HTS pulse-stretcher and second order modulator: design and first results

One of the remaining challenges in the application of superconducting electronics is the interfacing between superconducting and semiconducting environments. The voltage and speed mismatch between RSFQ pulses and semiconducting read-out electronics makes it necessary to amplify as well as stretch the RSFQ pulses. Moreover, circuits based on HTS (High Temperature Superconductor) technology are very attractive since they can operate under considerably relaxed cooling effort, which is one of the main problems with LTS (Low Temperature Superconductor) circuits. Within the European project SuperADC, a HTS second order sigma delta modulator and a pulse stretcher, used as an interface between the modulator and the first semi-conducting amplifier stage, have been designed at Twente University and will be presented here

Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics

Bioprospecting Finds the Toughest Biological Material: Extraordinary Silk from a Giant Riverine Orb Spider

Background Combining high strength and elasticity, spider silks are exceptionally tough, i.e., able to absorb massive kinetic energy before breaking. Spider silk is therefore a model polymer for development of high performance biomimetic fibers. There are over 41.000 described species of spiders, most spinning multiple types of silk. Thus we have available some 200.000+ unique silks that may cover an amazing breadth of material properties. To date, however, silks from only a few tens of species have been characterized, most chosen haphazardly as model organisms (Nephila) or simply from researchers' backyards. Are we limited to ‘blindly fishing’ in efforts to discover extraordinary silks? Or, could scientists use ecology to predict which species are likely to spin silks exhibiting exceptional performance properties? Methodology We examined the biomechanical properties of silk produced by the remarkable Malagasy ‘Darwin's bark spider’ (Caerostris darwini), which we predicted would produce exceptional silk based upon its amazing web. The spider constructs its giant orb web (up to 2.8 m2) suspended above streams, rivers, and lakes. It attaches the web to substrates on each riverbank by anchor threads as long as 25 meters. Dragline silk from both Caerostris webs and forcibly pulled silk, exhibits an extraordinary combination of high tensile strength and elasticity previously unknown for spider silk. The toughness of forcibly silked fibers averages 350 MJ/m3, with some samples reaching 520 MJ/m3. Thus, C. darwini silk is more than twice tougher than any previously described silk, and over 10 times better than Kevlar®. Caerostris capture spiral silk is similarly exceptionally tough. Conclusions Caerostris darwini produces the toughest known biomaterial. We hypothesize that this extraordinary toughness coevolved with the unusual ecology and web architecture of these spiders, decreasing the likelihood of bridgelines breaking and collapsing the web into the river. This hypothesis predicts that rapid change in material properties of silk co-occurred with ecological shifts within the genus, and can thus be tested by combining material science, behavioral observations, and phylogenetics. Our findings highlight the potential benefits of natural history–informed bioprospecting to discover silks, as well as other materials, with novel and exceptional properties to serve as models in biomimicry.Primary funding for this work came from the Slovenian Research Agency (grant Z1-9799-0618-07 to I. Agnarsson), the National Geographic Society (grant 8655-09 to the authors), and the National Science Foundation (grants DBI-0521261, DEB-0516038 and IOS-0745379 to T. Blackledge). Additional funding came from the European Community 6th Framework Programme (a Marie Curie International Reintegration Grant MIRG-CT-2005 036536 to M. Kuntner). The 2001 field work was supported by the Sallee Charitable Trust grant to I. Agnarsson and M. Kuntner and by a United States National Science Foundation grant (DEB-9712353) to G. Hormiga and J. A. Coddington. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Angiotensin converting enzyme gene polymorphism is associated with severity of coronary artery disease in men with high total cholesterol levels

This study examines whether renin-angiotensin-aldosterone system gene polymorphisms: ACE (encoding for angiotensin converting enzyme) c.2306-117_404 I/D, AGTR1 (encoding for angiotensin II type-1 receptor) c.1080*86A>C and CYP11B2 (encoding for aldosterone synthase) c.-344C>T are associated with the extension of coronary atherosclerosis in a group of 647 patients who underwent elective coronary angiography. The extension of CAD was evaluated using the Gensini score. The polymorphisms were determined by PCR and RFLP assays. The associations between genotypes and the extent of coronary atherosclerosis were tested by the Kruskal-Wallis test, followed by pairwise comparisons using Wilcoxon test. The population has been divided into groups defined by: sex, smoking habit, past myocardial infarction, BMI (>, ≤ 25), age (>, ≤ 55), diabetes mellitus, level of total cholesterol (>, ≤ 200 mg/dl), LDL cholesterol (>, ≤ 130 mg/dl), HDL cholesterol (>, ≤ 40 mg/dl), triglycerides (>, ≤ 150 mg/dl). Significant associations between the ACE c.2306-117_404 I/D polymorphism and the Gensini score in men with high total cholesterol levels (PKruskal-Wallis = 0.008; Padjusted = 0.009), high level of LDL cholesterol (PKruskal-Wallis = 0.016; Padjusted = 0.028) and low level of HDL cholesterol (PKruskal-Wallis = 0.04; Padjusted = 0.055) have been found. No association between the AGTR1 c.1080*86A>C and CYP11B2 c.-344C>T and the Gensini score has been found. These results suggest that men who carry ACE c.2306-117_404 DD genotype and have high total cholesterol, high LDL cholesterol and low HDL cholesterol levels may be predisposed to the development of more severe CAD

Plasticity in Major Ampullate Silk Production in Relation to Spider Phylogeny and Ecology

Spider major ampullate silk is a high-performance biomaterial that has received much attention. However, most studies ignore plasticity in silk properties. A better understanding of silk plasticity could clarify the relative importance of chemical composition versus processing of silk dope for silk properties. It could also provide insight into how control of silk properties relates to spider ecology and silk uses

ACE (I/D) polymorphism and response to treatment in coronary artery disease: a comprehensive database and meta-analysis involving study quality evaluation

<p>Abstract</p> <p>Background</p> <p>The role of angiotensin-converting enzyme (<it>ACE</it>) gene insertion/deletion (<it>I/D</it>) polymorphism in modifying the response to treatment modalities in coronary artery disease is controversial.</p> <p>Methods</p> <p>PubMed was searched and a database of 58 studies with detailed information regarding <it>ACE I/D </it>polymorphism and response to treatment in coronary artery disease was created. Eligible studies were synthesized using meta-analysis methods, including cumulative meta-analysis. Heterogeneity and study quality issues were explored.</p> <p>Results</p> <p>Forty studies involved invasive treatments (coronary angioplasty or coronary artery by-pass grafting) and 18 used conservative treatment options (including anti-hypertensive drugs, lipid lowering therapy and cardiac rehabilitation procedures). Clinical outcomes were investigated by 11 studies, while 47 studies focused on surrogate endpoints. The most studied outcome was the restenosis following coronary angioplasty (34 studies). Heterogeneity among studies (p < 0.01) was revealed and the risk of restenosis following balloon angioplasty was significant under an additive model: the random effects odds ratio was 1.42 (95% confidence interval:1.07–1.91). Cumulative meta-analysis showed a trend of association as information accumulates. The results were affected by population origin and study quality criteria. The meta-analyses for the risk of restenosis following stent angioplasty or after angioplasty and treatment with angiotensin-converting enzyme inhibitors produced non-significant results. The allele contrast random effects odds ratios with the 95% confidence intervals were 1.04(0.92–1.16) and 1.10(0.81–1.48), respectively. Regarding the effect of <it>ACE I/D </it>polymorphism on the response to treatment for the rest outcomes (coronary events, endothelial dysfunction, left ventricular remodeling, progression/regression of atherosclerosis), individual studies showed significance; however, results were discrepant and inconsistent.</p> <p>Conclusion</p> <p>In view of available evidence, genetic testing of <it>ACE I/D </it>polymorphism prior to clinical decision making is not currently justified. The relation between <it>ACE </it>genetic variation and response to treatment in CAD remains an unresolved issue. The results of long-term and properly designed prospective studies hold the promise for pharmacogenetically tailored therapy in CAD.</p

The M235T Polymorphism in the AGT Gene and CHD Risk: Evidence of a Hardy-Weinberg Equilibrium Violation and Publication Bias in a Meta-Analysis

BACKGROUND: The M235T polymorphism in the AGT gene has been related to an increased risk of hypertension. This finding may also suggest an increased risk of coronary heart disease (CHD). METHODOLOGY/PRINCIPAL FINDINGS: A case-cohort study was conducted in 1,732 unrelated middle-age women (210 CHD cases and 1,522 controls) from a prospective cohort of 15,236 initially healthy Dutch women. We applied a Cox proportional hazards model to study the association of the polymorphism with acute myocardial infarction (AMI) (n = 71) and CHD. In the case-cohort study, no increased risk for CHD was found under the additive genetic model (hazard ratio [HR] = 1.20; 95% confidence interval [CI], 0.86 to 1.68; P = 0.28). This result was not changed by adjustment (HR = 1.17; 95% CI, 0.83 to 1.64; P = 0.38) nor by using dominant, recessive and pairwise genetic models. Analyses for AMI risk under the additive genetic model also did not show any statistically significant association (crude HR = 1.14; 95% CI, 0.93 to 1.39; P = 0.20). To evaluate the association, a comprehensive systematic review and meta-analysis were undertaken of all studies published up to February 2007 (searched through PubMed/MEDLINE, Web of Science and EMBASE). The meta-analysis (38 studies with 13284 cases and 18722 controls) showed a per-allele odds ratio (OR) of 1.08 (95% CI, 1.01 to 1.15; P = 0.02). Moderate to large levels of heterogeneity were identified between studies. Hardy-Weinberg equilibrium (HWE) violation and the mean age of cases were statistically significant sources of the observed variation. In a stratum of non-HWE violation studies, there was no effect. An asymmetric funnel plot, the Egger's test (P = 0.066), and the Begg-Mazumdar test (P = 0.074) were all suggestive of the presence of publication bias. CONCLUSIONS/SIGNIFICANCE: The pooled OR of the present meta-analysis, including our own data, presented evidence that there is an increase in the risk of CHD conferred by the M235T variant of the AGT gene. However, the relevance of this weakly positive overall association remains uncertain because it may be due to various residual biases, including HWE-violation and publication biases