Theory of Chiral Modulations and Fluctuations in Smectic-A Liquid Crystals Under an Electric Field

Chiral liquid crystals often exhibit periodic modulations in the molecular director; in particular, thin films of the smectic-C* phase show a chiral striped texture. Here, we investigate whether similar chiral modulations can occur in the induced molecular tilt of the smectic-A phase under an applied electric field. Using both continuum elastic theory and lattice simulations, we find that the state of uniform induced tilt can become unstable when the system approaches the smectic-A--smectic-C* transition, or when a high electric field is applied. Beyond that instability point, the system develops chiral stripes in the tilt, which induce corresponding ripples in the smectic layers. The modulation persists up to an upper critical electric field and then disappears. Furthermore, even in the uniform state, the system shows chiral fluctuations, including both incipient chiral stripes and localized chiral vortices. We compare these predictions with observed chiral modulations and fluctuations in smectic-A liquid crystals.Comment: 11 pages, including 9 postscript figures, uses REVTeX 3.0 and epsf.st

Lentiviral shRNA knock-down of ADAMTS-5 and-9 restores matrix deposition in 3D chondrocyte culture

Aggrecan is one of the two major constituents of articular cartilage, and during diseases such as osteoarthritis (OA) it is subject to degradation by proteolytic enzymes. The primary proteases responsible for aggrecan cleavage are the aggrecanases, identified as members of the ADAMTS family of proteases, which are upregulated in response to inflammatory stimuli. It is uncertain which of the six aggrecanases (ADAMTS‐1, ‐4, ‐5, ‐8, ‐9 and ‐15) are primarily responsible for the degradation of aggrecan in human cartilage. Here we show that four of the six aggrecanases are expressed in immortalized chondrocyte cell‐lines and can be upregulated in response to inflammatory cytokines. Using RNA interference, we demonstrate robust knock‐down of ADAMTS‐5 and ‐9 expression in these cells and, by culturing them on three‐dimensional (3D) scaffolds, show that reduction in expression of ADAMTS‐5 enzyme results in an increase in matrix deposition. These data suggest that the quality of tissue‐engineered cartilage matrix might be improved by targeted depletion of aggrecanase expression. Moreover, this work also provides further evidence that ADAMTS‐5 may be a therapeutic target in the treatment of arthritic disease

Phenotypic Variation in FAM83H- associated Amelogenesis Imperfecta

FAM83H gene mutations are associated with autosomal-dominant hypocalcified amelogenesis imperfecta (ADHCAI), which is typically characterized by enamel having normal thickness and a markedly decreased mineral content. This study tested the hypothesis that there are phenotype and genotype associations in families with FAM83H-associated ADHCAI. Seven families segregating ADHCAI (147 individuals) were evaluated. Phenotyping included clinical, radiographic, histological, and biochemical studies, and genotyping was by mutational analysis. Multiple novel FAM83H mutations were identified, including two 2-bp-deletion mutations, the first non-nonsense mutations identified. Craniofacial deviation from normal was more prevalent in the affected individuals. Affected individuals having truncating FAMH3H mutations of 677 or fewer amino acids presented a generalized ADHCAI phenotype, while those having mutations capable of producing a protein of at least 694 amino acids had a unique and previously unreported phenotype affecting primarily the cervical enamel. This investigation shows that unique phenotypes are associated with specific FAM83H mutations

An Experimental Investigation of Colonel Blotto Games

"This article examines behavior in the two-player, constant-sum Colonel Blotto game with asymmetric resources in which players maximize the expected number of battlefields won. The experimental results support all major theoretical predictions. In the auction treatment, where winning a battlefield is deterministic, disadvantaged players use a 'guerilla warfare' strategy which stochastically allocates zero resources to a subset of battlefields. Advantaged players employ a 'stochastic complete coverage' strategy, allocating random, but positive, resource levels across the battlefields. In the lottery treatment, where winning a battlefield is probabilistic, both players divide their resources equally across all battlefields." (author's abstract)"Dieser Artikel untersucht das Verhalten von Individuen in einem 'constant-sum Colonel Blotto'-Spiel zwischen zwei Spielern, bei dem die Spieler mit unterschiedlichen Ressourcen ausgestattet sind und die erwartete Anzahl gewonnener Schlachtfelder maximieren. Die experimentellen Ergebnisse bestätigen alle wichtigen theoretischen Vorhersagen. Im Durchgang, in dem wie in einer Auktion der Sieg in einem Schlachtfeld deterministisch ist, wenden die Spieler, die sich im Nachteil befinden, eine 'Guerillataktik' an, und verteilen ihre Ressourcen stochastisch auf eine Teilmenge der Schlachtfelder. Spieler mit einem Vorteil verwenden eine Strategie der 'stochastischen vollständigen Abdeckung', indem sie zufällig eine positive Ressourcenmenge auf allen Schlachtfeldern positionieren. Im Durchgang, in dem sich der Gewinn eines Schlachtfeldes probabilistisch wie in einer Lotterie bestimmt, teilen beide Spieler ihre Ressourcen gleichmäßig auf alle Schlachtfelder auf." (Autorenreferat

Au+Au Reactions at the AGS: Experiments E866 and E917

Particle production and correlation functions from Au+Au reactions have been measured as a function of both beam energy (2-10.7AGeV) and impact parameter. These results are used to probe the dynamics of heavy-ion reactions, confront hadronic models over a wide range of conditions and to search for the onset of new phenomena.Comment: 12 pages, 14 figures, Talk presented at Quark Matter '9

Enrichment analyses identify shared associations for 25 quantitative traits in over 600,000 individuals from seven diverse ancestries

Since 2005, genome-wide association (GWA) datasets have been largely biased toward sampling European ancestry individuals, and recent studies have shown that GWA results estimated from self-identified European individuals are not transferable to non-European individuals because of various confounding challenges. Here, we demonstrate that enrichment analyses that aggregate SNP-level association statistics at multiple genomic scales—from genes to genomic regions and pathways—have been underutilized in the GWA era and can generate biologically interpretable hypotheses regarding the genetic basis of complex trait architecture. We illustrate examples of the robust associations generated by enrichment analyses while studying 25 continuous traits assayed in 566,786 individuals from seven diverse self-identified human ancestries in the UK Biobank and the Biobank Japan as well as 44,348 admixed individuals from the PAGE consortium including cohorts of African American, Hispanic and Latin American, Native Hawaiian, and American Indian/Alaska Native individuals. We identify 1,000 gene-level associations that are genome-wide significant in at least two ancestry cohorts across these 25 traits as well as highly conserved pathway associations with triglyceride levels in European, East Asian, and Native Hawaiian cohorts

Physical and optical properties of the International Simple Glass

Radioactive waste immobilization is a means to limit the release of radionuclides from various waste streams into the environment over a timescale of hundreds to many thousands of years. Incorporation of radionuclide-containing wastes into borosilicate glass during vitrification is one potential route to accomplish such immobilization. To facilitate comparisons and assessments of reproducibility across experiments and laboratories, a six-component borosilicate glass (Si, B, Na, Al, Ca, Zr) known as the International Simple Glass (ISG) was developed by international consensus as a compromise between simplicity and similarity to waste glasses. Focusing on a single glass composition with a multi-pronged approach utilizing state-of-the-art, multi-scale experimental and theoretical tools provides a common database that can be used to assess relative importance of mechanisms and models. Here we present physical property data (both published and previously unpublished) on a single batch of ISG, which was cast into individual ingots that were distributed to the collaborators. Properties from the atomic scale to the macroscale, including composition and elemental impurities, phase purity, density, thermal properties, mechanical properties, optical and vibrational properties, and the results of molecular dynamics simulations are presented. In addition, information on the surface composition and morphology after polishing is included. Although the existing literature on the alteration of ISG is not extensively reviewed here, the results of well-controlled static alteration experiments are presented here as a point of reference for other performance investigations

Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV

A search for pair-production of supersymmetric particles under the assumption that R-parity is violated via a dominant LQDbar coupling has been performed using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV. The observed candidate events in the data are in agreement with the Standard Model expectation. This result is translated into lower limits on the masses of charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81 GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the 95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure

The use of phenome-wide association studies (PheWAS) for exploration of novel genotype-phenotype relationships and pleiotropy discovery

The field of phenomics has been investigating network structure among large arrays of phenotypes, and genome-wide association studies (GWAS) have been used to investigate the relationship between genetic variation and single diseases/outcomes. A novel approach has emerged combining both the exploration of phenotypic structure and genotypic variation, known as the phenome-wide association study (PheWAS). The Population Architecture using Genomics and Epidemiology (PAGE) network is a National Human Genome Research Institute (NHGRI)-supported collaboration of four groups accessing eight extensively characterized epidemiologic studies. The primary focus of PAGE is deep characterization of well-replicated GWAS variants and their relationships to various phenotypes and traits in diverse epidemiologic studies that include European Americans, African Americans, Mexican Americans/Hispanics, Asians/Pacific Islanders, and Native Americans. The rich phenotypic resources of PAGE studies provide a unique opportunity for PheWAS as each genotyped variant can be tested for an association with the wide array of phenotypic measurements available within the studies of PAGE, including prevalent and incident status for multiple common clinical conditions and risk factors, as well as clinical parameters and intermediate biomarkers. The results of PheWAS can be used to discover novel relationships between SNPs, phenotypes, and networks of interrelated phenotypes; identify pleiotropy; provide novel mechanistic insights; and foster hypothesis generation. The PAGE network has developed infrastructure to support and perform PheWAS in a high-throughput manner. As implementing the PheWAS approach has presented several challenges, the infrastructure and methodology, as well as insights gained in this project, are presented herein to benefit the larger scientific community

Replication of genetic loci for ages at menarche and menopause in the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) study

Do genetic associations identified in genome-wide association studies (GWAS) of age at menarche (AM) and age at natural menopause (ANM) replicate in women of diverse race/ancestry from the Population Architecture using Genomics and Epidemiology (PAGE) Study