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At least 811 records · Page 45Linked to original sources

Computer-assisted quality assurance: development and performance of a respiratory care program.

The Departments of Respiratory Care and Medical Informatics at LDS Hospital, Salt Lake City, developed a computer-assisted system (HELP) to monitor the quality assurance (QA) of respiratory care services. The system addresses the immediate needs of patients through a daily medical director's alert report, which allows the medical director to intervene in acute situations as they arise. The department's QA program monitors and evaluates clinical indicators of staff performance in terms of stated policies and procedures. The integrated data base allows functions to be performed without labor-intensive chart reviews.

Hospital Bed Capacity, 500 and over↗

Consistent integration of non-reliable heterogeneous information resources applied to the annotation of transmembrane proteins.

Information agents integrate multiple distributed heterogeneous information sources. The challenging yet unsolved problem that remains, is to ensure the semantic consistency of the integrated data. In this paper we set out to develop a general approach to inconsistency management for information agents. It is implemented as part of the EDITtoTrEMBL system and applied on a large real-world problem in the domain of bioinformatics.

Amino Acid Sequence↗

Patch-clamping arthropod olfactory receptor neurons to study mechanisms of olfactory transduction.

The olfactory organ of arthropods such as lobsters and insects consists of an array of hair-like sensilla located on the antenna. Each sensillum contains from two to several hundred primary olfactory receptor neurons. The receptor neurons can be patch-clamped in three different types of preparations: intact cells in situ, cultured cells and outer dendrites. These preparations permit using a wide range of experimental strategies to study mechanisms of olfactory transduction. The ability to integrate data from three complementary preparations is a particular advantage of using arthropod models to understand how odor information is encoded by the primary receptor cell in olfaction.

Animals↗

Comparison of estimated daily per capita intakes of flavouring substances with no-observed-effect levels from animal studies.

A study was conducted to determine the margins of safety between no-observed-effect levels (NOELs) and daily per capita intake of flavouring substances evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) using the safety evaluation procedure for flavouring substances. The safety evaluation procedure provides a practical method for integrating data on intake, structure-activity relationships, metabolism and toxicity to evaluate flavouring substances. The comparison of NOELs to intake reinforces the fact that the margins of safety between intake of flavouring substances and their representative NOELs is very large. 98% of flavouring substances have margins of safety greater than 1000, illustrating that even if intake was underestimated by several fold, in almost every case, a wide margin of safety would still exist.

Animals↗

The future of bedside monitoring.

Today's intensivists are provided with more information than ever before, yet current monitors present data from multiple sources in a relatively raw form with virtually no intelligent data integration and processing. In the next century, technological advances in miniaturization, biosensors and computer processing, coupled with an improved understanding of critical illnesses at the molecular level, will lead to the development of a new generation of monitors. Monitoring will move from the traditional macroscopic invasive approach to a noninvasive, molecular analysis of evolving critical disease processes. It is likely that disturbances in homeostasis will become known immediately or before they would otherwise be manifest clinically. Nanotechnology will permit monitoring of critical changes in the intracellular environment or the by-products of cellular metabolism and signal messaging. This article discusses monitoring technologies that hold promise for further development in the next century and point out techniques likely to be abandoned.

Artificial Intelligence↗

The psychopathological model of mental retardation: theoretical and therapeutic considerations.

Mental retardation has heterogenous elements including genetic-biological and environmental factors that occur in a complex relationship. One construction commonly utilized is the overlapping etiologies, pathogenesis, and symptomatology in a bio-psycho-social model framework. A new integrated bio-psycho-social model we call "universe line" provides the possibility of integrating data from different research areas, specially cognitive and psychopathologic indicators. However, further methodology to refine and experimentally verify that model need to be elaborated. Implications of this theoretical approach are discussed.

Cognition↗

Recent developments in biological sequence databases.

Biological sequence databases are currently being re-engineered to make them more efficient and easier to use. This re-engineering is also providing an infrastructure to make it easier to interrogate and integrate data from different sources. The net result of this effort should be a great improvement in the power and availability of bioinformatics resources to the general biology community.

Databases, Factual↗

The evolution of protein domains and the organizational complexities of metazoans.

There is an increasingly heated debate on the very existence of a 'universe of exons' and on the types of genomes that existed after the RNA world. What has been lost in the excitement are the biological issues that relate to the rapid emergence of phenotypic novelties. These issues can be examined by integrating data on protein domains and genomic evolution with the geochemical and palaeontological records.

Animals↗

Excitation functions of 125Te(p, xn)-reactions from their respective thresholds up to 100 MeV with special reference to the production of 124I.

Excitation functions of the nuclear reactions 125Te(p, xn) (119,120m, 120g, 121,122,123,124,125)I were measured for the first time from their respective thresholds up to 100 MeV using the stacked-foil technique. Thin samples were prepared by electrolytic deposition of 98.3% enriched 125Te on Ti-backing. In addition to experimental studies, excitation functions were calculated by the modified hybrid model code ALICE-IPPE. The experimental and theoretical data generally showed good agreement. From the measured cross section data, integral yields of (123,124,125)I were calculated. The energy range Ep 21 --> 15 MeV appears to be very suitable for the production of the medically interesting radionuclide 124I (T(1/2) = 4.18 d; I(beta)+ = 25%). The thick target yield of 124I amounts to 81 MBq/microA h and the level of 125I-impurity to 0.9%. The 125Te(p,2n)124I reaction gives 124I yield about four times higher than the commonly used 124Te(p,n)124I and 124Te(d,2n)124I reactions. The proposed production energy range is too high for small cyclotrons but large quantities of 124I can be produced with medium-sized commercial machines.

Cyclotrons↗

Raloxifene effects on vasomotor and other climacteric symptoms in postmenopausal women.

Introduction and Objectives: Raloxifene, a novel selective estrogen receptor modulator (SERM), is under investigation for the prevention of osteoporosis in postmenopausal women. Like traditional estrogen replacement therapy, raloxifene has beneficial effects on bone and on serum lipids whereas, in contrast to estrogen's adverse effects in the breast and uterus, raloxifene is an estrogen antagonist in the breast and is nonstimulatory in the uterus. This study examines the effects of raloxifene 60 mg/day compared with placebo on: 1) the incidence of vasomotor symptoms: hot flashes (flushing) and sweating (including night sweats), 2) the severity and time course of hot flashes, and 3) the relation of hot flashes to baseline subject characteristics and study discontinuations. Additionally, the study explores the effects of raloxifene 60 mg/day compared with placebo on other climacteric symptoms that affect the quality of life of postmenopausal women, such as depression, insomnia, mood lability and genitourinary complaints.Methods: Integrated data from five randomized, placebo-controlled studies involving 1,165 healthy, postmenopausal women, with up to 30 months of study drug exposure, were analyzed. The incidence and severity of hot flashes and other climacteric symptoms were compared in patients treated with placebo or raloxifene (60 mg/day) via open-ended, non-directed subject self-assessment questionnaires. Data were analyzed for subgroup-by-therapy interactions using many baseline subject characteristics such as age, body mass index, smoking, alcohol, and years post-menopause, as well as preexisting conditions such as hot flashes, sweating, insomnia, depression, and history of hysterectomy. The overall incidence of other climacteric symptoms were reported as adverse events.Results: The increase in overall incidence of hot flashes in raloxifene-treated (24.6%) and placebo-treated (18.3%) subjects was modest, but statistically significant. However, this difference was significant only during the first 6 months of therapy, raloxifene (20.1%) compared with placebo (14.4%). After 6 months of treatment, there was no statistically significant difference in the incidence of hot flashes between the two treatment groups. The majority of hot flashes in raloxifene-treated subjects were subject-assessed as "mild-to-moderate" in severity (89%). The incidence of hot flashes reported as "severe" did not differ significantly in raloxifene- or placebo-treated subjects. Subgroup analyses revealed the overall incidence of hot flashes to be highest for both raloxifene and placebo-treated subjects, in younger (age < 55 years) women (P =.004), in women who had previously experienced hot flashes (P =.031), and in women having had hysterectomies (P <.001). Within each of these subgroups, there was no statistical difference in the incidence of hot flashes between the raloxifene and placebo groups. Between the two treatment groups, there was no difference in the overall incidence of subject discontinuations from study due to hot flashes. The occurrence of the other common vasomotor symptom, sweating (which includes night sweats), was not statistically different for the raloxifene- or placebo-treated subjects.Genitourinary complaints are often symptoms related to vaginal dryness, such as dyspareunia and decreased libido, as well as other symptoms of vaginitis and leukorrhea. No statistically significant differences occurred for raloxifene- or placebo-treated subjects in reports of these genitourinary symptoms. Similarly, for the other common climacteric symptoms; depression, insomnia, and mood lability, no significant differences in incidence between the raloxifene and placebo treatment groups were observed.Conclusions: Raloxifene (60 mg/day) treatment modestly increased the incidence of hot flashes compared with placebo, however, this difference was only statistically significant during the first 6 months of treatment. There were no differences in the severity of hot flashes between treatment groups, and this symptom did not adversely affect subjects' study participation. In both the raloxifene and placebo treatment groups, young postmenopausal women (age < 55), those with baseline hot flashes, and those with histories of hysterectomy were most likely to experience hot flashes. Raloxifene therapy did not affect the occurrence of other climacteric symptoms commonly affecting the quality of life of women after menopause.

Journal Article↗

Support for Barker hypothesis upheld in rat model of maternal undernutrition during the preimplantation period: application of integrated 'random effects' statistical model.

In response to a recent paper published in Reproductive BioMedicine Online by Walters and Edwards (2003), this study reports the application of a random effects regression analysis for evaluation of integrated data involving maternal and embryo/offspring components. Using this method, it is possible to confirm the conclusions of an earlier study that rat maternal undernutrition during the preimplantation period results in blastocyst cell number reduction and post-natal outcomes, including altered growth rates and elevated blood pressure.

Animals↗

Goals and objectives for molecular pathology education in residency programs. The Association for Molecular Pathology Training and Education Committee.

Increasing knowledge of the molecular basis of disease and advances in technology for analyzing nucleic acids and gene products are changing pathology practice. The explosion of information regarding inherited susceptibility to disease is an important aspect of this transformation. Pathology residency programs are incorporating molecular pathology education into their curricula to prepare newly trained pathologists for the future, yet little guidance has been available regarding the important components of molecular pathology training. We present general goals for pathology training programs for molecular pathology education. These include recommendations to pathology residents for the acquisition of both basic knowledge in human genetics and molecular biology and specific skills relevant to microbiology, molecular oncology, genetics, histocompatibility, and identity determination. The importance of residents gaining facility in integrating data gained via nucleic acid based-technology with other laboratory and clinical information available in the care of patients is emphasized.

Communicable Diseases↗

Development and performance of the diffusive gradients in thin-films technique for the measurement of technetium-99 in seawater.

A novel technique for obtaining time-integrated 99Tc concentrations in seawater has been developed, using diffusive gradients in thin films (DGT). The performance of TEVA resin as a binding agent for 99Tc was investigated via laboratory experiments. The accumulated 99Tc activity per unit area of resin-gel was proportional to both the bulk solution activity and the exposure time for deployments of up to 2 weeks. The response of DGT was found to be independent of solution chemistries over the pH range 3-8 and ionic strength range 0.01-1.3 M. Seawater has pH 8 and ionic strength of approximately 0.7 M; therefore, the potential of the technique for field deployment in seawater was demonstrated. Detection limits of 0.05 and 0.025 Bq L(-1), for 2- and 4-week DGT deployments, respectively, were calculated for 99Tc measurement by liquid scintillation spectrometry. Using quadrupole ICPMS to measure bound 99Tc could reduce these detection limits to 0.125 mBq L(-1) for a 4-week deployment. These detection limits are sufficiently low for monitoring contaminated environments, including the Irish Sea. This method is simpler and faster than other 99Tc analysis methods and represents the only means of obtaining time-integrated data.

Journal Article↗

1H NMR studies of human C3a anaphylatoxin in solution: sequential resonance assignments, secondary structure, and global fold.

The spin systems that comprise the 1H nuclear magnetic resonance (NMR) spectrum of the complement fragment C3a (Mr 8900) have been completely identified by an approach which integrates data from a wide range of two-dimensional NMR experiments. Both relayed and multiple quantum experiments play an essential role in the analysis. After the first stage of analysis the spin systems of 60 of the 77 residues were assigned to the appropriate residue type, providing an ample basis for subsequent sequence-specific assignments. Elements of secondary structure were identified on the basis of networks of characteristic sequential and medium-range nuclear Overhauser effects (NOEs), values of 3JHN alpha, and locations of slowly exchanging backbone amide protons. Three well-defined helical segments are found. Gradients of increasing mobility in distinct segments of the C3a polypeptide are observed, with very high mobilities for several residues near the C- and N-termini, including the complete C-terminal receptor binding site pentapeptide LGLAR. The NMR data, combined with known disulfide linkages and a small number of critical long-range NOEs, provide the global folding pattern of C3a in solution. Identical solution structures were found for both the intact active protein and the largely inactive physiologic product des-Arg77-C3a.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

1H NMR studies of porcine calbindin D9k in solution: sequential resonance assignment, secondary structure, and global fold.

The 1H nuclear magnetic resonance (NMR) spectrum of Ca2+-saturated porcine calbindin D9k (78 amino acids, Mr 8800) has been assigned. Greater than 98% of the 1H resonances, including spin systems for each amino acid residue, have been identified by using an approach that integrates data from a wide range of two-dimensional scalar correlated NMR experiments [Chazin, Rance, & Wright (1988) J. Mol. Biol. 202, 603-626]. Due to the limited quantity of sample and conformational heterogeneity of the protein, two-dimensional nuclear Overhauser effect (NOE) experiments also played an essential role in the identification of spin systems. On the basis of the pattern of scalar connectivities, 43 of the 78 spin systems could be directly assigned to the appropriate residue type. This provided an ample basis for obtaining the sequence-specific resonance assignments. The elements of secondary structure are identified from sequential and medium-range NOEs, values of 3JNH alpha, and the location of slowly exchanging backbone amide protons. Four well-defined helices and a mini beta-sheet between the two calcium binding loops are present in solution. These elements of secondary structure and a few key long-range NOEs provided sufficient information to define the global fold of the protein in solution. Generally good agreement is found between the crystal structure of the minor A form of bovine calbindin D9k and the solution structure of intact porcine calbindin D9k. The only significant difference is a short one-turn helix in the loop between helices II and III in the bovine crystal structure, which is clearly absent in the porcine solution structure.

Amino Acid Sequence↗

The active site loop of S-adenosylmethionine synthetase modulates catalytic efficiency.

Crystallographic studies of Escherichia coli S-adenosylmethionine synthetase (ATP:L-methionine S-adenosyltransferase, MAT) have defined a flexible polypeptide loop that can gate access to the active site without contacting the substrates. The influence of the length and sequence of this active site loop on catalytic efficiency has been characterized in a mutant in which the E. coli MAT sequence (DRADPLEQ) has been replaced with the distinct sequence of the corresponding region of the otherwise highly homologous rat liver enzyme (HDLRNEEDV). Four additional mutants in which the entire DRADPLEQ sequence was replaced by five, six, seven, or eight glycines have been studied to unveil the effects of loop length and the influence of side chains. In all of the mutants, the maximal rate of S-adenosylmethionine formation (k(cat)) is diminished by more than 200-fold whereas the rate of hydrolysis of the tripolyphosphate intermediate is decreased by less than 3-fold. Thus, the function of the loop is localized to the first step in the overall reaction. The K(m) for methionine increases in all of the oligoglycine mutants, whereas the K(m) values for ATP are not substantially different. The k(cat) for the wild-type enzyme is decreased by increases in solution microviscosity with 55% of the maximal dependence. Thus, a diffusional event is coupled to the chemical step of AdoMet formation, which is known to be rate-limiting. The results indicate that a conformational change, possibly loop closure, is associated with AdoMet synthesis. The data integrate a previously discovered conformational change associated with PPP(i) binding to the E x AdoMet complex into the reaction sequence, reflecting a difference in protein conformation in the E x AdoMet x PPP(i) complex whether it is formed from the E x ATP x methionine complex or from binding of exogenous PPP(i). The temperature dependence of the k(cat) for S-adenosylmethionine formation shows that the removal of the side chains in the glycine mutants causes the activation enthalpy of the reaction to approximately double in each case, while the activation entropy changes from negative in the wild-type enzyme to positive in the mutants. The favorable activation entropy in the mutant-catalyzed reactions may reflect release of water during catalysis, while the negative activation entropy in the reaction catalyzed by the wild-type enzyme apparently reflects reorganization of the loop. The observations point to how nature can fine-tune the activity of an enzyme by modifying substrate and product access to the active site rather than by altering the enzyme x substrate contacts or the catalytic machinery itself.

Base Sequence↗

A new model for the K+-induced macromolecular structure of guanosine 5'-monophosphate in solution.

The (31)P NMR spectra of (TMA)(2)(5'-GMP), where TMA is [(CH(3))(4)N](+) and 5'-GMP is guanosine 5'-monophosphate, and K(2)(5'-GMP), containing various amounts of KCl or TMACl, have been obtained at 2 degrees C. Variable-temperature spectra have also been obtained for K(2)(5'-GMP). The TMA(+) ion serves to neutralize the charge on the dianionic 5'-GMP and permits the added K(+) to bond preferentially in structure-forming sites. (1)H NMR spectra (one- and two-dimensional) have been obtained for K(2)(5'-GMP) and used to assign the proton resonances in the self-associated structures and determine that all residues have the anti glycosidic conformation. The (31)P and (1)H NMR spectra are very complex and indicate the presence of a large number of molecular environments and a structural variation dependent upon the mole ratio of 5'-GMP to K(+). A new model for the solution structure is proposed in which the 5'-GMP forms a pseudo-four-stranded helix with guanine-guanine hydrogen bonding forming a continuous helical strand, rather than the usual planar G-tetrad structure. The guanine-guanine hydrogen bonding sites are the same as that found in a G-tetrad. The K(+) ions would be located in the center of the helix and bonding to the carbonyl oxygens. They are interacting with the phosphates as well. Integration data from the largest sized species give an estimate of 14.3 +/- 1.1 residues in a helical structure.

Cations, Monovalent↗

Electron density topological analysis of hydrogen bonding in glucopyranose and hydrated glucopyranose.

Topological analysis of the electron density profiles and the atomic basin integration data for the most energetically favorable (4)C(1) and (1)C(4) conformers of beta-D-glucopyranose, calculated at the B3LYP/6-31+G(d), MPWlPW91/6-311+G(2d,p), and MP2/6-31+G(d) levels, demonstrates that intramolecular hydrogen bonding between adjacent ring OH groups does not occur in glucopyranose, given the need to demonstrate a bond critical point (BCP) of correct (3,-1) topology for such an interaction to be termed a hydrogen bond. On the other hand, pyranose ring OH groups separated by three, rather than just two, carbon atoms are able to form an intramolecular hydrogen bond similar in topological properties and geometry to that found for propane-1,3-diol. Vicinal, equatorial OH groups in the (4)C(1) conformer of glucopyranose are, however, able to form strong bidentate hydrogen bonds with water molecules in a cooperative manner, each water molecule acting simultaneously as both hydrogen bond donor and acceptor, and characterized by (3,-1) bond critical points with increased values for the electron density and the Laplacian of rho(r) compared to an isolated ethane-1,2-diol/water complex.

Electrons↗