Thermodynamics of the Stephani Universes

We examine the consistency of the thermodynamics of the most general class of conformally flat solution with an irrotational perfect fluid source (the Stephani Universes). For the case when the isometry group has dimension $r\ge2$, the Gibbs-Duhem relation is always integrable, but if $r<2$ it is only integrable for the particular subclass (containing FRW cosmologies) characterized by $r=1$ and by admitting a conformal motion parallel to the 4-velocity. We provide explicit forms of the state variables and equations of state linking them. These formal thermodynamic relations are determined up to an arbitrary function of time which reduces to the FRW scale factor in the FRW limit of the solutions. We show that a formal identification of this free parameter with a FRW scale factor determined by FRW dynamics leads to an unphysical temperature evolution law. If this parameter is not identified with a FRW scale factor, it is possible to find examples of solutions and formal equations of state complying with suitable energy conditions and reasonable asymptotic behavior and temperature laws.Comment: 25 pages, Plain.TeX, four figure

On the Thermodynamics of Simple Non-Isentropic Perfect Fluids in General Relativity

We examine the consistency of the thermodynamics of irrotational and non-isentropic perfect fluids complying with matter conservation by looking at the integrability conditions of the Gibbs-Duhem relation. We show that the latter is always integrable for fluids of the following types: (a) static, (b) isentropic (admits a barotropic equation of state), (c) the source of a spacetime for which $r\ge 2$, where $r$ is the dimension of the orbit of the isometry group. This consistency scheme is tested also in two large classes of known exact solutions for which $r< 2$, in general: perfect fluid Szekeres solutions (classes I and II). In none of these cases, the Gibbs-Duhem relation is integrable, in general, though specific particular cases of Szekeres class II (all complying with $r<2$) are identified for which the integrability of this relation can be achieved. We show that Szekeres class I solutions satisfy the integrability conditions only in two trivial cases, namely the spherically symmetric limiting case and the Friedman-Roberson-Walker (FRW) cosmology. Explicit forms of the state variables and equations of state linking them are given explicitly and discussed in relation to the FRW limits of the solutions. We show that fixing free parameters in these solutions by a formal identification with FRW parameters leads, in all cases examined, to unphysical temperature evolution laws, quite unrelated to those of their FRW limiting cosmologies.Comment: 29 pages, Plain.Te

Towards a physical interpretation for the Stephani Universes

A physicaly reasonable interpretation is provided for the perfect fluid, sphericaly symmetric, conformally flat ``Stephani Universes''. The free parameters of this class of exact solutions are determined so that the ideal gas relation $p=n k T$ is identicaly fulfiled, while the full equation of state of a classical monatomic ideal gas and a matter-radiation mixture holds up to a good approximation in a near dust, matter dominated regime. Only the models having spacelike slices with positive curvature admit a regular evolution domain that avoids an unphysical singularity. In the matter dominated regime these models are dynamicaly and observationaly indistinguishable from ``standard'' FLRW cosmology with a dust source.Comment: 17 pages, 2 figures, LaTeX with revtex style, submitted to General Relativity and Gravitatio

Administration of Harmine and Imipramine Alters Creatine Kinase and Mitochondrial Respiratory Chain Activities in the Rat Brain

The present study evaluated mitochondrial respiratory chain and creatine kinase activities after administration of harmine (5, 10, and 15 mg/kg) and imipramine (10, 20, and 30 mg/kg) in rat brain. After acute treatment occurred an increase of creatine kinase in the prefrontal with imipramine (20 and 30 mg/kg) and harmine in all doses, in the striatum with imipramine (20 and 30 mg/kg) and harmine (5 and 10 mg/kg); harmine (15 mg/kg) decreased creatine kinase. In the chronic treatment occurred an increase of creatine kinase with imipramine (20 mg/kg), harmine (5 mg/kg) in the prefrontal with imipramine (20 and 30 mg/kg) and harmine (5 and 10 mg/kg) in the striatum. In the acute treatment, the complex I increased in the prefrontal with harmine (15 mg/kg) and in the striatum with harmine (10 mg/kg); the complex II decreased with imipramine (20 and 30 mg/kg) in the striatum; the complex IV increased with imipramine (30 mg/kg) in the striatum. In the chronic treatment, the complex I increased with harmine (5 mg/kg) in the prefrontal; the complex II increased with imipramine (20 mg/kg) in the prefrontal; the complex IV increased with harmine (5 mg/kg) in the striatum. Finally, these findings further support the hypothesis that harmine and imipramine could be involved in mitochondrial function

Explicit de Sitter Flux Vacua for Global String Models with Chiral Matter

We address the open question of performing an explicit stabilisation of all closed string moduli (including dilaton, complex structure and Kaehler moduli) in fluxed type IIB Calabi-Yau compactifications with chiral matter. Using toric geometry we construct Calabi-Yau manifolds with del Pezzo singularities. D-branes located at such singularities can support the Standard Model gauge group and matter content. In order to control complex structure moduli stabilisation we consider Calabi-Yau manifolds which exhibit a discrete symmetry that reduces the effective number of complex structure moduli. We calculate the corresponding periods in the symplectic basis of invariant three-cycles and find explicit flux vacua for concrete examples. We compute the values of the flux superpotential and the string coupling at these vacua. Starting from these explicit complex structure solutions, we obtain AdS and dS minima where the Kaehler moduli are stabilised by a mixture of D-terms, non-perturbative and perturbative alpha'-corrections as in the LARGE Volume Scenario. In the considered example the visible sector lives at a dP_6 singularity which can be higgsed to the phenomenologically interesting class of models at the dP_3 singularity.Comment: 49 pages, 5 figures; v2: references adde

CDH1 promoter hypermethylation and E-cadherin protein expression in infiltrating breast cancer

BACKGROUND: The E-cadherin gene (CDH1) maps, at chromosome 16q22.1, a region often associated with loss of heterozygosity (LOH) in human breast cancer. LOH at this site is thought to lead to loss of function of this tumor suppressor gene and was correlated with decreased disease-free survival, poor prognosis, and metastasis. Differential CpG island methylation in the promoter region of the CDH1 gene might be an alternative way for the loss of expression and function of E-cadherin, leading to loss of tissue integrity, an essential step in tumor progression. METHODS: The aim of our study was to assess, by Methylation-Specific Polymerase Chain Reaction (MSP), the methylation pattern of the CDH1 gene and its possible correlation with the expression of E-cadherin and other standard immunohistochemical parameters (Her-2, ER, PgR, p53, and K-67) in a series of 79 primary breast cancers (71 infiltrating ductal, 5 infiltrating lobular, 1 metaplastic, 1 apocrine, and 1 papillary carcinoma). RESULTS: CDH1 hypermethylation was observed in 72% of the cases including 52/71 ductal, 4/5 lobular carcinomas and 1 apocrine carcinoma. Reduced levels of E-cadherin protein were observed in 85% of our samples. Although not statistically significant, the levels of E-cadherin expression tended to diminish with the CDH1 promoter region methylation. In the group of 71 ductal cancinomas, most of the cases of showing CDH1 hypermethylation also presented reduced levels of expression of ER and PgR proteins, and a possible association was observed between CDH1 methylation and ER expression (p = 0.0301, Fisher's exact test). However, this finding was not considered significant after Bonferroni correction of p-value. CONCLUSION: Our preliminary findings suggested that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression in a subgroup of cases characterized by loss of expression of other important genes to the mammary carcinogenesis process, probably due to the disruption of the mechanism of maintenance of DNA methylation in tumoral cells

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality