A microfluidic device for array patterning by perpendicular electrokinetic focusing

This paper describes a microfluidic chip in which two perpendicular laminar-flow streams can be operated to sequentially address the surface of a flow-chamber with semi-parallel sample streams. The sample streams can be controlled in position and width by the method of electrokinetic focusing. For this purpose, each of the two streams is sandwiched by two parallel sheath flow streams containing just a buffer solution. The streams are being electroosmotically pumped, allowing a simple chip design and a setup with no moving parts. Positioning of the streams was adjusted in real-time by controlling the applied voltages according to an analytical model. The perpendicular focusing gives rise to overlapping regions, which, by combinatorial (bio) chemistry, might be used for fabrication of spot arrays of immobilized proteins and other biomolecules. Since the patterning procedure is done in a closed, liquid filled flow-structure, array spots will never be exposed to air and are prevented from drying. With this device configuration, it was possible to visualize an array of 49 spots on a surface area of 1 mm2. This article describes the principle, fabrication, experimental results, analytical modeling and numerical simulations of the microfluidic chip.\ud \ud \ud \u

Response, relaxation and transport in unconventional superconductors

We investigate the collision-limited electronic Raman response and the attenuation of ultrasound in spin-singlet d-wave superconductors at low temperatures. The dominating elastic collisions are treated within a t-matrix approximation, which combines the description of weak (Born) and strong (unitary) impurity scattering. In the long wavelength limit a two-fluid description of both response and transport emerges. Collisions are here seen to exclusively dominate the relaxational dynamics of the (Bogoliubov) quasiparticle system and the analysis allows for a clear connection of response and transport phenomena. When applied to quasi-2-d superconductors like the cuprates, it turns out that the transport parameter associated with the Raman scattering intensity for B1g and B2g photon polarization is closely related to the corresponding components of the shear viscosity tensor, which dominates the attenuation of ultrasound. At low temperatures we present analytic solutions of the transport equations, resulting in a non-power-law behavior of the transport parameters on temperature.Comment: 22 pages, 3 figure

The molecular epidemiology of human immunodeficiency virus type 1 in six cities in Britain and Ireland

The authors sequenced the p17 coding regions of the gag gene from 211 patients infected either through injecting drug use (IDU) or by sexual intercourse between men from six cities in Scotland, N. England, N. Ireland, and the Republic of Ireland. All sequences were of subtype 5. Phylogenetic analysis revealed substantial heterogeneity in the sequences from homosexual men. In contrast, sequence from over 80% of IDUs formed a relatively tight cluster, distinct both from those of published isolates and of the gay men. There was no large-scale clustering of sequences by city in either risk group, although a number of close associations between pairs of individuals were observed. From the known date of the HIV-1 epidemic among IDUs in Edinburgh, the rate of sequence divergence at synonymous sites is estimated to be about 0.8%. On this basis it has been estimated that the date of divergence of the sequences among homosexual men to be about 1975, which may correspond to the origin of the B subtype epidemic

The CALBC Silver Standard Corpus for Biomedical Named Entities - A Study in Harmonizing the Contributions from Four Independent Named Entity Taggers

The production of gold standard corpora is time-consuming and costly. We propose an alternative: the 'silver standard corpus' (SSC), a corpus that has been generated by the harmonisation of the annotations that have been delivered from a selection of annotation systems. The systems have to share the type system for the annotations and the harmonisation solution has use a suitable similarity measure for the pair-wise comparison of the annotations. The annotation systems have been evaluated against the harmonised set (630.324 sentences, 15, 956, 841 tokens). We can demonstrate that the annotation of proteins and genes shows higher diversity across all used annotation solutions leading to a lower agreement against the harmonised set in comparison to the annotations of diseases and species. An analysis of the most frequent annotations from all systems shows that a high agreement amongst systems leads to the selection of terms that are suitable to be kept in the harmonised set. This is the first large-scale approach to generate an annotated corpus from automated annotation systems. Further research is required to understand, how the annotations from different systems have to be combined to produce the best annotation result for a harmonised corpus

Hard-Sphere Fluids in Contact with Curved Substrates

The properties of a hard-sphere fluid in contact with hard spherical and cylindrical walls are studied. Rosenfeld's density functional theory (DFT) is applied to determine the density profile and surface tension $\gamma$ for wide ranges of radii of the curved walls and densities of the hard-sphere fluid. Particular attention is paid to investigate the curvature dependence and the possible existence of a contribution to $\gamma$ that is proportional to the logarithm of the radius of curvature. Moreover, by treating the curved wall as a second component at infinite dilution we provide an analytical expression for the surface tension of a hard-sphere fluid close to arbitrary hard convex walls. The agreement between the analytical expression and DFT is good. Our results show no signs for the existence of a logarithmic term in the curvature dependence of $\gamma$.Comment: 15 pages, 6 figure

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Supermassive Black Hole Binaries: The Search Continues

Gravitationally bound supermassive black hole binaries (SBHBs) are thought to be a natural product of galactic mergers and growth of the large scale structure in the universe. They however remain observationally elusive, thus raising a question about characteristic observational signatures associated with these systems. In this conference proceeding I discuss current theoretical understanding and latest advances and prospects in observational searches for SBHBs.Comment: 17 pages, 4 figures. To appear in the Proceedings of 2014 Sant Cugat Forum on Astrophysics. Astrophysics and Space Science Proceedings, ed. C.Sopuerta (Berlin: Springer-Verlag

De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.

We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results