CiteULike: Author Meyer

CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection.

JM Doisne — 2008-07-26T02:16:03-00:00

Journal of immunology (Baltimore, Md. : 1950), Vol. 173, No. 4. (15 August 2004), pp. 2410-2418.

Primary viral infections, including primary HIV infection, trigger intense activation of the immune system, with marked expansion of CD38(+)CD8(+) T cells. Whether this expansion involves only viral-specific cells or includes a degree of bystander activation remains a matter of debate. We therefore examined the activation status of EBV-, CMV-, and influenza virus (FLU)-specific CD8(+) T cells during primary HIV infection, in comparison to HIV-specific CD8(+) T cells. The activation markers CD38 and HLA-DR were strongly expressed on HIV-specific CD8(+) T cells. Surprisingly, CD38 expression was also up-regulated on CD8(+) T cells specific for other viruses, albeit to a lesser extent. Activation marker expression returned to normal or near-normal values after 1 year of highly active antiretroviral therapy. HIV viral load correlated with CD38 expression on HIV-specific CD8(+) T cells but also on EBV-, CMV-, and FLU-specific CD8(+) T cells. In primary HIV infection, EBV-specific CD8(+) T cells also showed increased Ki67 expression and decreased Bcl-2 expression, compared with values observed in HIV-seronegative control subjects. These results show that bystander activation occurs during primary HIV infection, even though HIV-specific CD8(+) T cells express the highest level of activation. The role of this bystander activation in lymphocyte homeostasis and HIV pathogenesis remains to be determined.

Episodes of Collective Invention

Peter Meyer — 2008-07-25T18:42:34-00:00

The process of developing a new technology through open discussion has been called collective invention. This paper documents two episodes of collective invention and proposes a general model based on search theory. The first episode deals with the development of mass production steel in the U.S. (1866-1885), and the second with early personal computers (19751985) . In both cases technical people openly discussed and sometimes shared technology they were developing. Both technologies advanced...

The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL- 6 and prolongation of the plasma half-life of IL-6

M Peters — 2008-07-25T18:34:36-00:00

J. Exp. Med., Vol. 183, No. 4. (1 April 1996), pp. 1399-1406.

10.1084/jem.183.4.1399

Social patterning of stress and coping: Does disadvantaged social statuses confer more stress and fewer coping resources?

Ilan Meyer — 2008-07-25T15:28:28-00:00

Social Science & Medicine, Vol. 67, No. 3. (August 2008), pp. 368-379.

Despite its centrality to social stress theory, research on the social patterning of stress exposure and coping resources has been sparse and existing research shows conflicting results. We interviewed 396 gay, lesbian and bisexual, and 128 heterosexual people in New York City to examine variability in exposure to stress related to sexual orientation, gender, and race/ethnicity. Multiple linear regressions showed clear support for the social stress hypothesis with regard to race/ethnic minority status, somewhat mixed support with regard to sexual orientation, and no support with regard to gender. We discuss this lack of parsimony in social stress explanations for health disparities.

Performance of Amplified DNA in an Illumina GoldenGate BeadArray Assay.

JM Cunningham — 2008-07-25T06:26:26-00:00

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Vol. 17, No. 7. (July 2008), pp. 1781-1789.

Whole genome amplification (WGA) offers a means to enrich DNA quantities for epidemiologic studies. We used an ovarian cancer study of 1,536 single nucleotide polymorphisms (SNPs) and 2,368 samples to assess performance of multiple displacement amplification (MDA) WGA using an Illumina GoldenGate BeadArray. Initial screening revealed successful genotyping for 93.4% of WGA samples and 99.3% of genomic samples, and 93.2% of SNPs for WGA samples and 96.3% of SNPs for genomic samples. SNP failure was predicted by Illumina-provided designability rank, %GC (P </= 0.002), and for WGA only, distance to telomere and Illumina-provided SNP score (P </= 0.002). Distance to telomere and %GC were highly correlated; adjustment for %GC removed the association between distance to telomere and SNP failure. Although universally high, per-SNP call rates were related to designability rank, SNP score, %GC, minor allele frequency, distance to telomere (P </= 0.01), and, for WGA only, Illumina-provided validation class (P < 0.001). We found excellent concordance generally (>99.0%) among 124 WGA:genomic replicates, 15 WGA replicates, 88 replicate aliquots of the same WGA preparation, and 25 genomic replicates. Where there was discordance, it was across WGA:genomic replicates but limited to only a few samples among other replicates suggesting the introduction of error. Designability rank and SNP score correlated with WGA:genomic concordance (P < 0.001). In summary, use of MDA WGA DNA is feasible; however, caution is warranted regarding SNP selection and analysis. We recommend that biological SNP characteristics, notably distance to telomere and GC content (<50% GC recommended), as well as Illumina-provided metrics be considered in the creation of GoldenGate assays using MDA WGA DNA. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1781-9).

Nanomechanics from atomic resolution to molecular recognition based on atomic force microscopy technology

HP Lang — 2008-07-24T18:27:23-00:00

Nanotechnology, Vol. 13, No. 5. (2002), pp. R29-R36.

Atomic force microscopy (AFM) is a technique to image surfaces with unprecedented vertical and lateral resolution. Many related techniques have been derived from AFM, taking advantage of local interactions between a tip on a cantilever and a surface. However, cantilevers can also be used for sensing applications. These so-called nanosensors feature extreme sensitivity for the detection of chemical vapours or adsorption of molecules. Upon adsorption to the cantilever surface, the molecules cause the cantilever to bend. Thus physical, chemical or biochemical processes are directly transduced into nanomechanical motion. We show that measurement of the deflection of a single cantilever might be misleading. Reliable information can only be obtained by using a sensor cantilever and at least one reference cantilever integrated into an array. We have built an electronic nose using polymer layers as partially selective cantilever coatings to recognize chemical vapours and odours by evaluating the cantilevers' bending pattern. Major applications lie in the fields of process and quality control, biosensing, medical diagnostics, molecular recognition and proteomics.

The influence of tracheal pressure changes on the responses of the tympanal membrane and auditory receptors in the locust Locusta migratoria L

J Meyer — 2008-07-24T09:20:31-00:00

J Exp Biol, Vol. 198, No. 6. (1 June 1995), pp. 1327-1339.

Latent Fluorophores Based on a Self-Immolative Linker Strategy and Suitable for Protease Sensing

Jean-Alexandre Richard — 2008-07-23T04:16:20-00:00

Bioconjugate Chem. (22 July 2008)

Abstract: The self-immolative spacer para-aminobenzyl alcohol (PABA) was used as a key component in the design of new protease-sensitive fluorogenic probes whose parent phenol-based fluorophore is released through an enzyme-initiated domino reaction. First, the conjugation of the phenylacetyl moiety to 7-hydroxycoumarin (umbelliferone) and 7-hydroxy-9H-(9,9-dimethylacridin-2-one) (DAO) by means of the heterobifunctional PABA linker has led to pro-fluorophores 6a and 6d whose enzyme activation by penicillin amidase was demonstrated. The second part of this study was devoted to the extension of this latent fluorophore strategy to the caspase-3 protease, a key mediator of apoptosis in mammalian cells. Fluorogenic caspase-3 substrates 11 and 13 derived from umbelliferone and DAO, respectively, were prepared. It was demonstrated that pro-fluorophore 11 is a sensitive fluorimetric reagent for the detection of this cysteine protease. Furthermore, in vitro assays with fluorogenic probe 13 showed a deleterious effect of biological thiols on fluorescence of the released acridinone fluorophore DAO that, to our knowledge, had not been reported until now.

Determination of liver volume from CT scans using histogram cluster analysis.

LA Farjo — 2008-07-22T15:39:55-00:00

Journal of computer assisted tomography, Vol. 16, No. 5. (t 1992), pp. 674-683.

The histogram cluster analysis procedure (HICAP), which was developed by NASA for processing satellite images, classifies images into discrete clusters of pixels according to one or more arbitrary imaging variables. We incorporated this nonparametric, multivariate procedure in a semiautomatic computer algorithm for calculating total liver volume from CT scans and compared its performance with that of a human observer. Total liver volumes were calculated from CT scans in adult patients by the algorithm and by an experienced radiologist using the trackball controlled cursor at the CT console. Variability in the computer calculated volumes was determined by repeating calculations three times over the course of 3-12 months. Using HICAP in the univariate mode, we calculated total liver volumes from 28 contrast enhanced CT scans in 27 patients. Liver volumes calculated by the semiautomatic and manual methods had a median absolute difference of 3.6% (Vcomputer = 1.08 * Vmanual - 99.52 cc; r2 = 0.99). Median day-to-day variability of the computer calculated volumes was 1.9% (95% confidence interval: 1.3-2.7%). Using HICAP in a bivariate mode to illustrate its ability to incorporate two image features in one analysis, we studied an additional patient and compared total liver volume calculated from the univariate data set defined by the contrast enhanced CT scan with that calculated from the bivariate data set defined by nonenhanced and contrast enhanced CT scans. The HICAP errors were 4.1% in the univariate analysis and 0.4% in the bivariate analysis. It is concluded that this statistical clustering algorithm provides a clinically accurate, repeatable, and feasible method of in vivo liver volume determination.

Transgene 6A-99 is a molecular marker of developing somatosensory cortex in mice

Lazutkin — 2007-03-08T07:24:48-00:00

Russian Journal of Developmental Biology, Vol. 38, No. 1. (February 2007), pp. 15-24.

Bayesian inference for recurrent events data using time-dependent frailty.

SO Manda — 2008-07-21T23:42:21-00:00

Statistics in medicine, Vol. 24, No. 8. (30 April 2005), pp. 1263-1274.

In medical studies, we commonly encounter multiple events data such as recurrent infection or attack times in patients suffering from a given disease. A number of statistical procedures for the analysis of such data use the Cox proportional hazards model, modified to include a random effect term called frailty which summarizes the dependence of recurrent times within a subject. These unobserved random frailty effects capture subject effects that are not explained by the known covariates. They are typically modelled constant over time and are assumed to be independently and identically distributed across subjects. However, in some situations, the subject-specific random frailty may change over time in the same manner as time-dependent covariate effects. This paper presents a time-dependent frailty model for recurrent failure time data in the Bayesian context and estimates it using a Markov chain Monte Carlo method. Our approach is illustrated by a data set relating to patients with chronic granulomatous disease and it is compared to the constant frailty model using the deviance information criterion.

Ecosystem Service Supply and Vulnerability to Global Change in Europe

Dagmar Schroter — 2006-01-09T22:31:20-00:00

Science, Vol. 310, No. 5752. (25 November 2005), pp. 1333-1337.

Global change will alter the supply of ecosystem services that are vital for human well-being. To investigate ecosystem service supply during the 21st century, we used a range of ecosystem models and scenarios of climate and land-use change to conduct a Europe-wide assessment. Large changes in climate and land use typically resulted in large changes in ecosystem service supply. Some of these trends may be positive (for example, increases in forest area and productivity) or offer opportunities (for example, "surplus land" for agricultural extensification and bioenergy production). However, many changes increase vulnerability as a result of a decreasing supply of ecosystem services (for example, declining soil fertility, declining water availability, increasing risk of forest fires), especially in the Mediterranean and mountain regions.

Vitamin C elevates red blood cell glutathione in healthy adults

CS Johnston — 2008-07-21T15:29:13-00:00

Am J Clin Nutr, Vol. 58, No. 1. (1 July 1993), pp. 103-105.

Parallel tagged sequencing on the 454 platform.

M Meyer — 2008-06-19T19:21:01-00:00

Nature protocols, Vol. 3, No. 2. (2008), pp. 267-278.

Parallel tagged sequencing (PTS) is a molecular barcoding method designed to adapt the recently developed high-throughput 454 parallel sequencing technology for use with multiple samples. Unlike other barcoding methods, PTS can be applied to any type of double-stranded DNA (dsDNA) sample, including shotgun DNA libraries and pools of PCR products, and requires no amplification or gel purification steps. The method relies on attaching sample-specific barcoding adapters, which include sequence tags and a restriction site, to blunt-end repaired DNA samples by ligation and strand-displacement. After pooling multiple barcoded samples, molecules without sequence tags are effectively excluded from sequencing by dephosphorylation and restriction digestion, and using the tag sequences, the source of each DNA sequence can be traced. This protocol allows for sequencing 300 or more complete mitochondrial genomes on a single 454 GS FLX run, or twenty-five 6-kb plasmid sequences on only one 16th plate region. Most of the reactions can be performed in a multichannel setup on 96-well reaction plates, allowing for processing up to several hundreds of samples in a few days.

An overview of the epic architecture for cognition and performance with application to human-computer interaction

D Kieras — 2008-07-18T11:24:19-00:00

(1997)

This article provides an overview of the EPIC architecture being developed by Kieras and Meyer for modeling human cognition and performance (Kieras, Wood, & Meyer, 1997; Meyer & Kieras, 1997a, 1997b). EPIC is similar in spirit to the Model Human Processor (MHP; Card, Moran, & Newell, 1983), but EPIC incorporates many recent theoretical and empiri- cal results about human performance in the form of a software framework for computer simulation modeling. Using EPIC, a model can be con- structed...

Quantum theory of the mazer. I. General theory

Georg Meyer — 2008-04-13T00:01:39-00:00

Physical Review A, Vol. 56, No. 5. (1 November 1997), 4142.

Quantum theory of the mazer. II. Extensions and experimental considerations

Markus Löffler — 2008-04-12T23:27:03-00:00

Physical Review A, Vol. 56, No. 5. (1 November 1997), 4153.

Drugs, their targets and the nature and number of drug targets

Peter Imming — 2006-10-02T16:41:00-00:00

Nature Reviews Drug Discovery, Vol. 5, No. 10., pp. 821-834.

Breaking Dawn (The Twilight Saga, Book 4)

Stephenie Meyer — 2008-06-27T12:33:29-00:00

(02 August 2008)

>Twilight tempted the imagination. _New Moon_ made readers thirsty for more. _Eclipse _turned the saga into a worldwide phenomenon. And now, the book that everyone has been waiting for.... ** > > > >Breaking Dawn, the final book in the #1 bestselling Twilight Saga, will take your breath away.** >

Regionalmarketing: Grundlagen, Konzepte, Anwendung

Jörn-Axel Meyer — 2008-07-16T15:15:24-00:00

Are polymer melts "ideal"?

JP Wittmer — 2008-07-16T15:04:38-00:00

Computer Physics Communications, Vol. 177, No. 1-2. (July 2007), pp. 146-149.

It is commonly accepted that in concentrated solutions or melts high-molecular weight polymers display random-walk conformational properties without long-range correlations between subsequent bonds. This absence of memory means, for instance, that the bond-bond correlation function, P(s), of two bonds separated by s monomers along the chain should exponentially decay with s. Presenting numerical results and theoretical arguments for both monodisperse chains and self-assembled (essentially Flory size-distributed) equilibrium polymers we demonstrate that some long-range correlations remain due to self-interactions of the chains caused by the chain connectivity and the incompressibility of the melt. Suggesting a profound analogy with the well-known long-range velocity correlations in liquids we find, for instance, P(s) to decay algebraically as s-3/2. Our study suggests a precise method for obtaining the statistical segment length be in a computer experiment.

Protein labeling by iTRAQ: a new tool for quantitative mass spectrometry in proteome research.

S Wiese — 2007-07-13T01:50:39-00:00

Proteomics, Vol. 7, No. 3. (February 2007), pp. 340-350.

A novel, MS-based approach for the relative quantification of proteins, relying on the derivatization of primary amino groups in intact proteins using isobaric tag for relative and absolute quantitation (iTRAQ) is presented. Due to the isobaric mass design of the iTRAQ reagents, differentially labeled proteins do not differ in mass; accordingly, their corresponding proteolytic peptides appear as single peaks in MS scans. Because quantitative information is provided by isotope-encoded reporter ions that can only be observed in MS/MS spectra, we analyzed the fragmentation behavior of ESI and MALDI ions of peptides generated from iTRAQ-labeled proteins using a TOF/TOF and/or a QTOF instrument. We observed efficient liberation of reporter ions for singly protonated peptides at low-energy collision conditions. In contrast, increased collision energies were required to liberate the iTRAQ label from lysine side chains of doubly charged peptides and, thus, to observe reporter ions suitable for relative quantification of proteins with high accuracy. We then developed a quantitative strategy that comprises labeling of intact proteins by iTRAQ followed by gel electrophoresis and peptide MS/MS analyses. As proof of principle, mixtures of five different proteins in various concentration ratios were quantified, demonstrating the general applicability of the approach presented here to quantitative MS-based proteomics.

Behind the looking-glass

Antonio Damasio — 2008-07-10T18:32:03-00:00

Nature, Vol. 454, No. 7201. (09 July 2008), pp. 167-168.

Functional discovery via a compendium of expression profiles.

TR Hughes — 2004-11-22T00:17:30-00:00

Cell, Vol. 102, No. 1. (7 July 2000), pp. 109-126.

Ascertaining the impact of uncharacterized perturbations on the cell is a fundamental problem in biology. Here, we describe how a single assay can be used to monitor hundreds of different cellular functions simultaneously. We constructed a reference database or "compendium" of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae, and we show that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles. The utility of this approach is validated by examining profiles caused by deletions of uncharacterized genes: we identify and experimentally confirm that eight uncharacterized open reading frames encode proteins required for sterol metabolism, cell wall function, mitochondrial respiration, or protein synthesis. We also show that the compendium can be used to characterize pharmacological perturbations by identifying a novel target of the commonly used drug dyclonine.

The alliance for cellular signaling plasmid collection: a flexible resource for protein localization studies and signaling pathway analysis.

JR Zavzavadjian — 2007-06-27T02:46:42-00:00

Mol Cell Proteomics, Vol. 6, No. 3. (March 2007), pp. 413-424.

Cellular responses to inputs that vary both temporally and spatially are determined by complex relationships between the components of cell signaling networks. Analysis of these relationships requires access to a wide range of experimental reagents and techniques, including the ability to express the protein components of the model cells in a variety of contexts. As part of the Alliance for Cellular Signaling, we developed a robust method for cloning large numbers of signaling ORFs into Gateway entry vectors, and we created a wide range of compatible expression platforms for proteomics applications. To date, we have generated over 3000 plasmids that are available to the scientific community via the American Type Culture Collection. We have established a website at www.signaling-gateway.org/data/plasmid/ that allows users to browse, search, and blast Alliance for Cellular Signaling plasmids. The collection primarily contains murine signaling ORFs with an emphasis on kinases and G protein signaling genes. Here we describe the cloning, databasing, and application of this proteomics resource for large scale subcellular localization screens in mammalian cell lines.

Inhaled iloprost for severe pulmonary hypertension.

H Olschewski — 2008-07-11T15:52:16-00:00

The New England journal of medicine, Vol. 347, No. 5. (1 August 2002), pp. 322-329.

BACKGROUND: Uncontrolled studies suggested that aerosolized iloprost, a stable analogue of prostacyclin, causes selective pulmonary vasodilatation and improves hemodynamics and exercise capacity in patients with pulmonary hypertension. METHODS: We compared repeated daily inhalations of 2.5 or 5.0 microg of iloprost (six or nine times per day; median inhaled dose, 30 microg per day) with inhalation of placebo. A total of 203 patients with selected forms of severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (New York Heart Association [NYHA] functional class III or IV) were included. The primary end point was met if, after week 12, the NYHA class and distance walked in six minutes were improved by at least one class and at least 10 percent, respectively, in the absence of clinical deterioration according to predefined criteria and death. RESULTS: The combined clinical end point was met by 16.8 percent of the patients receiving iloprost, as compared with 4.9 percent of the patients receiving placebo (P=0.007). There were increases in the distance walked in six minutes of 36.4 m in the iloprost group as a whole (P=0.004) and of 58.8 m in the subgroup of patients with primary pulmonary hypertension. Overall, 4.0 percent of patients in the iloprost group (including one who died) and 13.7 percent of those in the placebo group (including four who died) did not complete the study (P=0.024); the most common reason for withdrawal was clinical deterioration. As compared with base-line values, hemodynamic values were significantly improved at 12 weeks when measured after iloprost inhalation (P<0.001), were largely unchanged when measured before iloprost inhalation, and were significantly worse in the placebo group. Further significant beneficial effects of iloprost treatment included an improvement in the NYHA class (P=0.03), dyspnea (P=0.015), and quality of life (P=0.026). Syncope occurred with similar frequency in the two groups but was more frequently rated as serious in the iloprost group, although this adverse effect was not associated with clinical deterioration. CONCLUSIONS: Inhaled iloprost is an effective therapy for patients with severe pulmonary hypertension.

Pharmacogenetics - five decades of therapeutic lessons from genetic diversity.

UA Meyer — 2008-07-09T17:51:31-00:00

Nature reviews. Genetics, Vol. 5, No. 9. (September 2004), pp. 669-676.

Physicians have long been aware of the subtle differences in the responses of patients to medication. The recognition that a part of this variation is inherited, and therefore predictable, created the field of pharmacogenetics fifty years ago. Knowing the gene variants that cause differences among patients has the potential to allow 'personalized' drug therapy and to avoid therapeutic failure and serious side effects.

Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients.

D Worlitzsch — 2006-11-20T01:20:07-00:00

J Clin Invest, Vol. 109, No. 3. (February 2002), pp. 317-325.

Current theories of CF pathogenesis predict different predisposing "local environmental" conditions and sites of bacterial infection within CF airways. Here we show that, in CF patients with established lung disease, Pseudomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In vitro studies revealed that CF-specific increases in epithelial O(2) consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate production. With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted. These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments.

Replication of 1q42 linkage in Finnish schizophrenia pedigrees.

J Ekelund — 2008-07-08T18:52:50-00:00

Molecular psychiatry, Vol. 9, No. 11. (November 2004), pp. 1037-1041.

Chromosome 1q has been implicated in the etiology of schizophrenia in several independent studies. However, the peak linkage findings have been dispersed over a large chromosomal region, with negative findings in this region also being reported. Our group has previously observed linkage on chromosome 1q42, maximizing within the DISC1 gene, which has also been implied in the etiology of schizophrenia based on functional studies. In the study presented here, we genotyped 300 polymorphic markers on chromosome 1 using a study sample of 70 families with multiple individuals affected with schizophrenia or related conditions, independent of the study samples in our previous reports. We again found evidence for linkage on 1q42 maximizing within the DISC1 gene (rs1000731, lod=2.70). Further, a haplotype containing the most strongly linked markers showed some evidence of association with the disease. This replicates the previous linkage finding in the same region and constitutes supportive evidence for a susceptibility gene in this region.

Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects

William Hennah — 2007-05-01T11:30:06-00:00

Hum. Mol. Genet., Vol. 12, No. 23. (1 December 2003), pp. 3151-3159.

We have previously reported a linkage peak on 1q42 in a Finnish schizophrenia sample. In this study we genotyped 28 single nucleotide polymorphisms (SNPs) from 1q42 covering the three candidate genes TRAX, DISC1 and DISC2, using a study sample of 458 Finnish families ascertained for schizophrenia. Two-point and haplotype association analysis revealed a significant region of interest within the DISC1 gene. A common haplotype (HEP3) was observed to be significantly under-transmitted to affected individuals (P=0.0031). HEP3 represents a two SNP haplotype spanning from intron 1 to exon 2 of DISC1. This haplotype also displayed sex differences in transmission distortion, the under-transmission being significant only to affected females (P=0.00024). Three other regions of interest were observed in the TRAX and DISC genes. However, analysis of only those families with complete genotype information specifically highlights the HEP3 haplotype as a true observation. The finding of a common under-transmitted SNP haplotype might imply that this particular allele offers some protection from the development of schizophrenia. Analysis of component-traits of schizophrenia, derived from the Operational Criteria Checklist of Psychotic Illness (OCCPI), displayed association of HEP3 to features of the general phenotype of schizophrenia, including traits representing delusions, hallucinations and negative symptoms. This study provides further evidence for the hypothesis that the DISC1 gene is involved in the aetiology of schizophrenia, and implies a putative sex difference for the effect of the gene. Our findings would also encourage more detailed analyses of the effect of DISC1 on the component-traits of schizophrenia. 10.1093/hmg/ddg341

Chromosome 1 loci in Finnish schizophrenia families.

J Ekelund — 2008-07-08T18:50:44-00:00

Human molecular genetics, Vol. 10, No. 15. (15 July 2001), pp. 1611-1617.

We have earlier reported evidence for linkage to two regions on chromosome 1q32--q42 in schizophrenia families collected for two separate studies in Finland. Here we report the results of a fine mapping effort aimed at further definition of the chromosomal region of interest using a large, population-based study sample (221 families, 557 affected individuals). Most affecteds (78%) had a DSM-IV schizophrenia diagnosis and the remaining had schizophrenia spectrum disorders. We genotyped a total of 147 microsatellite markers on a wide 45 cM region of chromosome 1q. The results were analyzed separately for families originating from an internal isolate of Finland and for families from the rest of Finland, as well as for all families jointly. We used traditional two-point linkage analysis, SimWalk2 multipoint analysis and a novel gamete-competition association/linkage method. Evidence for linkage was obtained for one locus in the combined sample (Z(max) = 2.71, D1S2709) and in the nuclear families from outside the internal isolate (Z(max) = 3.21, D1S2709). In the families from the internal isolate the strongest evidence for linkage was obtained with markers located 22 cM centromeric from this marker (Z(max) = 2.30, D1S245). Multipoint analysis also indicated these loci. Some evidence for association with several markers was observed using the gamete-competition method. Interestingly, the strongest evidence for linkage in the combined study sample was obtained for marker D1S2709, which is an intragenic marker of the DISC1 gene, previously suggested as a susceptibility gene for schizophrenia. These results are consistent with the presence of susceptibility gene(s) in this chromosomal region, a result also implied in other recent family studies of schizophrenia.

Pharmacogenetics and adverse drug reactions

Urs Meyer — 2008-07-08T08:43:26-00:00

The Lancet, Vol. 356, No. 9242. (11 November 2000), pp. 1667-1671.

Summary Polymorphisms in the genes that code for drug-metabolising enzymes, drug transporters, drug receptors, and ion channels can affect an individual's risk of having an adverse drug reaction, or can alter the efficacy of drug treatment in that individual. Mutant alleles at a single gene locus are the best studied individual risk factors for adverse drug reactions, and include many genes coding for drug-metabolising enzymes. These genetic polymorphisms of drug metabolism produce the phenotypes of "poor metabolisers" or "ultrarapid metabolisers" of numerous drugs. Together, such phenotypes make up a substantial proportion of the population. Pharmacogenomic techniques allow efficient analysis of these risk factors, and genotyping tests have the potential to optimise drug therapy in the future.

Hospital Utilization among Chronic Dialysis Patients

Pradeep Arora — 2008-07-08T06:49:37-00:00

J Am Soc Nephrol, Vol. 11, No. 4. (1 April 2000), pp. 740-746.

Abstract. Factors driving inpatient and outpatient utilization were studied among patients who began dialysis for chronic renal failure at the New England Medical Center (NEMC) between 1992 and 1997. Clinical, laboratory, and hospital resource utilization data were obtained from patient records and electronic databases. There were 2.2 hospitalizations and 14.8 hospital days per patient year at risk (PYAR). The number of hospitalizations and hospital days per PYAR were higher in the first 3 mo of initiating dialysis (4.3 and 28.3, respectively) compared to after 3 mo (1.9 and 12.9, respectively). Factors associated with increased risk of hospital days within the first 3 mo included non-health maintenance organization insurance, ischemic heart disease, late referral to the nephrologist, and use of temporary vascular access for the first dialysis. Patients with ischemic heart disease and who received dialysis during the years 1992-1994 compared with 1996-1997 had an increased risk of hospital days after 3 mo of initiating dialysis. There were 16.6 outpatient visits per PYAR, with significant differences in utilization between the first 3 mo and after 3 mo of initiating dialysis. Thus, hospital utilization was significantly higher in the first 3 mo compared to after 3 mo, and factors associated with hospital utilization depended on duration of dialysis. In particular, delayed referral to the nephrologist and lack of permanent vascular access were independently associated with increased risk of hospital utilization in the first 3 mo of dialysis. Greater attention to timely referral to the nephrologist and timely placement of vascular access could result in reduced utilization and cost savings.

Translational control of intron splicing in eukaryotes

Olivier Jaillon — 2008-01-16T20:57:48-00:00

Nature, Vol. 451, No. 7176. (17 January 2008), pp. 359-362.

Comorbidity assessment using the Index of Coexistent Diseases in a multicenter clinical trial

Dana Miskulin — 2008-07-08T03:24:29-00:00

Kidney Int, Vol. 60, No. 4. (October 2001), pp. 1498-1510.

The structure of suspended graphene sheets

Jannik Meyer — 2007-03-02T05:22:46-00:00

Nature, Vol. 446, No. 7131., pp. 60-63.

Untwisting of a Cholesteric Elastomer by a Mechanical Field

M Warner — 2008-07-07T15:24:49-00:00

Physical Review Letters, Vol. 85, No. 11. (2000), 2320.

Parrondo Games as Lattice Gas Automata

David Meyer — 2008-07-07T11:59:29-00:00

Journal of Statistical Physics, Vol. 107, No. 1. (1 April 2002), pp. 225-239.

Parrondo games are coin flipping games with the surprising property that alternating plays of two losing games can produce a winning game. We show that this phenomenon can be modelled by probabilistic lattice gas automata. Furthermore, motivated by the recent introduction of quantum coin flipping games, we show that quantum lattice gas automata provide an interesting definition for quantum Parrondo games.

Posttraumatic GABAA-Mediated [Ca2+]i Increase Is Essential for the Induction of Brain-Derived Neurotrophic Factor-Dependent Survival of Mature Central Neurons

Anastasia Shulga — 2008-07-07T11:39:07-00:00

J. Neurosci., Vol. 28, No. 27. (2 July 2008), pp. 6996-7005.

A shift of GABAA-mediated responses from hyperpolarizing to depolarizing after neuronal injury leads to GABAA-mediated increase in [Ca2+]i. In addition, central neurons become dependent on BDNF for survival. Whether these two mechanisms are causally interrelated is an open question. Here, we show in lesioned CA3 hippocampal neurons in vitro and in axotomized corticospinal neurons in vivo that posttraumatic downregulation of the neuron-specific K-Cl cotransporter KCC2 leads to intracellular chloride accumulation by the Na-K-2Cl cotransporter NKCC1, resulting in GABA-induced [Ca2+]i transients. This mechanism is required by a population of neurons to survive in a BDNF-dependent manner after injury, because blocking GABAA-depolarization with the NKCC1 inhibitor bumetanide prevents the loss of neurons on BDNF withdrawal. The resurgence of KCC2 expression during recovery coincides with loss of BDNF dependency for survival. This is likely mediated through BDNF itself, because injured neurons reverse their response to this neurotrophin by switching the BDNF-induced downregulation of KCC2 to upregulation. 10.1523/JNEUROSCI.5268-07.2008

Telomere length and cardiovascular risk factors in a middle-aged population free of overt cardiovascular disease

Bekaert — 2007-09-19T03:30:59-00:00

Aging Cell, Vol. 6, No. 5. (October 2007), pp. 639-647.

SimulFold: Simultaneously Inferring RNA Structures Including Pseudoknots, Alignments, and Trees Using a Bayesian MCMC Framework

Irmtraud Meyer — 2007-09-12T08:57:09-00:00

PLoS Computational Biology, Vol. 3, No. 8. (1 August 2007), e149.

Computational methods for predicting evolutionarily conserved rather than thermodynamic RNA structures have recently attracted increased interest. These methods are indispensable not only for elucidating the regulatory roles of known RNA transcripts, but also for predicting RNA genes. It has been notoriously difficult to devise them to make the best use of the available data and to predict high-quality RNA structures that may also contain pseudoknots. We introduce a novel theoretical framework for co-estimating an RNA secondary structure including pseudoknots, a multiple sequence alignment, and an evolutionary tree, given several RNA input sequences. We also present an implementation of the framework in a new computer program, called SimulFold, which employs a Bayesian Markov chain Monte Carlo method to sample from the joint posterior distribution of RNA structures, alignments, and trees. We use the new framework to predict RNA structures, and comprehensively evaluate the quality of our predictions by comparing our results to those of several other programs. We also present preliminary data that show SimulFold's potential as an alignment and phylogeny prediction method. SimulFold overcomes many conceptual limitations that current RNA structure prediction methods face, introduces several new theoretical techniques, and generates high-quality predictions of conserved RNA structures that may include pseudoknots. It is thus likely to have a strong impact, both on the field of RNA structure prediction and on a wide range of data analyses.

Energy-momentum tensor correlators and spectral functions

Harvey Meyer — 2008-07-03T08:53:38-00:00

(24 Jun 2008)

We calculate the thermal Euclidean correlators and the spectral functions of the energy-momentum tensor for pure gauge theories, including at non-zero spatial momentum, at leading order in perturbation theory. Our goal is to improve the extraction of transport properties from Euclidean correlators that are computable in lattice QCD. Based on our results and the predictions of hydrodynamics for the structure of the spectral functions at low frequencies, we show that the shear and bulk viscosities can advantageously be extracted from the Euclidean correlators of the conserved charges, energy and momentum, at small but non-vanishing spatial momentum. The spectral functions in these channels are free of the ultraviolet $ω^4$ term which represents a large background to the thermal physics encoded in the correlators of the fluxes.

Bisimulation can't be traced

Bard Bloom — 2008-07-02T16:46:52-00:00

J. ACM, Vol. 42, No. 1. (January 1995), pp. 232-268.

Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina.

S Blankenberg — 2008-07-02T03:46:22-00:00

Circulation, Vol. 106, No. 1. (2 July 2002), pp. 24-30.

BACKGROUND: Interleukin (IL)-18 plays a central role in orchestrating the cytokine cascade and accelerates atherosclerosis and plaque vulnerability in animal models. However, epidemiological data evaluating the role of IL-18 levels in atherosclerosis are lacking. METHODS AND RESULTS: In a prospective study of 1229 patients with documented coronary artery disease, we measured baseline serum concentrations of IL-18 and other markers of inflammation. During the follow-up period (median, 3.9 years), 95 patients died of cardiovascular causes. Median serum concentrations of IL-18 were significantly higher among patients who had a fatal cardiovascular event than among those who did not (68.4 versus 58.7 pg/mL; P<0.0001). The hazard risk ratio of future cardiovascular death increased with increasing quartiles of IL-18 (hazard risk ratio, 1.46; 95% CI 1.21 to 1.76; P for trend <0.0001). After adjustment for most potential confounders, including the strong predictor ejection fraction as well as the inflammatory variables IL-6, high-sensitive C-reactive protein, and fibrinogen, this relation remained almost unchanged, such that patients within the highest quartile of IL-18 had a 3.3-fold increase in hazard risk compared with those in the first quartile (95% CI, 1.3 to 8.4, P=0.01). This relation was observed in patients with stable angina and patients with unstable angina at baseline. CONCLUSIONS: Serum IL-18 level was identified as a strong independent predictor of death from cardiovascular causes in patients with coronary artery disease regardless of the clinical status at admission. This result strongly supports recent experimental evidence of IL-18-mediated inflammation leading to acceleration and vulnerability of atherosclerotic plaques.

Non-Arrhenius ionic conductivity in optimized fast ion conducting glasses: application of the Drude model to ion-ion scattering

Steve Martin — 2008-06-30T16:04:57-00:00

Journal of Non-Crystalline Solids, Vol. 307-310 (September 2002), pp. 981-991.

Enhancement of Auditory-evoked Potentials in Musicians Reflects an Influence of Expertise but not Selective Attention.

Simon Baumann — 2008-06-30T15:07:07-00:00

Journal of cognitive neuroscience (5 May 2008)

Abstract Instrumental tones and, in some instances, simple sine-wave tones were shown to evoke stronger auditory-evoked responses in musicians compared to nonmusicians. This effect was taken as an example for plasticity in the auditory cortex elicited by training. To date, however, it is unknown whether an enlarged cortical representation for (instrumental) tones or increased neuronal activity provoked by focused attention in musicians accounts for the reported difference. In an attempt to systematically investigate the influence of attention on the processing of simple sine wave and instrumental tones, we compared auditory-evoked potentials recorded from musicians and nonmusicians. During the electroencephalogram recording, the participants were involved in tasks requiring selective attention to specific sound features such as pitch or timbre. Our results demonstrate that the effect of selective attention on the auditory event-related potential (AEP) has a different time course and shows a different topography than the reproduced effect of music expertise at the N1 component or the previously demonstrated effect at the P2 component. N1 peak potentials were unaffected by attention modulation. These results indicate that the effect of music expertise, which was traced by current density mapping to the auditory cortex, is not primarily caused by selective attention, and it supports the view that increased AEPs on tones in musicians reflect an enlarged neuronal representation for specific sound features of these tones. However, independent from the N1-P2 complex, attention evoked an Nd-like negative component in musicians but not in nonmusicians, which suggests that plasticity also affects top-down processes.

Observation of spectral asymmetry in cw-pumped type-II spontaneous parametric down-conversion

Zhi Zhao — 2008-06-30T14:50:13-00:00

Physical Review A (Atomic, Molecular, and Optical Physics), Vol. 77, No. 6. (2008)

We report on a spectral asymmetry in cw-pumped type-II spontaneous parametric down-conversion. We observe that when the pump beam is focused, the spectra of ordinary and extraordinary down-converted photons broaden unequally. Theoretical analysis indicates that this asymmetry can be attributed to the difference in the angular dispersion (walk-off) of the two kinds of photons, coupled with the well-known correlation between wavelength and emission direction.

Recent progress in understanding hydrophobic interactions.

EE Meyer — 2007-11-23T03:42:48-00:00

Proc Natl Acad Sci U S A, Vol. 103, No. 43. (24 October 2006), pp. 15739-15746.

We present here a brief review of direct force measurements between hydrophobic surfaces in aqueous solutions. For almost 70 years, researchers have attempted to understand the hydrophobic effect (the low solubility of hydrophobic solutes in water) and the hydrophobic interaction or force (the unusually strong attraction of hydrophobic surfaces and groups in water). After many years of research into how hydrophobic interactions affect the thermodynamic properties of processes such as micelle formation (self-assembly) and protein folding, the results of direct force measurements between macroscopic surfaces began to appear in the 1980s. Reported ranges of the attraction between variously prepared hydrophobic surfaces in water grew from the initially reported value of 80-100 Angstrom to values as large as 3,000 Angstrom. Recent improved surface preparation techniques and the combination of surface force apparatus measurements with atomic force microscopy imaging have made it possible to explain the long-range part of this interaction (at separations >200 Angstrom) that is observed between certain surfaces. We tentatively conclude that only the short-range part of the attraction (<100 Angstrom) represents the true hydrophobic interaction, although a quantitative explanation for this interaction will require additional research. Although our force-measuring technique did not allow collection of reliable data at separations <10 Angstrom, it is clear that some stronger force must act in this regime if the measured interaction energy curve is to extrapolate to the measured adhesion energy as the surface separation approaches zero (i.e., as the surfaces come into molecular contact).

Insight into the proteome of the hyperthermophilic Crenarchaeon Ignicoccus hospitalis: the major cytosolic and membrane proteins.

Tillmann Burghardt — 2008-06-29T03:47:40-00:00

Archives of microbiology (27 June 2008)

Ignicoccus hospitalis, a hyperthermophilic, chemolithoautotrophic Crenarchaeon, is the host of Nanoarchaeum equitans. Together, they form an intimate association, the first among Archaea. Membranes are of fundamental importance for the interaction of I. hospitalis and N. equitans, as they harbour the proteins necessary for the transport of macromolecules like lipids, amino acids, and cofactors between these organisms. Here, we investigated the protein inventory of I. hospitalis cells, and were able to identify 20 proteins in total. Experimental evidence and predictions let us conclude that 11 are soluble cytosolic proteins, eight membrane or membrane-associated proteins, and a single one extracellular. The quantitatively dominating proteins in the cytoplasm (peroxiredoxin; thermosome) antagonize oxidative and temperature stress which I. hospitalis cells are exposed to at optimal growth conditions. Three abundant membrane protein complexes are found: the major protein of the outer membrane, which might protect the cell against the hostile environment, forms oligomeric complexes with pores of unknown selectivity; two other complexes of the cytoplasmic membrane, the hydrogenase and the ATP synthase, play a key role in energy production and conversion.

Expression of two T cell receptor alpha chains: dual receptor T cells

E Padovan — 2008-06-28T22:43:06-00:00

Science, Vol. 262, No. 5132. (15 October 1993), pp. 422-424.

Although many T cells carry two in-frame V alpha rearrangements, the products of both V alpha rearrangements have never been shown simultaneously on the surface of normal cells. With the use of monoclonal antibodies to V alpha 2, V alpha 12, and V alpha 24, up to one-third of mature T cells expressed two V alpha chains as part of two functional and independent T cell receptors (TCRs). Thus, the "one cell, one receptor" rule does not apply to a large subset of alpha beta T cells. Cells that belong to this dual TCR subset may be specific for a broader range of antigens than cells with a single receptor, which may be important for autoimmunity and alloreactivity. 10.1126/science.8211163