Fermions and Kaluza-Klein vacuum decay: a toy model

We address the question of whether or not fermions with twisted periodicity condition suppress the semiclassical decay of M^4xS^1 Kaluza--Klein vacuum. We consider a toy (1+1)-dimensional model with twisted fermions in cigar-shaped Euclidean background geometry and calculate the fermion determinant. We find that contrary to expectations, the determinant is finite. We consider this as an indication that twisted fermions do not stabilize the Kaluza--Klein vacuum.Comment: 13 pages, 2 figure

Fractional oscillator process with two indices

We introduce a new fractional oscillator process which can be obtained as solution of a stochastic differential equation with two fractional orders. Basic properties such as fractal dimension and short range dependence of the process are studied by considering the asymptotic properties of its covariance function. The fluctuation--dissipation relation of the process is investigated. The fractional oscillator process can be regarded as one-dimensional fractional Euclidean Klein-Gordon field, which can be obtained by applying the Parisi-Wu stochastic quantization method to a nonlocal Euclidean action. The Casimir energy associated with the fractional field at positive temperature is calculated by using the zeta function regularization technique.Comment: 32 page

Index-free Heat Kernel Coefficients

Using index-free notation, we present the diagonal values of the first five heat kernel coefficients associated with a general Laplace-type operator on a compact Riemannian space without boundary. The fifth coefficient appears here for the first time. For a flat space with a gauge connection, the sixth coefficient is given too. Also provided are the leading terms for any coefficient, both in ascending and descending powers of the Yang-Mills and Riemann curvatures, to the same order as required for the fourth coefficient. These results are obtained by directly solving the relevant recursion relations, working in Fock-Schwinger gauge and Riemann normal coordinates. Our procedure is thus noncovariant, but we show that for any coefficient the `gauged' respectively `curved' version is found from the corresponding `non-gauged' respectively `flat' coefficient by making some simple covariant substitutions. These substitutions being understood, the coefficients retain their `flat' form and size. In this sense the fifth and sixth coefficient have only 26 and 75 terms respectively, allowing us to write them down. Using index-free notation also clarifies the general structure of the heat kernel coefficients. In particular, in flat space we find that from the fifth coefficient onward, certain scalars are absent. This may be relevant for the anomalies of quantum field theories in ten or more dimensions.Comment: 38 pages, LaTe

SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism

It is well established that lncRNAs are aberrantly expressed in cancer where they have been shown to act as oncogenes or tumor suppressors. RNA profiling of 314 colorectal adenomas/adenocarcinomas and 292 adjacent normal colon mucosa samples using RNA‐sequencing demonstrated that the snoRNA host gene 16 (SNHG16) is significantly up‐regulated in adenomas and all stages of CRC. SNHG16 expression was positively correlated to the expression of Wnt‐regulated transcription factors, including ASCL2, ETS2, and c‐Myc. In vitro abrogation of Wnt signaling in CRC cells reduced the expression of SNHG16 indicating that SNHG16 is regulated by the Wnt pathway. Silencing of SNHG16 resulted in reduced viability, increased apoptotic cell death and impaired cell migration. The SNHG16 silencing particularly affected expression of genes involved in lipid metabolism. A connection between SNHG16 and genes involved in lipid metabolism was also observed in clinical tumors. Argonaute CrossLinking and ImmunoPrecipitation (AGO‐CLIP) demonstrated that SNHG16 heavily binds AGO and has 27 AGO/miRNA target sites along its length, indicating that SNHG16 may act as a competing endogenous RNA (ceRNA) “sponging” miRNAs off their cognate targets. Most interestingly, half of the miRNA families with high confidence targets on SNHG16 also target the 3′UTR of Stearoyl‐CoA Desaturase (SCD). SCD is involved in lipid metabolism and is down‐regulated upon SNHG16 silencing. In conclusion, up‐regulation of SNHG16 is a frequent event in CRC, likely caused by deregulated Wnt signaling. In vitro analyses demonstrate that SNHG16 may play an oncogenic role in CRC and that it affects genes involved in lipid metabolism, possible through ceRNA related mechanisms

Hrk1 Plays Both Hog1-Dependent and -Independent Roles in Controlling Stress Response and Antifungal Drug Resistance in Cryptococcus neoformans

The HOG (High Osmolarity Glycerol response) pathway plays a central role in controlling stress response, ergosterol biosynthesis, virulence factor production, and differentiation of Cryptococcus neoformans, which causes fatal fungal meningoencephalitis. Recent transcriptome analysis of the HOG pathway discovered a Hog1-regulated gene (CNAG_00130.2), encoding a putative protein kinase orthologous to Rck1/2 in Saccharomyces cerevisiae and Srk1 in Schizosaccharomyces pombe. Its function is not known in C. neoformans. The present study functionally characterized the role of Hrk1 in C. neoformans. Northern blot analysis confirmed that HRK1 expression depends on the Hog1 MAPK. Similar to the hog1Δ mutant, the hrk1Δ mutant exhibited almost complete resistance to fludioxonil, which triggers glycerol biosynthesis via the HOG pathway. Supporting this, the hrk1Δ mutant showed reduced intracellular glycerol accumulation and swollen cell morphology in response to fludioxonil, further suggesting that Hrk1 works downstream of the HOG pathway. However, Hrk1 also appeared to have Hog1-independent functions. Mutation of HRK1 not only further increased osmosensitivity of the hog1Δ mutant, but also suppressed increased azole-resistance of the hog1Δ mutant in an Erg11-independent manner. Furthermore, unlike the hog1Δ mutant, Hrk1 was not involved in capsule biosynthesis. Hrk1 was slightly involved in melanin production but dispensable for virulence of C. neoformans. These findings suggest that Hrk1 plays both Hog1-dependent and –independent roles in stress and antifungal drug susceptibility and virulence factor production in C. neoformans. Particularly, the finding that inhibition of Hrk1 substantially increases azole drug susceptibility provides a novel strategy for combination antifungal therapy

Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

One-Loop Divergences in Simple Supergravity: Boundary Effects

This paper studies the semiclassical approximation of simple supergravity in Riemannian four-manifolds with boundary, within the framework of $\zeta$-function regularization. The massless nature of gravitinos, jointly with the presence of a boundary and a local description in terms of potentials for spin ${3\over 2}$, force the background to be totally flat. First, nonlocal boundary conditions of the spectral type are imposed on spin-${3\over 2}$ potentials, jointly with boundary conditions on metric perturbations which are completely invariant under infinitesimal diffeomorphisms. The axial gauge-averaging functional is used, which is then sufficient to ensure self-adjointness. One thus finds that the contributions of ghost and gauge modes vanish separately. Hence the contributions to the one-loop wave function of the universe reduce to those $\zeta(0)$ values resulting from physical modes only. Another set of mixed boundary conditions, motivated instead by local supersymmetry and first proposed by Luckock, Moss and Poletti, is also analyzed. In this case the contributions of gauge and ghost modes do not cancel each other. Both sets of boundary conditions lead to a nonvanishing $\zeta(0)$ value, and spectral boundary conditions are also studied when two concentric three-sphere boundaries occur. These results seem to point out that simple supergravity is not even one-loop finite in the presence of boundaries.Comment: 37 pages, Revtex. Equations (5.2), (5.3), (5.5), (5.7), (5.8) and (5.13) have been amended, jointly with a few misprint

Pain in the lumbar, thoracic or cervical regions: do age and gender matter? A population-based study of 34,902 Danish twins 20–71 years of age

Background. It is unclear to what extent spinal pain varies between genders and in relation to age. It was the purpose of this study to describe the self-reported prevalence of 1) pain ever and pain in the past year in each of the three spinal regions, 2) the duration of such pain over the past year, 3) pain radiating from these areas, and 4) pain in one, two or three areas. In addition, 5) to investigate if spinal pain reporting is affected by gender and 6) to see if it increases gradually with increasing age. Method. A cross-sectional survey was conducted in 2002 on 34,902 twin individuals, aged 20 to 71 years, representative of the general Danish population. Identical questions on pain were asked for the lumbar, thoracic and cervical regions. Results. Low back pain was most common, followed by neck pain with thoracic pain being least common. Pain for at least 30 days in the past year was reported by 12%, 10%, and 4%, respectively. The one-yr prevalence estimates of radiating pain were 22% (leg), 16% (arm), and 5% (chest). Pain in one area only last year was reported by 20%, followed by two (13%) and three areas (8%). Women were always more likely to report pain and they were also more likely to have had pain for longer periods. Lumbar and cervical pain peaked somewhat around the middle years but the curves were flatter for thoracic pain. Similar patterns were noted for radiating pain. Older people did not have pain in a larger number of areas but their pain lasted longer. Conclusion. Pain reported for and from the lumbar and cervical spines was found to be relatively common whereas pain in the thoracic spine and pain radiating into the chest was much less common. Women were, generally, more likely to report pain than men. The prevalence estimates changed surprisingly little over age and were certainly not more common in the oldest groups, although the pain was reported as more long-lasting in the older group

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms