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PubMed1988

Transposon Tn21 encodes a RecA-independent site-specific integration system.

The IncW plasmid R388 and the DNA region of Tn21 containing the Smr and the Sur genes are capable of RecA-independent recombination. This recombination occurs at a relatively high frequency (up to 10(-4) recombinants per recipient molecule) and results in integration of the two plasmids. No detectable repeats are formed in the process. The crossover points have been confined to a 0.4-kb homologous segment in both plasmids which contains a 59-bp DNA sequence presumably involved in the acquisition of new genes by Tn21 and its relatives (Cameron et al. 1986). It is likely that the recombination occurs precisely at this point. At least one trans-acting function (an integrase) is required for the site-specific recombination. It has been localized to a 1456-bp BstEII-BamHI fragment of Tn21 and can efficiently complement the integration of plasmids containing the integration site.

DNA Transposable Elements↗
PubMed2000

Integrated systems to reduce length of stay for knee and hip joint replacement surgeries.

To reduce length of stay while maintaining quality of care, St. Joseph's Hospital, Hamilton, ON implemented a care path with three discharge options. Two of these discharge options were early discharge to integrated community services. Patients meeting early discharge criteria are discharged home five days post-operatively with follow-up by home care nursing and physiotherapy. Otherwise, patients are discharged on day four to a multi-disciplinary rehabilitation unit at a separate facility. Patients requiring acute medical services for complications or co-morbidity stay in the acute care hospital. A prospective cohort evaluation showed no difference in complications and similar functional outcomes for the three discharge options.

Arthroplasty, Replacement, Hip↗
PubMed2003

Rhinitis and asthma: evidence for respiratory system integration.

The vast majority of patients with asthma have rhinitis, and rhinitis is a major independent risk factor for asthma in cross-sectional and longitudinal studies. The relationships between rhinitis and asthma can be viewed under the concept that the 2 conditions are manifestations of one syndrome, the chronic allergic respiratory syndrome, in 2 parts of the respiratory tract. At the low end of the syndrome's severity spectrum, rhinitis appears to be the sole manifestation, although pathologic abnormalities in the lower airways are already present. At the higher end, rhinitis is worse, and the lower airways disease becomes clinically evident. Once manifested, the 2 conditions track in parallel in terms of severity. This parallel relationship is influenced by many interactions between the nasal and the lower airways: some interactions stem from the fact that the nasal passages play a major homeostatic role by conditioning inhaled air, but perhaps even more important is the bidirectional interaction that results from the systemic inflammation that is produced after local allergic reactions. Successful management of the chronic allergic respiratory syndrome requires an integrated view of the airways and an understanding of their interactions.

Asthma↗
PubMed2004

Changing the world: the design and implementation of comprehensive continuous integrated systems of care for individuals with co-occurring disorders.

This article has described the CCISC model and the process of implementation of systemic implementation of co-occurring disorder services enhancements within the context of existing resources. Four projects were described as illustrations of current implementation activities. Clearly, there is need for improved services for these individuals, and increasing recognition of the need for systemic change models that are effective and efficient. The CCISC model has been recognized by SAMHSA as a consensus best practice for system design, and initial efforts at implementation appear to be promising. The existing toolkit may permit a more formal process of data-driven evaluation of system, program, clinician, and client outcomes, to better measure the effectiveness of this approach. Some projects have begun such formal evaluation processes, but more work is needed, not only with individual projects, but also to develop opportunities for multi-system evaluation, as more projects come on line.

Comorbidity↗
PubMed2005

Glycomics: an integrated systems approach to structure-function relationships of glycans.

In comparison with genomics and proteomics, the advancement of glycomics has faced unique challenges in the pursuit of developing analytical and biochemical tools and biological readouts to investigate glycan structure-function relationships. Glycans are more diverse in terms of chemical structure and information density than are DNA and proteins. This diversity arises from glycans' complex nontemplate-based biosynthesis, which involves several enzymes and isoforms of these enzymes. Consequently, glycans are expressed as an 'ensemble' of structures that mediate function. Moreover, unlike protein-protein interactions, which can be generally viewed as 'digital' in regulating function, glycan-protein interactions impinge on biological functions in a more 'analog' fashion that can in turn 'fine-tune' a biological response. This fine-tuning by glycans is achieved through the graded affinity, avidity and multivalency of their interactions. Given the importance of glycomics, this review focuses on areas of technologies and the importance of developing a bioinformatics platform to integrate the diverse datasets generated using the different technologies to allow a systems approach to glycan structure-function relationships.

Animals↗
PubMed2006

An integrated systems approach for understanding cellular responses to gamma radiation.

Cellular response to stress entails complex mRNA and protein abundance changes, which translate into physiological adjustments to maintain homeostasis as well as to repair and minimize damage to cellular components. We have characterized the response of the halophilic archaeon Halobacterium salinarum NRC-1 to (60)Co ionizing gamma radiation in an effort to understand the correlation between genetic information processing and physiological change. The physiological response model we have constructed is based on integrated analysis of temporal changes in global mRNA and protein abundance along with protein-DNA interactions and evolutionarily conserved functional associations. This systems view reveals cooperation among several cellular processes including DNA repair, increased protein turnover, apparent shifts in metabolism to favor nucleotide biosynthesis and an overall effort to repair oxidative damage. Further, we demonstrate the importance of time dimension while correlating mRNA and protein levels and suggest that steady-state comparisons may be misleading while assessing dynamics of genetic information processing across transcription and translation.

Archaeal Proteins↗
PubMed2004

Evidence for complex system integration and dynamic neural regulation of skeletal muscle recruitment during exercise in humans.

A model is proposed in which the development of physical exhaustion is a relative rather than an absolute event and the sensation of fatigue is the sensory representation of the underlying neural integrative processes. Furthermore, activity is controlled as part of a pacing strategy involving active neural calculations in a "governor" region of the brain, which integrates internal sensory signals and information from the environment to produce a homoeostatically acceptable exercise intensity. The end point of the exercise bout is the controlling variable. This is an example of a complex, non-linear, dynamic system in which physiological systems interact to regulate activity before, during, and after the exercise bout.

Exercise↗
PubMed2006

Advancing health system integration through supply chain improvement.

Collaboration is a key element to success in the provision of sustainable and integrated healthcare services. Among the many initiatives undertaken to improve service quality and reduce costs, collaboration among hospitals in Ontario has been difficult to achieve; however, voluntary collaboration is vital to achieving transformation of the magnitude envisioned by system leaders.

Cooperative Behavior↗
PubMed1984

Heart, lungs, and blood as an integrated system: the alveolar-capillary barrier and the cardiorespiratory apparatus.

The living organism is complex and depends on information transfer for its effective operation. One way to regard the organism is as a biological hierarchy in which each level not only serves a particular, circumscribed function but also contributes in an important way to the integrated performance of the organism as a whole. Two levels in the organization of biological functions are discussed to illustrate the principle of biological hierarchy: a subsidiary role, as exemplified by the role of the lungs in water and macromolecular exchange, and a primary function, as typified by the integrated performance of the cardiorespiratory apparatus in accord with the metabolic needs of the whole body. This hierarchical approach not only preserves the perspective for appreciating the coordinated behavior of the normal individual but also provides a vantage for assessing derangements produced by disease at any level in the biological hierarchy.

Blood↗
PubMed2000

Dynamic optimal control of homeostasis: an integrative system approach for modeling of the central nitrogen metabolism in Saccharomyces cerevisiae.

The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the source of the cellular amino acids and proteins, including flavors and potentially valuable biomolecules; therefore, it is also of industrial interest. In the DOMC approach the cell is regarded as an optimally controlled system. Given the metabolic genotype, the cell faces a control problem to maintain an optimal flux distribution in a changing environment. The regulation is based on strategies and balances feedback control of homeostasis and feedforward regulation for adaptation. The DOMC approach is an integrative, holistic approach, not based on mechanistic descriptions and (therefore) not biased by the variation present in biochemical and molecular biological data. It is an effective tool to structure the rapidly increasing amount of data on the function of genes and pathways. The DOMC model is used successfully to predict the responses of pulses of ammonia and glutamine to nitrogen-limited continuous cultures of a wild-type strain and a glutamine synthetase-negative mutant. The simulation results are validated with experimental data.

Homeostasis↗
PubMed2003

Mechanisms of homing in the fiddler crab Uca rapax. 2. Information sources and frame of reference for a path integration system.

Fiddler crabs Uca rapax are central-place foragers, making feeding excursions of up to several meters from their burrows. This study investigates the sources of directional and distance information used by these crabs when returning to their burrows. We tested the spatial frame of reference (egocentric or exocentric), and the source of spatial information (idiothetic or allothetic) used during homing. We also tested which components of their locomotion they integrated (only voluntary, or voluntary plus reflexive). Fiddler crabs in their natural mudflat habitat were passively rotated during normal foraging behavior using experimenter-controlled disks, before they returned home. Crabs resisted passive rotations on the disk by counter-rotating when the disk turned, which was a compensatory response to unintended movement. Crabs were usually situated eccentrically on the disk, and therefore were also subjected to a translation when the disk rotated. No crab actively compensated for this translation. Crabs that fully compensated for disk rotation made no directional homing error. Crabs that did not fully compensate homed in a direction that reflected their new body orientation. In other words, if we succeeded in reorienting a crab (i.e. it undercompensated for disk rotation), its homing error was equal to the angle by which it had been reoriented, regardless of the magnitude of the optomotor compensation. Computer-modelled crabs, each equipped with a path integrator utilizing different combinations of external (allothetic) and path-related (idiothetic) input, traversed the digitized paths of the real crabs. The home vector computed by the model crab was then compared to the homing direction observed in the real crab. The model home vector that most closely matched that of the real crab was taken to comprise the path integration mechanism employed by fiddler crabs. The model that best matched the real crab gained direction and distance idiothetically (from internal sources such as proprioceptors), and integrated only voluntary locomotory information. Crabs were also made to run home across a patch of wet acetate, on which they slipped and were thus forced to take more steps on the homeward path than theoretically required by the home vector. Crabs whose running velocity across the patch was unusually low also stopped short of their burrow before finding it. Crabs whose running velocity was not impeded by the patch did not stop short, but ran straight to the burrow entrance, as did control crabs that ran home with no slippery patch. We interpret this to mean that the velocity of some crabs was impeded because of slipping, and these therefore stopped short of their burrow after having run out their homing vector. This is positive evidence in support of the hypothesis that path integration is mediated either by leg proprioceptors or by efferent commands, but our data do not allow us to distinguish between these two possibilities.

Animals↗
PubMed1991

Laboratory systems integration: robotics and automation.

Robotic technology is going to have a profound impact on the clinical laboratory of the future. Faced with increased pressure to reduce health care spending yet increase services to patients, many laboratories are looking for alternatives to the inflexible or "fixed" automation found in many clinical analyzers. Robots are being examined by many clinical pathologists as an attractive technology which can adapt to the constant changes in laboratory testing. Already, laboratory designs are being altered to accommodate robotics and automated specimen processors. However, the use of robotics and computer intelligence in the clinical laboratory is still in its infancy. Successful examples of robotic automation exist in several laboratories. Investigators have used robots to automate endocrine testing, high performance liquid chromatography, and specimen transportation. Large commercial laboratories are investigating the use of specimen processors which combine the use of fixed automation and robotics. Robotics have also reduced the exposure of medical technologists to specimens infected with viral pathogens. The successful examples of clinical robotics applications were a result of the cooperation of clinical chemists, engineers, and medical technologists. At the University of Virginia we have designed and implemented a robotic critical care laboratory. Initial clinical experience suggests that robotic performance is reliable, however, staff acceptance and utilization requires continuing education. We are also developing a robotic cyclosporine which promises to greatly reduce the labor costs of this analysis. The future will bring lab wide automation that will fully integrate computer artificial intelligence and robotics. Specimens will be transported by mobile robots. Specimen processing, aliquotting, and scheduling will be automated.(ABSTRACT TRUNCATED AT 250 WORDS)

Artificial Intelligence↗
PubMed2000

TRANSFAC: an integrated system for gene expression regulation.

TRANSFAC is a database on transcription factors, their genomic binding sites and DNA-binding profiles (http://transfac.gbf.de/TRANSFAC/). Its content has been enhanced, in particular by information about training sequences used for the construction of nucleotide matrices as well as by data on plant sites and factors. Moreover, TRANSFAC has been extended by two new modules: PathoDB provides data on pathologically relevant mutations in regulatory regions and transcription factor genes, whereas S/MARt DB compiles features of scaffold/matrix attached regions (S/MARs) and the proteins binding to them. Additionally, the databases TRANSPATH, about signal transduction, and CYTOMER, about organs and cell types, have been extended and are increasingly integrated with the TRANSFAC data sources.

Database Management Systems↗