NSeq: a multithreaded Java application for finding positioned nucleosomes from sequencing data

We introduce NSeq, a fast and efficient Java application for finding positioned nucleosomes from the high-throughput sequencing of MNase-digested mononucleosomal DNA. NSeq includes a user-friendly graphical interface, computes false discovery rates (FDRs) for candidate nucleosomes from Monte Carlo simulations, plots nucleosome coverage and centers, and exploits the availability of multiple processor cores by parallelizing its computations. Java binaries and source code are freely available at https://github.com/songlab/NSeq. The software is supported on all major platforms equipped with Java Runtime Environment 6 or later

Volume stabilization via α′ corrections in type IIB theory with fluxes

We consider the type IIB string theory in the presence of various extra 7/-brane pairs compactified on a warped Calabi-Yau threefold that admits a conifold singularity. We demonstrate that the volume modulus can be stabilized perturbatively at a non-supersymmetric AdS4/dS4 vacuum by the effective potential that includes the stringy (α')3 correction obtained by Becker et al. together with a combination of positive tension and anomalous negative tension terms generated by the additional 7-brane-antibrane pairs

Volume Stabilization via α′\alpha^\prime Corrections in Type IIB Theory with Fluxes

We consider the Type IIB string theory in the presence of various extra $7/\bar 7$-brane pairs compactified on a warped Calabi-Yau threefold that admits a conifold singularity. We demonstrate that the volume modulus can be stabilized perturbatively at a non-supersymmetric $AdS_4/dS_4$ vacuum by the effective potential that includes the stringy $(\alpha^\prime)^3$ correction obtained by Becker {\it et al.} together with a combination of positive tension and anomalous negative tension terms generated by the additional 7-brane-antibrane pairs.Comment: 20 pages, 4 figures, parts of introduction and conclusions are modifie

Non-Thermal Dark Matter and the Moduli Problem in String Frameworks

We address the cosmological moduli/gravitino problems and the issue of too little thermal but excessive non-thermal dark matter from the decays of moduli. The main examples we study are the G2-MSSM models arising from M theory compactifications, which allow for a precise calculation of moduli decay rates and widths. We find that the late decaying moduli satisfy both BBN constraints and avoid the gravitino problem. The non-thermal production of wino LSPs, which is a prediction of G2-MSSM models, gives a relic density of about the right order of magnitude

Kahler Independence of the G2-MSSM

The G{sub 2}-MSSM is a model of particle physics coupled to moduli fields with interesting phenomenology both for colliders and astrophysical experiments. In this paper we consider a more general model--whose moduli Kahler potential is a completely arbitrary G{sub 2}-holonomy Kahler potential and whose matter Kahler potential is also more general. We prove that the vacuum structure and spectrum of BSM particles is largely unchanged in this much more general class of theories. In particular, gaugino masses are still suppressed relative to the gravitino mass and moduli masses. We also consider the effects of higher order corrections to the matter Kahler potential and find a connection between the nature of the LSP and flavor effects

Stabilizing All Kahler Moduli in Type IIB Orientifolds

We describe a simple and robust mechanism that stabilizes all Kahler moduli in Type IIB orientifold compactifications. This is shown to be possible with just one non-perturbative contribution to the superpotential coming from either a D3-instanton or D7-branes wrapped on an ample divisor. This moduli-stabilization mechanism is similar to and motivated by the one used in the fluxless G_2 compactifications of M-theory. After explaining the general idea, explicit examples of Calabi-Yau orientifolds with one and three Kahler moduli are worked out. We find that the stabilized volumes of all two- and four-cycles as well as the volume of the Calabi-Yau manifold are controlled by a single parameter, namely, the volume of the ample divisor. This feature would dramatically constrain any realistic models of particle physics embedded into such compactifications. Broad consequences for phenomenology are discussed, in particular the dynamical solution to the strong CP-problem within the framework.Comment: RevTeX, 24 pages, 2 tables, 1 figure

Mutant huntingtin protein decreases with CAG repeat expansion: implications for therapeutics and bioassays

Huntington’s disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in the huntingtin (HTT) protein. The mutant CAG repeat is unstable and expands in specific brain cells and peripheral tissues throughout life. Genes involved in the DNA mismatch repair pathways, known to act on expansion, have been identified as genetic modifiers; therefore, it is the rate of somatic CAG repeat expansion that drives the age of onset and rate of disease progression. In the context of an expanded CAG repeat, the HTT pre-mRNA can be alternatively processed to generate the HTT1a transcript that encodes the aggregation prone and highly pathogenic HTT1a protein. This may be a mechanism through which somatic CAG repeat expansion exerts its pathogenic effects, as the longer the CAG repeat, the more HTT1a and HTT1a is produced. The allelic series of knock-in mouse models, HdhQ20, HdhQ50, HdhQ80, HdhQ111, CAG140 and zQ175 with polyglutamine expansions of 20, 50, 80, 111, 140 and ∼190, can be used to model the molecular and cellular consequences of CAG repeat expansion within a single neuron. By western blot of cortical lysates, we found that mutant HTT levels decreased with increasing CAG repeat length; mutant HTT was only 23 and 10% of wild-type levels in CAG140 and zQ175 cortices, respectively. To identify the optimal bioassays for detecting the full-length HTT and HTT1a isoforms, we interrogated the pairwise combinations of seven well-characterized antibodies on both the ‘homogeneous time-resolved fluorescence’ and ‘Meso Scale Discovery’ platforms. We tested 32 assays on each platform to detect ‘full-length mutant HTT’, HTT1a, ‘total mutant HTT’ (full-length HTT and HTT1a) and ‘total full-length HTT’ (mutant and wild type). None of these assays recapitulated the full-length mutant HTT levels as measured by western blot. We recommend using isoform- and species-specific assays that detect full-length mutant HTT, HTT1a or wild-type HTT as opposed to those that detect more than one isoform simultaneously. Our finding that as the CAG repeat expands, full-length mutant HTT levels decrease, while HTT1a and HTT1a levels increase has implications for therapeutic strategies. If mutant HTT levels in cells containing (CAG)200 are only 10% of wild-type, HTT-lowering strategies targeting full-length HTT at sequences 3̍ to Intron 1 HTT will predominantly lower wild-type HTT, as mutant HTT levels in these cells are already depleted. These data support a therapeutic strategy that lowers HTT1a and depletes levels of the HTT1a protein

Scanning the Fluxless G_2 Landscape

We show that there exists an exponentially large discretuum of vacua in G{sub 2}-compactifications of M-theory without flux. In M-theory-inspired G{sub 2}-MSSM, quantities relevant for particle physics remain virtually insensitive to large variations of the vacuum energy across the landscape. The purely non-perturbative vacua form a special subset of a more general class of vacua containing fractional Chern-Simons contributions. The cosmological constant can be dynamically neutralized via a chain of transitions interpolated by fractional gauge instantons describing spontaneous nucleation of M2-brane domain walls. Each transition is generically accompanied by a gauge symmetry breaking in some sector of the theory. In particular, the visible sector GUT symmetry breaking can likewise be triggered by a spontaneous nucleation of an M2-brane

Kahler Independence of the G(2)-MSSM

The G2-MSSM is a model of particle physics coupled to moduli fields with interesting phenomenology both for colliders and astrophysical experiments. In this paper we consider a more general model - whose moduli Kahler potential is a completely arbitrary G2-holonomy Kahler potential and whose matter Kahler potential is also more general. We prove that the vacuum structure and spectrum of BSM particles is largely unchanged in this much more general class of theories. In particular, gaugino masses are still supressed relative to the gravitino mass and moduli masses. We also consider the effects of higher order corrections to the matter Kahler potential and find a connection between the nature of the LSP and flavor effects.Comment: Final version, matches the version published in JHE