Computer simulations of nematic drops: Coupling between drop shape and nematic order

We perform Monte Carlo computer simulations of nematic drops in equilibrium with their vapor using a Gay-Berne interaction between the rod-like molecules. To generate the drops, we initially perform NPT simulations close to the nematic-vapor coexistence region, allow the system to equilibrate and subsequently induce a sudden volume expansion, followed with NVT simulations. The resultant drops coexist with their vapor and are generally not spherical but elongated, have the rodlike particles tangentially aligned at the surface and an overall nematic orientation along the main axis of the drop. We find that the drop eccentricity increases with increasing molecular elongation, κ. For small κ the nematic texture in the drop is bipolar with two surface defects, or boojums, maximizing their distance along this same axis. For sufficiently high κ, the shape of the drop becomes singular in the vicinity of the defects, and there is a crossover to an almost homogeneous texture; this reflects a transition from a spheroidal to a spindle-like dro

Prospects in Constraining the Dark Energy Potential

We generalize to non-flat geometries the formalism of Simon et al. (2005) to reconstruct the dark energy potential. This formalism makes use of quantities similar to the Horizon-flow parameters in inflation, can, in principle, be made non-parametric and is general enough to be applied outside the simple, single scalar field quintessence. Since presently available and forthcoming data do not allow a non-parametric and exact reconstruction of the potential, we consider a general parametric description in term of Chebyshev polynomials. We then consider present and future measurements of H(z), Baryon Acoustic Oscillations surveys and Supernovae type 1A surveys, and investigate their constraints on the dark energy potential. We find that, relaxing the flatness assumption increases the errors on the reconstructed dark energy evolution but does not open up significant degeneracies, provided that a modest prior on geometry is imposed. Direct measurements of H(z), such as those provided by BAO surveys, are crucially important to constrain the evolution of the dark energy potential and the dark energy equation of state, especially for non-trivial deviations from the standard LambdaCDM model.Comment: 22 pages, 7 figures. 2 references correcte

The dark side of curvature

Geometrical tests such as the combination of the Hubble parameter H(z) and the angular diameter distance d_A(z) can, in principle, break the degeneracy between the dark energy equation of state parameter w(z), and the spatial curvature Omega_k in a direct, model-independent way. In practice, constraints on these quantities achievable from realistic experiments, such as those to be provided by Baryon Acoustic Oscillation (BAO) galaxy surveys in combination with CMB data, can resolve the cosmic confusion between the dark energy equation of state parameter and curvature only statistically and within a parameterized model for w(z). Combining measurements of both H(z) and d_A(z) up to sufficiently high redshifts around z = 2 and employing a parameterization of the redshift evolution of the dark energy equation of state are the keys to resolve the w(z)-Omega_k degeneracy.Comment: 18 pages, 9 figures. Minor changes, matches version accepted in JCA

Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis

Purpose and Experimental Design: The stem cell factor/ KIT receptor loop may represent a novel target for molecular- based therapies of Ewing tumor. We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines. Results: KIT expression was detected in 4 of 4 Ewing tumor cell lines and in 49 of 110 patient samples (44.5%) by immunohistochemistry and/or Western blot analysis. KIT expression was stronger in Ewing tumors showing EWSFLI1 nontype 1 fusions. Despite absence of c-kit mutations, constitutive and ligand-inducible phosphorylation of KIT was found in all tumor cell lines, indicating an active receptor. Treatment with KIT tyrosine kinase inhibitor imatinib (0.5–20 M) induced down-regulation of KIT phosphorylation and dose response inhibition of cell proliferation (IC50, 12–15 M). However, imatinib administered alone at doses close to IC50 for growth inhibition (10 M) did not induce a significant increase in apoptosis. We then analyzed if blockade of KIT loop through imatinib (10 M) was able to increase the antitumor in vitro effect of doxorubicin (DXR)and vincristine (VCR), drugs usually used in Ewing tumor treatment. Addition of imatinib decreased in 15–20 and 15–36% of the proliferative rate of Ewing tumor cells exposed to DXR and VCR, respectively, and increased in 15 and 30% of the apoptotic rate of Ewing tumor cells exposed to the same drugs. Conclusions: Inhibition of Ewing tumor cell proliferation by imatinib is mediated through blockade of KIT receptor signaling. Inhibition of KIT increases sensitivity of these cells to DXR and VCR. This study supports a potential role for imatinib in the treatment of Ewing tumor

Molecular profiling of hepatocellular carcinoma in mice with a chronic deficiency of hepatic s-adenosylmethionine: relevance in human liver diseases

S-adenosylmethionine arises as a central molecule in the preservation of liver homeostasis as a chronic hepatic deficiency results in spontaneous development of steatohepatitis and hepatocellular carcinoma. In the present work, we have attempted a comprehensive analysis of proteins associated with hepatocarcinogenesis in MAT1A knock out mice using a combination of two-dimensional electrophoresis and mass spectrometry, to then apply the resulting information to identify hallmarks of human HCC. Our results suggest the existence of individual-specific factors that might condition the development of preneoplastic lesions. Proteomic analysis allowed the identification of 151 differential proteins in MAT1A-/- mice tumors. Among all differential proteins, 27 changed in at least 50% of the analyzed tumors, and some of these alterations were already detected months before the development of HCC in the KO liver. The expression level of genes coding for 13 of these proteins was markedly decreased in human HCC. Interestingly, seven of these genes were also found to be down-regulated in a pretumoral condition such as cirrhosis, while depletion of only one marker was assessed in less severe liver disorders

Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications

MTAP (5'-methylthioadenosine phosphorylase) catalyses the reversible phosphorolytic cleavage of methylthioadenosine leading to the production of methylthioribose-1-phosphate and adenine. Deficient MTAP activity has been correlated with human diseases including cirrhosis and hepatocellular carcinoma. In the present study we have investigated the regulation of MTAP by ROS (reactive oxygen species). The results of the present study support the inactivation of MTAP in the liver of bacterial LPS (lipopolysaccharide)-challenged mice as well as in HepG2 cells after exposure to t-butyl hydroperoxide. Reversible inactivation of purified MTAP by hydrogen peroxide results from a reduction of V(max) and involves the specific oxidation of Cys(136) and Cys(223) thiols to sulfenic acid that may be further stabilized to sulfenyl amide intermediates. Additionally, we found that Cys(145) and Cys(211) were disulfide bonded upon hydrogen peroxide exposure. However, this modification is not relevant to the mediation of the loss of MTAP activity as assessed by site-directed mutagenesis. Regulation of MTAP by ROS might participate in the redox regulation of the methionine catabolic pathway in the liver. Reduced MTA (5'-deoxy-5'-methylthioadenosine)-degrading activity may compensate for the deficient production of the precursor S-adenosylmethionine, allowing maintenance of intracellular MTA levels that may be critical to ensure cellular adaptation to physiopathological conditions such as inflammation

Adherence to Lung-Protective Ventilation Principles in Pediatric Acute Respiratory Distress Syndrome:A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study

OBJECTIVES: To describe mechanical ventilation management and factors associated with nonadherence to lung-protective ventilation principles in pediatric acute respiratory distress syndrome. DESIGN: A planned ancillary study to a prospective international observational study. Mechanical ventilation management (every 6 hr measurements) during pediatric acute respiratory distress syndrome days 0-3 was described and compared with Pediatric Acute Lung Injury Consensus Conference tidal volume recommendations (< 7 mL/kg in children with impaired respiratory system compliance, < 9 mL/kg in all other children) and the Acute Respiratory Distress Syndrome Network lower positive end-expiratory pressure/higher FIO2 grid recommendations. SETTING: Seventy-one international PICUs. PATIENTS: Children with pediatric acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analyses included 422 children. On pediatric acute respiratory distress syndrome day 0, median tidal volume was 7.6 mL/kg (interquartile range, 6.3-8.9 mL/kg) and did not differ by pediatric acute respiratory distress syndrome severity. Plateau pressure was not recorded in 97% of measurements. Using delta pressure (peak inspiratory pressure - positive end-expiratory pressure), median tidal volume increased over quartiles of median delta pressure (p = 0.007). Median delta pressure was greater than or equal to 18 cm H2O for all pediatric acute respiratory distress syndrome severity levels. In severe pediatric acute respiratory distress syndrome, tidal volume was greater than or equal to 7 mL/kg 62% of the time, and positive end-expiratory pressure was lower than recommended by the positive end-expiratory pressure/FIO2 grid 70% of the time. In multivariable analysis, tidal volume nonadherence was more common with severe pediatric acute respiratory distress syndrome, fewer PICU admissions/yr, non-European PICUs, higher delta pressure, corticosteroid use, and pressure control mode. Adherence was associated with underweight stature and cuffed endotracheal tubes. In multivariable analysis, positive end-expiratory pressure/FIO2 grid nonadherence was more common with higher pediatric acute respiratory distress syndrome severity, ventilator decisions made primarily by the attending physician, pre-ICU cardiopulmonary resuscitation, underweight stature, and age less than 2 years. Adherence was associated with respiratory therapist involvement in ventilator management and longer time from pediatric acute respiratory distress syndrome diagnosis. Higher nonadherence to tidal volume and positive end-expiratory pressure recommendations were independently associated with higher mortality and longer duration of ventilation after adjustment for confounding variables. In stratified analyses, these associations were primarily influenced by children with severe pediatric acute respiratory distress syndrome. CONCLUSIONS: Nonadherence to lung-protective ventilation principles is common in pediatric acute respiratory distress syndrome and may impact outcome. Modifiable factors exist that may improve adherence

Non-unitary Leptonic Mixing and Leptogenesis

We investigate the relation between non-unitarity of the leptonic mixing matrix and leptogenesis. We discuss how all parameters of the canonical type-I seesaw mechanism can, in principle, be reconstructed from the neutrino mass matrix and the deviation of the effective low-energy leptonic mixing matrix from unitary. When the mass M' of the lightest right-handed neutrino is much lighter than the masses of the others, we show that its decay asymmetries within flavour-dependent leptogenesis can be expressed in terms of two contributions, one depending on the unique dimension five (d=5) operator generating neutrino masses and one depending on the dimension six (d=6) operator associated with non-unitarity. In low-energy seesaw scenarios where small lepton number violation explains the smallness of neutrino masses, the lepton number conserving d=6 operator contribution generically dominates over the d=5 operator contribution which results in a strong enhancement of the flavour-dependent decay asymmetries without any resonance effects. To calculate the produced final baryon asymmetry, the flavour equilibration effects directly related to non-unitarity have to be taken into account. In a simple realization of this non-unitarity driven leptogenesis, the lower bound on M' is found to be about 10^8 GeV at the onset of the strong washout regime, more than one order of magnitude below the bound in "standard" thermal leptogenesis.Comment: 19 pages, REVTeX4, 2 eps and 2 axodraw figure

Progress in creating a joint research agenda that allows networked long-term socio-ecological research in southern South America : addressing crucial technological and human capacity gaps limiting its application in Chile and Argentina

Since 1980, more than 40 countries have implemented long-term ecological research (LTER) programs, which have shown their power to affect advances in basic science to understand the natural world at meaningful temporal and spatial scales and also help link research with socially relevant outcomes. Recently, a disciplinary paradigmatic shift has integrated the human dimensions of ecosystems, leading to a long-term socio-ecological research (LTSER) framework to address the world's current environmental challenges. A global gap in LTER/LTSER only exists in the latitudinal range of 40–60°S, corresponding to Argentina and Chile's temperate/sub-Antarctic biome. A team of Chilean, Argentine and US researchers has participated in an ongoing dialogue to define not only conceptual, but also practical barriers limiting LTER/LTSER in southern South America. We have found a number of existing long-term research sites and platforms throughout the region, but at the same time it has been concluded an agenda is needed to create and implement further training courses for students, postdoctoral fellows and young scientists, particularly in the areas of data and information management systems. Since LTER/LTSER efforts in Chile and Argentina are incipient, instituting such courses now will enhance human and technical capacity of the natural science and resource community to improve the collection, storage, analysis and dissemination of information in emerging LTER/LTSER platforms. In turn, having this capacity, as well as the ongoing formalization of LTER/LTSER programs at national levels, will allow the enhancement of crucial collaborations and comparisons between long-term research programs within the region and between hemispheres and continents. For Spanish version of the entire article, see Online Supporting Information (Appendix S1).Desde 1980, más de cuarenta países han implementado programas de Investigación Ecológica a Largo Plazo (LTER por sus siglas en inglés), los cuales han mostrado su capacidad para influir sobre los avances en las ciencias básicas que permiten entender el mundo natural en escalas temporales y espaciales significativas, y también ayudar a enfocar la investigación hacia estudios socialmente relevantes. Recientemente, gracias a un cambio de paradigma en la disciplina, se integró también la dimensión humana de los ecosistemas, llevándola a un marco conceptual de Investigación Socio-Ecológica a Largo Plazo (LTSER por sus siglas en inglés) para enfrentar los desafíos medio-ambientales del mundo actual. Existe un vacío global en LTER/LTSER en el rango latitudinal de 40–60°S, correspondiente a los biomas templados/subantárticos de Argentina y Chile. Un equipo de investigadores chilenos, argentinos y estadounidenses ha trabajado por varios años para definir cuáles son la barreras que actualmente limitan la creación de una Red de LTER/LTSER en el sur de Sudamérica, no solamente en términos conceptuales, sino también a nivel práctico. Existe un buen número de sitios de investigación a largo plazo en la región, pero también concluimos que es necesario crear e implementar más cursos de capacitación para estudiantes, investigadores post-doctorales y jóvenes científicos, particularmente en las áreas de sistemas de manejo de datos e información. Considerando que los esfuerzos LTER/LTSER en Chile y Argentina son incipientes, este tipo de cursos podría mejorar la capacidad humana y técnica en la comunidad de las ciencias y los recursos naturales, así como mejorar los procesos de recolección, almacenamiento, análisis y difusión de la información. A su vez, la formalización de cursos de programas LTER/LTSER a nivel nacional para adquirir dicha capacidad de manejo de la información, permitirá un fortalecimiento crucial de las colaboraciones y comparaciones entre programas de investigación a largo plazo dentro de la región, y entre hemisferios y continentes. La versión en castellano del artículo se encuentra disponible en forma digital como Online Supporting Information S1.Fil: Anderson, Chistopher B. University of North Texas. Department of Biological Sciences; Estados UnidosFil: Celis-Diez, Juan Luis. Pontificia Universidad Católica de Valparaíso, Escuela de Agronomía; ChileFil: Bond, Barbara J.H.G. Oregon State University. Andrews Forest Long-Term Ecological Research Site. Department of Forest Ecosystems and Society; Estados UnidosFil: Martínez Pastur, Guillermo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Cientificas; ArgentinaFil: Little, Christian. Universidad Austral de Chile. Facultad de Ciencias. Instituto de Ciencias de la Tierra y Evolución; Chile. Fundación Centro de los Bosques Nativos FORECOS; ChileFil: Armesto, Juan J. Pontificia Universidad Católica de Valparaíso, Escuela de Agronomía; ChileFil: Ghersa, Claudio Marco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Austin, Amy Theresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Schlichter, Tomas Miguel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Grupo de Ecología Forestal; ArgentinaFil: Lara, Antonio. Fundación Centro de los Bosques Nativos FORECOS; Chile. Universidad Austral de Chile. Facultad de Ciencias Forestales y Recursos Naturales. Instituto de Silvicultura; ChileFil: Carmona, Martin. Universidad de Chile. Instituto de Ecologıa y Biodiversidad; ChileFil: Chaneton, Enrique Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Recursos Naturales y Ambiente; ArgentinaFil: Gutierrez, Julio R. Universidad de La Serena. Departamento de Biología. Instituto de Ecología y Biodiversidad. Centro de Estudios Avanzados en Zonas Aridas; ChileFil: Rozzi, Ricardo. Universidad de La Serena. Departamento de Biología. Instituto de Ecología y Biodiversidad; ChileFil: Vanderbilt, Kristin University of New Mexico. Department of Biology. Sevilleta Long-Term Ecological Research Site; Estados UnidosFil: Oyarce, Guillermo University of North Texas. Library and Information Sciences; Estados UnidosFil: Fernandez, Roberto J. University of North Texas, Department of Biological Sciences; Estados Unido