Application of PGA on optimization of distribution of shopping centers

Series: Lecture notes in computer scienceAuthor name used in this publication: Chun-Tian ChengAuthor name used in this publication: Kwokwing Chau2004-2005 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Direct generation of intense extreme ultraviolet supercontinuum with 35 fs, 11 mJ pulses from a femtosecond laser amplifier

We report on the generation of intense extreme ultraviolet (EUV) supercontinuum with photon energies spanning from 35 eV to 50 eV (i. e., supporting an isolated attosecond pulse with a duration of ~271 as) by loosely focusing 35 fs, 11 mJ pulses from a femtosecond laser amplifier into a 10-mm long gas cell filled with krypton gas. The dramatic change of spectral and temporal properties of the driver pulses after passing through the gas cell indicates that propagation effects play a significant role in promoting the generation of the EUV supercontinuum.Comment: 14 pages, 4 figure

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Application of amino acid occurrence for discriminating different folding types of globular proteins

<p>Abstract</p> <p>Background</p> <p>Predicting the three-dimensional structure of a protein from its amino acid sequence is a long-standing goal in computational/molecular biology. The discrimination of different structural classes and folding types are intermediate steps in protein structure prediction.</p> <p>Results</p> <p>In this work, we have proposed a method based on linear discriminant analysis (LDA) for discriminating 30 different folding types of globular proteins using amino acid occurrence. Our method was tested with a non-redundant set of 1612 proteins and it discriminated them with the accuracy of 38%, which is comparable to or better than other methods in the literature. A web server has been developed for discriminating the folding type of a query protein from its amino acid sequence and it is available at http://granular.com/PROLDA/.</p> <p>Conclusion</p> <p>Amino acid occurrence has been successfully used to discriminate different folding types of globular proteins. The discrimination accuracy obtained with amino acid occurrence is better than that obtained with amino acid composition and/or amino acid properties. In addition, the method is very fast to obtain the results.</p

A comprehensive analysis of common genetic variation in prolactin (PRL) and PRL receptor (PRLR) genes in relation to plasma prolactin levels and breast cancer risk: the Multiethnic Cohort

<p>Abstract</p> <p>Background</p> <p>Studies in animals and humans clearly indicate a role for prolactin (PRL) in breast epithelial proliferation, differentiation, and tumorigenesis. Prospective epidemiological studies have also shown that women with higher circulating PRL levels have an increase in risk of breast cancer, suggesting that variability in PRL may also be important in determining a woman's risk.</p> <p>Methods</p> <p>We evaluated genetic variation in the PRL and PRL receptor (PRLR) genes as predictors of plasma PRL levels and breast cancer risk among African-American, Native Hawaiian, Japanese-American, Latina, and White women in the Multiethnic Cohort Study (MEC). We selected single nucleotide polymorphisms (SNPs) from both the public (dbSNP) and private (Celera) databases to construct high density SNP maps that included up to 20 kilobases (kb) upstream of the transcription initiation site and 10 kb downstream of the last exon of each gene, for a total coverage of 59 kb in PRL and 210 kb in PRLR. We genotyped 80 SNPs in PRL and 173 SNPs in PRLR in a multiethnic panel of 349 unaffected subjects to characterize linkage disequilibrium (LD) and haplotype patterns. We sequenced the coding regions of PRL and PRLR in 95 advanced breast cancer cases (19 of each racial/ethnic group) to uncover putative functional variation. A total of 33 and 60 haplotype "tag" SNPs (tagSNPs) that allowed for high predictability (R_h²≥ 0.70) of the common haplotypes in PRL and PRLR, respectively, were then genotyped in a multiethnic breast cancer case-control study of 1,615 invasive breast cancer cases and 1,962 controls in the MEC. We also assessed the association of common genetic variation with circulating PRL levels in 362 postmenopausal controls without a history of hormone therapy use at blood draw. Because of the large number of comparisons being performed we used a relatively stringent type I error criteria (p < 0.0005) for evaluating the significance of any single association to correct for performing approximately 100 independent tests, close to the number of tagSNPs genotyped for both genes.</p> <p>Results</p> <p>We observed no significant associations between PRL and PRLR haplotypes or individual SNPs in relation to breast cancer risk. A nominally significant association was noted between prolactin levels and a tagSNP (tagSNP 44, rs2244502) in intron 1 of PRL. This SNP showed approximately a 50% increase in levels between minor allele homozygotes vs. major allele homozygotes. However, this association was not significant (p = 0.002) using our type I error criteria to correct for multiple testing, nor was this SNP associated with breast cancer risk (p = 0.58).</p> <p>Conclusion</p> <p>In this comprehensive analysis covering 59 kb of the PRL locus and 210 kb of the PRLR locus, we found no significant association between common variation in these candidate genes and breast cancer risk or plasma PRL levels. The LD characterization of PRL and PRLR in this multiethnic population provide a framework for studying these genes in relation to other disease outcomes that have been associated with PRL, as well as for larger studies of plasma PRL levels.</p

cDNA sequencing improves the detection of P53 missense mutations in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Recently published data showed discrepancies beteween <it>P53 </it>cDNA and DNA sequencing in glioblastomas. We hypothesised that similar discrepancies may be observed in other human cancers.</p> <p>Methods</p> <p>To this end, we analyzed 23 colorectal cancers for <it>P53 </it>mutations and gene expression using both DNA and cDNA sequencing, real-time PCR and immunohistochemistry.</p> <p>Results</p> <p>We found <it>P53 </it>gene mutations in 16 cases (15 missense and 1 nonsense). Two of the 15 cases with missense mutations showed alterations based only on cDNA, and not DNA sequencing. Moreover, in 6 of the 15 cases with a cDNA mutation those mutations were difficult to detect in the DNA sequencing, so the results of DNA analysis alone could be misinterpreted if the cDNA sequencing results had not also been available. In all those 15 cases, we observed a higher ratio of the mutated to the wild type template by cDNA analysis, but not by the DNA analysis. Interestingly, a similar overexpression of <it>P53 </it>mRNA was present in samples with and without <it>P53 </it>mutations.</p> <p>Conclusion</p> <p>In terms of colorectal cancer, those discrepancies might be explained under three conditions: 1, overexpression of mutated <it>P53 </it>mRNA in cancer cells as compared with normal cells; 2, a higher content of cells without <it>P53 </it>mutation (normal cells and cells showing <it>K-RAS </it>and/or <it>APC </it>but not <it>P53 </it>mutation) in samples presenting <it>P53 </it>mutation; 3, heterozygous or hemizygous mutations of <it>P53 </it>gene. Additionally, for heterozygous mutations unknown mechanism(s) causing selective overproduction of mutated allele should also be considered. Our data offer new clues for studying discrepancy in <it>P53 </it>cDNA and DNA sequencing analysis.</p

Over-expression of adenosine deaminase in mouse podocytes does not reverse puromycin aminonucleoside resistance

<p>Abstract</p> <p>Background</p> <p>Edema in nephrotic syndrome results from renal retention of sodium and alteration of the permeability properties of capillaries. Nephrotic syndrome induced by puromycin aminonucleoside (PAN) in rats reproduces the biological and clinical signs of the human disease, and has been widely used to identify the cellular mechanisms of sodium retention. Unfortunately, mice do not develop nephrotic syndrome in response to PAN, and we still lack a good mouse model of the disease in which the genetic tools necessary for further characterizing the pathophysiological pathway could be used. Mouse resistance to PAN has been attributed to a defect in glomerular adenosine deaminase (ADA), which metabolizes PAN. We therefore attempted to develop a mouse line sensitive to PAN through induction of normal adenosine metabolism in their podocytes.</p> <p>Methods</p> <p>A mouse line expressing functional ADA under the control of the podocyte-specific podocin promoter was generated by transgenesis. The effect of PAN on urinary excretion of sodium and proteins was compared in rats and in mice over-expressing ADA and in littermates.</p> <p>Results</p> <p>We confirmed that expression of ADA mRNAs was much lower in wild type mouse than in rat glomerulus. Transgenic mice expressed ADA specifically in the glomerulus, and their ADA activity was of the same order of magnitude as in rats. Nonetheless, ADA transgenic mice remained insensitive to PAN treatment in terms of both proteinuria and sodium retention.</p> <p>Conclusions</p> <p>Along with previous results, this study shows that adenosine deaminase is necessary but not sufficient to confer PAN sensitivity to podocytes. ADA transgenic mice could be used as a background strain for further transgenesis.</p

Variability of wavefront aberration measurements in small pupil sizes using a clinical Shack-Hartmann aberrometer

BACKGROUND: Recently, instruments for the measurement of wavefront aberration in the living human eye have been widely available for clinical applications. Despite the extensive background experience on wavefront sensing for research purposes, the information derived from such instrumentation in a clinical setting should not be considered a priori precise. We report on the variability of such an instrument at two different pupil sizes. METHODS: A clinical aberrometer (COAS Wavefront Scienses, Ltd) based on the Shack-Hartmann principle was employed in this study. Fifty consecutive measurements were perfomed on each right eye of four subjects. We compared the variance of individual Zernike expansion coefficients as determined by the aberrometer with the variance of coefficients calculated using a mathematical method for scaling the expansion coefficients to reconstruct wavefront aberration for a reduced-size pupil. RESULTS: Wavefront aberration exhibits a marked variance of the order of 0.45 microns near the edge of the pupil whereas the central part appears to be measured more consistently. Dispersion of Zernike expansion coefficients was lower when calculated by the scaling method for a pupil diameter of 3 mm as compared to the one introduced when only the central 3 mm of the Shack – Hartmann image was evaluated. Signal-to-noise ratio was lower for higher order aberrations than for low order coefficients corresponding to the sphero-cylindrical error. For each subject a number of Zernike expansion coefficients was below noise level and should not be considered trustworthy. CONCLUSION: Wavefront aberration data used in clinical care should not be extracted from a single measurement, which represents only a static snapshot of a dynamically changing aberration pattern. This observation must be taken into account in order to prevent ambiguous conclusions in clinical practice and especially in refractive surgery