Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3(+) T-regulatory cells.

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death among women. Despite its immunogenicity, effective antitumor responses are limited, due, in part, to the presence of forkhead box protein 3-positive (Foxp3(+)) T regulatory (Treg) cells in the tumor microenvironment. However, the mechanisms that regulate the accumulation and the suppressive function of these Foxp3(+) Treg cells are poorly understood. Here, we found that the majority of Foxp3(+) Treg cells accumulating in the tumor microenvironment of EOCs belong to the subset of Foxp3(+) Treg cells expressing inducible costimulator (ICOS). The expansion and the suppressive function of these cells were strictly dependent on ICOS-L costimulation provided by tumor plasmacytoid dendritic cells (pDC). Accordingly, ICOS(+) Foxp3(+) Treg cells were found to localize in close vicinity of tumor pDCs, and their number directly correlated with the numbers of pDCs in the tumors. Furthermore, pDCs and ICOS(+) Foxp3(+) Treg cells were found to be strong predictors for disease progression in patients with ovarian cancer, with ICOS(+) Treg cell subset being a stronger predictor than total Foxp3(+) Treg cells. These findings suggest an essential role for pDCs and ICOS-L in immunosuppression mediated by ICOS(+) Foxp3(+) Treg cells, leading to tumor progression in ovarian cancer.

Optimization of multiclass queueing networks with changeover times via the achievable region method: Part II, the multi-station case

We address the problem of scheduling a multi-station multiclassqueueing network (MQNET) with server changeover times to minimizesteady-state mean job holding costs. We present new lower boundson the best achievable cost that emerge as the values ofmathematical programming problems (linear, semidefinite, andconvex) over relaxed formulations of the system's achievableperformance region. The constraints on achievable performancedefining these formulations are obtained by formulatingsystem's equilibrium relations. Our contributions include: (1) aflow conservation interpretation and closed formulae for theconstraints previously derived by the potential function method;(2) new work decomposition laws for MQNETs; (3) new constraints(linear, convex, and semidefinite) on the performance region offirst and second moments of queue lengths for MQNETs; (4) a fastbound for a MQNET with N customer classes computed in N steps; (5)two heuristic scheduling policies: a priority-index policy, anda policy extracted from the solution of a linear programmingrelaxation.

Protonation controls ASIC1a activity via coordinated movements in multiple domains.

Acid-sensing ion channels (ASICs) are neuronal Na(+)-conducting channels activated by extracellular acidification. ASICs are involved in pain sensation, expression of fear, and neurodegeneration after ischemic stroke. Functional ASICs are composed of three identical or homologous subunits, whose extracellular part has a handlike structure. Currently, it is unclear how protonation of residues in extracellular domains controls ASIC activity. Knowledge of these mechanisms would allow a rational development of drugs acting on ASICs. Protonation may induce conformational changes that control the position of the channel gate. We used voltage-clamp fluorometry with fluorophores attached to residues in different domains of ASIC1a to detect conformational changes. Comparison of the timing of fluorescence and current signals identified residues involved in movements that preceded desensitization and may therefore be associated with channel opening or early steps leading to desensitization. Other residues participated in movements intimately linked to desensitization and recovery from desensitization. Fluorescence signals of all mutants were detected at more alkaline pH than ionic currents. Their midpoint of pH dependence was close to that of steady-state desensitization, whereas the steepness of the pH fluorescence relationship was closer to that of current activation. A sequence of movements was observed upon acidification, and its backward movements during recovery from desensitization occurred in the reverse order, indicating that the individual steps are interdependent. Furthermore, the fluorescence signal of some labeled residues in the finger domain was strongly quenched by a Trp residue in the neighboring β-ball domain. Upon channel activation, their fluorescence intensity increased, indicating that the finger moved away from the β ball. This extensive analysis of activity-dependent conformational changes in ASICs sheds new light on the mechanisms by which protonation controls ASIC activity.

Factores que influenciam na escolha vocacional dos alunos do 12o ano da Via Técnica. O caso da Escola Secundária Polivalente Cesaltina Ramos

A orientação vocacional tem tido uma parte activa no desenvolvimento educacional, e tem sido alvo de uma evolução que assume uma relação cada vez mais estreita com a comunidade educativa, patenteado, ao longo do tempo, a necessidade de uma visão não só informativa, e construtiva, mas também desenvolvimental e ecológica, abarcando todos os contextos da vida do aluno. Esta evolução é denotada de um grande potencial, dado que também traz consigo um maior leque de possibilidades de modos e campos de intervenção na área da orientação. Intitulado “ Factores que interferem na escolha vocacional”, este trabalho de investigação, de carácter exploratório e de teor essencialmente quantitativo, tem como amostra representativa da população em estudo 121 alunos do 12o ano da via técnica da escola Secundária Polivalente Cesaltina Ramos. Todos os alunos da população do estudo não tiveram a mesma probabilidade de integrar esta amostra, dado que distribuímos o questionário que utilizamos era apenas para uma amostra representativa da nossa população (178). No que refere ao tratamento de dados usamos o SPSS (Statistical Package for Social Sciences) como recurso informático, fazendo análise das frequências, cruzamento e media dos dados, possibilitando-nos assim uma melhor análise dos resultados obtidos da aplicação dos questionários. Nesse trabalho procura-se diagnosticar quais os factores que influenciam a escolha vocacional dos alunos do 12o ano da Via Técnica da Escola Secundária Polivalente Cesaltina Ramos. O mesmo procura realçar os pontos mais importantes do tema em questão, dando assim um conhecer mais profundo do trabalho aos leitos Fazendo enfoque aos factores que interferem na escolha vocacional dos alunos do 12o ano da Via Técnica da Escola Secundária Polivalente Cesaltina Ramos, o trabalho teve como suporte teórico alguns autores tais como: Young, Bohoslavsky, Bock, Imaginário, Campos, Lucchiari, Nérici, Bem, Oliveira, Lassance, Unger, Levenfus, Coimbra e entre outros. Tentaremos ser claros e objectivos no que diz respeito ao tema. A metodologia adoptada foi a utilização do questionário como instrumento de medida. Questionário esse que foi elaborado pela autora da monografia. Este questionário é fechado composta por 18 (dezoito) itens com escala de respostas predefinidas. Ainda o referido questionário encontra-se estruturada de forma a responder aos objectivos do estudo em causa No que concerne à análise de dados, enfatizamos/privilegiamos a utilização de gráficos e tabelas que contribuíram realmente para decompor/analisar os dados conseguidos com a referida investigação. Também fez - se a recolha de algumas informações junto do Ministério da Educação e Ensino Superior (MEES).

Canalização das Remessas de Emigrantes para as Actividades Produtivas via Diáspora Bonds - Caso de Cabo Verde -

As remessas dos emigrantes desde sempre têm sido um fenómeno de grande importância para o desenvolvimento económico dos países em via de desenvolvimento e dos países do desenvolvimento médio, mas a sua utilização nem sempre têm um impacto significativo no crescimento económico dos países. É neste sentido que o presente trabalho visa abordar “Canalização das Remessas de Emigrantes para as Actividades Produtivas via Diáspora Bonds caso de Cabo Verde”, procurando demonstrá-lo através de um estudo de análise de dados e informações recolhidos junto da Bolsa de Valores de Cabo Verde, Banco de Cabo Verde, Instituto de Comunidades e Instituto Nacional das Estatísticas. O objectivo do referido estudo é avaliar a possibilidade da canalização das remessas dos emigrantes nas actividades produtivas, através do produto financeiro, Diáspora Bonds. Os resultados do estudo demonstraram que Diáspora Bonds é um mecanismo de canalização das remessas dos emigrantes nas actividades produtivas, isto porque o estudo revela, que garante a sustentabilidade futura do país, promove a criação da riqueza interna do país, permite a diversificação das fontes de financiamento, e fundamentalmente evidencia um veiculo de captação de fundos nos mercados internacionais a um custo muito mais baixo, por outro lado notou-se que as remessas dos emigrantes as não têm sido utilizada nas actividades produtivas em Cabo Verde, o que isto significa que a maioria dos volumes das remessas destinam-se as despesas do consumo, educação e saúde.

Induction of the Arabidopsis PHO1;H10 gene by 12-oxo-phytodienoic acid but not jasmonic acid via a CORONATINE INSENSITIVE1-dependent pathway

Expression of AtPHO1;H10, a member of the Arabidopsis (Arabidopsis thaliana) PHO1 gene family, is strongly induced following numerous abiotic and biotic stresses, including wounding, dehydration, cold, salt, and pathogen attack. AtPHO1;H10 expression by wounding was localized to the cells in the close vicinity of the wound site. AtPHO1;H10 expression was increased by application of the jasmonic acid (JA) precursor 12-oxo-phytodienoic acid (OPDA), but not by JA or coronatine. Surprisingly, induction of AtPHO1;H10 by OPDA was dependent on the presence of CORONATINE INSENSITIVE1 (COI1). The induction of AtPHO1;H10 expression by wounding and dehydration was dependent on COI1 and was comparable in both the wild type and the OPDA reductase 3-deficient (opr3) mutant. In contrast, induction of AtPHO1;H10 expression by exogenous abscisic acid (ABA) was independent of the presence of either OPDA or COI1, but was strongly decreased in the ABA-insensitive mutant abi1-1. The involvement of the ABA pathway in regulating AtPHO1;H10 was distinct between wounding and dehydration, with induction of AtPHO1;H10 by wounding being comparable to wild type in the ABA-deficient mutant aba1-3 and abi1-1, whereas a strong reduction in AtPHO1;H10 expression occurred in aba1-3 and abi1-1 following dehydration. Together, these results reveal that OPDA can modulate gene expression via COI1 in a manner distinct from JA, and independently from ABA. Furthermore, the implication of the ABA pathway in coregulating AtPHO1;H10 expression is dependent on the abiotic stress applied, being weak under wounding but strong upon dehydration

Automatização de processo de negócio usando ferramentas de BPM Open Source Automatização do processo Segunda Via

Este trabalho foi realizado no âmbito dos regulamentos dos cursos de graduação para a obtenção do grau de licenciatura na universidade Jean Piaget de Cabo Verde. Nele abordamos os conceitos de Bussines Process Management (BPM), Bussines Process Automation (BPA) e Open Source, cujo seu principal objectivo é dar a conhecer o estudo e implementação de automatização de processo de negócio usando ferramentas de BPM Open Source e o seu impacto depois da implementação. No presente trabalho fez-se uma investigação sobre algumas ferramentas Open Source usadas na automatização de processos de negócio, e implementado um processo BPM no framework Activiti para automatização do processo de negócio segunda via dos números dos clientes da Unitel T+. Para a automatização do processo Segunda Via foi integrado os frameworks Activiti e o Liferay, visto que dado a realidade de uma operadora de telecomunicação existe uma plataforma de gestão dos dados dos clientes implementado no Liferay, e havia necessidade de integrar estes dois frameworks distintos. Um dos maiores desafios na integração dos dois frameworks foi a autenticação. Para dar resposta a este problema, obter maior nível de segurança e sincronizar os frameworks foi utilizado o Hook que permite uma única autenticação e balanceamento (sincronização) dos dados no Activiti e no Liferay.

Creació de cartelleria via web

Projecte d'aplicació real de generació i impressió de cartelleria. Encara que el seu disseny s'ha fet de la manera més general possible, la finalitat d'aquest és que sigui funcional.

Lung microbiota promotes tolerance to allergens in neonates via PD-L1.

Epidemiological data point toward a critical period in early life during which environmental cues can set an individual on a trajectory toward respiratory health or disease. The neonatal immune system matures during this period, although little is known about the signals that lead to its maturation. Here we report that the formation of the lung microbiota is a key parameter in this process. Immediately following birth, neonatal mice were prone to develop exaggerated airway eosinophilia, release type 2 helper T cell cytokines and exhibit airway hyper-responsiveness following exposure to house dust mite allergens, even though their lungs harbored high numbers of natural CD4(+)Foxp3(+)CD25(+)Helios(+) regulatory T (Treg) cells. During the first 2 weeks after birth, the bacterial load in the lungs increased, and representation of the bacterial phyla shifts from a predominance of Gammaproteobacteria and Firmicutes towards Bacteroidetes. The changes in the microbiota were associated with decreased aeroallergen responsiveness and the emergence of a Helios(-) Treg cell subset that required interaction with programmed death ligand 1 (PD-L1) for development. Absence of microbial colonization(10) or blockade of PD-L1 during the first 2 weeks postpartum maintained exaggerated responsiveness to allergens through to adulthood. Adoptive transfer of Treg cells from adult mice to neonates before aeroallergen exposure ameliorated disease. Thus, formation of the airway microbiota induces regulatory cells early in life, which, when dysregulated, can lead to sustained susceptibility to allergic airway inflammation in adulthood.

Mutant HbpR transcription activator isolation for 2-chlorobiphenyl via green fluorescent protein-based flow cytometry and cell sorting.

Mutants were produced in the A-domain of HbpR, a protein belonging to the XylR family of σ(54)-dependent transcription activators, with the purpose of changing its effector recognition specificity from 2-hydroxybiphenyl (2-HBP, the cognate effector) to 2-chlorobiphenyl (2-CBP). Mutations were introduced in the hbpR gene part for the A-domain via error-prone polymerase chain reaction, and assembled on a gene circuitry plasmid in Escherichia coli, permitting HbpR-dependent induction of the enhanced green fluorescent protein (egfp). Cells with mutant HbpR proteins responsive to 2-CBP were enriched and separated in a flow cytometry-assisted cell-sorting procedure. Some 70 mutants were isolated and the A-domain mutations mapped. One of these had acquired true 2-CBP recognition but reacted hypersensitively to 2-HBP (20-fold more than the wild type), whereas others had reduced sensitivity to 2-HBP but a gain of 2-CBP recognition. Sequencing showed that most mutants carried double or triple mutations in the A-domain gene part, and were not located in previously recognized conserved residues within the XylR family members. Further selection from a new mutant pool prepared of the hypersensitive mutant did not result in increased 2-CBP or reduced 2-HBP recognition. Our data thus demonstrate that a one-step in vitro 'evolutionary' adaptation of the HbpR protein can result in both enhancement and reduction of the native effector recognition.

Antiapoptotic role of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway.

Apoptosis, differentiation, and proliferation are cellular responses which play a pivotal role in wound healing. During this process PPARbeta translates inflammatory signals into prompt keratinocyte responses. We show herein that PPARbeta modulates Akt1 activation via transcriptional upregulation of ILK and PDK1, revealing a mechanism for the control of Akt1 signaling. The resulting higher Akt1 activity leads to increased keratinocyte survival following growth factor deprivation or anoikis. PPARbeta also potentiates NF-kappaB activity and MMP-9 production, which can regulate keratinocyte migration. Together, these results provide a molecular mechanism by which PPARbeta protects keratinocytes against apoptosis and may contribute to the process of skin wound closure.

NOTCH1 can initiate NF-κB activation via cytosolic interactions with components of the T cell Signalosome.

T cell stimulation requires the input and integration of external signals. Signaling through the T cell receptor (TCR) is known to induce formation of the membrane-tethered CBM complex, comprising CARMA1, BCL10, and MALT1, which is required for TCR-mediated NF-κB activation. TCR signaling has been shown to activate NOTCH proteins, transmembrane receptors also implicated in NF-κB activation. However, the link between TCR-mediated NOTCH signaling and early events leading to induction of NF-κB activity remains unclear. In this report, we demonstrate a novel cytosolic function for NOTCH1 and show that it is essential to CBM complex formation. Using a model of skin allograft rejection, we show in vivo that NOTCH1 acts in the same functional pathway as PKCθ, a T cell-specific kinase important for CBM assembly and classical NF-κB activation. We further demonstrate in vitro NOTCH1 associates physically with PKCθ and CARMA1 in the cytosol. Unexpectedly, when NOTCH1 expression was abrogated using RNAi approaches, interactions between CARMA1, BCL10, and MALT1 were lost. This failure in CBM assembly reduced inhibitor of kappa B alpha phosphorylation and diminished NF-κB-DNA binding. Finally, using a luciferase gene reporter assay, we show the intracellular domain of NOTCH1 can initiate robust NF-κB activity in stimulated T cells, even when NOTCH1 is excluded from the nucleus through modifications that restrict it to the cytoplasm or hold it tethered to the membrane. Collectively, these observations provide evidence that NOTCH1 may facilitate early events during T cell activation by nucleating the CBM complex and initiating NF-κB signaling.

Importancia predominante de los abonos potásicos para el cultivo de la viña en el Perú

Realiza un análisis físico de los suelos donde existe campos de viña, comentando que es necesario dotar a estas tierras abono potásico necesario para la mejora de la producción y de las plantaciones de cepas y se desarrolle una vegetación más abundante en todas las zonas y e especial en los valles de Lima.

Estudio experimental sobre la acción dinámica especifica (SDA) y la eficiencia digestiva de juveniles de Sardinas Sardinops sagax sagax (Jenyns)

Una dieta rica en Noctiluca, equivalente al 6.2% del peso húmedo en un experimento y al 15.5% en otro, fue suministrado a dos individuos muy parecidos en talla y peso; los cálculos indican un gasto en SDA equivalente al 27.6% de las calorias ingeridas en el primer caso y al 24.1% en el segundo. La eficiencia digestiva o de asimilación resultó ser en el primer experimento del 84.7% de la energía ingerida y de 87.7% en el segundo. El equipo utilizado no incluyó control de flujo de agua.