Orientiholes

By T-dualizing space-filling D-branes in IIB orientifold compactifications along the three non-internal spatial directions, we obtain black hole bound states living in a universe with a gauged spatial reflection symmetry. We call these objects orientiholes. The gravitational entropy of various IIA orientihole configurations provides an "experimental" estimate of the number of vacua in various sectors of the IIB landscape. Furthermore, basic physical properties of orientiholes map to (sometimes subtle) microscopic features, thus providing a useful alternative viewpoint on a number of issues arising in D-brane model building. More generally, we give orientihole generalizations of recently derived wall crossing formulae, and conjecture a relation to the topological string analogous to the OSV conjecture, but with a linear rather than a quadratic identification of partition functions

Merkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic Perturbations Required for Transformation

An accurate analytic model describing the microscopic mechanism of high-harmonic generation (HHG) in solids is derived. Extensive first-principles simulations within a time-dependent density-functional framework corroborate the conclusions of the model. Our results reveal that (i) the emitted HHG spectra are highly anisotropic and laser-polarization dependent even for cubic crystals; (ii) the harmonic emission is enhanced by the inhomogeneity of the electron-nuclei potential; the yield is increased for heavier atoms; and (iii) the cutoff photon energy is driver-wavelength independent. Moreover, we show that it is possible to predict the laser polarization for optimal HHG in bulk crystals solely from the knowledge of their electronic band structure. Our results pave the way to better control and optimize HHG in solids by engineering their band structure

Non-Supersymmetric Attractor Flow in Symmetric Spaces

We derive extremal black hole solutions for a variety of four dimensional models which, after Kaluza-Klein reduction, admit a description in terms of 3D gravity coupled to a sigma model with symmetric target space. The solutions are in correspondence with certain nilpotent generators of the isometry group. In particular, we provide the exact solution for a non-BPS black hole with generic charges and asymptotic moduli in N=2 supergravity coupled to one vector multiplet. Multi-centered solutions can also be generated with this technique. It is shown that the non-supersymmetric solutions lack the intricate moduli space of bound configurations that are typical of the supersymmetric case.Comment: 50 pages, 4 figures; v2: Reference added. To appear in JHE

Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper Factor

The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT

Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development

It has been previously reported that ursodeoxycholic acid (UDCA), a therapeutic bile acid, reduced risk for advanced colorectal adenoma in men but not women. Interactions between the gut microbiome and fecal bile acid composition as a factor in colorectal cancer neoplasia have been postulated but evidence is limited to small cohorts and animal studies. Using banked stool samples collected as part of a phase III randomized clinical trial of UDCA for the prevention of colorectal adenomatous polyps, we compared change in the microbiome composition after a 3-year intervention in a subset of participants randomized to oral UDCA at 8-10 mg/kg of body weight per day (n = 198) or placebo (n = 203). Study participants randomized to UDCA experienced compositional changes in their microbiome that were statistically more similar to other individuals in the UDCA arm than to those in the placebo arm. This reflected a UDCA-associated shift in microbial community composition (P 0.05). These UDCA-associated shifts in microbial community distance metrics from baseline to end-of-study were not associated with risk of any or advanced adenoma (all P > 0.05) in men or women. Separate analyses of microbial networks revealed an overrepresentation of Faecalibacterium prausnitzii in the post-UDCA arm and an inverse relationship between F prausnitzii and Ruminococcus gnavus. In men who received UDCA, the overrepresentation of F prausnitzii and underrepresentation of R gnavus were more prominent in those with no adenoma recurrence at follow-up compared to men with recurrence. This relationship was not observed in women. Daily UDCA use modestly influences the relative abundance of microbial species in stool and affects the microbial network composition with suggestive evidence for sex-specific effects of UDCA on stool microbial community composition as a modifier of colorectal adenoma risk.Partnership for Native American Cancer Prevention [NIH/NCI U54CA143924, U54CA143925]; NSF [1565100]; Biostatistics and Tissue Acquisition and Cellular/Molecular Analysis Shared Resources - NCI [P30CA023074]; [R01 CA151708]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Warped AdS_3 Black Holes

Three dimensional topologically massive gravity (TMG) with a negative cosmological constant -\ell^{-2} and positive Newton constant G admits an AdS_3 vacuum solution for any value of the graviton mass \mu. These are all known to be perturbatively unstable except at the recently explored chiral point \mu\ell=1. However we show herein that for every value of \mu\ell< 3 there are two other (potentially stable) vacuum solutions given by SL(2,R)x U(1)-invariant warped AdS_3 geometries, with a timelike or spacelike U(1) isometry. Critical behavior occurs at \mu\ell=3, where the warping transitions from a stretching to a squashing, and there are a pair of warped solutions with a null U(1) isometry. For \mu\ell>3, there are known warped black hole solutions which are asymptotic to warped AdS_3. We show that these black holes are discrete quotients of warped AdS_3 just as BTZ black holes are discrete quotients of ordinary AdS_3. Moreover new solutions of this type, relevant to any theory with warped AdS_3 solutions, are exhibited. Finally we note that the black hole thermodynamics is consistent with the hypothesis that, for \mu\ell>3, the warped AdS_3 ground state of TMG is holographically dual to a 2D boundary CFT with central charges c_R={15(\mu\ell)^2+81\over G\mu((\mu\ell)^2+27)} and c_L={12 \mu\ell^2\over G((\mu\ell)^2+27)}.Comment: 29 page

Viral Perturbations of Host Networks Reflect Disease Etiology

Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia

The CHR promoter element controls cell cycle-dependent gene transcription and binds the DREAM and MMB complexes

Cell cycle-dependent gene expression is often controlled on the transcriptional level. Genes like cyclin B, CDC2 and CDC25C are regulated by cell cycle-dependent element (CDE) and cell cycle genes homology region (CHR) promoter elements mainly through repression in G0/G1. It had been suggested that E2F4 binding to CDE sites is central to transcriptional regulation. However, some promoters are only controlled by a CHR. We identify the DREAM complex binding to the CHR of mouse and human cyclin B2 promoters in G0. Association of DREAM and cell cycle-dependent regulation is abrogated when the CHR is mutated. Although E2f4 is part of the complex, a CDE is not essential but can enhance binding of DREAM. We show that the CHR element is not only necessary for repression of gene transcription in G0/G1, but also for activation in S, G2 and M phases. In proliferating cells, the B-myb-containing MMB complex binds the CHR of both promoters independently of the CDE. Bioinformatic analyses identify many genes which contain conserved CHR elements in promoters binding the DREAM complex. With Ube2c as an example from that screen, we show that inverse CHR sites are functional promoter elements that can bind DREAM and MMB. Our findings indicate that the CHR is central to DREAM/MMB-dependent transcriptional control during the cell cycle