Neutrino Masses and GUT Baryogenesis

We reconsider the GUT-baryogenesis mechanism for generating the baryon asymmetry of the Universe. The baryon asymmetry is produced by the out of equilibrium decay of coloured Higgs bosons at the GUT scale, conserving B-L. If neutrinos are Majorana particles, lepton number violating interactions erase the lepton number excess, but part of the baryon asymmetry may be preserved, provided those interactions are not in thermal equilibrium when the sphaleron processes become effective, at $T \sim 10^{12}~ GeV$. We analyse whether this mechanism for baryogenesis is feasible in a variety of GUT models of fermion masses proposed in the literature, based on horizontal symmetries.Comment: Talk presented at AHEP2003, Valencia, Spain, October 200

Chimeric glutamate receptor subunits reveal the transmembrane domain is sufficient for NMDA receptor pore properties but some positive allosteric modulators require additional domains

NMDA receptors are ligand-gated ion channels that underlie transmission at excitatory synapses and play an important role in regulating synaptic strength and stability. Functional NMDA receptors require two copies of the GluN1 subunit coassembled with GluN2 (and/or GluN3) subunits into a heteromeric tetramer. A diverse array of allosteric modulators can upregulate or downregulate NMDA receptor activity. These modulators include both synthetic compounds and endogenous modulators, such as cis-unsaturated fatty acids, 24(S)-hydroxycholesterol, and various neurosteroids. To evaluate the structural requirements for the formation and allosteric modulation of NMDA receptor pores, we have replaced portions of the rat GluN1, GluN2A, and GluN2B subunits with homologous segments from the rat GluK2 kainate receptor subunit. Our results with these chimeric constructs show that the NMDA receptor transmembrane domain is sufficient to account for most pore properties, but that regulation by some allosteric modulators requires additional cytoplasmic or extracellular domains. SIGNIFICANCE STATEMENT Glutamate receptors mediate excitatory synaptic transmission by forming cation channels through the membrane that open upon glutamate binding. Although many compounds have been identified that regulate glutamate receptor activity, in most cases the detailed mechanisms that underlie modulation are poorly understood. To identify what parts of the receptor are essential for pore formation and sensitivity to allosteric modulators, we generated chimeric subunits that combined segments from NMDA and kainate receptors, subtypes with distinct pharmacological profiles. Surprisingly, our results identify separate domain requirements for allosteric potentiation of NMDA receptor pores by pregnenolone sulfate, 24(S)-hydroxycholesterol, and docosahexaenoic acid, three endogenous modulators derived from membrane constituents. Understanding where and how these compounds act on NMDA receptors should aid in designing better therapeutic agents

Multiphysical failure processes in concrete: a consistent multiscale homogenization procedure

Durability and strength capabilities of concrete materials are vastly affected by the combined action of temperature and mechanical loading, which give rise to multiphysical failure processes. Such a phenomenon involves complex cracking, degradation and transport mechanisms on different scale lengths of concrete mixtures which, in turn, depend on the particular properties of the different constituents. Thus, the macroscopic observation of relevant concrete mechanical features such as strength, ductility and durability are the result of several different properties, processes and mechanisms which are not only coupled but moreover, depend on multiple scales. Particularly, regarding the pore pressure and thermal actions, most of the degradation processes in concrete are controlled by the heterogeneities of the microscopic scale. In the case of the mechanical actions both the micro and mesoscales play a relevant role. In this context, multiphysical failure processes in cementitious material-based mixtures like concrete can only and fully be understood and accurately described when considering its multiscale and multiconstituent features. In the realm of the theoretical and computational solid mechanics many relevant proposals were made to model the complex and coupled thermo-hydromechanical response behavior of concrete. Most of them are related to macroscopic formulations which account for the different mechanisms and transport phenomena through empirical, dissipative, poromechanical theories. Moreover, although relevant progress was made regarding the formulation of multiscale theories and approaches, none of the existing proposals deal with multiphysical failure processes in concrete. It should be said in this sense that, among the different multiscale approaches for material modeling proposed so far, those based on computational homogenization methods have demonstrated to be the most effective ones due to the involved versatility and accuracy. In this work a thermodynamically consistent semi-concurrent multiscale approach is formulated for modeling the thermo-poro-plastic failure behavior of concrete materials. A discrete approach is considered to represent the RVE material response. After formulating the fundamental equations describing the proposed homogenizations of the thermodynamical variables, the constitutive models for both the skeleton and porous phases are described. Then, numerical analyses are presented to demonstrate the predictive capabilities of the proposed thermodynamically consistent multiscale homogenization procedure for thermo-mechanical failure processes in concrete mixtures

Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone-a pilot study

Spironolactone improves outcome in dogs with advanced myxomatous mitral valve disease (MMVD). Its efficacy in preclinical MMVD is unknown. The hypothesis was the administration of spironolactone to dogs with compensated MMVD demonstrating risk factors for poorer prognosis will decrease the rate of disease progression. The aim was to provide pilot data to evaluate preliminary effects and sample size calculation for a definitive clinical trial

Olfactory variation in mouse husbandry and its implications for refinement and standardisation: UK survey of non-animal scents

With their highly sensitive olfactory system, the behaviour and physiology of mice are not only influenced by the scents of conspecifics and other species, but also by many other chemicals in the environment. The constraints of laboratory housing limit a mouse’s capacity to avoid aversive odours that could be present in the environment. Potentially odorous items routinely used for husbandry procedures, such as sanitizing products and gloves, could be perceived by mice as aversive or attractive, and affect their behaviour, physiology and experimental results. A survey was sent to research institutions in the UK to enquire about husbandry practices that could impact on the olfactory environment of the mouse. Responses were obtained from 80 individuals working in 51 institutions. Husbandry practices varied considerably. Seventy percent of respondents reported always wearing gloves for handling mice, with nitrile being the most common glove material (94%) followed by latex (23%) and vinyl (14%). Over six different products were listed for cleaning surfaces, floors, anaesthesia and euthanasia chambers and behavioural apparatus. In all cases Trigene™ (now called Anistel™) was the most common cleaning product used (43, 41, 40 and 49%, respectively). Depending on the attribute considered, between 7 and 19% of respondents thought that cleaning products definitely, or were likely to, have strong effects on standardization, mouse health, physiology or behaviour. Understanding whether and how these odours affect mouse welfare will help to refine mouse husbandry and experimental procedures through practical recommendations, to improve the quality of life of laboratory animals and the experimental data obtained

Culture Counts: Examinations of Recent Applications of the Penn Resiliency Program or, Toward a Rubric for Examining Cultural Appropriateness of Prevention Programming

It is imperative that researchers pay close attention to the influences of culture on mental health, and acknowledge a cultural context of illness and change when designing prevention programming. Researchers E. V. Cardemil, K. J. Reivich, and M. E. P. Seligman (2002) and D. L. Yu and M. E. P. Seligman (2002) have made attempts at adapting the existing Penn Resiliency Program (PRP) for culturally appropriate use cross-culturally and interculturally. The success of these modifications is discussed within a framework of guidelines designed to remind scientists how much culture counts. Finally, informative resources and a rubric are shared with prevention scientists for use in future development of culturally appropriate prevention programming

Enhancement of the immunoregulatory potency of mesenchymal stromal cells by treatment with immunosuppressive drugs

Background aims Multipotent mesenchymal stromal cells (MSCs) are distinguished by their ability to differentiate into a number of stromal derivatives of interest for regenerative medicine, but they also have immunoregulatory properties that are being tested in a number of clinical settings. Methods We show that brief incubations with rapamycin, everolimus, FK506 or cyclosporine A increase the immunosuppressive potency of MSCs and other cell types. Results The treated MSCs are up to 5-fold more potent at inhibiting the induced proliferation of T lymphocytes in vitro. We show that this effect probably is due to adsorption of the drug by the MSCs during pre-treatment, with subsequent diffusion into co-cultures at concentrations sufficient to inhibit T-cell proliferation. MSCs contain measurable amounts of rapamycin after a 15-min exposure, and the potentiating effect is blocked by a neutralizing antibody to the drug. With the use of a pre-clinical model of acute graft-versus-host disease, we demonstrate that a low dose of rapamycin-treated but not untreated umbilical cord–derived MSCs significantly inhibit the onset of disease. Conclusions The use of treated MSCs may achieve clinical end points not reached with untreated MSCs and allow for infusion of fewer cells to reduce costs and minimize potential side effects

Mixed-mode impedance and reflection coefficient of two-port devices

From the point of view of mixed-mode scattering parameters, Smm, a two-port device can be excited using different driving conditions. Each condition leads to a particular set of input reflection and input impedance coefficient definitions that should be carefully applied depending on the type of excitation and symmetry of the two-port device. Therefore, the aim of this paper is to explain the general analytic procedure for the evaluation of such reflection and impedance coefficients in terms of mixed-mode scattering parameters. Moreover, the driving of a two-port device as a one-port device is explained as a particular case of a two-port mixed-mode excitation using a given set of mixed-mode loads. The theory is applied to the evaluation of the quality factor, Q, of symmetrical and non- symmetrical inductors.Ministerio de Innovación y Ciencia TEC2010-14825/MIC, TEC2010-21484Junta de Andalucía TIC-253