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PubMedDate not supplied

Community orientation, strategic flexibility, and financial performance in hospitals.

The objective of this study was to examine how community orientation and strategic flexibility affect accounting measures of financial performance in acute care hospitals. This cross-sectional study used organizational data from the American Hospital Association, environmental data from the Area Resource File, and financial data from the Healthcare Cost Report Information System. We tested our hypotheses on 1,779 hospitals using OLS regression models that controlled for organizational and environmental factors that might affect financial performance. The community orientation of a hospital had a negative impact on its short-term financial performance. However, the strategic flexibility of a hospital with regard to structure and resources was significantly and positively associated with hospital performance. Our findings are important to healthcare managers. Specifically, although a community orientation is thought to be essential for improving the health of populations, the healthcare market may lack clarity concerning the wants and needs of patients and payers to such a degree that this orientation does not result in improved short-term financial performance. In contrast, when a hospital maintains flexibility in its resource allocations and organizational structure, it can meet changing needs and uncertainties and thereby enhance financial performance.

Community-Institutional Relations↗
PubMed1995

Regional variation in service system performance: comparing the perceptions of key stakeholders.

Area variation studies rarely focus on perceptions of service system performance in their comparative analyses. Using an instrument designed specifically for assessing key stakeholders' perceptions of the performance of mental health service delivery systems, this study compared three areas in Massachusetts that differ significantly with regard to service system structure and resource allocation. Despite these differences, key stakeholders' perceptions of service adequacy, availability, quality, and coordination did not vary substantially, although the findings suggest that to some extent organizational structure may have more effect than resource availability and allocation on perceptions of key stakeholders within the three systems. These differences were also of far less magnitude than differences in hospitalization rates and other more traditional measures of service system performance. The authors argue that stakeholders' perceptions should be considered, along with other standard performance measures, in evaluating service system performance.

Efficiency, Organizational↗
PubMed2002

Gene3D: structural assignment for whole genes and genomes using the CATH domain structure database.

We present a novel web-based resource, Gene3D, of precalculated structural assignments to gene sequences and whole genomes. This resource assigns structural domains from the CATH database to whole genes and links these to their curated functional and structural annotations within the CATH domain structure database, the functional Dictionary of Homologous Superfamilies (DHS) and PDBsum. Currently Gene3D provides annotation for 36 complete genomes (two eukaryotes, six archaea, and 28 bacteria). On average, between 30% and 40% of the genes of a given genome can be structurally annotated. Matches to structural domains are found using the profile-based method (PSI-BLAST). and a novel protocol, DRange, is used to resolve conflicts in matches involving different homologous superfamilies.

Animals↗
PubMed2001

Population structure inhibits evolutionary diversification under competition for resources.

A model is presented that explores how population structure affects the evolutionary outcome of ecological competition for resources. The model assumes that competition for resources occurs within groups of a finite number of individuals (interaction groups), and that limited dispersal of individuals between groups (according to Wright's island model of population structure) results in genetic structuring of the population. It is found that both finite-sized interaction groups and limited dispersal can have substantial effects on the evolution of resource exploitation strategies as compared to models with a single, infinitely large, well-mixed interaction group. Both effects, in general, tend to select for less aggressive competitive strategies. Moreover, both effects also tend to reduce the likelihood of the evolutionary diversification of resource exploitation strategies that often occurs in models of resource competition with infinite populations. The results are discussed in the context of theories of the evolutionary diversification of resource exploitation strategies and speciation.

Biological Evolution↗
PubMed1985

Use of selected toxicology information resources in assessing relationships between chemical structure and biological activity.

This paper addresses the subject of the use of selected toxicology information resources in assessing relationships between chemical structure and specific biological end points. To assist the researcher in how to access the primary literature of genetic toxicology, teratogenesis, and carcinogenesis, three specific specialized information centers are discussed--Environmental Mutagen Information Center, Environmental Teratology Information Center, and Environmental Carcinogenesis Information Center. Also included are descriptions of information resources that contain evaluated (peer-reviewed) biological research results. The U.S. Environmental Protection Agency Genetic Toxicology Program, the International Agency for Research on Cancer Monographs, and the Toxicology Data Bank are the best sources currently available to obtain peer-reviewed results for compounds tested for genotoxicity, carcinogenicity, and other toxicological end points. The value of published information lies in its use. It has become evident that most information cannot be accepted at face value for interpretation and analysis when subjected to stringent quality evaluation criteria. This deficit can be corrected by rigid editorship and the cognizance of authors. Increased interest in alternative methods to in vivo animal testing will be exemplified by use of short-term bioassays and in structure-activity relationship studies. With respect to this latter area, it must be remembered that mechanically (computer generated) derived data cannot substitute, at least at this stage, for data obtained from actual animal testing. The future of structure-activity relationship studies will rest only in their use as a predictive tool.

Carcinogens, Environmental↗
PubMed1998

Integrated enterprise management: a look at the functions, the enterprise, and the environment--can you see the difference?

The performance of an organization is paced by its use of resources, including its ability to acquire, access, and use knowledge. A high-performance organization, more than likely, has structured its resources around process linkages and is characterized by a horizontal organization chart, teams and teamwork, empowerment, and operational excellence. Organizational researchers hypothesize that performance improves with fuzzy internal boundaries, cross-functional participation, and goals anchored in the interests of customers and other external stakeholders. This article looks at the competitive need for more integration of resources and greater sharing of knowledge, the integrated nature of work within emerging types of organizations, how expanded views can improve the marketplace centering of processes and individuals, and how combining a model of integration and individual work challenges thinking and actions in the new environment.

Economic Competition↗
PubMed2003

Enhancing marine natural product structural diversity and bioactivity through semisynthesis and biocatalysis.

In the last several decades the plants, animals and microbes from the marine environment have revealed a portion of what is clearly a tremendous resource for structurally diverse and bioactive secondary metabolites. Many of these extraordinarily sophisticated and bioactive natural products can be isolated in significant quantities without great difficulty. As a result these readily available bioactive natural products provide valuable starting materials for the rational generation of libraries of compounds prepared through semisynthesis and biocatalysis. A review of our work using marine natural products to generate rationally designed compound libraries and their biological activity against infectious diseases, cancer and neurological targets is presented. The marine natural products utilized to date as starting materials consist of compounds from a variety of structural classes and include: aureol, puupehenone, sarcophine, palinurin, and the manzamine alkaloids. The possibility to generate diverse bioactive products beginning with a marine natural product scaffold is a direct result of improvements made in the technologies to harvest samples from the ocean, purify and characterize complex natural products quickly and complete chemical reactions and biotransformations in parallel. As a result the vast resources of the ocean can now be utilized routinely to design and produce countless products to be evaluated as part of drug discovery and development programs.

Animals↗
PubMed2003

Health care leadership in an age of change.

This study examined the leadership practices of a sample of network and hospital administrators in metropolitan Victoria, Australia. It was undertaken in the mid-1990s when the State Liberal-National (Coalition) Government in Victoria established Melbourne's metropolitan health care networks. I argue that leadership, and the process of leading, contributes significantly to the success of the hospital in a time of turmoil and change. The sample was taken from the seven health care networks and consisted of 15 network and hospital administrators. Bolman and Deal's frames of leadership--structural, human resource, political and symbolic--were used as a framework to categorize the leadership practices of the administrators. The findings suggest a preference for the structural frame--an anticipated result, since the hospital environment is more conducive to a style of leadership that emphasizes rationality and objectivity. The human resource frame was the second preferred frame, followed by the political and symbolic. These findings suggest that network and hospital administrators focus more on intellectual than spiritual development, and perhaps this tendency needs to be addressed when educating present and future hospital leaders.

Delivery of Health Care↗
PubMed1992

Regional variation in Medicare hospital mortality.

This study examines variation in severity-adjusted Medicare hospital mortality rates across nine U.S. census regions. The extent to which regional variation is reduced by controlling for differences in hospital resources and structure, county-level population characteristics, and the level of federal SuperPRO-identified hospital quality problems is estimated. Hospital resources, population characteristics, and SuperPro process quality scores are significant predictors of hospital mortality rates, but they do not explain the important, highly significant regional differences observed after controlling for hospital case-mix severity.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1998

Spatial scales of desert locust gregarization.

Central to swarm formation in migratory locusts is a crowding-induced change from a "solitarious" to a "gregarious" phenotype. This change can occur within the lifetime of a single locust and accrues across generations. It represents an extreme example of phenotypic plasticity. We present computer simulations and a laboratory experiment that show how differences in resource distributions, conspicuous only at small spatial scales, can have significant effects on phase change at the population level; local spatial concentration of resource induces gregarization. Simulations also show that populations inhabiting a locally concentrated resource tend to change phase rapidly and synchronously in response to altered population densities. Our results show why information about the structure of resource at small spatial scales should become key components in monitoring and control strategies.

Journal Article↗
PubMed2026

Searching the druggable genome using large language models.

SUMMARY: The druggable genome encompasses the genes that are known or predicted to interact with drugs. The Drug-Gene Interaction Database (DGIdb) provides an integrated resource for discovering and contextualizing these interactions, supporting a broad range of research and clinical applications. DGIdb is currently accessed through structured web interfaces and API calls, requiring users to translate natural-language questions into database-specific query patterns. To allow for the use of DGIdb through natural language, we developed the DGIdb Model Context Protocol (MCP) server, which allows large language models (LLMs) access to up-to-date information through the DGIdb API. We demonstrate that the MCP server improves an LLM's ability to answer questions requiring accurate, up-to-date biomedical knowledge drawn from structured external resources. AVAILABILITY AND IMPLEMENTATION: The DGIdb MCP server is detailed at https://github.com/dgidb/dgidb-mcp-server and includes instructions for accessing the server through the Claude desktop app.

Large Language Models↗
PubMed2026

Searching the Druggable Genome using Large Language Models.

SUMMARY: The druggable genome encompasses the genes that are known or predicted to interact with drugs. The Drug-Gene Interaction Database (DGIdb) provides an integrated resource for discovering and contextualizing these interactions, supporting a broad range of research and clinical applications. DGIdb is currently accessed through structured web interfaces and API calls, requiring users to translate natural-language questions into database-specific query patterns. To allow for the use of DGIdb through natural language, we developed the DGIdb Model Context Protocol (MCP) server, which allows large language models (LLMs) access to up-to-date information through the DGIdb API. We demonstrate that the MCP server greatly enhances an LLM's ability to answer questions requiring accurate, up-to-date biomedical knowledge drawn from structured external resources. AVAILABILITY AND IMPLEMENTATION: The DGIdb MCP server is detailed at https://github.com/griffithlab/dgidb-mcp-server and includes instructions for accessing the server through the Claude desktop app.

Journal Article↗
PubMed2005

An experimental assessment of biodiversity and species turnover in terrestrial vs canopy leaf litter.

Forest canopies support diverse assemblages of free-living mites. Recent studies suggest mite species complementarity between canopy and terrestrial soils is as high as 80-90%. However, confounding variation in habitat quality and resource patchiness between ground and canopy has not been controlled in previous comparative studies. We used experimental litter bags with standardized microhabitat structure and resource quality to contrast the colonization dynamics of 129 mite species utilizing needle accumulations on the ground vs in the canopy of Abies amabilis trees in a temperate montane forest in Canada. Mite abundance and species richness per litter bag were five to eight times greater on the ground than in the canopy, and composition differed markedly at family-, genus-, and species-level. Seventy-seven species (57%) were restricted to either ground or canopy litter bags, but many of these species were rare (n<5 individuals). Of 49 'common' species, 30.6% were entirely restricted to one habitat, which is considerably lower than most published estimates. In total, 87.5% of canopy specialists had rare vagrants on the ground, whereas only 51.9% of ground specialists had rare vagrants in the canopy. Canonical correspondence analysis of mite community structure showed high species turnover through time and a high degree of specialization for early-, mid-, and late-successional stages of litter decomposition, in both ground and canopy mites. In addition, distinct assemblages of ground-specialist mites dominated each elevation (800, 1000, and 1200 m), whereas few canopy-specialist mites had defined elevational preferences. This suggests that canopy mites may have greater tolerance for wide variation in environmental conditions than soil mites. The degree of species turnover between adjacent mountains also differed markedly, with 46.5% turnover of ground species, but 63.4% turnover of canopy species between the two montane areas. While ground and canopy assemblages are similar in total biodiversity, it appears that local mite richness (alpha diversity) is higher on the ground, whereas species turnover between sites (beta diversity) is higher in the canopy.

Acari↗
PubMed2004

A novel database of disulfide patterns and its application to the discovery of distantly related homologs.

Disulfide bonds are conserved strongly among proteins of related structure and function. Despite the explosive growth of protein sequence databases and the vast numbers of sequence search tools, no tool exists to draw relations between the disulfide patterns of homologous proteins. We present a comprehensive database of disulfide bonding patterns and a search method to find proteins with similar disulfide patterns. The disulfide database was constructed using disulfide annotations extracted from SwissProt, and was expanded significantly from 16,736 to 94,499 disulfide-containing domains by an inference method that combines SwissProt annotations with Pfam multiple alignments. To search the database, we define a disulfide description, called the disulfide signature, which encodes both spacings between cysteine residues and cysteine connectivity. A web tool was developed that allows users to search for related disulfide patterns and for subpatterns resulting from the removal of one or more disulfides from the pattern. We explore the possibility of using disulfide pattern conservation to identify protein homologs that are undetectable by PSI-BLAST. Examples include the homology between a sea anemone antihypertensive/antiviral protein and a sea anemone neurotoxin, and the homology between tick anticoagulant peptide and bovine trypsin inhibitor. In both examples, there is a clear structural similarity and a functional relationship. We used the database to find structural homologs for the Cripto CFC domain. The identification of a von Willebrand Factor C (VWFC)-like domain agrees with its functional role and explains mutation data. We believe that the rapid increase in structure determinations arising from structural genomics efforts and advances in mass spectrometry techniques will greatly increase the number of disulfide annotations. This information will become a valuable resource for structural and functional annotations of proteins. The availability of a searchable disulfide pattern database will thus provide a powerful new addition to existing homolog discovery methods.

Amino Acid Sequence↗
PubMed2003

Making decisions for structural genomics.

A large number of structural genomics programmes have been established worldwide with the common aim of large-scale, high-throughput protein structure determination. Due to the considerable challenges posed by the experimental methods of structural determination (primarily X-ray crystallography and nuclear magnetic resonance spectroscopy) it is important to select and prioritise candidate molecules that will maximise the information gained from each new structure. This paper describes the scientific principles that underlie target selection and the various bioinformatics tools that may be employed in such selection procedures. Then follows a discussion of the availability of resources incorporating these methods and a description of the design and application of a purpose-built target selection resource for structural genomics.

Animals↗
PubMed2004

Structural proteomics of the poxvirus family.

Recent concerns over the potential use of variola virus-commonly known as smallpox-and other orthopox viruses as weapons of bioterrorism have increased research efforts towards creating new antiviral drugs and safer more effective vaccines. Here we introduce a new resource for structural information of poxvirus proteins: the poxvirus proteomics database (PPDB). In the PPDB, we leverage recently developed bioinformatics structure prediction tools on a genomic scale and provide results in a publicly accessible format. The current version of the system contains both experimentally determined and predicted information about protein structural features, such as secondary structure and relative solvent accessibility, as well as tertiary structure and homology information. The system is automated to read the primary sequences from the database, produce the new information for each sequence, and update the database monthly and as new tools are incorporated. The PPDB contains detailed information on the open reading frames (ORFs) in the Copenhagen strain of the vaccinia virus genome. The contents of the PPDB can be accessed through a simple web interface. Inclusion of additional poxvirus genomes in the PPDB is in progress. The PPDB has an upward scalable informatics infrastructure that can readily be applied to viral, bacterial, as well as eukaryotic genomes.

Antiviral Agents↗
PubMed1999

Metabolic engineering from a cybernetic perspective. 2. Qualitative investigation of nodal architechtures and their response to genetic perturbation

A cybernetic representation of the branch point development of Stephanopoulos and Vallino is formulated. The model systems are employed to translate the qualitative properties of the nodal control architectures characterized by Stephanopoulos and Vallino into a mathematical context. It is shown that a cybernetic model in which the objective is the independent maximization of the levels of branch point products is consistent with the characterization of a flexible node. In contrast, the rigid control architecture is shown to be equivalent to the maximization of the mathematical product of the branch point products. It has been demonstrated subsequently that cybernetic metabolic network models are capable of predicting the system response to enzymatic amplification. However, given the complicated nature of the subsequent models, a clear illustration of the basic mechanism by which such predictions are manifested is not forthwith. Thus, a second objective of the present work is the examination of the response of the flexible and rigid control architectures to genetic perturbation, specifically enzymatic overexpression, with the expressed aim of elucidating the mechanism by which a cybernetic model predicts metabolic network responsiveness. It is shown that the ramifications of genetic perturbation are transmitted through the cybernetic representation of a metabolic network via the resource allocation structure which acts as the conduit by which regulatory signals are transmitted to seemingly unconnected portions of the network. It is postulated that enzymatic overexpression under an artificial promoter represents, from the perspective of the microorganism, an uncontrollable resource drain that forces the metabolic network control architecture to reevaluate the standing resource allocation policy as implemented via the cybernetic control variables. In biological terms, the reevaluation of allocation policy implies a shift in the level and activity of network enzymes yielding, in some cases, qualitatively different network function. It is our position that, conceptually, this is equivalent to the conventional wisdom that genetic manipulation of a metabolic network is the impetus for shifts in the network functionality, i.e., enzyme levels as well as activity. Thus, this development provides a necessary intellectual precursor for the formulation and analysis of the model systems that follow.

Journal Article↗
PubMedDate not supplied

Modeling changes in red spruce carbon balance and allocation in response to interacting ozone and nutrient stresses.

The simulation model TREGRO was developed to analyze the response of red spruce saplings to multiple stresses, such as drought, nutrient deficiency, and exposure to pollutants. The model provides a method of identifying changes in structural and non-structural carbon resources in the tree that may become measurable only after many years of exposure. The model is based on the assumption that the ability of plants to take up and use carbon, water, and nutrients depends on the interrelationships in availability among the three resources. Consequently, the model simulates the simultaneous cycling of these resources. In the model, the tree is divided into the following compartments: a canopy of leaves grouped by age class, branches, stem, and coarse and fine roots in a number of soil horizons. In each of these compartments we track three carbon pools: living structure, dead structure or wood, and total non-structural carbohydrate. The model calculates the photosynthesis of an entire red spruce tree each hour as a function of ambient environmental conditions and the availability of light, water, and nutrients; the daily redistribution of carbon throughout the plant; and the loss of carbon by respiration and senescence. To accomplish this task, the model tracks the flow of carbon dioxide to the sites of fixation within the leaves, the availability of light in the canopy, water and nutrient resources in each of three soil horizons, and the amounts of these resources taken up by the tree. Soil and plant water potentials, photosynthesis, and leaf respiration are simulated on an hourly timestep; nutrient uptake, allocation and growth are computed on a daily timestep. Through a set of example simulations, we demonstrate how the model can be used to examine the mechanisms by which plants respond to stresses experienced alone and in combination. The model was used to predict the growth decrease and the shifting pattern of carbon allocation expected for an isolated tree exposed to ozone and decreased nutrient availability due to acidic deposition. Decreased nutrient availability resulted in decreased growth and preferential carbon allocation to roots, which helped to alleviate the nutrient stress. Ozone stress also resulted in decreased plant growth but had the opposite effect on allocation patterns, with most of the growth reduction occurring in roots. The effect of simultaneous ozone and nutrient stress on tree growth was less than the sum of the independent single stresses, contrary to our expectation. This modeling approach can aid in evaluating the long-term effect of stress on resource availability, the potential for gradual deterioration of tree health under long periods of stress, and imbalances in growth accompanying shifts in carbon allocation caused by stress.

Journal Article↗