Heterogeneous biomedical database integration using a hybrid strategy: a p53 cancer research database.

Complex problems in life science research give rise to multidisciplinary collaboration, and hence, to the need for heterogeneous database integration. The tumor suppressor p53 is mutated in close to 50% of human cancers, and a small drug-like molecule with the ability to restore native function to cancerous p53 mutants is a long-held medical goal of cancer treatment. The Cancer Research DataBase (CRDB) was designed in support of a project to find such small molecules. As a cancer informatics project, the CRDB involved small molecule data, computational docking results, functional assays, and protein structure data. As an example of the hybrid strategy for data integration, it combined the mediation and data warehousing approaches. This paper uses the CRDB to illustrate the hybrid strategy as a viable approach to heterogeneous data integration in biomedicine, and provides a design method for those considering similar systems. More efficient data sharing implies increased productivity, and, hopefully, improved chances of success in cancer research. (Code and database schemas are freely downloadable, http://www.igb.uci.edu/research/research.html.)

Trends and abrupt changes in 104 years of ice cover and water temperature in a dimictic lake in response to air temperature, wind speed, and water clarity drivers

The one-dimensional hydrodynamic ice model, DYRESM-WQ-I, was modified to simulate ice cover and thermal structure of dimictic Lake Mendota, Wisconsin, USA, over a continuous 104-year period (1911-2014). The model results were then used to examine the drivers of changes in ice cover and water temperature, focusing on the responses to shifts in air temperature, wind speed, and water clarity at multiyear timescales. Observations of the drivers include a change in the trend of warming air temperatures from 0.081°C per decade before 1981 to 0.334°C per decade thereafter, as well as a shift in mean wind speed from 4.44ms-1 before 1994 to 3.74ms-1 thereafter. Observations show that Lake Mendota has experienced significant changes in ice cover: later ice-on date(9.0 days later per century), earlier ice-off date (12.3 days per century), decreasing ice cover duration (21.3 days per century), while model simulations indicate a change in maximum ice thickness (12.7cm decrease per century). Model simulations also show changes in the lake thermal regime of earlier stratification onset (12.3 days per century), later fall turnover (14.6 days per century), longer stratification duration (26.8 days per century), and decreasing summer hypolimnetic temperatures (-1.4°C per century). Correlation analysis of lake variables and driving variables revealed ice cover variables, stratification onset, epilimnetic temperature, and hypolimnetic temperature were most closely correlated with air temperature, whereas freeze-over water temperature, hypolimnetic heating, and fall turnover date were more closely correlated with wind speed. Each lake variable (i.e., ice-on and ice-off dates, ice cover duration, maximum ice thickness, freeze-over water temperature, stratification onset, fall turnover date, stratification duration, epilimnion temperature, hypolimnion temperature, and hypolimnetic heating) was averaged for the three periods (1911-1980, 1981-1993, and 1994-2014) delineated by abrupt changes in air temperature and wind speed. Average summer hypolimnetic temperature and fall turnover date exhibit significant differences between the third period and the first two periods. Changes in ice cover (ice-on and ice-off dates, ice cover duration, and maximum ice thickness) exhibit an abrupt change after 1994, which was related in part to the warm El Niño winter of 1997-1998. Under-ice water temperature, freeze-over water temperature, hypolimnetic temperature, fall turnover date, and stratification duration demonstrate a significant difference in the third period (1994-2014), when air temperature was warmest and wind speeds decreased rather abruptly. The trends in ice cover and water temperature demonstrate responses to both long-term and abrupt changes in meteorological conditions that can be complemented with numerical modeling to better understand how these variables will respond in a future climate

Genome wide screens in yeast to identify potential binding sites and target genes of DNA-binding proteins

Knowledge of all binding sites for transcriptional activators and repressors is essential for computationally aided identification of transcriptional networks. The techniques developed for defining the binding sites of transcription factors tend to be cumbersome and not adaptable to high throughput. We refined a versatile yeast strategy to rapidly and efficiently identify genomic targets of DNA-binding proteins. Yeast expressing a transcription factor is mated to yeast containing a library of genomic fragments cloned upstream of the reporter gene URA3. DNA fragments with target-binding sites are identified by growth of yeast clones in media lacking uracil. The experimental approach was validated with the tumor suppressor protein p53 and the forkhead protein FoxI1 using genomic libraries for zebrafish and mouse generated by shotgun cloning of short genomic fragments. Computational analysis of the genomic fragments recapitulated the published consensus-binding site for each protein. Identified fragments were mapped to identify the genomic context of each binding site. Our yeast screening strategy, combined with bioinformatics approaches, will allow both detailed and high-throughput characterization of transcription factors, scalable to the analysis of all putative DNA-binding proteins

The stability of axisymmetric Taylor-Couette flow in hydromagnetics

The linear marginal instability of an axisymmetric MHD Taylor-Couette flow of infinite vertical extension is considered. The dependence of the flow stability on magnetic Prandtl number, Pm, and gap-width between rotating cylinders is investigated. There is an unstability for flows with resting outer cylinder even without a magnetic field. Nevertheless, there are solutions with smaller critical Reynolds numbers for certain (weak) magnetic fields. These solutions, however, exist for not too small Pm or large enough gap. For hydrodynamically stable flow, we found that a magnetic field amplitude always exsits where the critical Reynolds number is minimal. In all calculated cases the minimal critical Reynolds numbers are running with 1/Pm for small Pm and the critical Reynolds numbers exceed value of 10^6 for Pm of sodium (10^{-5}) or gallium (10^{-6}).Comment: 8 pages, 17 figure

The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

<p>Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.</p> <p>Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.</p> <p>Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).</p> <p>Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.</p&gt

Average fraction of jet momentum carried by high P ⊥ leading hadrons

The average fraction, , of jet momentum carried by the associated charged leading hadron has been determined in the reaction p + N → h 1 + h 2 + X where N is the target nucleon; h 1 , h 2 are the leading particles of two jets produced at high P ⊥ . An 800 GeV/c proton beam and 4 nuclear targets: Be, Al, Fe and W were used. The distributions agree with the QCD-parton model predictions for single independent protonnucleon scattering and independent fragmentation process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47888/1/10052_2005_Article_BF01483569.pd