.5/100,000 and 19.7/100,000 population, respectively. The prevalence of DCM in persons less than 55 years old was 17.9/100,000, over a third of whom were New York Heart Association functional Class III or IV at diagnosis. These estimates may be of value in determining the potential use of health care resources, particularly cardiac transplantation.

Age Factors↗
PubMed1999

Managed care of children with special health care needs: the ABC Program.

Families of children voluntarily enrolled in a managed care program for children with special health care needs receiving SSI and Medicaid benefits and their case managers were surveyed regarding care satisfaction, quality, and access. Claims data were used to compare the cost and utilization of health care before and during program enrollment. Families rated health care quality improved in 43%, unchanged as "excellent" in 50% of cases. The care received was seen as more nearly complete and of higher quality when the provider was based in the hospital or the hospital's community clinics as compared with "private" community pediatricians. Hospitalization decreased, but no decrease in cost was demonstrated. A carefully planned and implemented managed care program can improve patient perception of quality among chronically ill children.

Child↗
PubMed1998

Destruction of serotonergic neurons in the median raphe nucleus blocks circadian rhythm phase shifts to triazolam but not to novel wheel access.

Systematic treatment of hamsters with triazolam (TRZ) or novel wheel (NW) access will yield PRCs similar to those for neuropeptide Y. Both TRZ and NW access require an intact intergeniculate leaflet (IGL) to modulate circadian rhythm phase. It is commonly suggested that both stimulus types influence rhythm phase response via a mechanism associated with drug-induced or wheel access-associated locomotion. Furthermore, there have been suggestions that one or both of these stimulus conditions require an intact serotonergic system for modulation of rhythm phase. The present study investigated these issues by making serotonin neuron-specific neurotoxic lesions of the median or dorsal raphe nuclei and evaluating phase response of the hamster circadian locomotor rhythm to TRZ treatment or NW access. The expected effect of TRZ injected at CT 6 h on the average phase advance was virtually eliminated by destruction of serotonin neurons in the median, but not the dorsal, raphe nucleus. No control or lesioned animal engaged in substantial wheel running in response to TRZ. By contrast, all median raphe-lesioned hamsters that engaged in substantial amounts of running when given access to a NW had phase shifts comparable to control or dorsal raphe-lesioned animals. The results demonstrate that serotonergic neurons in the median raphe nucleus contribute to the regulation of rhythm phase response to TRZ and that it is unlikely that these neurons are necessary for phase response to NW access. The data further suggest the presence of separate pathways mediating phase response to the two stimulus conditions. These pathways converge on the IGL, a nucleus afferent to the circadian clock, that is necessary for the expression of phase response to each stimulus type.

5,7-Dihydroxytryptamine↗
PubMed1979

Drug information--the problems and some solutions.

Several problems evident in the drug information delivery process and some solutions are presented. Major problems with current sources of drug information are accessibility of data, completeness of data, validity of information, appropriateness in the clinical setting, and currency. Better drug information sources are needed to provide rapid answers to patient-related questions routinely occurring in the clinical setting. Currently available mechanisms described to solve existing drug information problems are clinical pharmacologists and specialists, clinical pharmacists, drug information centers, and a computer-output microfiche drug information system (DRUGDEX).

Anticoagulants↗