A formalism based on moments for classical and quantum cosmology

Spanish Relativity Meeting (ERE 2014) Valencia, SPAIN, SEP 01-05, 2014

FTY720 attenuates excitotoxicity and neuroinflammation

Background: FTY720 (fingolimod, Gilenya(TM)), a structural analog of sphingosine-1-phosphate (S1P), is the first oral drug approved for treatment the relapsing-remitting form of multiple sclerosis (MS), and its efficacy has been related to induced lymphopenia and consequent immunosuppression via modulation of S1P(1) receptors (S1P(1)R). However, due to its lipophilic nature, FTY720 crosses the blood brain barrier (BBB) and could act directly on neural cells. In this study, we investigated the effectiveness of FTY720 as a neuroprotective agent using in vitro and in vivo models of excitotoxic neuronal death and examined if FTY720 exerts a direct action on neurons, or/and an indirect modulation of inflammation-mediated neurodegeneration as a possible mechanism of neuroprotection. Methods: Primary neuronal and organotypic cortical cultures were treated with N-methyl-D-aspartic acid (NMDA) to induce excitotoxic cell death (measured by lactate dehydrogenase (LDH) assay or propidium iodide uptake, respectively). The effects of FTY720 treatment (10, 100 and 1,000 nM) on neuronal survival were examined. As an in vivo model of neuronal death and inflammation, we used intracerebroventricular (icv) administration of kainic acid (KA; 0.5 mu g/2 mu l) in Sprague-Dawley rats. FTY720 was applied icv (1 mu g/2 mu l), together with KA, plus intraperitoneally (ip; 1 mg/kg) 24 h before, and daily, until sacrifice 3 days after icv. Rats were evaluated for neurological score, neuronal loss in CA3 hippocampal region and activation of microglia at the lesion site. In addition, we tested FTY720 as a modulator of microglia responses using microglial cell cultures activated with lipopolysaccharide (LPS) and its effects in stress signalling pathways using western blotting for p38 and JNK1/2 mitogen-activated protein kinases (MAPKs). Results: FTY720 was able to reduce excitotoxic neuronal death in vitro. Moreover, in vivo repeated FTY720 administration attenuated KA-induced neurodegeneration and microgliosis at the CA3 lesion site. Furthermore, FTY720 negatively modulates p38 MAPK in LPS-activated microglia, whereas it had no effect on JNK1/2 activation. Conclusions: These data support a role for FTY720 as a neuroprotective agent against excitotoxin-induced neuronal death and as a negative modulator of neuroinflammation by targeting the p38 MAPK stress signalling pathway in microglia.

Approximate Best Proximity Points of Cyclic Self-maps in Metric Spaces and Cyclic Asymptotic Regularity

3rd International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE) Madrid, AUG 28-31, 2014 / editado por Vagenas, EC; Vlachos, DS; Bastos, C; Hofer, T; Kominis, Y; Kosmas, O; LeLay, G; DePadova, P; Rode, B; Suraud, E; Varga, K

The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals

Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance'', being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

Association between CASP8-652 6N Del Polymorphism (rs3834129) and Colorectal Cancer Risk: Results from a Multi-Centric Study

The common 2652 6N del variant in the CASP8 promoter (rs3834129) has been described as a putative low-penetrance risk factor for different cancer types. In particular, some studies suggested that the deleted allele (del) was inversely associated with CRC risk while other analyses failed to confirm this. Hence, to better understand the role of this variant in the risk of developing CRC, we performed a multi-centric case-control study. In the study, the variant 2652 6N del was genotyped in a total of 6,733 CRC cases and 7,576 controls recruited by six different centers located in Spain, Italy, USA, England, Czech Republic and the Netherlands collaborating to the international consortium COGENT (COlorectal cancer GENeTics). Our analysis indicated that rs3834129 was not associated with CRC risk in the full data set. However, the del allele was under-represented in one set of cases with a family history of CRC (per allele model OR = 0.79, 95% CI = 0.69-0.90) suggesting this allele might be a protective factor versus familial CRC. Since this multi-centric case-control study was performed on a very large sample size, it provided robust clarification of the effect of rs3834129 on the risk of developing CRC in Caucasians.

Self-Similarity and helical symmetry in vortex generator flow simulations

According to experimental observations, the vortices generated by vortex generators have previously been observed to be self-similar for both the axial (u(z)) and azimuthal (u(circle minus)) velocity profiles. Further, the measured vortices have been observed to obey the criteria for helical symmetry. This is a powerful result, since it reduces the highly complex flow to merely four parameters. In the present work, corresponding computer simulations using Reynolds-Averaged Navier-Stokes equations have been carried out and compared to the experimental observations. The main objective of this study is to investigate how well the simulations can reproduce the physics of the flow and if the same analytical model can be applied. Using this model, parametric studies can be significantly reduced and, further, reliable simulations can substantially reduce the costs of the parametric studies themselves.

Optimizing the Curie temperature of pseudo-binary RxR2-x ' Fe-17 (R, R ' = rare earth) for magnetic refrigeration

Several pseudo-binary RxR2-x'Fe-17 alloys (with R = Y, Ce, Pr, Gd and Dy) were synthesized with rhombohedral Th2Zn17-type crystal structure determined from x-ray and neutron powder diffraction. The choice of compositions was done with the aim of tuning the Curie temperature (T-C) in the 270 +/- 20 K temperature range, in order to obtain the maximum magneto-caloric effect around room temperature. The investigated compounds exhibit broad isothermal magnetic entropy changes, Delta S-M(T), with moderate values of the refrigerant capacity, even though the values of Delta S-M(Peak) are relatively low compared with those of the R2Fe17 compounds with R = Pr or Nd. The reduction on the Delta S-M(Peak) is explained in terms of the diminution in the saturation magnetization value. Furthermore, the Delta S-M(T) curves exhibit a similar caret-like behavior, suggesting that the magneto-caloric effect is mainly governed by the Fe-sublattice. A single master curve for Delta S-M/Delta S-M(Peak)(T) under different values of the magnetic field change are obtained for each compound by rescaling of the temperature axis.

Computational study of the vortex path variation with the VG height

An extensive range of conventional, vane-type, passive vortex generators (VGs) are in use for successful applications of flow separation control. In most cases, the VG height is designed with the same thickness as the local boundary layer at the VG position. However, in some applications, these conventional VGs may produce excess residual drag. The so-called low-profile VGs can reduce the parasitic drag associated to this kind of passive control devices. As suggested by many authors, low-profile VGs can provide enough momentum transfer over a region several times their own height for effective flow-separation control with much lower drag. The main objective of this work is to study the variation of the path and the development of the primary vortex generated by a rectangular VG mounted on a flat plate with five different device heights h = delta, h(1) = 0.8 delta, h(2) = 0.6 delta, h(3) = 0.4 delta and h(4) = 0.2 delta, where delta is the local boundary layer thickness. For this purpose, computational simulations have been carried out at Reynolds number Re = 1350 based on the height of the conventional VG h = 0.25m with the angle of attack of the vane to the oncoming flow beta = 18.5 degrees. The results show that the VG scaling significantly affects the vortex trajectory and the peak vorticity generated by the primary vortex.

A novel brain partition highlights the modular skeleton shared by structure and function

Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent progress in neuroimaging has helped advance our understanding of this important issue, with diffusion images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). Here, we adopt a systems approach, relying on modular hierarchical clustering, to study together SC and rsFC datasets gathered independently from healthy human subjects. Our novel approach allows us to find a common skeleton shared by structure and function from which a new, optimal, brain partition can be extracted. We describe the emerging common structure-function modules (SFMs) in detail and compare them with commonly employed anatomical or functional parcellations. Our results underline the strong correspondence between brain structure and resting-state dynamics as well as the emerging coherent organization of the human brain.

Cosmological constrains on fast transition Unified Dark Matter models

In this work we show the results obtained applying a Unified Dark Matter (UDM) model with a fast transition to a set of cosmological data. Two different functions to model the transition are tested, and the feasibility of both models is explored using CMB shift data from Planck [1], Galaxy Clustering data from [2] and [3], and Union2.1 SNe Ia [4]. These new models are also statistically compared with the ACDM and quiessence models using Bayes factor through evidence. Bayesian inference does not discard the UDM models in favor of ACDM.

Fitting BICEP2 with defects, primordial gravitational waves and dust

In this work we discuss the possibility of cosmic defects being responsible for the B-mode signal measured by the BICEP2 collaboration. We also allow for the presence of other cosmological sources of B-modes such as inflationary gravitational waves and polarized dust foregrounds, which might contribute to or dominate the signal. On the one hand, we find that defects alone give a poor fit to the data points. On the other, we find that defects help to improve the fit at higher multipoles when they are considered alongside inflationary gravitational waves or polarized dust. Finally, we derive new defect constraints from models combining defects and dust. This proceeding is based on previous works [1, 2].

Calibrating Analytical Models for Semilocal Strings

In this work we calibrate two different analytic models of semilocal strings by constraining the values of their free parameters. In order to do so, we use data obtained from the largest and most accurate field theory simulations of semilocal strings to date, and compare several key properties with the predictions of the models. As this is still work in progress, we present some preliminary results together with descriptions of the methodology we are using in the characterisation of semilocal string networks.

Hartle's model within the general theory of perturbatiye matchings: the change in mass

Hartle's model provides the most widely used analytic framework to describe isolated compact bodies rotating slowly in equilibrium up to second order in perturbations in the context of General Relativity. Apart from some explicit assumptions, there are some implicit, like the "continuity" of the functions in the perturbed metric across the surface of the body. In this work we sketch the basics for the analysis of the second order problem using the modern theory of perturbed matchings. In particular, the result we present is that when the energy density of the fluid in the static configuration does not vanish at the boundary, one of the functions of the second order perturbation in the setting of the original work by Hartle is not continuous. This discrepancy affects the calculation of the change in mass of the rotating star with respect to the static configuration needed to keep the central energy density unchanged.

Double layers in gravity theories

Gravitational double layers, unlike their classical electromagnetic counterparts, are thought to be forbidden in gravity theories. It has been recently shown, however, that they are feasible in, for instance, gravity theories with a Lagrangian quadratic in the curvature. This is surprising with many potential consequences and the possibility of new physical behaviours. While a clear interpretation seems elusive, several lines of research are open. I present the field equations for double layers, the new physical quantities arising, and several explicit examples