Astrophysical Implications of a Visible Dark Matter Sector from a Custodially Warped-GUT

We explore, within the warped extra dimensional framework, the possibility of finding anti-matter signals in cosmic rays (CRs) from dark matter (DM) annihilation. Exchange of order 100 GeV radion, an integral part of our setup, generically results in Sommerfeld enhancement of the annihilation rate for TeV DM mass. No dark sector is required to obtain boosted annihilation cross sections. A mild hierarchy between the radion and DM masses can be natural due to the pseudo-Goldstone boson nature of the radion. Implications of Sommerfeld enhancement in warped grand unified theory (GUT) models, where proton stability implies a DM candidate, are studied. We show, via partially unified Pati-Salam group, how to incorporate a custodial symmetry for Z->b\bar b into the GUT framework such that a few TeV Kaluza-Klein (KK) mass scale is allowed by precision tests. The model with smallest fully unified SO(10) representation allows us to decouple the DM from the electroweak sector. Thus, a correct DM relic density is obtained and direct detection bounds are satisfied. Looking at robust CR observables, a possible future signal in the \bar p / p flux ratio is found. We show how to embed a similar custodial symmetry for the right handed tau, allowing it to be strongly coupled to KK particles. Such a scenario might lead to observed signal in CR positrons; however, the DM candidate in this case can not constitute all of the DM in the universe. Independently of the above, the strong coupling between KK particles and tau's can lead to striking LHC signals.Comment: 53 pages, 9 figure

Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure.

SUMMARY We and others have previously demonstrated that heme oxygenase 1 (HO-1) induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight) every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO). These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO) activity, interleukin 1β (IL-1β) production and tumor necrosis factor-α (TNFα) production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg) lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade

Holographic approach to a minimal Higgsless model

In this work, following an holographic approach, we carry out a low energy effective study of a minimal Higgsless model based on SU(2) bulk symmetry broken by boundary conditions, both in flat and warped metric. The holographic procedure turns out to be an useful computation technique to achieve an effective four dimensional formulation of the model taking into account the corrections coming from the extra dimensional sector. This technique is used to compute both oblique and direct contributions to the electroweak parameters in presence of fermions delocalized along the fifth dimension.Comment: Latex file, 23 page

po 472 chemotherapy resistance associated epithelial to endothelial transition in gastric cancer

Introduction Gastric cancer (GC) is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths. To date, gastrectomy and chemotherapy are the only therapeutic options, but drug resistance is the main cause for treatment failure. Vasculogenic mimicry (VM) is a new model of neovascularization in aggressive tumours and has been correlated with poor prognosis in GC patients. Our group has developed chemotherapy-resistant GC cells using the Caucasian adenocarcinoma cell line AGS and three drugs among the most used in clinic (5-fluorouracil, cisplatin and paclitaxel) henceforward denominated 5FUr, CISr, TAXr. Our study has highlighted phenotypical differences among chemo-sensitive and chemo-resistant cell lines such as acquisition of stem-like phenotype and increased capacity to form vessels. Material and methods Establishment of AGS resistant cell lines exposing cells to increasing dilution of drugs for over 9 months up to dilutions higher than IC50 values initially verified on AGS cells through MTT analysis. Quantitative RT-PCR, flow cytometry and western blot analysis for stemness and VM markers. Vasculogenic mimicryassay Results and discussions AGS cells acquired chemoresistance as indicated by the increase of IC50 values in drug-treated cells with respect to AGS. Furthermore, MTT assay highlighted that there is not cross-resistance among 5FUr, CISr and TAXr. Supportive data is that cells are MDR1 negative. Resistant cells showed an upregulation of Yamanaka factors either in qPCR and flow cytometer analysis, and particularly interesting is ALDH overexpression in 5FUr. TWIST upregulation suggested the investigation of VM which resulted particularly enhanced in 5FUr cells which demonstrated their ability to form and sustain vessels up to 96 hours in the tube formation assay. Markers of VM such Laminin γ2 and Ephrin A2 showed an increase in resistant cells and especially in 5FUr. Conclusion One of the most interesting result is that 5FUr cells acquire stemness properties and are positive to the tube formation assay suggesting that VM might be one mechanisms adopted by cells to avoid drugs exposure. These findings suggest that acquisition of chemoresistance could cause a relapse of disease in which tumour cells take advantage of their capability to perform VM in order to self-sustain their growth and that may be cause of poor outcomes

Constraints on Decaying Dark Matter from Fermi Observations of Nearby Galaxies and Clusters

We analyze the impact of Fermi gamma-ray observations (primarily non-detections) of selected nearby galaxies, including dwarf spheroidals, and of clusters of galaxies on decaying dark matter models. We show that the fact that galaxy clusters do not shine in gamma rays puts the most stringent limits available to-date on the lifetime of dark matter particles for a wide range of particle masses and decay final states. In particular, our results put strong constraints on the possibility of ascribing to decaying dark matter both the increasing positron fraction reported by PAMELA and the high-energy feature in the electron-positron spectrum measured by Fermi. Observations of nearby dwarf galaxies and of the Andromeda Galaxy (M31) do not provide as strong limits as those from galaxy clusters, while still improving on previous constraints in some cases.Comment: 27 pages, 5 figures, submitted to JCAP, revised version with some additions and correction

MSSM in view of PAMELA and Fermi-LAT

We take the MSSM as a complete theory of low energy phenomena, including neutrino masses and mixings. This immediately implies that the gravitino is the only possible dark matter candidate. We study the implications of the astrophysical experiments such as PAMELA and Fermi-LAT, on this scenario. The theory can account for both the realistic neutrino masses and mixings, and the PAMELA data as long as the slepton masses lie in the $500-10^6$TeV range. The squarks can be either light or heavy, depending on their contribution to radiative neutrino masses. On the other hand, the Fermi-LAT data imply heavy superpartners, all out of LHC reach, simply on the grounds of the energy scale involved, for the gravitino must weigh more than 2 TeV. The perturbativity of the theory also implies an upper bound on its mass, approximately $6-7$TeV.Comment: Published version, figures update