Evolution, Explosion and Nucleosynthesis of Core Collapse Supernovae

We present a new set of presupernova evolutions and explosive yields of massive stars of initial solar composition (Y=0.285, Z=0.02) in the mass range 13-35 Msun. All the models have been computed with the latest version (4.97) of the FRANEC code that now includes a nuclear network extending from neutrons to Mo98. The explosive nucleosynthesis has been computed twice: a first one with an hydro code and a second one following the simpler radiation dominated shock approximation (RDA).Comment: 20 pages, 10 figures, 12 tables. Accepted for publication on Ap

A physics-based life prediction methodology for thermal barrier coating systems

A novel mechanistic approach is proposed for the prediction of the life of thermal barrier coating (TBC) systems. The life prediction methodology is based on a criterion linked directly to the dominant failure mechanism. It relies on a statistical treatment of the TBC's morphological characteristics, non-destructive stress measurements and on a continuum mechanics framework to quantify the stresses that promote the nucleation and growth of microcracks within the TBC. The last of these accounts for the effects of TBC constituents' elasto-visco-plastic properties, the stiffening of the ceramic due to sintering and the oxidation at the interface between the thermally insulating yttria stabilized zirconia (YSZ) layer and the metallic bond coat. The mechanistic approach is used to investigate the effects on TBC life of the properties and morphology of the top YSZ coating, metallic low-pressure plasma sprayed bond coat and the thermally grown oxide. Its calibration is based on TBC damage inferred from non-destructive fluorescence measurements using piezo-spectroscopy and on the numerically predicted local TBC stresses responsible for the initiation of such damage. The potential applicability of the methodology to other types of TBC coatings and thermal loading conditions is also discussed

Expression of protease-activated receptors in arthritic synovial tissues

Clinical and experimental evidence suggests that synovial thrombin formation in arthritic joints is prominent and deleterious, leading to exacerbation of rheumatoid arthritis (RA). In this context, cellular effects of thrombin mediated by the protease-activated receptors (PARs) in arthritic joints may be of paramount significance. Four PARs have now been identified. PAR1, PAR3, and PAR4 can all be activated by thrombin whereas PAR2 is activated by trypsin and few other proteases.We first explored PARs expression in RA synovial tissues. Synovial membranes from 11 RA patients were analyzed for PARs expression by RT-PCR and by immunohistology. PAR4 was found in all the biopsies, whereas the expression of PAR1, PAR 2 and PAR3 was more restricted (8/11, 5/11 and 3/11 respectively). In the arthritic synovial membrane of murine antigen-induced arthritis (AIA) we found coexpression of the four different PARs. Next, we explored the functional importance of PAR1 during AIA in vivo using PAR-1 deficient mice. The phenotype of PAR1-deficient mice (n = 22), based on the analysis of arthritis severity (as measured by 99 m tecnetium uptake, histological scoring and intra-articular fibrin measurements) was similar to that of wild-type mice (n = 24). In addition, the in vivo production of antibodies against mBSA was also similar. By contrast, the mBSA-induced in vitro lymph node cell proliferation was significantly decreased in PAR1-deficient mice as compared with controls. Accordingly, mBSA-induced production of interferon-γ by lymph node cells in culture was significantly decreased in PAR1-deficient mice as compared with controls, whereas opposite results were observed for production of IL-10

Sodium Thiosulfate Prevents Chondrocyte Mineralization and Reduces the Severity of Murine Osteoarthritis.

Calcium-containing crystals participate in the pathogenesis of OA. Sodium thiosulfate (STS) has been shown to be an effective treatment in calcification disorders such as calciphylaxis and vascular calcification. This study investigated the effects and mechanisms of action of STS in a murine model of OA and in chondrocyte calcification. Hydroxyapatite (HA) crystals-stimulated murine chondrocytes and macrophages were treated with STS. Mineralization and cellular production of IL-6, MCP-1 and reactive oxygen species (ROS) were assayed. STS's effects on genes involved in calcification, inflammation and cartilage matrix degradation were studied by RT-PCR. STS was administered in the menisectomy model of murine OA, and the effect on periarticular calcific deposits and cartilage degeneration was investigated by micro-CT-scan and histology. In vitro, STS prevented in a dose-dependent manner calcium crystal deposition in chondrocytes and inhibited Annexin V gene expression. In addition, there was a reduction in crystal-induced IL-6 and MCP-1 production. STS also had an antioxidant effect, diminished HA-induced ROS generation and abrogated HA-induced catabolic responses in chondrocytes. In vivo, administration of STS reduced the histological severity of OA, by limiting the size of new periarticular calcific deposits and reducing the severity of cartilage damage. STS reduces the severity of periarticular calcification and cartilage damage in an animal model of OA via its effects on chondrocyte mineralization and its attenuation of crystal-induced inflammation as well as catabolic enzymes and ROS generation. Our study suggests that STS may be a disease-modifying drug in crystal-associated OA

Microcrystals as DAMPs and their role in joint inflammation.

Microcrystals associated with joint diseases, namely monosodium urate, calcium pyrophosphate and basic calcium phosphate, can be considered as 'danger signals' to the innate immune system and provoke inflammation through inflammasome-dependent as well as inflammasome-independent pathways. Direct crystal membrane interactions can also lead to cell activation. The result is the generation of IL-1β and other pro-inflammatory cytokines. The primacy of IL-1β in the case of gouty inflammation has been demonstrated by the efficacy of IL-1 inhibitors in clinical studies. These findings may be relevant to other diseases where crystal formation is found, such as OA and atherosclerosis

Respuestas judiciales a la violencia de género: el derecho como discurso y práctica sociales

Generalmente los estudios sobre el sistema jurídico entre los/las juristas, suelen limitarse al análisis normativo o jurisprudencial. Sin embargo, hace ya mucho tiempo que sabemos que comprender al Derecho requiere conocer sus significados, sus valores precedentes y también sus discursos y prácticas; esto es, entenderlo como un fenómeno social. Fenómeno social que implica y expresa mucho más que un conjunto de normas. Esta es una idea que no sólo proviene de la Sociología del Derecho, sino que las teorías jurídicas feministas han incorporada claramente. Es dentro de este marco teórico que, en sus relaciones con el género, el Derecho puede ser entendido como un discurso social que dota de sentido a las conductas de varones y mujeres, a la vez que opera como el gran legitimador del poder que se impone a través de las palabras de la ley. De forma que, la construcción social de los roles, las posiciones correspondientes y la relación de los géneros en sí, no pueden comprenderse cabalmente si no se considera la contribución que brindan a estos efectos no sólo las leyes, sino también las instituciones, los sistemas, y también los discursos y el hablar de los jueces a través de sus sentencias. Así, y dentro de este contexto de ideas, este trabajo se propone comprender y analizar cómo se construye y expresa desde la voz de los propios jueces, el fenómeno social de la violencia de género; sus discursos, sus conceptualizaciones, su legitimación; mediante el análisis de las propias sentencias en las que emiten su propia voz.Fil: Sánchez Busso, Mariana N. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Otras Derech

Febuxostat, an Inhibitor of Xanthine Oxidase, Suppresses Lipopolysaccharide-Induced MCP-1 Production via MAPK Phosphatase-1-Mediated Inactivation of JNK.

Excess reactive oxygen species (ROS) formation can trigger various pathological conditions such as inflammation, in which xanthine oxidase (XO) is one major enzymatic source of ROS. Although XO has been reported to play essential roles in inflammatory conditions, the molecular mechanisms underlying the involvement of XO in inflammatory pathways remain unclear. Febuxostat, a selective and potent inhibitor of XO, effectively inhibits not only the generation of uric acid but also the formation of ROS. In this study, therefore, we examined the effects of febuxostat on lipopolysaccharide (LPS)-mediated inflammatory responses. Here we show that febuxostat suppresses LPS-induced MCP-1 production and mRNA expression via activating MAPK phosphatase-1 (MKP-1) which, in turn, leads to dephosphorylation and inactivation of JNK in macrophages. Moreover, these effects of febuxostat are mediated by inhibiting XO-mediated intracellular ROS production. Taken together, our data suggest that XO mediates LPS-induced phosphorylation of JNK through ROS production and MKP-1 inactivation, leading to MCP-1 production in macrophages. These studies may bring new insights into the novel role of XO in regulating inflammatory process through MAPK phosphatase, and demonstrate the potential use of XO inhibitor in modulating the inflammatory processes

Architectural changes in superficial and deep compartments of the tibialis anterior during electrical stimulation over different sites

Electrical stimulation is widely used in rehabilitation to prevent muscle weakness and to assist the functional recovery of neural deficits. Its application is however limited by the rapid development of muscle fatigue due to the non-physiological motor unit (MU) recruitment. This issue can be mitigated by interleaving muscle belly (mStim) and nerve stimulation (nStim) to distribute the temporal recruitment among different MU groups. To be effective, this approach requires the two stimulation modalities to activate minimally-overlapped groups of MUs. In this manuscript, we investigated spatial differences between mStim and nStim MU recruitment through the study of architectural changes of superficial and deep compartments of tibialis anterior (TA). We used ultrasound imaging to measure variations in muscle thickness, pennation angle, and fiber length during mStim, nStim, and voluntary (Vol) contractions at 15% and 25% of the maximal force. For both contraction levels, architectural changes induced by nStim in the deep and superficial compartments were similar to those observed during Vol. Instead, during mStim superficial fascicles underwent a greater change compared to those observed during nStim and Vol, both in absolute magnitude and in their relative differences between compartments. These observations suggest that nStim results in a distributed MU recruitment over the entire muscle volume, similarly to Vol, whereas mStim preferentially activates the superficial muscle layer. The diversity between spatial recruitment of nStim and mStim suggests the involvement of different MU populations, which justifies strategies based on interleaved nerve/muscle stimulation to reduce muscle fatigue during electrically-induced contractions of TA

The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H₂S) pathway against experimental osteoarthritis.

Osteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (H <sub>2</sub> S) has been implicated in mineralization but has never been studied in OA. Here, we investigated the role of the H <sub>2</sub> S-producing enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) in cartilage calcification and OA development. 3-MST expression was analyzed in cartilage from patients with different OA degrees, and in cartilage stimulated with hydroxyapatite (HA) crystals. The modulation of 3-MST expression in vivo was studied in the meniscectomy (MNX) model of murine OA, by comparing sham-operated to MNX knee cartilage. The role of 3-MST was investigated by quantifying joint calcification and cartilage degradation in WT and 3-MST <sup>-/-</sup> meniscectomized knees. Chondrocyte mineralization in vitro was measured in WT and 3-MST <sup>-/-</sup> cells. Finally, the effect of oxidative stress on 3-MST expression and chondrocyte mineralization was investigated. 3-MST expression in human cartilage negatively correlated with calcification and OA severity, and diminished upon HA stimulation. In accordance, cartilage from menisectomized OA knees revealed decreased 3-MST if compared to sham-operated healthy knees. Moreover, 3-MST <sup>-/-</sup> mice showed exacerbated joint calcification and OA severity if compared to WT mice. In vitro, genetic or pharmacologic inhibition of 3-MST in chondrocytes resulted in enhanced mineralization and IL-6 secretion. Finally, oxidative stress decreased 3-MST expression and increased chondrocyte mineralization, maybe via induction of pro-mineralizing genes. 3-MST-generated H <sub>2</sub> S protects against joint calcification and experimental OA. Enhancing H <sub>2</sub> S production in chondrocytes may represent a potential disease modifier to treat OA