Q-band electron nuclear double resonance (ENDOR) and X-band EPR of the sulfobetaine 12 heat-treated cytochrome c oxidase complex

Heat treatment of the bovine cytochrome c oxidase complex in the zwitterionic detergent sulfobetaine 12 (SB-12) results in loss of subunit III and the appearance of a type II copper center as characterized by electron paramagnetic resonance (EPR) spectroscopy. Previous authors (Nilsson, T., Copeland, R. A., Smith, P. A., and Chan, S. I. (1988) Biochemistry 27, 8254-8260) have interpreted this type II copper center as a modified version of the CuA site. By using electron nuclear double resonance spectroscopy, it is found that the CuA proton and nitrogen resonances remain present in the SB-12 heat-treated enzyme and that three new nitrogen resonances appear having hyperfine coupling constants consistent with histidine ligation. These hyperfine coupling constants correlate well with those recently found for the CuB histidines from the cytochrome aa3-600 quinol oxidase from Bacillus subtilis (Fann, Y. C., Ahmed, I., Blackburn, N. J., Boswell, J. S., Verkhovskaya, M. L., Hoffman, B. M., and Wikström, M. (1995) Biochemistry 34, 10245-10255). In addition, the total EPR-detectable copper concentration per enzyme molecule approximately doubles upon SB-12 heat treatment. Finally, the observed type II copper EPR spectrum is virtually indistinguishable from the EPR spectrum of CuB of the as-isolated cytochrome bo3 complex from Escherichia coli. These data indicate that the type II copper species that appears results from a breaking of the strong antiferromagnetic coupling of the heme a3-CuB binuclear center

Heating effects on laminar flow through a rotating square channel

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76719/1/AIAA-537-695.pd

PDA: Pooled DNA analyzer

BACKGROUND: Association mapping using abundant single nucleotide polymorphisms is a powerful tool for identifying disease susceptibility genes for complex traits and exploring possible genetic diversity. Genotyping large numbers of SNPs individually is performed routinely but is cost prohibitive for large-scale genetic studies. DNA pooling is a reliable and cost-saving alternative genotyping method. However, no software has been developed for complete pooled-DNA analyses, including data standardization, allele frequency estimation, and single/multipoint DNA pooling association tests. This motivated the development of the software, 'PDA' (Pooled DNA Analyzer), to analyze pooled DNA data. RESULTS: We develop the software, PDA, for the analysis of pooled-DNA data. PDA is originally implemented with the MATLAB(® )language, but it can also be executed on a Windows system without installing the MATLAB(®). PDA provides estimates of the coefficient of preferential amplification and allele frequency. PDA considers an extended single-point association test, which can compare allele frequencies between two DNA pools constructed under different experimental conditions. Moreover, PDA also provides novel chromosome-wide multipoint association tests based on p-value combinations and a sliding-window concept. This new multipoint testing procedure overcomes a computational bottleneck of conventional haplotype-oriented multipoint methods in DNA pooling analyses and can handle data sets having a large pool size and/or large numbers of polymorphic markers. All of the PDA functions are illustrated in the four bona fide examples. CONCLUSION: PDA is simple to operate and does not require that users have a strong statistical background. The software is available at

Local heat transfer in a rotating serpentine passage with rib-roughened surfaces

An experimental study is conducted on heat transfer in a rotating serpentine passage with ribroughened walls under uniform wall heat flux. Seven roughness configurations are tested to determine their effects on convective heat transfer enhancement. Results are obtained for heat transfer distributions which are compared with those having smooth surfaces. It is revealed that rotation, roughness and the angle-of-attack of ribs have significant influences on the heat transfer performance with 45PR having the best enhancement in both stationary and rotating cases. The flow mechanism in a rib-roughened passage is proposed to explain its effect on heat transfer performance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31906/1/0000859.pd

Rapid detection and curation of conserved DNA via enhanced-BLAT and EvoPrinterHD analysis

<p>Abstract</p> <p>Background</p> <p>Multi-genome comparative analysis has yielded important insights into the molecular details of gene regulation. We have developed <it>EvoPrinter</it>, a web-accessed genomics tool that provides a single uninterrupted view of conserved sequences as they appear in a species of interest. An <it>EvoPrint </it>reveals with near base-pair resolution those sequences that are essential for gene function.</p> <p>Results</p> <p>We describe here <it>EvoPrinterHD</it>, a 2^nd-generation comparative genomics tool that automatically generates from a single input sequence an enhanced view of sequence conservation between evolutionarily distant species. Currently available for 5 nematode, 3 mosquito, 12 <it>Drosophila</it>, 20 vertebrate, 17 <it>Staphylococcus </it>and 20 enteric bacteria genomes, <it>EvoPrinterHD </it>employs a modified BLAT algorithm [<it>enhanced</it>-BLAT (<it>e</it>BLAT)], which detects up to 75% more conserved bases than identified by the BLAT alignments used in the earlier <it>EvoPrinter </it>program. The new program also identifies conserved sequences within rearranged DNA, highlights repetitive DNA, and detects sequencing gaps. <it>EvoPrinterHD </it>currently holds over 112 billion bp of indexed genomes in memory and has the flexibility of selecting a subset of genomes for analysis. An <it>EvoDifferences </it>profile is also generated to portray conserved sequences that are uniquely lost in any one of the orthologs. Finally, <it>EvoPrinterHD </it>incorporates options that allow for (1) re-initiation of the analysis using a different genome's aligning region as the reference DNA to detect species-specific changes in less-conserved regions, (2) rapid extraction and curation of conserved sequences, and (3) for bacteria, identifies unique or uniquely shared sequences present in subsets of genomes.</p> <p>Conclusion</p> <p><it>EvoPrinterHD </it>is a fast, high-resolution comparative genomics tool that automatically generates an uninterrupted species-centric view of sequence conservation and enables the discovery of conserved sequences within rearranged DNA. When combined with <it>cis</it>-Decoder, a program that discovers sequence elements shared among tissue specific enhancers, <it>EvoPrinterHD </it>facilitates the analysis of conserved sequences that are essential for coordinate gene regulation.</p

A genome-wide scan using tree-based association analysis for candidate loci related to fasting plasma glucose levels

BACKGROUND: In the analysis of complex traits such as fasting plasma glucose levels, researchers often adjust the trait for some important covariates before assessing gene susceptibility, and may at times encounter confounding among the covariates and the susceptible genes. Previously, the tree-based method has been employed to accommodate the heterogeneity in complex traits. In this study, we performed a genome-wide screen on fasting glucose levels in the offspring generation of the Framingham Heart Study provided by the Genetic Analysis Workshop 13. We defined one quantitative trait and converted it to a dichotomous trait based on a predetermined cut-off value, and performed association analyses using regression and classification trees for the two traits, respectively. A marker was interpreted as positive if at least one of its alleles exhibited association in both analyses. Our purpose was to identify candidate genes susceptible to fasting glucose levels in the presence of other covariates. The covariates entered in the analysis including sex, body mass index, and lipids (total plasma cholesterol, high density lipoprotein cholesterol, and triglycerides) of the subjects, and those of their parents. RESULTS: Four out of seven positive regions in chromosomes 1, 2, 6, 11, 16, 18, and 19 from our analyses harbored or were very close to previously reported diabetes related genes or potential candidate genes. CONCLUSION: This screen method that employed tree-based association showed promise for identifying candidate loci in the presence of covariates in genome scans for complex traits

Surface collective excitations in ultrafast pump-probe spectroscopy of metal nanoparticles

The role of surface collective excitations in the electron relaxation in small metal particles is studied. It is shown that the dynamically screened electron-electron interaction in a nanoparticle contains a size-dependent correction induced by the surface. This leads to new channels of quasiparticle scattering accompanied by the emission of surface collective excitations. In noble-metal particles, the dipole collective excitations (surface plasmons) mediate a resonant scattering of d-holes to the conduction band. The role of this effect in the ultrafast optical dynamics of small nanoparticles is studied. With decreasing nanoparticle size, it leads to a strong change in the differential absorption lineshape and a strong frequency dependence of the relaxation near the surface plasmon resonance. The experimental implications of these results in ultrafast pump-probe spectroscopy are addressed. The size-dependence of conduction electron scattering rates is also discussed.Comment: 26 pages including 10 figures. Invited paper for Special Issue of Chemical Physics on "Electron Dynamics in Metals

A genome-wide scanning and fine mapping study of COGA data

A thorough genetic mapping study was performed to identify predisposing genes for alcoholism dependence using the Collaborative Study on the Genetics of Alcoholism (COGA) data. The procedure comprised whole-genome linkage and confirmation analyses, single locus and haplotype fine mapping analyses, and gene × environment haplotype regression. Stratified analysis was considered to reduce the ethnic heterogeneity and simultaneously family-based and case-control study designs were applied to detect potential genetic signals. By using different methods and markers, we found high linkage signals at D1S225 (253.7 cM), D1S547 (279.2 cM), D2S1356 (64.6 cM), and D7S2846 (56.8 cM) with nonparametric linkage scores of 3.92, 4.10, 4.44, and 3.55, respectively. We also conducted haplotype and odds ratio analyses, where the response was the dichotomous status of alcohol dependence, explanatory variables were the inferred individual haplotypes and the three statistically significant covariates were age, gender, and max drink (the maximum number of drinks consumed in a 24-hr period). The final model identified important AD-related haplotypes within a candidate region of NRXN1 at 2p21 and a few others in the inter-gene regions. The relative magnitude of risks to the identified risky/protective haplotypes was elucidated

An Interpretable Framework to Identify Responsive Subgroups From Clinical Trials Regarding Treatment Effects: Application to Treatment of Intracerebral Hemorrhage

Randomized Clinical trials (RCT) suffer from a high failure rate which could be caused by heterogeneous responses to treatment. Despite many models being developed to estimate heterogeneous treatment effects (HTE), there remains a lack of interpretable methods to identify responsive subgroups. This work aims to develop a framework to identify subgroups based on treatment effects that prioritize model interpretability. The proposed framework leverages an ensemble uplift tree method to generate descriptive decision rules that separate samples given estimated responses to the treatment. Subsequently, we select a complementary set of these decision rules and rank them using a sparse linear model. To address the trial\u27s limited sample size problem, we proposed a data augmentation strategy by borrowing control patients from external studies and generating synthetic data. We apply the proposed framework to a failed randomized clinical trial for investigating an intracerebral hemorrhage therapy plan. The Qini-scores show that the proposed data augmentation strategy plan can boost the model\u27s performance and the framework achieves greater interpretability by selecting complementary descriptive rules without compromising estimation quality. Our model derives clinically meaningful subgroups. Specifically, we find those patients with Diastolic Blood Pressure≥70 mm hg and Systolic Blood Pressuresubgroups, our framework can contribute to developing personalized treatment strategies for patients more efficiently