3D cloud reconstructions: evaluation of scanning radar scan strategy with a view to surface shortwave radiation closure

The ability of six scanning cloud radar scan strategies to reconstruct cumulus cloud fields for radiation study is assessed. Utilizing snapshots of clean and polluted cloud fields from large eddy simulations, an analysis is undertaken of error in both the liquid water path and monochromatic downwelling surface irradiance at 870 nm of the reconstructed cloud fields. Error introduced by radar sensitivity, choice of radar scan strategy, retrieval of liquid water content (LWC), and reconstruction scheme is explored. Given an in␣nitely sensitive radar and perfect LWC retrieval, domain average surface irradiance biases are typically less than 3 W m␣2 ␣m␣1, corresponding to 5–10% of the cloud radiative effect (CRE). However, when using a realistic radar sensitivity of ␣37.5 dBZ at 1 km, optically thin areas and edges of clouds are dif␣cult to detect due to their low radar re-ectivity; in clean conditions, overestimates are of order 10 W m␣2 ␣m␣1 (~20% of the CRE), but in polluted conditions, where the droplets are smaller, this increases to 10–26 W m␣2 ␣m␣1 (~40–100% of the CRE). Drizzle drops are also problematic; if treated as cloud droplets, reconstructions are poor, leading to large underestimates of 20–46 W m␣2 ␣m␣1 in domain average surface irradiance (~40–80% of the CRE). Nevertheless, a synergistic retrieval approach combining the detailed cloud structure obtained from scanning radar with the droplet-size information and location of cloud base gained from other instruments would potentially make accurate solar radiative transfer calculations in broken cloud possible for the first time.

Regulation of KCa2.3 andendothelium-dependent hyperpolarization (EDH) in the rat middle cerebral artery: the role of lipoxygenase metabolites and isoprostanes

Background and Purpose. In rat middle cerebral arteries, endothelium-dependent hyperpolarization (EDH) is mediated by activation of calcium-activated potassium(KCa) channels specifically KCa2.3 and KCa3.1. Lipoxygenase (LOX) products function as endothelium-derived hyperpolarizing factors (EDHFs) in rabbit arteries by stimulating KCa2.3. We investigated if LOX products contribute to EDH in rat cerebral arteries. Methods. Arachidonic acid (AA) metabolites produced in middle cerebral arteries were measured using HPLC and LC/MS. Vascular tension and membrane potential responses to SLIGRL were simultaneously recorded using wire myography and intracellular microelectrodes. Results. SLIGRL, an agonist at PAR2 receptors, caused EDH that was inhibited by a combination of KCa2.3 and KCa3.1 blockade. Non-selective LOX-inhibition reduced EDH, whereas inhibition of 12-LOX had no effect. Soluble epoxide hydrolase (sEH) inhibition enhanced the KCa2.3 component of EDH. Following NO synthase (NOS) inhibition, the KCa2.3 component of EDH was absent. Using HPLC, middle cerebral arteries metabolized 14C-AA to 15- and 12-LOX products under control conditions. With NOS inhibition, there was little change in LOX metabolites, but increased F-type isoprostanes. 8-iso-PGF2α inhibited the KCa2.3 component of EDH. Conclusions. LOX metabolites mediate EDH in rat middle cerebral arteries. Inhibition of sEH increases the KCa2.3 component of EDH. Following NOS inhibition,loss of KCa2.3 function is independent of changes in LOX production or sEH inhibition but due to increased isoprostane production and subsequent stimulation of TP receptors. These findings have important implications in diseases associated with loss of NO signaling such as stroke; where inhibition of sEH and/or isoprostane formation may of benefit.

The N-terminal SH2 domain of Syk is required for (hem)ITAM, but not integrin, signaling in mouse platelets

We have used a novel knockin mouse to investigate the effect of disruption of phosphotyrosine binding of the N-terminal SH2 domain of Syk on platelet activation by GPVI, CLEC-2, and integrin αIIbβ3. The Syk(R41Afl/fl) mouse was crossed to a PF4-Cre(+) mouse to induce expression of the Syk mutant in the megakaryocyte/platelet lineage. Syk(R41Afl/fl;PF4-Cre) mice are born at approximately 50% of the expected frequency and have a similar phenotype to Syk(fl/fl;PF4-Cre) mice, including blood-lymphatic mixing and chyloascites. Anastomosis of the venous and lymphatic vasculatures can be seen in the mesenteric circulation accounting for rapid and continuous mixing of the 2 vasculatures. Platelet activation by CLEC-2 and GPVI is abolished in Syk(R41Afl/fl;PF4-Cre) platelets. Syk phosphorylation on Tyr519/20 is blocked in CLEC-2-stimulated platelets, suggesting a model in which binding of Syk via its N-terminal SH2 domain regulates autophosphorylation. In contrast, outside-in signaling by integrin αIIbβ3 is not altered, but it is inhibited in the presence of inhibitors of Src and Syk tyrosine kinases. These results demonstrate that αIIbβ3 regulates Syk through an ITAM-independent pathway in mice and provide novel insight into the course of events underlying Syk activation and hemITAM phosphorylation by CLEC-2.

A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function

Filamin A (FlnA) cross-links actin filaments and connects the Von Willebrand factor receptor GPIb-IX-V to the underlying cytoskeleton in platelets. Because FlnA deficiency is embryonic lethal, mice lacking FlnA in platelets were generated by breeding FlnA(loxP/loxP) females with GATA1-Cre males. FlnA(loxP/y) GATA1-Cre males have a macrothrombocytopenia and increased tail bleeding times. FlnA-null platelets have decreased expression and altered surface distribution of GPIbalpha because they lack the normal cytoskeletal linkage of GPIbalpha to underlying actin filaments. This results in approximately 70% less platelet coverage on collagen-coated surfaces at shear rates of 1,500/s, compared with wild-type platelets. Unexpectedly, however, immunoreceptor tyrosine-based activation motif (ITAM)- and ITAM-like-mediated signals are severely compromised in FlnA-null platelets. FlnA-null platelets fail to spread and have decreased alpha-granule secretion, integrin alphaIIbbeta3 activation, and protein tyrosine phosphorylation, particularly that of the protein tyrosine kinase Syk and phospholipase C-gamma2, in response to stimulation through the collagen receptor GPVI and the C-type lectin-like receptor 2. This signaling defect was traced to the loss of a novel FlnA-Syk interaction, as Syk binds to FlnA at immunoglobulin-like repeat 5. Our findings reveal that the interaction between FlnA and Syk regulates ITAM- and ITAM-like-containing receptor signaling and platelet function.

Connections between clouds, radiation, and midlatitude dynamics: a review

We review the effects of dynamical variability on clouds and radiation in observations and models and discuss their implications for cloud feedbacks. Jet shifts produce robust meridional dipoles in upper-level clouds and longwave cloud-radiative effect (CRE), but low-level clouds, which do not simply shift with the jet, dominate the shortwave CRE. Because the effect of jet variability on CRE is relatively small, future poleward jet shifts with global warming are only a second-order contribution to the total CRE changes around the midlatitudes, suggesting a dominant role for thermodynamic effects. This implies that constraining the dynamical response is unlikely to reduce the uncertainty in extratropical cloud feedback. However, we argue that uncertainty in the cloud-radiative response does affect the atmospheric circulation response to global warming, by modulating patterns of diabatic forcing. How cloud feedbacks can affect the dynamical response to global warming is an important topic of future research.

Trends in the CERES dataset, 2000–13: the effects of sea ice and jet shifts and comparison to climate models

We review the effects of dynamical variability on clouds and radiation in observations and models and discuss their implications for cloud feedbacks. Jet shifts produce robust meridional dipoles in upper-level clouds and longwave cloud-radiative effect (CRE), but low-level clouds, which do not simply shift with the jet, dominate the shortwave CRE. Because the effect of jet variability on CRE is relatively small, future poleward jet shifts with global warming are only a second-order contribution to the total CRE changes around the midlatitudes, suggesting a dominant role for thermodynamic effects. This implies that constraining the dynamical response is unlikely to reduce the uncertainty in extratropical cloud feedback. However, we argue that uncertainty in the cloud-radiative response does affect the atmospheric circulation response to global warming, by modulating patterns of diabatic forcing. How cloud feedbacks can affect the dynamical response to global warming is an important topic of future research.

Endothelin-1 promotes phosphorylation of CREB transcription factor in primary cultures of neonatal rat cardiac myocytes: implications for the regulation of c-jun expression.

Cardiac myocyte hypertrophy is associated with an increase in expression of immediate early genes (e.g. c-jun) via activation of pre-existing transcription factors. The activity of CREB transcription factor is regulated through phosphorylation of Ser-133 by one of several protein kinases (e.g. protein kinase A (PKA), p90 ribosomal S6 kinases (RSKs) and the related kinase, MSK1). A cell-permeable form of cAMP, hypertrophic agonists (endothelin-1 (ET-1), phenylephrine (PE)) and hyperosmotic shock all promoted phosphorylation of CREB(Ser-133) in rat neonatal cardiac myocytes. The response to endothelin-1 required the extracellular signal-regulated kinase cascade which stimulates both RSKs and MSK1. Phosphorylation of CREB(Ser-133) in response to ET-1 was not associated with any increase in DNA binding to a consensus cAMP-response element (CRE). The rat c-jun promoter contains elements which may bind either c-Jun/ATF2 or CREB/ATF1 dimers. Using extracts from rat cardiac myocytes, we identified at least two complexes which bind to the most proximal of these elements, one of which contained CREB and the other c-Jun. Thus, phosphorylation and activation of CREB in cardiac myocytes may be effected by a range of different stimuli to influence the expression of immediate early genes such as c-jun.

Leptin Targets in the Mouse Brain

The central actions of leptin are essential for homeostatic control of adipose tissue mass, glucose metabolism, and many autonomic and neuroendocrine systems. In the brain, leptin acts on numerous different cell types via the long-form leptin receptor (LepRb) to elicit its effects. The precise identification of leptin`s cellular targets is fundamental to understanding the mechanism of its pleiotropic central actions. We have systematically characterized LepRb distribution in the mouse brain using in situ hybridization in wildtype mice as well as by EYFP immunoreactivity in a novel LepRb-IRES-Cre EYFP reporter mouse line showing high levels of LepRb mRNA/EYFP coexpression. We found substantial LepRb mRNA and EYFP expression in hypothalamic and extrahypothalamic sites described before, including the dorsomedial nucleus of the hypothalamus, ventral premammillary nucleus, ventral tegmental area, parabrachial nucleus, and the dorsal vagal complex. Expression in insular cortex, lateral septal nucleus, medial preoptic area, rostral linear nucleus, and in the Edinger-Westphal nucleus was also observed and had been previously unreported. The LepRb-IRES-Cre reporter line was used to chemically characterize a population of leptin receptor-expressing neurons in the midbrain. Tyrosine hydroxylase and Cre reporter were found to be coexpressed in the ventral tegmental area and in other midbrain dopaminergic neurons. Lastly, the LepRbI-RES-Cre reporter line was used to map the extent of peripheral leptin sensing by central nervous system (CNS) LepRb neurons. Thus, we provide data supporting the use of the LepRb-IRES-Cre line for the assessment of the anatomic and functional characteristics of neurons expressing leptin receptor. J. Comp. Neurol. 514:518-532, 2009. (C) 2009 Wiley-Liss, Inc.

Arachidonic acid actions on functional integrity and attenuation of the negative effects of palmitic acid in a clonal pancreatic beta-cell line

Chronic exposure of pancreatic beta-cells to saturated non-esterified fatty acids can lead to inhibition of insulin secretion and apoptosis. Several previous studies have demonstrated that saturated fatty acids such as PA (palmitic acid) are detrimental to beta-cell function compared with unsaturated fatty acids. In the present study, we describe the effect of the polyunsaturated AA (arachidonic acid) on the function of the clonal pancreatic beta-cell line BRIN-BD11 and demonstrate AA-dependent attenuation of PA effects. When added to beta-cell incubations at 100 mu M, AA can stimulate cell proliferation and chronic (24 h) basal insulin secretion. Microarray analysis and/or real-time PCR indicated significant AA-dependent up-regulation of genes involved in proliferation and fatty acid metabolism [e.g. Angptl (angiopoietin-like protein 4), Ech1 (peroxisomal Delta(3.5),Delta(2.4)-dienoyl-CoA isomerase), Cox-1 (cyclo-oxygenase-1) and Cox-2, P < 0.05]. Experiments using specific COX and LOX (lipoxygenase) inhibitors demonstrated the importance of COX-1 activity for acute (20 min) stimulation of insulin secretion, suggesting that AA metabolites may be responsible for the insulinotropic effects. Moreover, concomitant incubation of AA with PA dose-dependently attenuated the detrimental effects of the saturated fatty acid, so reducing apoptosis and decreasing parameters of oxidative stress [ROS (reactive oxygen species) and NO levels] while improving the GSH/GSSG ratio. AA decreased the protein expression of iNOS (inducible NO synthase), the p65 subunit of NF-kappa B (nuclear factor kappa B) and the p47 subunit of NADPH oxidase in PA-treated cells. These findings indicate that AA has an important regulatory and protective beta-cell action, which may be beneficial to function and survival in the `lipotoxic` environment commonly associated with Type 2 diabetes mellitus.

Notch signaling controls the balance of ciliated and secretory cell fates in developing airways

Although there is accumulated evidence of a role for Notch in the developing lung, it is still unclear how disruption of Notch signaling affects lung progenitor cell fate and differentiation events in the airway epithelium. To address this issue, we inactivated Notch signaling conditionally in the endoderm using a Shh-Cre deleter mouse line and mice carrying floxed alleles of the Pofut1 gene, which encodes an O-fucosyltransferase essential for Notch-ligand binding. We also took the same conditional approach to inactivate expression of Rbpjk, which encodes the transcriptional effector of canonical Notch signaling. Strikingly, these mutants showed an almost identical lung phenotype characterized by an absence of secretory Clara cells without evidence of cell death, and showed airways populated essentially by ciliated cells, with an increase in neuroendocrine cells. This phenotype could be further replicated in cultured wild-type lungs by disrupting Notch signaling with a gamma-secretase inhibitor. Our data suggest that Notch acts when commitment to a ciliated or non-ciliated cell fate occurs in proximal progenitors, silencing the ciliated program in the cells that will continue to expand and differentiate into secretory cells. This mechanism may be crucial to define the balance of differentiated cell profiles in different generations of the developing airways. It might also be relevant to mediate the metaplastic changes in the respiratory epithelium that occur in pathological conditions, such as asthma and chronic obstructive pulmonary disease.

Una memoria consensuada : El Informe Rettig

No cabe duda que hoy día la memoria de la dictadura militar (1973-1990) está presente en la vida cotidiana de Chile más que ningún otro periodo histórico. La razón se encuentra en los trágicos sucesos que se vivieron duran- te esos años en materia de derechos humanos. Don Patricio Aylwin, primer presidente electo democráticamente en tras 17 años de autoritarismo y una figura comprometida con los derechos humanos, era consciente de la necesi- dad de investigar la verdad de los crímenes de lesa humanidad ocurridos en Chile. Para ello creó la Comisión Nacional de Verdad y Reconciliación, aunque consideró menester limitar el contenido de su informe con el fin de no amedrentar a las Fuerzas Armadas, las cuales gozaban todavía de mucho poder. Asimismo, el apoyo electoral de los partidos de derecha fue un factor que logró coartar el contenido del informe de la comisión. En este trabajo se presentan aquellas cuestiones que más relevancia tuvieron en la conformación de la verdad de la represión, tales como sus objetivos, sus integrantes y su metodología.

Harold Pinter, cinema e literatura : os limites da realidade

Partindo de duas questões teóricas preliminares, uma, da representação (literária e cinematográfica)do real e do imaginário, tanto no ângulo da produção como no da sua recepção e, a outra, da articulação entre formas de expressão artísticas distintas, ou seja, da interdisciplinaridade, este trabalho examina a presença do tema relativo aos limites entre realidade e fantasia no teatro, no cinema e na literatura, centrando sua atenção na obra de Harold Pinter. Consta de duas partes, cada uma com três capítulos. Na primeira, "Os pressupostos," discute-se as questões que fornecem seu substrato teórico. A segunda é dedicada ao corpus, identificando em seu título o tema investigado: "Os limites da realidade." Quanto à questão da representação, procura-se refutar "a afirmação de que a arte seja uma imitação da realidade. Uma releitura da Poética, de Aristóteles, reforçada pela opinião de diversos estudiosos da mesma, permite afirmar que a mÍmese corresponde, isto sim, a uma representação que envolve uma construção em que elementos da realidade são organizados segundo uma verdade criada pela própria obra, de acordo com critérios inerentes a ela. Além disso, através de uma leitura de Kathryn Hume, procura-se afirmar a interação sinestésica quase que permanente dos impulsos realista e da fantasiana literatura, identificando os tipos com que a fantasia se manifesta e as técnicas usadas para sua criação. A primeira parte encerra-se com um exame do relacionamento da literatura com as artes visuais e dramáticas, relações inter-disciplinares que situam este trabalho na literatura comparada.Dentre vários autores cujas obras contribuem para tal fim, destaca-se Martin Esslin, que estabelece os limitesde cada uma das artes dramáticas, identifica contatos delas com a literatura e permite, através de uma leitura de seu estudo sobre o teatro do absurdo, seja estabelecida a evolução que liga Aristóteles a Pinter. O corpus centra-se na obra de Pinterpara o teatro e para o cinema, sem limitar-se a ela,pois são também analisadas obras de outros escritores e cineastas, estabelendo-se aproximações ou contrastes entre elas. No quarto capítulo estão agrupadas obras nas quais desponta a imposição de verdades pela força fisica ou verbal. A luta pelo poder, a expulsão de elementos estranhos, dúvidas sobre a identidade e a inter-penetrablidade arte-vida caracterizam o capítulo seguinte. A ênfase temática do sexto capítulo recai sobre as limitações impostas pela condição humana. Praticamente todas as obras expressam a impossibilidade da existência de certezas absolutas e de uma perfeita distinção dos limites da realidade. Com isso, é possível afirmar não ser o objetivo da arte reproduzir a realidade. Mesmo que o fosse, tal tentativa resultaria infrutífera devido às limitações humanas.

Singularidade ou mesmice?: uma incursão pelo discurso pedagógico em São João-Del Rei

A proposta deste trabalho consiste, primeiramente, em apresentar a questão do discurso que, na filosofia ocidental, ficou confinado a um espaço entre pensamento e linguagem, confundindo- se ora com o primeiro, ora com a segunda. A seguir, procura-se mostrar que Foucault, ao libertar o discurso, torna-o objeto de saber e cria o saber apropriado a este objeto, deixando claro que todo discurso é um processo de produção de sentido. o discurso que circula nos interstícios da prática pedagógica produz um determinado sentido que muitas vezes se caracteriza pelo silêncio. Tal discurso pode configurar-se de forma autoritária, crítica ou singular. Para penetrar neste último modo de engendramento do discurso, estudam-se os processos de singularização, procurando compreendê-los e estendê-los aos espaços pedagógicos. Este estudo conta com a análise das contribuições de Guattari. Os lugares pedagógicos, onde poderia florescer este discurso de singularização, tomam forma e se definem em um espaço pedagógico concreto, na cidade de São João del-Rei que, impregnada pelo estilo barroco, possui características culturais,históricas e artísticas que propIcIam um clima favorável aos processos de singularização. Em decorrência, as produções pedagógicas também se aliam a tais processos e, assim, através da análise temática destas produções, pode-se apontar pistas ou sinais que indicam o caminho para o qual tende o discurso pedagógico. Na concl usão, traça-se uma síntese onde se procura evidenciar que as produções pedagógicas, em São João del-Rei, participam do dinamismo de um discurso afeito aos processos de singularização.

Descentralização administrativa: o caso da coordenação regional de polícia técnica do planalto - BA

O Departamento de Polícia Técnica (DPT) é um órgão da Secretaria de Segurança Pública do Estado da Bahia (SSP/BA), que tem por finalidade gerir os serviços no campo da polícia-técnica-científica, promovendo estudos e realizando exames e outros procedimentos, visando à prova pericial. Possui diversas coordenadorias regionais que recebem suporte das seis coordenações regionais distribuídas pelo interior do Estado. Tais coordenações foram criadas para atender a uma demanda crescente pelos trabalhos periciais ao longo do processo de interiorização da Polícia Técnica pelos municípios baianos. O objetivo do estudo exploratório aqui relatado foi descrever a maneira como o processo de descentralização administrativa se efetivou na Coordenação Regional de Polícia Técnica do Planalto-BA. Para isso, foram adotados os procedimentos de uma pesquisa bibliográfica a fim de aprofundar as definições dos diversos conceitos de centralização, descentralização, concentração e desconcentração, de modo a possibilitar a análise dos principais aspectos e a relevância da descentralização administrativa para a administração pública. Por meio de observação sistemática, foi delineada uma descrição do funcionamento da Coordenação Regional do Planalto-BA e foram empregadas técnicas de entrevista semiestruturada e de aplicação de questionário estruturado fechado para ouvir os dirigentes das coordenadorias vinculadas à Coordenação Regional do Planalto, entre os quais o seu coordenador e as diretorias do DPT. Foram também ouvidos os peritos que laboram nas coordenadorias envolvidas, para colher dados que possibilitaram identificar, dentre as atividades administrativas realizadas pela coordenação, aquelas que apresentam as características da descentralização. Ao final do estudo foi possível concluir que o DPT ainda não alcançou a descentralização que vem almejando desde 2004, processo que iniciou com a interiorização das Coordenadorias Regionais. A pesquisa de campo revelou carências de ordens diversas que resultam em trabalhos incompletos, ineficientes e sem a celeridade que a justiça necessita. Tudo isso aponta para a urgência na elaboração de um estudo aprofundado que tenha como resultado uma proposta de padronização procedimentais e estruturais que tornem efetiva a descentralização do DPT.

O voto e seus enigmas: A dimensão subjetiva das escolhas eleitorais

Ce travail analyse la portée subjective des Choix Électoraux à travers la notion psychanalytique du désarroi humain. Nous avons développé cette recherche ayant pour référence la pensée de Freud et de Lacan et suivant les jalons posés par les penseurs des sciences sociales nous nous sommes rapprochées de la réalité sociale pour y « atteindre sur son horizon la subjectivité de notre époque ». La condition de désarroi fait partie de la structuration du sujet, du fait qu il dépend entièrement de l Autre pour se construire. Cependant l être humain se crée des mécanismes pour se protéger du désarroi absolu, il trouve des arts de vivre qui lui rendent plus facile sa condition d être. Les idéaux, les pactes sociaux ce sont des modalités de sécurité sans lesquelles le sujet fixe ses particularités sans s engager dans le processus civilisatoire. Nous caractérisons la société contemporaine par la chute successive d une série d idéaux qui fait monter de plus en plus le désarroi. Dans l absence d idéaux sociaux et politiques sur lesquels l électeur puisse se repérer, nous remaquons une tendance vers l individualisme et vers l absence d investissements dans des projets colectifs. Cette façon d opérer se dévoile aussi au moment de choisir un candidat, ce qui se base sur la logique du particulier motivée par des perspectives individuelles, sans liens avec la promotion de la vie publique. Notre enquête a été réalisée à Natal durant la campagne électorale de 2002. Notre objectif est de comprendre surtout la logique des choix électoraux de la population de la périphérie, celle qui se trouve devant un double désarroi : celle de sa condition humaine et celle qu advient de la précaire condition de subsistance. Nous soutenons que l idée selon laquelle le candidat, par la position qu il occupe dans la société, détient la fonction d offrir quelques garanties à l électeur et de cette manière il entre dans la série de ce qui peut soulager et promouvoir un certain réconfort aux personnes, même si l on considère le fait que l électeur ne croit plus à ses représentants. Nous sommes partis des questions suivantes: comment identifier la dimension subjective des choix électoraux et de quelle manière celle-ci se manifeste-t-elle de nos jours ? Comment se passe le choix éléctoral de la population qui est à la marge du système? La thèse que nous soutenons est que l état de désarroi est un substrat subjectif qui est la base de tout choix éléctoral mais qui se configure de façon différenciée à partir des références de l électeur, de son contexte historique, des facteurs économiques, etc. Le sujet, face à son désarroi, construit des chemins pour pouvoir soutenir son existence ce que nous appellons ici un Projet Directionnel. Ce facteur directionnel est l un des éléments de motivation des électeurs dans leurs choix électoraux