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Improving RNA Secondary Structure Prediction Through Expanded Training Data.

In recent years, deep learning has revolutionized protein structure prediction, achieving remarkable speed and accuracy. RNA structure prediction, however, has lagged behind. Although several methods have shown some success in predicting RNA secondary and tertiary structures, none have reached the accuracy observed with contemporary protein models. The lack of success of these RNA structure prediction models has been proposed to be due to limited high-quality structural information that can be used as training data. To probe this proposed limitation, we developed a large and diverse dataset comprising paired RNA sequences and their corresponding secondary structures. We assess the utility of this enhanced dataset by retraining on a deep learning model, SincFold. We find that SincFold exhibited improved generalization to some previously unseen RNA families, enhancing its capability to predict accurate de novo RNA secondary structures. The RNASSTR dataset provides a substantial advance for RNA structure modeling, laying a strong foundation for the development of future RNA secondary structure prediction algorithms.

Journal Article↗

Europe supports UK government in putting quality at the heart of health care.

The new government drive for quality to be at the heart of health care is discussed, following which an insight into the membership and remit of the new European Health-Care Working Group is given. The article also provides a brief description of the European Foundation for Quality Management model and the benefits associated with applying self-assessment as a tool for attaining business excellence. Finally, the first stages of the work proposed by the European Health-Care Working Group is highlighted along with the potential effect on health care within the UK.

Delivery of Health Care↗

CAPPS II: the foundation of aviation security?

A new computer system is being developed to classify U.S. air travelers by the degree of terrorist threat they might pose. Reports indicate that the system--called CAPPS II--would use large amounts of information about each passenger, perhaps including such personal details as his or her magazine-subscription behavior. We argue that what is publicly known about CAPPS II raises questions about how substantially the system would improve aviation security. We discuss conditions under which CAPPS II could yield safety benefits, but suggest that it might be more prudent to view the system as one component of future security arrangements rather than the centerpiece of these arrangements.

Accidents, Aviation↗

Spectroscopic and microscopic characteristics of human skin autofluorescence emission.

To improve the understanding of human skin autofluorescence emission, the spectroscopic and microscopic characteristics of skin autofluorescence were studied using a combined fluorescence and reflectance spectroanalyzer and a fiber optic microspectrophotometer. The autofluorescence spectra of in vivo human skin were measured over a wide excitation wavelength range (350-470 nm). The excitation-emission matrices of in vivo skin were obtained. An excitation-emission maximum pair (380 nm, 470 nm) was identified. It was revealed that the most probable energy of skin autofluorescence emission photons increases monotonically and near linearly with increasing excitation photon energy. It was demonstrated that the diffuse reflectance, R, can be used as a first order approximation of the fluorescence distortion factor f to correct the measured in vivo autofluorescence spectra for the effect of tissue reabsorption and scattering. The microscopic in vitro autofluorescence properties of excised skin tissue sections were examined using 442 nm He-Cd laser light excitation as an example. It was demonstrated that the fluorophore distribution inside the skin tissue is not uniform and the shapes of the autofluorescence spectra of different anatomical skin layers vary. The result of this study confirms that the major skin fluorophores are located in the dermis and provides an excellent foundation for Monte Carlo modeling of in vivo autofluorescence measurements.

Fluorescent Dyes↗

The human physiome as an information environment.

Modern biology is rapidly laying the foundation necessary for integrated modeling of physiological processes in living organisms. The human physiome project attempts to model interactions between biochemicals, cellular organelles, cells, tissues, and organs within whole organisms. One of the first challenges that this project faces is the development of a database environment flexible enough to accommodate the diversity in structure and content of physiological data. This paper reviews the current state of database technology, presents our understanding of the physiome database problem, and proposes a preliminary strategy for addressing it.

Computer Simulation↗

Engraftment of immune-deficient mice with human hematopoietic stem cells.

A system in which immune-deficient mice are repopulated with cells from the human myeloid lineage, and that provides an in vivo stem cell assay for human hematopoietic cells is described. Generation of the chimeric human/immune-deficient (HID) mice was dependent on the use of immune-deficient bg/nu/xid mice. Infusion of these mice with human bone marrow gave rise to increases in human macrophage progenitors during more than 5 weeks of in vivo growth, indicating the seeding, proliferation, and differentiation of human stem cells. The human identity of the progenitors was confirmed by sequence analysis and their dependence on human growth factors. The creation of HID mice lays the foundation for establishing animal models for a wide variety of human hemopathies, from leukemia to infectious disease.

Animals↗

A developmental metatheory of psychopathology.

The author proposes an integrative model of psychopathology in light of the contemporary need to bridge diverse ideological frameworks. This model has its major foundations in drive, ego, object relations, and self psychoanalytic perspectives as they impact upon interactional patterns of infancy. The chronology of these theoretical orientations is presented as parallel to a changing focus upon different successive stages in the course of individual development. The longstanding controversy between conflict and deficit theories, which undergirds the various schools of thought, is addressed: a developmental orientation is offered as the overriding conceptual connection between them. Conflict and deficit phenomena are regarded as intertwined and not incompatible: Unconscious drives, desires and wishes, ego defenses, and compromise formations as well as object relationship deficiencies and structural voids and defects in the self are combined to encompass a broad spectrum of psychopathology and its sources: the above intrapsychic and interpersonal factors are interfaced with significant reciprocal dyadic (mother/child) and triadic (father/mother/child) influences upon ongoing maturational processes. For heuristic purposes, a fourfold matrix--dyadic deficit, dyadic conflict, triadic deficit, and triadic conflict--is delineated. Clinical characteristics and developmental precursors of each of the four prototypes, especially with regard to early relational events, are examined.

Conflict, Psychological↗

"This is a Spiritual Experience": perspectives of Latter-Day Saint families living with a child with disabilities.

The presence of a child with disabilities elicits a variety of stress demands on the family. Religion is recognized as a powerful personal, family, and cultural variable. However, little is known about the influence of religion in dealing with disability among families within particular religious groups. This descriptive study explored themes of spiritual belief and religious support among families of the Church of Jesus Christ of Latter-Day Saints (LDS, or Mormon) with a child with developmental disabilities. Parents shared perspectives of meaning that emerged from experiences with religion and family beliefs perceived to be unique. The core theme, "This is a Spiritual Experience," provides the foundation for a descriptive model that depicts aspects of finding meaning and perceived transcendence.

Adaptation, Psychological↗

Susceptibility of avian ovarian granulosa cells to apoptosis is dependent upon stage of follicle development and is related to endogenous levels of bcl-xlong gene expression.

Studies were conducted to evaluate the susceptibility of avian ovarian granulosa cells to apoptosis when incubated in vitro and to relate this relative susceptibility to both the stage of follicle development from which granulosa cells were collected (atresia-prone vs. -resistant) and to the expression of a gene previously linked to the regulation of cell viability, bcl-xlong. Granulosa cells from slow growing, prehierarchal (4- to 8-mm diameter; atresia-prone) follicles were found to undergo rapid and progressively extensive apoptosis after incubation in defined medium for 6-24 h (P < 0.05 vs. unincubated controls). By contrast, cells from the largest preovulatory (F1) follicle, as well as from follicles most recently recruited into the follicle hierarchy (9- to 12-mm diameter), showed significantly less low molecular wt labeling at 6 h of incubation (P < 0.05 vs. 4- to 8-mm follicles). Furthermore, the amount of low molecular wt labeling did not significantly increase in cells from either stage of follicle development at 12 or 24 h of incubation (P < 0.05 vs. 6 h incubation). This biochemical indication of ongoing apoptosis in prehierarchal follicle granulosa cells was confirmed by an increased incidence of pyknotic nuclei detected by morphological analysis. Thus, increased susceptibility to apoptosis in incubated prehierarchal follicle granulosa cells is correlated with the high rate of follicle atresia that is known to occur at this stage of development in vivo. Recombinant human FSH (100 mIU) and transforming growth factor-alpha (3.3 nM) partially suppressed apoptosis in prehierarchal follicle granulosa cells after 6 h of incubation (by 46-57%; P < 0.05 vs. control), as did the cAMP analog, 8-Br-cAMP (1 mM; by 59%; P < 0.05). A single form of the bcl-2-related gene, bcl-x, was detected in hen ovarian tissues; this transcript corresponded to bcl-xlong, the death-suppressing form of bcl-x. The highest levels of bcl-xlong messenger RNA were found in granulosa tissue from preovulatory follicles, with significantly lower levels detected in prehierarchal follicle granulosa tissue (P < 0.05). Elevated expression of bcl-xlong in preovulatory follicles was correlated to increased resistance to the process of apoptosis, in vitro, and the virtual absence of follicle atresia at this stage of development, in vivo. We conclude that there is a direct relationship between the inherent susceptibility of avian granulosa cells to apoptosis and the high rate of follicle atresia in follicles not yet selected into the preovulatory hierarchy. Moreover, our results are consistent with the proposal that the expression of death-suppressing genes, including bcl-xlong, is capable of rendering cells resistant to the process of apoptosis. The findings reported herein provide the foundation for a novel model with which to further elucidate molecular mechanisms related not only to the initiation of follicle atresia, but also events associated with the process of follicle selection.

Alternative Splicing↗

Toward atomic-scale understanding of ligand recognition in the muscle nicotinic receptor.

The nicotinic receptor at the motor endplate has served as a prototype for understanding structure, function and ligand recognition in the superfamily of pentameric ligand-gated ion channels. Yet despite this advanced state of knowledge, atomic-scale understanding of such elementary processes as ligand recognition has remained elusive owing to the lack of a high-resolution x-ray structure. However, the field has recently entered a state of rapid advancement following the discovery and atomic structural determination of the water-soluble acetylcholine binding protein (AChBP), a homolog of the receptor ligand binding domain. The AChBP structure provides the theoretical foundation for generating homology models of the corresponding receptor ligand binding domains within this structural family of receptors. Experimental assignment of residue equivalence between AChBP and receptor subunits subsequently yielded homology models ready for experimental testing. One such test is computational determination of ligand docking orientation in conjunction with mutagenesis of predicted contact residues and measurements of ligand binding affinity. Applied to different analogs of the competitive antagonist curare, docking computations that incorporate intrinsic protein flexibility reveal fundamentally distinct orientations of each analog bound to AChBP. The different contact residues predicted for each analog were tested and confirmed by mutagenesis of AChBP followed by measurements of ligand binding. By applying the same computational and experimental approaches to the adult human muscle AChR, we find that the two curare analogs also dock in distinctly different orientations. Thus subtle structural changes in the ligand, and by extension, structural differences in non-conserved residues among receptor subtypes and species, can dramatically alter the orientation of the bound ligand. The results have important implications for design of drugs targeting nicotinic receptors and members of the superfamily of pentameric ligand-gated ion channels.

Amino Acid Sequence↗

Meeting the continuing education needs of nurses in rural settings.

Access to continuing education (CE) for rural nurses is hampered by distance, cost factors, and the lack of sufficient personnel to provide coverage when nurses are away from work. Additionally, because rural nurses function as generalists rather than specialists, CE programs should focus on the generalist perspective. The Nevada Area Health Education Center (AHEC) has developed a partnership model for providing CE that addresses these considerations, bringing educational programs to the rural site eliminates travel, cost, and coverage problems for the hospitals. In turn, a close working relationship between AHEC and rural personnel to assess needs and coordinate the planning is critical. Attention to logistical detail is critical. The partnership model described is the foundation of a year-round CE program for nurses working in rural and frontier areas.

Education, Nursing, Continuing↗

Assessing the extent of integration achieved through physician-hospital arrangements.

In this article we examine management service organizations (MSOs), physician-hospital organizations (PHOs), hospital-affiliated independent practice associations (IPAs), and hospital-sponsored "group practices without walls" (GPWWs) that allow physicians to retain their practices and link hospitals and health systems to physicians through contractual arrangements. Also examined were medical foundations (MFs), integrated salary models (ISMs), and integrated health organizations (IHOs) that own the physical assets of physician practices and contract with payors for physician and hospital services. The research provides several new insights for understanding the structure and process of physician-hospital integration. It was found that the extent of processual integration in physician-hospital organizational arrangements can be measured along six dimensions: administrative and practice management services; physician financial risk-sharing; joint ventures to create new services; computer linkages; physician involvement in strategic planning; and salaried physician arrangements. These dimensions are consistent with the conceptual and empirical dimensions developed by others. These findings refute the notion raised by some industry observers that the new physician-hospital organizational models simply formalize integrative activities already in place. Earlier studies from the 1980s reported that hospitals integrated physicians through involvement in governance, capital planning, and the provision of practice management services. In contrast, we found that current integration.

American Hospital Association↗

[The reform of primary health care: the economic, care and satisfaction results].

OBJECTIVE: To compare the overall effect on the general public before and after the primary care reform, its economic outcome and professional satisfaction, following the model of the European Foundation for Quality Management. DESIGN: A descriptive analysis of results at reformed primary care centres compared with results at non-reformed centres in the same city. SETTING: The study was conducted at Sant Boi de Llobregat, a town of 77,591 inhabitants in Baix Llobregat county (Barcelona). 32.7% of the population was covered by two reformed centres. The rest was covered by one single non-reformed primary care centre. MEASUREMENTS AND RESULTS: Clinical audits and data on pharmaceutical prescription quality were used to find attendance. For economic results, the formula of attribution of cost/inhabitant and cost/inhabitant seen, including the costs of labour, structure, referral, further tests and pharmacy, were used. The satisfaction of the outside customer (user) was measured by a population survey. Internal customer satisfaction was measured by a survey of the professionals. Results were compared with those for 1997. The study showed that the reformed primary care sector's results, measured in terms of professional satisfaction, user-outside customer, attendance, economic results and social impact, were better than the non-reformed sector's. Inside and outside customers' satisfaction was higher in the reformed network. The cost per inhabitant in the reformed network was 31,874 pesetas, against 25,177 in the non-reformed network. The cost per inhabitant seen was 34,482 and 44,603, respectively. CONCLUSIONS: The reform creates efficient resource management and greater satisfaction of the general public and professionals, when an indicator sensitive to the real use of services is used.

Costs and Cost Analysis↗

[Quality management and consumer orientation: survey of referring pediatricians of a Berlin pediatric clinic].

Quality management in hospitals not only includes performance according to international medical standards but also the optimization of processes regarding internal staff as well as external customers. Total Quality Management (TQM) and the Business Excellence Model of the European Foundation of Quality Management (EFQM) require continuous evaluation of customer satisfaction. Specialists and family physician as external customers influence the patient's choice of a hospital. The aim of the present study is to evaluate the satisfaction of admitting physicians of a children's hospital with the help of a questionnaire. The results describe their needs and their level of satisfaction regarding service, information, cooperation and communication within the hospital.

Berlin↗

[Quantitative assessment of cancer risk following epidemiological studies].

The role of data derived from epidemiological studies in the quantitative assessment of cancer risk has been constantly growing. That results from the fact that epidemiological studies are performed directly on humans so that it is possible to avoid bias very often associated with methods of extrapolation between animals and humans. Moreover, a slow but continuous increase in the number of well designed epidemiological studies with results which can be used to estimate dose-response relationship is being observed. In this paper, the methodological foundations of cancer risk modelling on the basis of epidemiological studies are discussed, and the dose-response relationship based on epidemiological study carried out in an occupational cohort of workers employed in a pulp and paper plant was estimated. The epidemiological study was performed by the team of the Department of Epidemiology, The Nofer Institute of Occupational Medicine, Lódź. Lung cancer was adopted as the effect of occupational exposure. In oder to estimate the increase in cancer risk induced by occupational exposure, the risk for the whole occupational life was calculated by employing the methods of competitive risks, essential relative risks were modelled using Poisson means for data divided into groups, and a Cox proportional-hazards model was used for single data. The analysis indicated, that the data from epidemiological studies render it possible to carry out a more thorough investigation as compared to data obtained from animal experiments. As to the cohort under study, a certain effect of age at which workers enter into exposure on lung cancer risk was observed. A risk 'outfit' the workers bring in at the beginning of their employment is clearly visible in older age groups. A general conclusion drawn from the study may be formulated as follows: epidemiological studies play a major role in assessing the effect of working conditions on the increase in the morbidity risk, however, they are not a panacea for all the problems emerging in the cancer risk assessment in exposed persons. Therefore, information obtained from epidemiological and toxicological studies should supplement and reinforce one another, and data from both sources should be used to obtain the best possible characteristics of risk cancer in humans.

Adult↗

[Construction of gene targeting vector for duplicating p35Nck5a gene and its application in the gene targeting of ES cells].

To duplicating the regulatory subunit p35Nck5a gene of mouse neuronal cdc2-like kinase in embryonic stem (ES) cells, about 12.2 kb of pGDTV vector for p35Nck5a gene duplication was constructed. The linearized pGDTV vectors were transfected into ES cells by electroporation. 245 drug-resistant cell clones were obtained in both G418 and GANC medium and the frequency of surviving cells was 6.22 x 10(-5). The ES cell clones were identified to have duplicated the p35Nck5a gene by use of both PCR and genomic Southern blotting, and the frequency of homologous recombination is 5.08 x 10(-7). The use of negative selection gene (HSV-tk) results in 7-fold increase at selection efficiency. This study lays the foundations of preparing mouse models of Alzheimer's disease.

Alzheimer Disease↗

The development of a survey instrument for community health improvement.

OBJECTIVE: To develop a survey instrument that could be used both to guide and evaluate community health improvement efforts. DATA SOURCES/STUDY SETTING: A randomized telephone survey was administered to a sample of about 250 residents in two communities in Lehigh Valley, Pennsylvania in the fall of 1997. METHODS: The survey instrument was developed by health professionals representing diverse health care organizations. This group worked collaboratively over a period of two years to (1) select a conceptual model of health as a foundation for the survey; (2) review relevant literature to identify indicators that adequately measured the health constructs within the chosen model; (3) develop new indicators where important constructs lacked specific measures; and (4) pilot test the final survey to assess the reliability and validity of the instrument. PRINCIPAL FINDINGS: The Evans and Stoddart Field Model of the Determinants of Health and Well-Being was chosen as the conceptual model within which to develop the survey. The Field Model depicts nine domains important to the origins and production of health and provides a comprehensive framework from which to launch community health improvement efforts. From more than 500 potential indicators we identified 118 survey questions that reflected the multiple determinants of health as conceptualized by this model. Sources from which indicators were selected include the Behavior Risk Factor Surveillance Survey, the National Health Interview Survey, the Consumer Assessment of Health Plans Survey, and the SF-12 Summary Scales. The work group developed 27 new survey questions for constructs for which we could not locate adequate indicators. Twenty-five questions in the final instrument can be compared to nationally published norms or benchmarks. The final instrument was pilot tested in 1997 in two communities. Administration time averaged 22 minutes with a response rate of 66 percent. Reliability of new survey questions was adequate. Face validity was supported by previous findings from qualitative and quantitative studies. CONCLUSIONS: We developed, pilot tested, and validated a survey instrument designed to provide more comprehensive and timely data to communities for community health assessments. This instrument allows communities to identify and measure critical domains of health that have previously not been captured in a single instrument.

Adolescent↗