Testing Multiple Hypotheses through IMP weighted FDR Based on a Genetic Functional Network with Application to a New Zebrafish Transcriptome Study

In genome-wide studies, hundreds of thousands of hypothesis tests are performed simultaneously. Bonferroni correction and False Discovery Rate (FDR) can effectively control type I error but often yield a high false negative rate. We aim to develop a more powerful method to detect differentially expressed genes. We present a Weighted False Discovery Rate (WFDR) method that incorporate biological knowledge from genetic networks. We first identify weights using Integrative Multi-species Prediction (IMP) and then apply the weights in WFDR to identify differentially expressed genes through an IMP-WFDR algorithm. We performed a gene expression experiment to identify zebrafish genes that change expression in the presence of arsenic during a systemic Pseudomonas aeruginosa infection. Zebrafish were exposed to arsenic at 10 parts per billion and/or infected with P. aeruginosa. Appropriate controls were included. We then applied IMP-WFDR during the analysis of differentially expressed genes. We compared the mRNA expression for each group and found over 200 differentially expressed genes and several enriched pathways including defense response pathways, arsenic response pathways, and the Notch signaling pathway

Willingness to Participate in HIV Cure Research: Survey Results from 400 People Living with HIV in the United States

Introduction Participation in early-phase HIV cure studies includes clinical risks with little to no likelihood of clinical benefit. Examining the willingness of people living with HIV to participate is important to guide study design and informed consent. Our study examined the overall willingness of people living with HIV to participate in HIV cure research in the US, focusing on perceived risks and benefits of participation. Methods We undertook an online survey of adults living with HIV in the US. Survey questions were developed based on previous research and a scoping review of the literature. We quantitatively assessed individuals’ perceived risks and benefits of HIV cure-related research and respondents’ willingness to participate in different modalities of HIV cure studies. Results We recruited 409 study participants of whom 400 were eligible for the study and were included in the analysis (nine were not eligible due to self-declared HIV-negative status). We found >50% willingness to participate in 14 different types of HIV cure studies. Perceived clinical benefits and social benefits were important motivators, while personal clinical risks appeared to deter potential participation. Roughly two-thirds of survey respondents (68%) indicated that they were somewhat willing to stop treatment as part of HIV cure research. In the bivariate models, females, African Americans/blacks, Hispanics, individuals in the lowest income bracket, people living with HIV for longer periods of their lives, and people who were self-perceived ‘very healthy’ were less willing to participate in certain types of HIV cure studies than others. Multivariate results showed the perceived benefits (adjusted odds ratios >1) and perceived risks (adjusted odds ratios <1) acted as potential motivators and deterrents to participation, respectively. Conclusion Our study is the first attempt to quantify potential motivators and deterrents of participation in HIV cure research in the US using perceived risks and benefits. The results offer guidance to HIV cure researchers and developers of interventions about the beneficial and detrimental characteristics of HIV cure strategies that are most meaningful to people living with HIV. The study also highlights new potential lines of inquiry for further social science and ethics research

Superstrings and Topological Strings at Large N

We embed the large N Chern-Simons/topological string duality in ordinary superstrings. This corresponds to a large $N$ duality between generalized gauge systems with N=1 supersymmetry in 4 dimensions and superstrings propagating on non-compact Calabi-Yau manifolds with certain fluxes turned on. We also show that in a particular limit of the N=1 gauge theory system, certain superpotential terms in the N=1 system (including deformations if spacetime is non-commutative) are captured to all orders in 1/N by the amplitudes of non-critical bosonic strings propagating on a circle with self-dual radius. We also consider D-brane/anti-D-brane system wrapped over vanishing cycles of compact Calabi-Yau manifolds and argue that at large $N$ they induce a shift in the background to a topologically distinct Calabi-Yau, which we identify as the ground state system of the Brane/anti-Brane system.Comment: 30 pages, some minor clarifications adde

Green Plants in the Red: A Baseline Global Assessment for the IUCN Sampled Red List Index for Plants

Plants provide fundamental support systems for life on Earth and are the basis for all terrestrial ecosystems; a decline in plant diversity will be detrimental to all other groups of organisms including humans. Decline in plant diversity has been hard to quantify, due to the huge numbers of known and yet to be discovered species and the lack of an adequate baseline assessment of extinction risk against which to track changes. The biodiversity of many remote parts of the world remains poorly known, and the rate of new assessments of extinction risk for individual plant species approximates the rate at which new plant species are described. Thus the question ‘How threatened are plants?’ is still very difficult to answer accurately. While completing assessments for each species of plant remains a distant prospect, by assessing a randomly selected sample of species the Sampled Red List Index for Plants gives, for the first time, an accurate view of how threatened plants are across the world. It represents the first key phase of ongoing efforts to monitor the status of the world’s plants. More than 20% of plant species assessed are threatened with extinction, and the habitat with the most threatened species is overwhelmingly tropical rain forest, where the greatest threat to plants is anthropogenic habitat conversion, for arable and livestock agriculture, and harvesting of natural resources. Gymnosperms (e.g. conifers and cycads) are the most threatened group, while a third of plant species included in this study have yet to receive an assessment or are so poorly known that we cannot yet ascertain whether they are threatened or not. This study provides a baseline assessment from which trends in the status of plant biodiversity can be measured and periodically reassessed

NC Calabi-Yau Orbifolds in Toric Varieties with Discrete Torsion

Using the algebraic geometric approach of Berenstein et {\it al} (hep-th/005087 and hep-th/009209) and methods of toric geometry, we study non commutative (NC) orbifolds of Calabi-Yau hypersurfaces in toric varieties with discrete torsion. We first develop a new way of getting complex $d$ mirror Calabi-Yau hypersurfaces $H_{\Delta}^{\ast d}$ in toric manifolds $M_{\Delta }^{\ast (d+1)}$ with a $C^{\ast r}$ action and analyze the general group of the discrete isometries of $H_{\Delta}^{\ast d}$. Then we build a general class of $d$ complex dimension NC mirror Calabi-Yau orbifolds where the non commutativity parameters $\theta_{\mu \nu}$ are solved in terms of discrete torsion and toric geometry data of $M_{\Delta}^{(d+1)}$ in which the original Calabi-Yau hypersurfaces is embedded. Next we work out a generalization of the NC algebra for generic $d$ dimensions NC Calabi-Yau manifolds and give various representations depending on different choices of the Calabi-Yau toric geometry data. We also study fractional D-branes at orbifold points. We refine and extend the result for NC $T^{2})/(\mathbf{{Z_{2}}\times {Z_{2})}}$ to higher dimensional torii orbifolds in terms of Clifford algebra.Comment: 38 pages, Late

Inflationary Reheating in Grand Unified Theories

Grand unified theories may display multiply interacting fields with strong coupling dynamics. This poses two new problems: (1) What is the nature of chaotic reheating after inflation, and (2) How is reheating sensitive to the mass spectrum of these theories ? We answer these questions in two interesting limiting cases and demonstrate an increased efficiency of reheating which strongly enhances non-thermal topological defect formation, including monopoles and domain walls. Nevertheless, the large fluctuations may resolve this monopole problem via a modified Dvali-Liu-Vachaspati mechanism in which non-thermal destabilsation of discrete symmetries occurs at reheating.Comment: 4 pages, 5 ps figures - 1 colour, Revtex. Further (colour & 3-D) figures available from http://www.sissa.it/~bassett/reheating/ . Matched to version to appear in Phys. Rev. let

Effective superpotentials for compact D5-brane Calabi-Yau geometries

For compact Calabi-Yau geometries with D5-branes we study N=1 effective superpotentials depending on both open- and closed-string fields. We develop methods to derive the open/closed Picard-Fuchs differential equations, which control D5-brane deformations as well as complex structure deformations of the compact Calabi-Yau space. Their solutions encode the flat open/closed coordinates and the effective superpotential. For two explicit examples of compact D5-brane Calabi-Yau hypersurface geometries we apply our techniques and express the calculated superpotentials in terms of flat open/closed coordinates. By evaluating these superpotentials at their critical points we reproduce the domain wall tensions that have recently appeared in the literature. Finally we extract orbifold disk invariants from the superpotentials, which, up to overall numerical normalizations, correspond to orbifold disk Gromov-Witten invariants in the mirror geometry.Comment: 55 pages; v2: references added, typos correcte

A Classification of 3-Family Grand Unification in String Theory I. The SO(10) and E_6 Models

We give a classification of 3-family SO(10) and E_6 grand unification in string theory within the framework of conformal field theory and asymmetric orbifolds. We argue that the construction of such models in the heterotic string theory requires certain Z_6 asymmetric orbifolds that include a Z_3 outer-automorphism, the latter yielding a level-3 current algebra for the grand unification gauge group SO(10) or E_6. We then classify all such Z_6 asymmetric orbifolds that result in models with a non-abelian hidden sector. All models classified in this paper have only one adjoint (but no other higher representation) Higgs field in the grand unified gauge group. In addition, all of them are completely anomaly free. There are two types of such 3-family models. The first type consists of the unique SO(10) model with SU(2) X SU(2) X SU(2) as its hidden sector (which is not asymptotically-free at the string scale). This SO(10) model has 4 left-handed and 1 right-handed 16s. The second type is described by a moduli space containing 17 models (distinguished by their massless spectra). All these models have an SU(2) hidden sector, and 5 left-handed and 2 right-handed families in the grand unified gauge group. One of these models is the unique E_6 model with an asymptotically-free SU(2) hidden sector. The others are SO(10) models, 8 of them with an asymptotically free hidden sector at the string scale.Comment: 35 pages, Revtex 3.0, one eps figure (to appear in Phys. Rev. D

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

D-branes, Categories and N=1 Supersymmetry

We show that boundary conditions in topological open string theory on Calabi-Yau manifolds are objects in the derived category of coherent sheaves, as foreseen in the homological mirror symmetry proposal of Kontsevich. Together with conformal field theory considerations, this leads to a precise criterion determining the BPS branes at any point in CY moduli space, completing the proposal of Pi-stability.Comment: harvmac, 41 pp., 2 figures. (v4: corrected errors; added explanations