New Solution for Neutrino Masses and Leptogenesis in Adjoint SU(5)

We investigate baryogenesis via leptogenesis and generation of neutrino masses and mixings through the Type I plus Type III seesaw plus an one-loop mechanism in the context of Renormalizable Adjoint SU(5) theory. One light neutrino remains massless, because the contributions of three heavy Majorana fermions \rho_0, \rho_3 and \rho_8 to the neutrino mass matrix are not linearly independent. However none of these heavy fermions is decoupled from the generation of neutrino masses. This opens a new range in parameter space for successful leptogenesis, in particular, allows for inverted hierarchy of the neutrino masses.Comment: 16 pages, 4 figures; references added and typos fixe

An A4 flavor model for quarks and leptons in warped geometry

We propose a spontaneous A4 flavor symmetry breaking scheme implemented in a warped extra dimensional setup to explain the observed pattern of quark and lepton masses and mixings. The main advantages of this choice are the explanation of fermion mass hierarchies by wave function overlaps, the emergence of tribimaximal neutrino mixing and zero quark mixing at the leading order and the absence of tree-level gauge mediated flavor violations. Quark mixing is induced by the presence of bulk flavons, which allow for cross-brane interactions and a cross-talk between the quark and neutrino sectors, realizing the spontaneous symmetry breaking pattern A4 --> nothing first proposed in [X.G.\,He, Y.Y.\,Keum, R.R.\,Volkas, JHEP{0604}, 039 (2006)]. We show that the observed quark mixing pattern can be explained in a rather economical way, including the CP violating phase, with leading order cross-interactions, while the observed difference between the smallest CKM entries V_{ub} and V_{td} must arise from higher order corrections. We briefly discuss bounds on the Kaluza-Klein scale implied by flavor changing neutral current processes in our model and show that the residual little CP problem is milder than in flavor anarchic models.Comment: 34 pages, 2 figures; version published in JHE

First order phase transition from ferromagnetism to antiferromagnetism in Ce(Fe0.96_{0.96}Al0.04_{0.04})2_2

Taking the pseudobinary C15 Laves phase compound Ce(Fe$_{0.96}$Al$_{0.04}$)$_2$ as a paradigm for studying a ferromagnetic to antiferromagnetic phase transition, we present interesting thermomagnetic history effects in magnetotransport as well as magnetisation measurements across this phase transition. A comparison is made with history effects observed across the ferromagnetic to antiferromagnetic transition in R$_{0.5}$Sr$_{0.5}$MnO$_3$ crystals.Comment: 11 pages of text and 4 figures; submitted to Physical Review Letter

Neutralino dark matter in mSUGRA/CMSSM with a 125 GeV light Higgs scalar

The minimal supergravity (mSUGRA or CMSSM) model is an oft-used framework for exhibiting the properties of neutralino (WIMP) cold dark matter (CDM). However, the recent evidence from Atlas and CMS on a light Higgs scalar with mass m_h\simeq 125 GeV highly constrains the superparticle mass spectrum, which in turn constrains the neutralino annihilation mechanisms in the early universe. We find that stau and stop co-annihilation mechanisms -- already highly stressed by the latest Atlas/CMS results on SUSY searches -- are nearly eliminated if indeed the light Higgs scalar has mass m_h\simeq 125 GeV. Furthermore, neutralino annihilation via the A-resonance is essentially ruled out in mSUGRA so that it is exceedingly difficult to generate thermally-produced neutralino-only dark matter at the measured abundance. The remaining possibility lies in the focus-point region which now moves out to m_0\sim 10-20 TeV range due to the required large trilinear soft SUSY breaking term A_0. The remaining HB/FP region is more fine-tuned than before owing to the typically large top squark masses. We present updated direct and indirect detection rates for neutralino dark matter, and show that ton scale noble liquid detectors will either discover mixed higgsino CDM or essentially rule out thermally-produced neutralino-only CDM in the mSUGRA model.Comment: 17 pages including 9 .eps figure

The minimal adjoint-SU (5) x Z(4) GUT model

An extension of the adjoint SU (5) model with a flavour symmetry based on the Z(4) group is investigated. The Z(4) symmetry is introduced with the aim of leading the up-and down-quark mass matrices to the Nearest-Neighbour-Interaction form. As a consequence of the discrete symmetry embedded in the SU (5) gauge group, the charged lepton mass matrix also gets the same form. Within this model, light neutrinos get their masses through type-I, type-III and one-loop radiative seesaw mechanisms, implemented, respectively, via a singlet, a triplet and an octet from the adjoint fermionic 24 fields. It is demonstrated that the neutrino phenomenology forces the introduction of at least three 24 fermionic multiplets. The symmetry SU (5) x Z(4) allows only two viable zero textures for the effective neutrino mass matrix. It is showed that one texture is only compatible with normal hierarchy and the other with inverted hierarchy in the light neutrino mass spectrum. Finally, it is also demonstrated that Z(4) freezes out the possibility of proton decay through exchange of coloured Higgs triplets at tree-level

Clinical implications of novel activating EGFR mutations in malignant peritoneal mesothelioma

<p>Abstract</p> <p>Background</p> <p>There is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma.</p> <p>Methods</p> <p>Twenty-nine patients were evaluated and their tumors were probed for mutations in the catalytic TK-domain. Twenty-five patients were treated with cytoreductive surgery and complete clinical data was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine mutation activating profiles and response to erlotinib.</p> <p>Results</p> <p>Functional mutations were found in 31%(9/29) of patients; 7 of these mutations were novel and another was the L858R mutation. All missense mutations were found to be activating mutations and responsive to erlotinib. Of the 25 patients managed surgically, there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months.</p> <p>Conclusions</p> <p>The novel EGFR mutations identified are activating mutations responsive to erlotinib. The mut+ subset have a 'relative' improved outcome. Erlotinib may have a role in MPM and exploration for mutations in a larger patient cohort is warranted.</p

Proton Magnetic Resonance Spectroscopy Reveals Neuroprotection by Oral Minocycline in a Nonhuman Primate Model of Accelerated NeuroAIDS

Background: Despite the advent of highly active anti-retroviral therapy (HAART), HIV-associated neurocognitive disorders continue to be a significant problem. In efforts to understand and alleviate neurocognitive deficits associated with HIV, we used an accelerated simian immunodeficiency virus (SIV) macaque model of NeuroAIDS to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury. Methodology/Principal Findings: Eleven rhesus macaques were infected with SIV, depleted of CD8+ lymphocytes, and studied until eight weeks post inoculation (wpi). Seven animals received daily minocycline orally beginning at 4 wpi. Neuronal integrity was monitored in vivo by proton magnetic resonance spectroscopy and post-mortem by immunohistochemistry for synaptophysin (SYN), microtubule-associated protein 2 (MAP2), and neuronal counts. Astrogliosis and microglial activation were quantified by measuring glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (IBA-1), respectively. SIV infection followed by CD8+ cell depletion induced a progressive decline in neuronal integrity evidenced by declining N-acetylaspartate/creatine (NAA/Cr), which was arrested with minocycline treatment. The recovery of this ratio was due to increases in NAA, indicating neuronal recovery, and decreases in Cr, likely reflecting downregulation of glial cell activation. SYN, MAP2, and neuronal counts were found to be higher in minocycline-treated animals compared to untreated animals while GFAP and IBA-1 expression were decreased compared to controls. CSF and plasma viral loads were lower in MN-treated animals. Conclusions/Significance: In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus

Self-Reactivities to the Non-Erythroid Alpha Spectrin Correlate with Cerebral Malaria in Gabonese Children

BACKGROUND: Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children. METHODOLOGY: To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFα concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. RESULTS/CONCLUSION: The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFα concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM

Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. Aim: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. Methods: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. Results: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-beta protein production was significantly lower in Hemin-treated animals. Conclusion: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.Fundacao de Amparo Pesquisa do Estado de Sao Paulo-FAPESP[07/07139-3]Coordenaco de Aperfeioamento de Pessoal de Nivel Superior-CAPESInstituto Nacional de Ciencia e Tecnologia de Complexos Fluidos (INCT)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNP

Radiative Electroweak symmetry breaking in the MSSM and Low Energy Thresholds

We study Radiative Electroweak Symmetry Breaking in the Minimal Supersymmetric Standard Model (MSSM). We employ the 2-loop Renormalization Group equations for running masses and couplings taking into account sparticle threshold effects. The decoupling of each particle below its threshold is realized by a step function in all one-loop Renormalization Group equations (RGE). This program requires the calculation of all wavefunction, vertex and mass renormalizations for all particles involved. Adapting our numerical routines to take care of the succesive decoupling of each particle below its threshold, we compute the mass spectrum of sparticles and Higgses consistent with the existing experimental constraints. The effect of the threshold corrections is in general of the same order of magnitude as the two-loop contributions with the exception of the heavy Higgses and those neutralino and chargino states that are nearlyComment: 39 pages, Latex, conclusions,description of numerical analysis expanded.References adde