1,774 research outputs found

    The Tevatron at the Frontier of Dark Matter Direct Detection

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    Direct detection of dark matter (DM) requires an interaction of dark matter particles with nucleons. The same interaction can lead to dark matter pair production at a hadron collider, and with the addition of initial state radiation this may lead to mono-jet signals. Mono-jet searches at the Tevatron can thus place limits on DM direct detection rates. We study these bounds both in the case where there is a contact interaction between DM and the standard model and where there is a mediator kinematically accessible at the Tevatron. We find that in many cases the Tevatron provides the current best limit, particularly for light dark matter, below 5 GeV, and for spin dependent interactions. Non-standard dark matter candidates are also constrained. The introduction of a light mediator significantly weakens the collider bound. A direct detection discovery that is in apparent conflict with mono-jet limits will thus point to a new light state coupling the standard model to the dark sector. Mono-jet searches with more luminosity and including the spectrum shape in the analysis can improve the constraints on DM-nucleon scattering cross section.Comment: 20 pages, 8 figures, final version in JHE

    Accelerated apoptotic death and <i>in vivo</i> turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2

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    The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in apoptosis. In analogy to apoptosis of nucleated cells, suicidal erythrocyte death called eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Here, we explored whether MSK1/2 participates in the regulation of eryptosis. To this end, erythrocytes were isolated from mice lacking functional MSK1/2 (msk−/−) and corresponding wild-type mice (msk+/+). Blood count, hematocrit, hemoglobin concentration and mean erythrocyte volume were similar in both msk−/− and msk+/+ mice, but reticulocyte count was significantly increased in msk−/− mice. Cell membrane PS exposure was similar in untreated msk−/− and msk+/+ erythrocytes, but was enhanced by pathophysiological cell stressors ex vivo such as hyperosmotic shock or energy depletion to significantly higher levels in msk−/− erythrocytes than in msk+/+ erythrocytes. Cell shrinkage following hyperosmotic shock and energy depletion, as well as hemolysis following decrease of extracellular osmolarity was more pronounced in msk−/− erythrocytes. The in vivo clearance of autologously-infused CFSE-labeled erythrocytes from circulating blood was faster in msk−/− mice. The spleens from msk−/− mice contained a significantly greater number of PS-exposing erythrocytes than spleens from msk+/+ mice. The present observations point to accelerated eryptosis and subsequent clearance of erythrocytes leading to enhanced erythrocyte turnover in MSK1/2-deficient mice

    Uso de fármacos psicoestimulantes en drogodependencias

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    El uso de medicamentos estimulantes es una cuestión de plena actualidad en psiquiatría, aunque su utilización y prescripción es controvertida . Fármacos como el metilfenidato, las anfetaminas, o el modafinilo están siendo utilizados y estudiados en distintas enfermedades psiquiátricas como el trastorno por déficit de atención e hiperactividad (TDAH), la dependencia de cocaína, en trastornos del sueño y en la depresión resistente. Todos estos fármacos tienen en común, igual que las drogas de abuso, que son medicamentos que actúan sobre el sistema dopaminérgico, que constituye la base neurobiológica del refuerzo fisiológico. Los estimulantes como el metilfenidato o el modafinilo son fármacos eficaces en el TDAH y han sido estudiados en el tratamiento de la dependencia de cocaína. En niños con TDAH el metilfenidato es un factor protector para el desarrollo de fármaco en la dependencia de cocaína, aunque son estudios preliminares, por lo que no se debe considerar que este totalmente demostrado que los fármacos psicoestimulantes sean eficaces en el tratamiento de esta dependencia. Aunque no son conocidos todos los mecanismos fisiopatológicos, parece crítico que el refuerzo, y por lo tanto el riesgo de dependencia, aparece cuando se producen incrementos rápidos dopaminérgicos y que los efectos terapéuticos aparecen cuando son lentos y mantenidos. Las características de uso a dosis bajas administradas por vía oral disminuyen el riesgo de abuso. Para realizar una adecuada prescripción es necesario aclarar, definitivamente, los mecanismos neuroquímicos en los que intervienen, y sus indicaciones en drogodependenciasStimulant drugs prescription is a controversial and current topic in psychiatry. Drugs such as methylphenidate, amphetamine compounds and modafinil have been trialed and used in attention deficit hyperactivity disorder (ADHD), sleep conditions, cocaine dependence and as an adjunct to antidepressants for depression. All these drugs, like stimulant drugs abuse, increase extracellular dopamine in the brain.This effect is associated with reinforcing as well as therapeutic effects. Methylphenidate and modafinil treatment of ADHD are associated with a reduced risk for later substance abuse among ADHD patients. There is evidence of the beneficial effects of the use of modafinil in cocaine dependence, altough there isn't conclusive evidence for the stimulants' efficacy in treatment of the stimulants' dependence. At this time, the physiopathology of drug abuse and dependence is unknown, but it's known that the very critical point is that the reinforcing effects are associated with rapid changes in dopamine increases, whereas the therapeutic effects are associated with slowly and smoothly rising dopamine levels, such as are achieved with low doses and oral administration. Due to this, it's necessary to study the neurobiological bases on which stimulants drugs are related, and their clinical use in dependence treatment

    Heart rate variability and target organ damage in hypertensive patients

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    Background: We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD). Methods: A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index. Results: Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors. Conclusions: Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD

    Left ventricular non-compaction: clinical features and cardiovascular magnetic resonance imaging

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    Background: It is apparent that despite lack of family history, patients with the morphological characteristics of left ventricular non-compaction develop arrhythmias, thrombo-embolism and left ventricular dysfunction. METHODS: Forty two patients, aged 48.7 +/- 2.3 yrs (mean +/- SEM) underwent cardiovascular magnetic resonance (CMR) for the quantification of left ventricular volumes and extent of non-compacted (NC) myocardium. The latter was quantified using planimetry on the two-chamber long axis LV view (NC area). The patients included those referred specifically for CMR to investigate suspected cardiomyopathy, and as such is represents a selected group of patients. RESULTS: At presentation, 50% had dyspnoea, 19% chest pain, 14% palpitations and 5% stroke. Pulmonary embolism had occurred in 7% and brachial artery embolism in 2%. The ECG was abnormal in 81% and atrial fibrillation occurred in 29%. Transthoracic echocardiograms showed features of NC in only 10%. On CMR, patients who presented with dyspnoea had greater left ventricular volumes (both p < 0.0001) and a lower left ventricular ejection fraction (LVEF) (p < 0.0001) than age-matched, healthy controls. In patients without dyspnoea (n = 21), NC area correlated positively with end-diastolic volume (r = 0.52, p = 0.0184) and end-systolic volume (r = 0.56, p = 0.0095), and negatively with EF (r = -0.72, p = 0.0001). CONCLUSION: Left ventricular non-compaction is associated with dysrrhythmias, thromboembolic events, chest pain and LV dysfunction. The inverse correlation between NC area and EF suggests that NC contributes to left ventricular dysfunction

    Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study

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    &lt;p&gt;&lt;b&gt;Background&lt;/b&gt; Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods&lt;/b&gt; We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, &#8805;2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results&lt;/b&gt; Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 &#8804; P &#8804; .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 &#8804; P &#8804; .04), hair color (.006 &#8804; P &#8804; .06), and number of nevi (6.9 × 10−6 &#8804; P &#8804; .02).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion&lt;/b&gt; Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.&lt;/p&gt

    Quantum dynamics in strong fluctuating fields

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    A large number of multifaceted quantum transport processes in molecular systems and physical nanosystems can be treated in terms of quantum relaxation processes which couple to one or several fluctuating environments. A thermal equilibrium environment can conveniently be modelled by a thermal bath of harmonic oscillators. An archetype situation provides a two-state dissipative quantum dynamics, commonly known under the label of a spin-boson dynamics. An interesting and nontrivial physical situation emerges, however, when the quantum dynamics evolves far away from thermal equilibrium. This occurs, for example, when a charge transferring medium possesses nonequilibrium degrees of freedom, or when a strong time-dependent control field is applied externally. Accordingly, certain parameters of underlying quantum subsystem acquire stochastic character. Herein, we review the general theoretical framework which is based on the method of projector operators, yielding the quantum master equations for systems that are exposed to strong external fields. This allows one to investigate on a common basis the influence of nonequilibrium fluctuations and periodic electrical fields on quantum transport processes. Most importantly, such strong fluctuating fields induce a whole variety of nonlinear and nonequilibrium phenomena. A characteristic feature of such dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres

    Entrepreneurs’ age, institutions, and social value creation goals: a multi-country study

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    This study explores the relationship between an entrepreneur's age and his/her social value creation goals. Building on the lifespan developmental psychology literature and institutional theory, we hypothesize a U-shaped relationship between entrepreneurs’ age and their choice to create social value through their ventures, such that younger and older entrepreneurs create more social value with their businesses while middle age entrepreneurs are relatively more economically and less socially oriented with their ventures. We further hypothesize that the quality of a country’s formal institutions in terms of economic, social, and political freedom steepen the U-shaped relationship between entrepreneurs’ age and their choice to pursue social value creation as supportive institutional environments allow entrepreneurs to follow their age-based preferences. We confirm our predictions using multilevel mixed-effects linear regressions on a sample of over 15,000 entrepreneurs (aged between 18 and 64 years) in 45 countries from Global Entrepreneurship Monitor data. The findings are robust to several alternative specifications. Based on our findings, we discuss implications for theory and practice, and we propose future research directions

    Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

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    We study the process e+eJ/ψπ+πe^+e^-\to J/\psi\pi^{+}\pi^{-} with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 fb1\mathrm{fb^{-1}}. We investigate the J/ψπ+πJ/\psi \pi^{+}\pi^{-} mass distribution in the region from 3.5 to 5.5 GeV/c2\mathrm{GeV/c^{2}}. Below 3.7 GeV/c2\mathrm{GeV/c^{2}} the ψ(2S)\psi(2S) signal dominates, and above 4 GeV/c2\mathrm{GeV/c^{2}} there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 GeV/c2\mathrm{GeV/c^{2}} yields a mass value 4244±54244 \pm 5 (stat) ±4 \pm 4 (syst)MeV/c2\mathrm{MeV/c^{2}} and a width value 11415+16114 ^{+16}_{-15} (stat)±7 \pm 7(syst)MeV\mathrm{MeV} for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 GeV/c2\mathrm{GeV/c^{2}}. In addition, we investigate the π+π\pi^{+}\pi^{-} system which results from Y(4260) decay
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