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PubMed1996

Predictive strategy for the rapid structure elucidation of drug degradants.

Structural information on drug degradants and impurities can serve to accelerate the drug discovery and development cycle. Traditional structure elucidation methodologies for obtaining this information are often slow and resource-consuming; therefore, LC/MS profiling and LC/MS/MS substructural analysis methodologies have been developed to rapidly and accurately elucidate structures of impurities and degradants. This work is a further development of methodologies used for the elucidation of degradation products of paclitaxel [K.J. Volk et al., Proc. 9th AAPS Ann. Meeting, 1994, p.29]. In this study cefadroxil was used as a model compound for the evaluation of a predictive strategy for the production and elucidation of impurities and degradants induced by acid, base, and heat, using LC/MS and LC/MS/MS profiling methodology, resulting in an LC/MS degradant database which includes information on molecular structures, chromatographic behavior, molecular weight, UV data, and MS/MS substructural information. Furthermore, libraries such as this can provide a predictive foundation for pre-clinical development work involving drug stability, synthesis, and monitoring.

Cefadroxil↗
PubMed2005

Using a set of strategic indicator systems as a decision-making support implement for establishing a recycling-oriented society. A Taiwanese case study.

UNLABELLED: BACKGROUND, SCOPE AND AIMS: To realize the vision of sustainable development (SD) originating from the 'only one earth' philosophy, and to integrate the conceptions of ecology and sustainability into the planning and decision-making criteria of urban growth management, the establishment of a recycling-oriented society (ROS) is essential. However, before the above intention can be achieved, it is indispensable to develop a system of strategic indicators for supporting a radical reformation of the urban development plan. Therefore, this study, based on the conception of the new urban development pattern ROS, attempted to carefully choose a sample city in Taiwan for launching a preliminary case study, and furthermore designed and proposed a concise and strategy-oriented assessment indicator system termed ROSAIS. ROSAIS, on the one hand, can act as a compass for understanding resource using efficiency and recycling status during city development and, on the other hand, can serve as an implement supporting decision-making for ROS construction. METHODS: According to the definition and spirit of ROS, the structure of ROSAIS should clearly represent the relationship between resources and environment in human activities. The eco-efficiency indicator system (EEIS) and environmental symbiosis indicator system (ESIS) can be considered two key subindicator systems, and are the necessary components of ROSAIS. EEIS chooses the dominant production sectors in urban economic activities to calculate their eco-efficiency (EE). Separately, for obtaining a consensus regarding the framework of ESIS, the questionnaire approaches and expert consultation, together with the research experience and foundation of current relevant studies and indicator systems, are applied when crucial resource and environmental issues and respective indicators are selected. RESULTS AND DISCUSSION: The calculation results of EEIS in this case study indicated that among the three dominant production activities (agricultural, fishery, and animal husbandry sector) the fishery sector has the highest EE, which indicates that the fishery activities and resources significantly influence the sustainability of the economic-environmental system of the sample city. Furthermore, according to a consensus achieved in ESIS, local green spaces, resource recovery, energy consumption pattern change, freshwater conservation and greenhouse effect abatement were considered as the five crucial issues influencing how the case study city can develop into an ES-city. The rate of local green spaces, resource recycling, freshwater conservation and the rate of reduction of nonrenewable energy use as well as carbon dioxide (CO2) emissions were used to evaluate the above five issues. CONCLUSION: This case study is unparalleled in Taiwan. Even in Japan, where ROS legislation has been implemented, this kind of study remains in the preliminary stages. Furthermore, when communicating the indicator results, it is essential to provide the context and countermeasures of the crucial issues that are faced. The two sub-indicator systems proposed in this case study could comply completely with the above-mentioned requirements. For example, the EEIS provides information for achieving a balance between environmental burden and economic benefits among dominant production sectors; the ESIS provides information for setting strategies for overcoming the crucial issues faced. RECOMMENDATION AND OUTLOOK: This study recommends that urban planers should consider the construction of the corresponding strategic indicator system to be indispensable, and makes further use of the indicator results related to the environmental education of residents for identifying and promoting participation with ROS, and turning them into implements for supporting urban SD decision-making. Furthermore, a successful indicator system depends on data availability and quality. This study recommends that urban planers should pay considerable attention to constructing relevant data collection channels, databases and the data quality.

Cities↗
PubMed2000

Mouse-human comparative map resources on the Web.

Comparative maps have been a valuable resource for extrapolating biological information among organisms. The relationship between mouse and human maps provides a framework for integrating information from each species and thereby increasing the utility of all available data such as gene location, structure and function. This review describes the various public resources, both databases and web sites, containing genome-wide mouse-human comparative map information available through the World-Wide Web. We will focus on the use and applicability of these resources in their current form and consider future potential directions.

Animals↗
PubMed1988

Involving human resources in strategic planning.

Too often, human-resources departments are not fully involved in strategic planning. However, any plan that neglects work-force recruitment, structure and motivation is incomplete. The author explains how a human-resources department can strengthen its function and become part of the planning process from the beginning.

Efficiency↗
PubMed1994

A formal analysis of stressor and stress-proneness effects on simple information processing.

This study examined visual information processing under a stressor of recurring loud sound among groups divided according to psychometrically identified stress susceptibility. Formal models of task performance were employed to address several issues concerning stress effects on cognitive functioning. Examined were effects on parallel versus serial processing structure, task-wise processing capacity, strategies of allocating processing resources to task components, and curtailment of processing of relevant task elements. Contrary to prediction, stressor presence generated slightly more rather than less evidence of a parallel versus serial processing structure. There was some suggestion of central-task capacity depletion among more susceptible subjects, in line with certain theoretical positions. Evidence of curtailed exhaustive processing of relevant stimulus items was negative. Most notable was the disruption by stress among susceptible subjects of performance-enhancing strategies of deploying processing resources across the different task components (elements of the visual display and within-trial stages of processing). Such effects have received relatively little attention in this research domain; their investigation is shown to be made tractable, however, through the application of selected formal models of information processing.

Acoustic Stimulation↗
PubMed2004

Structure-function relationship of the extracellular calcium-sensing receptor.

The extracellular calcium-sensing receptor (CaR) originally cloned from bovine parathyroid gland is a G protein-coupled receptor. The physiological relevance of the cloned CaR for sensing and regulating the extracellular calcium concentration has been established by identifying hyper- and hypocalcemic disorders resulting from inactivating and activating mutations, respectively, in the CaR. The cloned CaR has been stably or transiently expressed in human embryonic kidney cells and significant progress has been made in elucidating its regulation and activation process using physiological, biochemical and molecular biological methods. A large collection of naturally occurring CaR mutations offers a valuable resource for studies aimed at understanding the structure-function relationships of the receptor, including functional importance of CaR dimerization. In turn, characterization of these naturally occurring mutations has clarified the pathogenesis of clinical conditions involving abnormalities in the CaR, such as familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.

Allosteric Regulation↗
PubMed2004

[Allocation of resources and restrictive standards in hospitals in the face of economic and personnel shortages].

The allocation of financial resources between both hospitals and the departments within a single hospital follows historically grown structures. Concepts on the basis of well-established factors for the systematic allocation of resources are rarely if ever used. Systematic approaches are needed, especially in times of decreasing resources, but they have to be grounded in a detailed understanding of both the customers and the products offered. The application of standards is a vital factor in order to simultaneously enhance operational efficiency and strategic effectiveness.

Costs and Cost Analysis↗
PubMed2003

Improving parents' early recognition and understanding of infant cranial abnormalities through Web-based 2-D animations of 3-D structures.

A prototype Web site, "HeadStart: a craniosynostosis and positional plagiocephaly resource," was developed to help parents of children with cranial abnormalities access information about their child's condition. An on-line survey of 30 parents confirmed the need for information regarding the early diagnosis and treatment of cranial abnormalities. Three methods of creating the illusion of 3-D in a 2-D interactive animation were investigated. The final prototype Web site was developed using a novel approach to rendering 3-D models for use on the Web using a non-photorealistic rendering technique which emulated a hand-drawn appearance. Many advantages were found when creating 2-D animations based on 3-D files. A formative evaluation with parents revealed that the 3-D feature added to their understanding of cranial structures and led to a more complete understanding of their child's condition. Although the small sample size limits the ability to generalize about the success of including 3-D elements in educational programs, the research demonstrated that involving parents in the development process was successful in prioritizing the program content to fit with their needs.

Comprehension↗
PubMed1999

Structure and function of the extracellular calcium-sensing receptor (Review).

The extracellular calcium-sensing receptor (CaR) originally cloned from bovine parathyroid gland is a G protein-coupled receptor. The physiological relevance of the cloned CaR for sensing and regulating the extracellular calcium concentration has been established by identifying hyper- and hypocalcemic disorders resulting from inactivating and activating mutations, respectively, in the CaR. The cloned CaR has been stably or transiently expressed in human embryonic kidney cells and significant progress has been made in elucidating its biochemical and functional features using physiological, biochemical and molecular biological methods. A large collection of naturally occurring CaR mutations offers a valuable resource for studies aimed at understanding the structure-function relationships of the receptor, including receptor-receptor interactions. In turn, characterization of these naturally occurring mutations has clarified the pathogenesis of clinical conditions involving abnormalities in the CaR, such as familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism, and the physiology of certain cell types, such as keratinocytes.

Humans↗
PubMed2004

Pseudogenes in metazoa: origin and features.

The complete genome sequences with their annotations are a considerable resource in biology, particularly in understanding the global structure of the genetic material at the molecular level. The reason why some eukaryotic genomes contain large quantities of apparently unnecessary DNA, namely pseudogenes, while others seem to invest in more efficient thinning processes or are equipped with protection systems against parasitic elements still remains a mystery. Several genome-wide surveys have been undertaken to identify pseudogenes in the completely sequenced genome, bringing to light some differences both in their amount and distribution. Since pseudogenes are important resources in evolutionary and comparative genomics - as 'molecular fossils' - in this paper, a survey on the origins, features, abundance and localisation of the different pseudogenes is reported. As an example of genes producing processed pseudogenes, some experimental data obtained in the authors' laboratories from the study of a nuclear gene coding for the mitochondrial transcription factor A (mtTFA), a key regulator of mitochondrial biogenesis, are also reported.

Animals↗
PubMed1988

Cluster analysis of amino acid indices for prediction of protein structure and function.

The relationship among 222 published indices representing various physicochemical and biochemical properties of amino acid residues has been investigated by hierarchical cluster analysis. The clustering result is illustrated by the minimum spanning tree, which is conveniently divided into four regions: alpha and turn propensities, beta propensity, hydrophobicity and other physicochemical properties including, among others, bulkiness of amino acid residues. In addition, several subclasses of hydrophobicity scales have been identified: preference of inside and outside, accessible surface area, surrounding hydrophobicity and other mostly experimental scales including transfer free energy, partition coefficients, HPLC parameters and polarity. Representative amino acid indices are identified in each of these groups. The collection of amino acid indices is a useful resource for empirical analyses correlating sequence information with structural and functional properties of proteins. As an example, the indices that best reproduce the amino acid mutation data matrix are searched against this collection.

Amino Acids↗
PubMed2000

A realistic theory of health sector management. The case for critical realism.

To date the practice of health sector management has not been sufficiently theorised. An adequate theory should be able to answer the pre-eminent critique of managerial rationality and ethics mounted by Alasdair MacIntyre in After Virtue and should also offer robust analytical and ethical resources to identify and engage with the social, political, economic and moral issues underlying health sector management. Critical realism with its ontology of generative mechanisms, agency-structure relationships, valorisation of activity and ideology critique offers such resources in an empirically orientated but adequately theorised realist framework. Rather than negate MacIntyre, critical realism incorporates and transcends his key arguments regarding the rationality and ethics of management. This article introduces the main elements of critical realism and clears a conceptual space for the cumulation of critical realist case-studies and managerial craft knowledge.

Ethics, Professional↗
PubMed2001

Is the impact of environmental noise visible in the dynamics of age-structured populations?

Climate change has ignited lively research into its impact on various population-level processes. The research agenda in ecology says that some of the fluctuations in population size are accountable for by the external noise (e.g. weather) modulating the dynamics of populations. We obeyed the agenda by assuming population growth after a resource-limited Leslie matrix model in an age-structured population. The renewal process was disturbed by superimposing noise on the development of numbers in one or several age groups. We constructed models for iteroparous and semelparous breeders so that, for both categories, the population growth rate was matching. We analysed how the modulated population dynamics correlates with the noise signal with different time-lags. No significant correlations were observed for semelparous breeders, whereas for iteroparous breeders high correlations were frequently observed with time-lags of 71 year or longer. However, the latter occurs under red-coloured noise and for low growth rates when the disturbance is on the youngest age group only. It is laborious to find any clear signs of the (red) noise- and age group-specific fluctuations if the disturbance influences older age groups only. These results cast doubts on the possibility of detecting the signature of external disturbance after it has modulated temporal fluctuations in age-structured populations.

Age Factors↗
PubMed1989

Long-range structure of H-ras 1-selected transgenomes.

We have used chromosome-mediated gene transfer (CMGT) and whole cell fusion to derive human-mouse hybrid cells carrying reduced human chromosomes 11, by selecting for expression of the transforming H-ras 1 oncogene. To realize the full potential of these somatic cell genetic techniques as resources for enriched DNA probe isolation and the fine structure mapping of chromosomes, the nature of any molecular rearrangements that may accompany the process of DNA transfer must be understood. We have analyzed the long-range structure of our transgenomes by pulsed field gel electrophoresis (PFGE) and show here that, whereas during cell fusion several megabase pairs (Mb) of DNA can be transferred intact, multiple rearrangements of DNA accompany CMGT even in transgenomes where other methods of analysis gave no indication of such molecular scrambling.

Animals↗
PubMed2005

Finances and well-being: a dynamic equilibrium model of resources.

This study of 513 Dutch farmers tested a dynamic equilibrium model of resources (an extension of the conservation of resources theory; S. E. Hobfoll, 1989, 1998, 2001). With structural equation modeling, the advantages of a 3-wave longitudinal design were comprehensively used, such as addressing bidirectional causal effects and within-individual vs. between-individual change. This allowed for a careful analysis of the management function of resources in the stress process. Results showed that well-being had stronger within-person stability than finances. Increased levels of financial problems temporarily increased psychological distress but not self-reported illness. Conversely, farmers with higher stable baselines of psychological distress also had higher baselines of self-reported illness and experienced more negative changes in their financial situation.

Adult↗
PubMed2005

SuperLigands - a database of ligand structures derived from the Protein Data Bank.

BACKGROUND: Currently, the PDB contains approximately 29,000 protein structures comprising over 70,000 experimentally determined three-dimensional structures of over 5,000 different low molecular weight compounds. Information about these PDB ligands can be very helpful in the field of molecular modelling and prediction, particularly for the prediction of protein binding sites and function. DESCRIPTION: Here we present an Internet accessible database delivering PDB ligands in the MDL Mol file format which, in contrast to the PDB format, includes information about bond types. Structural similarity of the compounds can be detected by calculation of Tanimoto coefficients and by three-dimensional superposition. Topological similarity of PDB ligands to known drugs can be assessed via Tanimoto coefficients. CONCLUSION: SuperLigands supplements the set of existing resources of information about small molecules bound to PDB structures. Allowing for three-dimensional comparison of the compounds as a novel feature, this database represents a valuable means of analysis and prediction in the field of biological and medical research.

Animals↗
PubMed1990

Molecular evolutionary genetics of isozymes: pattern, theory, and application.

Isozyme studies at the population genetics-ecology interface conducted at the Institute of Evolution, University of Haifa, during 15 years, 1974-1989, are reviewed in terms of the evidence, theoretical, and practical implications. These studies involve numerous individuals, populations, species, and higher taxa in nature of plants, animals, and humans tested for variation at 15 to 50 primary isozyme loci. The isozyme studies have been conducted mainly in individuals sampled in natural populations at the local, regional, and global levels. Two of the species studied were wild cereals, the progenitors of wheat and barley in the Near East Fertile Crescent. These studies have been complemented by laboratory controlled a priori experimentation of inorganic and organic pollution biology. The human genetics laboratory compared isozyme structure of Jewish and non-Jewish populations. Our results indicate that: (i) isozyme diversity in nature in abundant, at least partly adaptive, and is oriented and maintained primarily by ecological factors. (ii) Natural selection in action is highlighted by stresses involving among others thermal, chemical, and climatic factors. (iii) Speciation can occur with little change in isozyme diversity. (iv) Jews from diverse countries, and in spite of 2,000 years of Diaspora, retain in the frequencies of some isozymes their Near Eastern origins. (v) Wild cereals harbor rich genetic resources exploitable in breeding either directly as adaptive structures, or indirectly as genetic markers for genotypic production of elite agronomic traits. (vi) Isozymes have been utilized as genetic monitors of marine pollution thereby contributing to environmental quality and conservation. (vii) Isozymes can substantially contribute to conservation biology. (viii) Isozymes have been successfully utilized in constructing molecular phylogenies and in revealing new sibling species. (ix) Future theoretical and practical directions of isozyme studies at the protein and DNA levels are outlined.

Animals↗
PubMedDate not supplied

[Organization and functioning of health services of the IMSS-Solidaridad program].

In this report the organization and performance of the IMSS-Solidaridad Program of Mexico is described. This program is managed by the Mexican Institute for Social Security, which services 10.5 million inhabitants of the rural underserved areas, with federal government resources in 18 states. This study compares the structure and functioning of the IMSS-Solidaridad Program with Local Health Systems, as they have been proposed by the Panamerican Health Organization for country members and by the Ministry of Health of Mexico, particularly in relation to the decision-making process at local level. Some assets and limitations of the IMSS-Solidaridad Program are analyzed and, finally, concrete procedures to improve coordination between the IMSS-Solidaridad Program and other health services for similar populations (populations without social security protection) in Mexico are suggested, with the purpose of using resources more adequately and succeed in the national goal to achieve equity in health.

Health Services Administration↗