The Geometric Phase and Gravitational Precession of D-Branes

We study Berry's phase in the D0-D4-brane system. When a D0-brane moves in the background of D4-branes, the first excited states undergo a holonomy described by a non-Abelian Berry connection. At weak coupling this is an SU(2) connection over R^5, known as the Yang monopole. At strong coupling, the holonomy is recast as the classical gravitational precession of a spinning particle. The Berry connection is the spin connection of the near-horizon limit of the D4-branes, which is a continuous deformation of the Yang and anti-Yang monopole.Comment: 23 pages; v3: typos correcte

The Geometric Phase in Supersymmetric Quantum Mechanics

We explore the geometric phase in N=(2,2) supersymmetric quantum mechanics. The Witten index ensures the existence of degenerate ground states, resulting in a non-Abelian Berry connection. We exhibit a non-renormalization theorem which prohibits the connection from receiving perturbative corrections. However, we show that it does receive corrections from BPS instantons. We compute the one-instanton contribution to the Berry connection for the massive CP^1 sigma-model as the potential is varied. This system has two ground states and the associated Berry connection is the smooth SU(2) 't Hooft-Polyakov monopole.Comment: 28 pages, 2 figures, references added. v2: clarification of possible corrections to Abelian Berry phase. v3: footnotes added to point the reader towards later development

A directly comparative two-gate case–control diagnostic accuracy study of the pure tone screen and HearCheck screener tests for identifying hearing impairment in school children

Objectives: This study directly compared the accuracy of two audiometry-based tests for screening school children for hearing impairment: the currently used test, pure tone screen and a device newly applied to children, HearCheck Screener. Design: Two-gate case–control diagnostic test accuracy study. Setting and participants: Hearing impaired children (‘intended cases’) aged 4–6 years were recruited between February 2013 and August 2014 from collaborating audiology services. Children with no previously identified impairment (‘intended controls’) were recruited from Foundation and Year 1 of schools between February 2013 and June 2014 in central England. The reference standard was pure tone audiometry. Tests were administered at Nottingham Hearing Biomedical Research Unit or, for some intended cases only, in the participant’s home. Main outcome measures: Sensitivity and specificity of the pure tone screen and HearCheck tests based on pure tone audiometry result as reference standard. Results: 315 children (630 ears) were recruited; 75 from audiology services and 240 from schools. Full test and reference standard data were obtained for 600 ears; 155 ears were classified as truly impaired and 445 as truly hearing based on the pure tone audiometry assessment. Sensitivity was estimated to be 94.2% (95% CI 89.0% to 97.0%) for pure tone screen and 89.0% (95% CI 82.9% to 93.1%) for HearCheck (difference=5.2% favouring pure tone screen; 95% CI 0.2% to 10.1%; p=0.02). Estimates for specificity were 82.2% (95% CI 77.7% to 86.0%) for pure tone screen and 86.5% (95% CI 82.5% to 89.8%) for HearCheck (difference=4.3% favouring HearCheck; 95% CI0.4% to 8.2%; p=0.02). Conclusion: Pure tone screen was better than HearCheck with respect to sensitivity but inferior with respect to specificity. As avoiding missed cases is arguably of greater importance for school entry screening, pure tone screen is probably preferable in this context

SNX27–Retromer directly binds ESCPE-1 to transfer cargo proteins during endosomal recycling

Coat complexes coordinate cargo recognition through cargo adaptors with biogenesis of transport carriers during integral membrane protein trafficking. Here, we combine biochemical, structural, and cellular analyses to establish the mechanistic basis through which SNX27-Retromer, a major endosomal cargo adaptor, couples to the membrane remodeling endosomal SNX-BAR sorting complex for promoting exit 1 (ESCPE-1). In showing that the SNX27 FERM (4.1/ezrin/radixin/moesin) domain directly binds acidic-Asp-Leu-Phe (aDLF) motifs in the SNX1/SNX2 subunits of ESCPE-1, we propose a handover model where SNX27-Retromer captured cargo proteins are transferred into ESCPE-1 transport carriers to promote endosome-to-plasma membrane recycling. By revealing that assembly of the SNX27:Retromer:ESCPE-1 coat evolved in a stepwise manner during early metazoan evolution, likely reflecting the increasing complexity of endosome-to-plasma membrane recycling from the ancestral opisthokont to modern animals, we provide further evidence of the functional diversification of yeast pentameric Retromer in the recycling of hundreds of integral membrane proteins in metazoans

High throughput analysis of epistasis in genome-wide association studies with BiForce

Motivation: Gene–gene interactions (epistasis) are thought to be important in shaping complex traits, but they have been under-explored in genome-wide association studies (GWAS) due to the computational challenge of enumerating billions of single nucleotide polymorphism (SNP) combinations. Fast screening tools are needed to make epistasis analysis routinely available in GWAS. Results: We present BiForce to support high-throughput analysis of epistasis in GWAS for either quantitative or binary disease (case–control) traits. BiForce achieves great computational efficiency by using memory efficient data structures, Boolean bitwise operations and multithreaded parallelization. It performs a full pair-wise genome scan to detect interactions involving SNPs with or without significant marginal effects using appropriate Bonferroni-corrected significance thresholds. We show that BiForce is more powerful and significantly faster than published tools for both binary and quantitative traits in a series of performance tests on simulated and real datasets. We demonstrate BiForce in analysing eight metabolic traits in a GWAS cohort (323 697 SNPs, >4500 individuals) and two disease traits in another (>340 000 SNPs, >1750 cases and 1500 controls) on a 32-node computing cluster. BiForce completed analyses of the eight metabolic traits within 1 day, identified nine epistatic pairs of SNPs in five metabolic traits and 18 SNP pairs in two disease traits. BiForce can make the analysis of epistasis a routine exercise in GWAS and thus improve our understanding of the role of epistasis in the genetic regulation of complex traits. Availability and implementation: The software is free and can be downloaded from http://bioinfo.utu.fi/BiForce/. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

The 2dF Galaxy Redshift Survey: Wiener reconstruction of the cosmic web

We reconstruct the underlying density field of the Two-degree Field Galaxy Redshift Survey (2dFGRS) for the redshift range 0.035 < z < 0.200 using the Wiener filtering method. The Wiener filter suppresses shot noise and accounts for selection and incompleteness effects. The method relies on prior knowledge of the 2dF power spectrum of fluctuations and the combination of matter density and bias parameters, however the results are only slightly affected by changes to these parameters. We present maps of the density field. We use a variable smoothing technique with two different effective resolutions: 5 and 10 h−1 Mpc at the median redshift of the survey. We identify all major superclusters and voids in the survey. In particular, we find two large superclusters and two large local voids. The full set of colour maps can be viewed on the World Wide Web a

Two-Photon Imaging of Cortical Surface Microvessels Reveals a Robust Redistribution in Blood Flow after Vascular Occlusion

A highly interconnected network of arterioles overlies mammalian cortex to route blood to the cortical mantle. Here we test if this angioarchitecture can ensure that the supply of blood is redistributed after vascular occlusion. We use rodent parietal cortex as a model system and image the flow of red blood cells in individual microvessels. Changes in flow are quantified in response to photothrombotic occlusions to individual pial arterioles as well as to physical occlusions of the middle cerebral artery (MCA), the primary source of blood to this network. We observe that perfusion is rapidly reestablished at the first branch downstream from a photothrombotic occlusion through a reversal in flow in one vessel. More distal downstream arterioles also show reversals in flow. Further, occlusion of the MCA leads to reversals in flow through approximately half of the downstream but distant arterioles. Thus the cortical arteriolar network supports collateral flow that may mitigate the effects of vessel obstruction, as may occur secondary to neurovascular pathology