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.)

Myotonic Dystrophy Initially Presenting as Tachycardiomyopathy Successful Catheter Ablation of Atrial Flutter

Myotonic dystrophy is a genetic muscular disease that is frequently associated with cardiac arrhythmias. Bradyarrhythmias, such as sinus bradycardia and atrioventricular block, are more common than tachyarrhythmias. Rarely, previously undiagnosed patients with myotonic dystrophy initially present with a tachyarrhythmia. We describe the case of a 14-year-old boy, who was admitted to the hospital with clinical signs and symptoms of decompensated heart failure and severely reduced left ventricular function. Electrocardiography showed common-type atrial flutter with 2 : 1 conduction resulting in a heart rate of 160 bpm. Initiation of medical therapy for heart failure as well as electrical cardioversion led to a marked clinical improvement. Catheter ablation of atrial flutter was performed to prevent future cardiac decompensations and to prevent development of tachymyopathy. Left ventricular function normalized during followup. Genetic analysis confirmed the clinical suspicion of myotonic dystrophy as known in other family members in this case

Current Status of Quark Gluon Plasma Signals

Compelling evidence for the creation of a new form of matter has been claimed to be found in Pb+Pb collisions at SPS. We discuss the uniqueness of often proposed experimental signatures for quark matter formation in relativistic heavy ion collisions. It is demonstrated that so far none of the proposed signals like J\psi meson production/suppression, strangeness enhancement, dileptons, and directed flow unambigiously show that a phase of deconfined matter has been formed in SPS Pb+Pb collisions. We emphasize the need for systematic future measurements to search for simultaneous irregularities in the excitation functions of several observables in order to come close to pinning the properties of hot, dense QCD matter from data.Comment: 12 pages, 6 figures, Proceedings of the Symposium on Fundamental Issues in Elementary Matter In Honor and Memory of Michael Danos 241. WE-Heraeus-Seminar Bad Honnef, Germany, 25--29 September 2000. To appear in Heavy Ion Phy

Capability study of Ti, Cr, W, Ta and Pt as seed layers for electrodeposited platinum films on γ-Al2O3 for high temperature and harsh environment applications

High temperature surface acoustic wave sensors based on radio frequency identification technology require adequate antennas of high efficiency and thermal stability for the signal transmission. Platinum is well known and frequently used as a material of choice for high temperature and harsh environment applications because of the high melting point and its chemical stability. Therefore, one way to realize high temperature stable antennas is the combination of a Pt metallization on an Al 2 O 3 substrate. As a cost-effective technique, the Pt film is deposited via electrochemical deposition. For this growth procedure, a pre-deposited metallization on the Al 2 O 3 layer is required. This paper analyzes the influence of various seed layers (Ta, Ti, W, Cr, Pt) on the morphology, stability and electrical properties of the electrochemically-grown Pt thick film after heat treatments up to 1000 ∘ C in air. We find an oxidation of all adhesion layers except for Pt, for which the best electrical properties were measured. Although significant areas of the films delaminate from the substrate, individual anchor structures retain a stable connection between the Pt layer and the rough Al 2 O 3 substrate

The initial state of ultra-relativistic heavy ion collision

A model for energy, pressure and flow velocity distributions at the beginning of ultra-relativistic heavy ion collisions is presented, which can be used as an initial condition for hydrodynamic calculations. Our model takes into account baryon recoil for both target and projectile, arising from the acceleration of partons in an effective field, produced in the collision. The typical field strength (string tension) for RHIC energies is about 5-12 GeV/fm, what allows us to talk about "string ropes". The results show that a QGP forms a tilted disk, such that the direction of the largest pressure gradient stays in the reaction plane, but deviates from both the beam and the usual transverse flow directions. Such initial conditions may lead to the creation of "antiflow" or "third flow component".Comment: 28 pages, 9 figures. The presentation has been changed considerably. Some parts of the model have been reformulated, what led to modifications in several equations: (20-38), Apps. A, B. All the figures have been changed from 100 GeV/nucl initial energy to the achieved RHIC energy of 65 GeV/nucl. The last subplots in the Figs. 3, 4, 5, 6 present E=T^{00} in the laboratory frame now, instead of the energy density in the local rest frame, e, shown in the initial version. We also added the App. C to clarify the transformation from space-time to lightcone coordinates and bac

Do Acute Coronary Events Affect Lipid Management and Cholesterol Goal Attainment in Germany?

Objective To document utilization of lipid-lowering therapy, attainment of low-density lipoprotein cholesterol target values, and cardiovascular outcomes in patients hospitalized for acute coronary syndrome in Germany. Methods The Dyslipidemia International Study II was a multicenter, observational study of the prevalence of dyslipidemia and lipid target value attainment in patients surviving any acute coronary syndrome event. Among patients on lipid-lowering therapy for ≥3 months, use of lipid-lowering therapy and lipid profiles were assessed at admission and again at 120 ± 15 days after admission (the follow-up time point). Multivariate logistic regression was used to identify variables predictive of low-density lipoprotein cholesterol target value attainment in patients using lipid-lowering therapy. Results A total of 461 patients hospitalized for acute coronary syndrome were identified, 270 (58.6%) of whom were on lipid-lowering therapy at admission. Among patients on lipid-lowering therapy, 90.7% and 85.9% were receiving statin monotherapy at admission and follow-up, respectively. Mean (SD) lowdensity lipoprotein cholesterol levels in patients on lipid-lowering therapy were 101 (40) mg/dl and 95 (30) mg/dl at admission and follow-up, respectively. In patients with data at both admission and followup (n= 61), low-density lipoprotein cholesterol target value attainment rates were the same (19.7%) at both time points. Smoking was associated with a 77% lower likelihood of attaining the low-density lipoprotein cholesterol target value. Conclusion Hospitalization for an acute event does not greatly alter lipid management in acute coronary syndrome patients in Germany. Both lipid-lowering therapy doses and rates of low-density lipoprotein cholesterol target value attainment remained essentially the same several months after the event

SLAC's polarized electron source laser system for the E-158 parity violation experiment

SLAC E158 is an experiment to make the first measurement of parity violation in Moller scattering. The left-right cross-section asymmetry in the elastic scattering of a 45-GeV polarized electron beam off unpolarized electrons in a liquid hydrogen target will be measured to an accuracy of better than 10-8, with the expected Standard Model asymmetry being approximately 10-7. An intense circularly polarized laser beam for the polarized electron source is required with the ability to quickly switch between left and right polarization states with minimal left-right asymmetries in the parameters of the electron beam. This laser beam is produced by a unique SLAC-designed, flash-lamp pumped, Ti:Sapphire laser. We present this laser system design and initial results from recent commissioning runs

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