A powerful and efficient set test for genetic markers that handles confounders

Approaches for testing sets of variants, such as a set of rare or common variants within a gene or pathway, for association with complex traits are important. In particular, set tests allow for aggregation of weak signal within a set, can capture interplay among variants, and reduce the burden of multiple hypothesis testing. Until now, these approaches did not address confounding by family relatedness and population structure, a problem that is becoming more important as larger data sets are used to increase power. Results: We introduce a new approach for set tests that handles confounders. Our model is based on the linear mixed model and uses two random effects-one to capture the set association signal and one to capture confounders. We also introduce a computational speedup for two-random-effects models that makes this approach feasible even for extremely large cohorts. Using this model with both the likelihood ratio test and score test, we find that the former yields more power while controlling type I error. Application of our approach to richly structured GAW14 data demonstrates that our method successfully corrects for population structure and family relatedness, while application of our method to a 15,000 individual Crohn's disease case-control cohort demonstrates that it additionally recovers genes not recoverable by univariate analysis. Availability: A Python-based library implementing our approach is available at http://mscompbio.codeplex.comComment: * denotes equal contribution

Isostructural Phase Transition of TiN Under High Pressure

In situ high-pressure energy dispersive x-ray diffraction experiments on polycrystalline powder TiN with NaCl-type structure have been conducted with the pressure up to 30.1 GPa by using the diamond anvil cell instrument with synchrotron radiation at room tempearture. The experimental results suggested that an isostructural phase transition might exist at about 7 GPa as revealed by the discontinuity of V/V0 with pressure.Comment: submitte

Doppler Parameters in Renal Transplant Dysfunction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135678/1/jum2011302169.pd

Single-layer graphene on silicon nitride micromembrane resonators

Due to their exceptional mechanical and optical properties, dielectric silicon nitride (SiN) micromembrane resonators have become the centerpiece of many optomechanical experiments. Efficient capacitive coupling of the membrane to an electrical system would facilitate exciting hybrid optoelectromechanical devices. However, capacitive coupling of such dielectric membranes is rather weak. Here we add a single layer of graphene on SiN micromembranes and compare electromechanical coupling and mechanical properties to bare dielectric membranes and to membranes metallized with an aluminium layer. The electrostatic coupling of graphene coated membranes is found to be equal to a perfectly conductive membrane. Our results show that a single layer of graphene substantially enhances the electromechanical capacitive coupling without significantly adding mass, decreasing the superior mechanical quality factor or affecting the optical properties of SiN micromembrane resonators

Acoustic detection of microbubble formation induced by enhanced optical breakdown of silver/dendrimer nanocomposites

We utilize a real-time acoustic technique, based on pulse-echo measurements to detect formation of microbubbles in an aqueous solution of a silver/dendrimer nanocomposite (DNC). Wave-field plots of successive recordings illustrate the generation and behavior of bubbles created by the optical breakdown process. A significant threshold reduction is achieved with DNC particles compared to its host dendrimer, enabling a diverse field of low-threshold breakdown applications. © 2003 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70570/2/APPLAB-82-6-994-1.pd

Dynamic expression of cytokine and transcription factor genes during experimental Fasciola gigantica infection in buffaloes

Background Determining the mechanisms involved in the immune-pathogenesis of the tropical liver fluke, Fasciola gigantica, is crucial to the development of any effective therapeutic intervention. Here, we examined the differential gene expression of cytokines and transcription factors in the liver of F. gigantica-infected buffaloes, over the course of infection. Methods Water buffaloes (swamp type) were infected orally with 500 F. gigantica encysted metacercariae. Liver tissue samples were collected 3, 10, 28, 42, 70 and 98 days post-infection (dpi). Levels of gene expression of nine cytokines (IFN-γ, TGF-β, IL-1β, IL-4, IL-6, IL-10, IL-12B, IL-13 and IL-17A) and four transcription factors (T-bet, GATA-3, Foxp3 and ROR-γτ) were determined using quantitative real-time PCR (qRT-PCR). We evaluated any correlation between gene expression of these immune-regulatory factors and the severity of liver pathology. Results Histopathological examination revealed that cellular infiltration, hemorrhage and fibrosis without calcification in the liver parenchyma of infected buffaloes, increased over the course of infection. This progressive pathology was attributed to dysregulated and excessive inflammatory responses induced by infection. The early infection phase (3–10 dpi) was marked by a generalized immunosuppression and elevated TGF-β expression in order to facilitate parasite colonization. A mixed Th1/Th2 immune response was dominant from 28 to 70 dpi, to promote parasite survival while minimizing host tissue damage. During late infection (98 dpi), the response was biased towards Th1/Treg in order to inhibit the host’s Th2 protective response and promote chronic infection. Both IL-10 and IL-17A and the Th17/Treg balance, played key roles in mediating the inflammatory and immunoregulatory mechanisms in the liver during chronic fasciolosis. Conclusions Our data showed distinct CD4+ T helper (Th) polarization and cytokine dysregulation in response to F. gigantica infection in water buffaloes over the course of infection. Characterizing the temporal expression profiles for host immune genes during infection should provide important information for defining how F. gigantica adapts and survives in the liver of buffaloes and how host immune responses influence F. gigantica pathogenicity

Generation of cloned transgenic pigs rich in omega-3 fatty acids

Meat products are generally low in omega-3 (n-3) fatty acids, which are beneficial to human health. We describe the generation of cloned pigs that express a humanized Caenorhabditis elegans gene, fat-1, encoding an n-3 fatty acid desaturase. The hfat-1 transgenic pigs produce high levels of n-3 fatty acids from n-6 analogs, and their tissues have a significantly reduced ratio of n-6/n-3 fatty acids (P < 0.001). © 2006 Nature Publishing Group

Quantum Algebras Associated With Bell States

The antisymmetric solution of the braided Yang--Baxter equation called the Bell matrix becomes interesting in quantum information theory because it can generate all Bell states from product states. In this paper, we study the quantum algebra through the FRT construction of the Bell matrix. In its four dimensional representations via the coproduct of its two dimensional representations, we find algebraic structures including a composition series and a direct sum of its two dimensional representations to characterize this quantum algebra. We also present the quantum algebra using the FRT construction of Yang--Baxterization of the Bell matrix.Comment: v1: 15 pages, 2 figures, latex; v2: 18 pages, 2 figures, latex, references and notes adde

The splicing factor SR2 is an important virulence factor of Toxoplasma gondii

Serine/arginine-rich (SR) proteins are key factors with important roles in constitutive and alternative splicing (AS) of pre-mRNAs. However, the role of SR splicing factors in the pathogenicity of T. gondii remains largely unexplored. Here, we investigated the role of splicing factor SR2, a homolog of Plasmodium falciparum SR1, in the pathogenicity of T. gondii. We functionally characterized the predicted SR2 in T. gondii by gene knockout and studied its subcellular localization by endogenous protein HA tagging using CRISPR-Cas9 gene editing. The results showed that SR2 was localized in the nucleus and expressed in the tachyzoite and bradyzoite stages. In vitro studies including plaque formation, invasion, intracellular replication, egress and bradyzoite differentiation assays showed that deletion of SR2 in type I RH strain and type II Pru strains had no significant effect on the parasite growth and bradyzoite differentiation (p &gt; 0.05). Interestingly, the disruption of SR2 in RH type I (p &lt; 0.0001) and Pru type II (p &lt; 0.05) strains resulted in varying degrees of attenuated virulence. In addition, disruption of SR2 in type II Pru strain significantly reduced brain cyst burden by ~80% (p &lt; 0.0001). Collectively, these results suggest that splicing factor SR2 is important for the pathogenicity of T. gondii, providing a new target for the control and treatment of toxoplasmosis