Expression of neutral endopeptidase, endothelin-1, and nuclear factor kappa B in prostate cancer: interrelations and associations with prostate-specific antigen recurrence after radical prostatectomy.

Objective. To study the impact of the neutral endopeptidase (NEP)/neuropeptides (NPs) axis and nuclear factor kappa B (NFκB) as predictors of prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Patients and Methods. 70 patients with early-stage PC were treated with RP and their tumor samples were evaluated for expression of NEP, endothelin-1 (ET-1) and NFκB (p65). Time to PSA recurrence was correlated with the examined parameters and combined with preoperative PSA level, Gleason score, pathological TNM (pT) stage, and surgical margin (SM) assessment. Results and Limitations. Membranous expression of NEP (P < 0.001), cytoplasmic ET-1 (P = 0.002), and cytoplasmic NFκB (P < 0.001) were correlated with time to PSA relapse. NEP was associated with ET-1 (P < 0.001) and NFκB (P < 0.001). ET-1 was also correlated with NFκB (P < 0.001). NEP expression (P = 0.017), pT stage (P = 0.013), and SMs (P = 0.036) were independent predictors of time to PSA recurrence. Conclusions. There seems to be a clinical model of NEP/NPs and NFκB pathways interconnection, with their constituents following inverse patterns of expression in accordance with their biological roles and molecular interrelations.

Factor analysis of the North American Spine Society outcome assessment instrument: a study based on a spine registry of patients treated with lumbar and cervical disc arthroplasty.

BACKGROUND CONTEXT: Studies involving factor analysis (FA) of the items in the North American Spine Society (NASS) outcome assessment instrument have revealed inconsistent factor structures for the individual items. PURPOSE: This study examined whether the factor structure of the NASS varied in relation to the severity of the back/neck problem and differed from that originally recommended by the developers of the questionnaire, by analyzing data before and after surgery in a large series of patients undergoing lumbar or cervical disc arthroplasty. STUDY DESIGN/SETTING: Prospective multicenter observational case series. PATIENT SAMPLE: Three hundred ninety-one patients with low back pain and 553 patients with neck pain completed questionnaires preoperatively and again at 3 to 6 and 12 months follow-ups (FUs), in connection with the SWISSspine disc arthroplasty registry. OUTCOME MEASURES: North American Spine Society outcome assessment instrument. METHODS: First, an exploratory FA without a priori assumptions and subsequently a confirmatory FA were performed on the 17 items of the NASS-lumbar and 19 items of the NASS-cervical collected at each assessment time point. The item-loading invariance was tested in the German version of the questionnaire for baseline and FU. RESULTS: Both NASS-lumbar and NASS-cervical factor structures differed between baseline and postoperative data sets. The confirmatory analysis and item-loading invariance showed better fit for a three-factor (3F) structure for NASS-lumbar, containing items on "disability," "back pain," and "radiating pain, numbness, and weakness (leg/foot)" and for a 5F structure for NASS-cervical including disability, "neck pain," "radiating pain and numbness (arm/hand)," "weakness (arm/hand)," and "motor deficit (legs)." CONCLUSIONS: The best-fitting factor structure at both baseline and FU was selected for both the lumbar- and cervical-NASS questionnaires. It differed from that proposed by the originators of the NASS instruments. Although the NASS questionnaire represents a valid outcome measure for degenerative spine diseases, it is able to distinguish among all major symptom domains (factors) in patients undergoing lumbar and cervical disc arthroplasty; overall, the item structure could be improved. Any potential revision of the NASS should consider its factorial structure; factorial invariance over time should be aimed for, to allow for more precise interpretations of treatment success.

ZNRD1 (zinc ribbon domain-containing 1) is a host cellular factor that influences HIV-1 replication and disease progression.

BACKGROUND: Human immunodeficiency virus (HIV) takes advantage of multiple host proteins to support its own replication. The gene ZNRD1 (zinc ribbon domain-containing 1) has been identified as encoding a potential host factor that influenced disease progression in HIV-positive individuals in a genomewide association study and also significantly affected HIV replication in a large-scale in vitro short interfering RNA (siRNA) screen. Genes and polymorphisms identified by large-scale analysis need to be followed up by means of functional assays and resequencing efforts to more precisely map causal genes. METHODS: Genotyping and ZNRD1 gene resequencing for 208 HIV-positive subjects (119 who experienced long-term nonprogression [LTNP] and 89 who experienced normal disease progression) was done by either TaqMan genotyping assays or direct sequencing. Genetic association analysis was performed with the SNPassoc package and Haploview software. siRNA and short hairpin RNA (shRNA) specifically targeting ZNRD1 were used to transiently or stably down-regulate ZNRD1 expression in both lymphoid and nonlymphoid cells. Cells were infected with X4 and R5 HIV strains, and efficiency of infection was assessed by reporter gene assay or p24 assay. RESULTS: Genetic association analysis found a strong statistically significant correlation with the LTNP phenotype (single-nucleotide polymorphism rs1048412; [Formula: see text]), independently of HLA-A10 influence. siRNA-based functional analysis showed that ZNRD1 down-regulation by siRNA or shRNA impaired HIV-1 replication at the transcription level in both lymphoid and nonlymphoid cells. CONCLUSION: Genetic association analysis unequivocally identified ZNRD1 as an independent marker of LTNP to AIDS. Moreover, in vitro experiments pointed to viral transcription as the inhibited step. Thus, our data strongly suggest that ZNRD1 is a host cellular factor that influences HIV-1 replication and disease progression in HIV-positive individuals.

Development of a Selective Peptide Macrocycle Inhibitor of Coagulation Factor XII toward the Generation of a Safe Antithrombotic Therapy.

Inhibition of coagulation factor XII (FXII) activity represents an attractive approach for the treatment and prevention of thrombotic diseases. The few existing FXII inhibitors suffer from low selectivity. Using phage display combined to rational design, we developed a potent inhibitor of FXII with more than 100-fold selectivity over related proteases. The highly selective peptide macrocycle is a promising candidate for the control of FXII activity in antithrombotic therapy and a valuable tool in hematology research.

Neutralization of Macrophage Migration Inhibitory Factor (MIF) by Fully Human Antibodies Correlates with Their Specificity for the β-Sheet Structure of MIF.

The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that recently emerged as an attractive therapeutic target for a variety of diseases. A diverse panel of fully human anti-MIF antibodies was generated by selection from a phage display library and extensively analyzed in vitro. Epitope mapping studies identified antibodies specific for linear as well as structural epitopes. Experimental animal studies revealed that only those antibodies binding epitopes within amino acids 50-68 or 86-102 of the MIF molecule exerted protective effects in models of sepsis or contact hypersensitivity. Within the MIF protein, these two binding regions form a β-sheet structure that includes the MIF oxidoreductase motif. We therefore conclude that this β-sheet structure is a crucial region for MIF activity and a promising target for anti-MIF antibody therapy.

Fate of linear and supercoiled multinucleosomic templates during transcription.

Electron microscopy was used to monitor the fate of reconstituted nucleosome cores during in vitro transcription of long linear and supercoiled multinucleosomic templates by the prokaryotic T7 RNA polymerase and the eukaryotic RNA polymerase II. Transcription by T7 RNA polymerase disrupted the nucleosomal configuration in the transcribed region, while nucleosomes were preserved upstream of the transcription initiation site and in front of the polymerase. Nucleosome disruption was independent of the topology of the template, linear or supercoiled, and of the presence or absence of nucleosome positioning sequences in the transcribed region. In contrast, the nucleosomal configuration was preserved during transcription from the vitellogenin B1 promoter with RNA polymerase II in a rat liver total nuclear extract. However, the persistence of nucleosomes on the template was not RNA polymerase II-specific, but was dependent on another activity present in the nuclear extract. This was demonstrated by addition of the extract to the T7 RNA polymerase transcription reaction, which resulted in retention of the nucleosomal configuration. This nuclear activity, also found in HeLa cell nuclei, is heat sensitive and could not be substituted by nucleoplasmin, chromatin assembly factor (CAF-I) or a combination thereof. Altogether, these results identify a novel nuclear activity, called herein transcription-dependent chromatin stabilizing activity I or TCSA-I, which may be involved in a nucleosome transfer mechanism during transcription.

Spanning tests in return and stochastic discount factor mean-variance frontiers: A unifying approach

We propose new spanning tests that assess if the initial and additional assets share theeconomically meaningful cost and mean representing portfolios. We prove their asymptoticequivalence to existing tests under local alternatives. We also show that unlike two-step oriterated procedures, single-step methods such as continuously updated GMM yield numericallyidentical overidentifyng restrictions tests, so there is arguably a single spanning test.To prove these results, we extend optimal GMM inference to deal with singularities in thelong run second moment matrix of the influence functions. Finally, we test for spanningusing size and book-to-market sorted US stock portfolios.

Turismo Rural na Ilha de Santo Antão como factor de Desenvolvimento das Aldeias de Fontaínhas, Corvo e Formiguinhas

Santo Antão é uma ilha onde a oferta turística passa pelo turismo de natureza, e pretendese criar um projecto ligado ao Turismo Rural nas aldeias de Fontaínhas, Corvo e Formiguinhas. As aldeias são rurais e enfrentam vários constrangimentos e é necessário implementar um leque de infra-estruturas como alojamento, estradas, postos de saúde, saneamento para o suporto do Turismo e optar por uma alternativa do desenvolvimento local. O objectivo é criar uma proposta de desenvolvimento do Turismo Rural que seja viável para estas aldeias. Numa segunda fase pretende-se também envolver as famílias rurais no desenvolvimento do turismo. As aldeias em questão reúnem condições naturais para o Turismo Rural, mas pretende apostar na valorização cultura, história e nos produtos locais. Having in mind that Santo Antão is an island where the offer is almost mandatory for nature tourism, it intends to develop a project connected to the Rural Tourism in the following villages of “Fontaínhas,” “Corvo” and “Formiguinhas”. These villages are rural and face various constraints, so it is necessary to implement a range of infrastructures to support Tourism and opt for an alternative that promotes local development. The aim is to create a model of development of Rural Tourism practicable to these villages. We also intend to involve local families in rural tourism development. The villages in question have natural conditions for Rural Tourism, but we want to focus on enhancing products like cultural and historical sites.

Insulin-like growth factor I (IGF I) stimulates DNA synthesis in fetal rat brain cell cultures.

Addition of insulin, IGF I or IGF II to serum-free cultures of fetal rat brain cells (gestation day 15/16) significantly stimulates DNA synthesis. The dose-response curves show that IGF I is more potent than insulin; half maximal stimulation of [3H]thymidine incorporation is obtained at about 0.4 nM IGF I and 14 nM insulin, respectively. Cultures initiated 2 days later (gestation day 17/18) showed a decreased responsiveness to both peptides. No additive effect was observed after combined addition of both peptides at near-maximal doses. Both peptides show a latency of action of about 12-18 h. In the presence of either IGF or insulin, neuronal as well as glial enzymes are increased, suggesting that neuronal and glial precursor cell division is influenced. IGF I and IGF II interact with a specific binding site for which insulin competes very weakly; however IGF I and IGF II bind with relatively high affinity to the insulin specific binding site. The present results support the hypothesis that both insulin and IGF stimulate mitotic activity by interacting with specific somatomedin receptors and suggest a physiological role of IGF in the developing brain.

Satisfação dos clientes como um factor de sucesso empresarial

A crescente competitividade entre as operadoras CV Móvel e T+, fez com que as mesmas procurassem medidas e ou formas para conseguir satisfazer os seus clientes, angariar novos, e assim conseguir o maior número de cliente possível. Muitas empresas e outras instituições falham na sua relação com o cliente, porque muitas vezes ignoram aspectos importantes como a qualidade dos serviços e produtos, esquecem-se da importância do cliente e dos colaboradores. Este trabalho aborda alguns conceitos importantes que as empresas não devem ignorar, principalmente quando estes procuram arranjar medidas para satisfazerem os seus clientes de modo que eles voltem sempre a comprar da empresa. Procurou-se saber qual é o nível de satisfação dos Cabo-Verdianos com as operadoras T+ e CV Móvel. Para isso lançou-se um questionário online, aos clientes dessas duas operadoras, procurando com isso encontrar a resposta necessária. É necessário levar em consideração que os colaboradores têm uma grande importância no tocante a satisfação dos clientes.

Comunicação interna como factor de motivação.Estudo de casoTACV

Este trabalho tem por finalidade analisar a relação existente entre a comunicação interna e a motivação dos colaboradores dos TACV Cabo Verde Airlines. A comunicação interna é uma ferramenta fundamental para a elevação da motivação de colaboradores de qualquer organização. O sistema organizacional se viabiliza graças ao sistema de comunicação nele existente, pois permitirá sua continua realimentação e sua sobrevivência. Assim esse sistema é fundamental para o processamento das funções administrativas internas. (KUNSCH, 2003). Esta pesquisa cujo tema é Comunicação Interna como Factor de Motivação, tem como objectivo principal, descobrir a influência da comunicação interna na motivação dos colaboradores dos TACV. Propôs-se ainda descobrir o grau de motivação dos colaboradores bem como analisar a importância da comunicação para a elevação da motivação dos mesmos. De forma a esclarecer a hipótese de que a comunicação interna pode ou não influenciar a motivação, será feito o estudo com base na teoria dos Dois Factores de Frederick Herzeberg. Foi nessa óptica que se despertou o interesse por esse tema no sentido de dar algum contributo para a organização em estudo. Para a aquisição de informações, foi aplicado questionários do tipo misto, fechado, aplicados aos 42 colaboradores com a idade compreendia entre os 21 e os 55, tendo em conta a amostra estratificada de 10% sobre o total dos colaboradores de cinco departamentos escolhidos. Os departamentos escolhidos para o estudo foram: Comercial, Financeiro, Handling, Manutenção e Operações. No questionário destacou-se primeiramente com a identificação e caracterização dos colaboradores mediante sexo, idade, profissão e nível de escolaridade, seguido de, questões relacionadas com a comunicação, relacionamentos, valorização, imagem da empresa e finalmente, questões motivacionais. As informações recolhidas foram primeiramente introduzidas no Excel e depois no programa SPSS como forma de serem melhores analisadas e obter resultados satisfatórios capazes de responder as inquietações surgidas anteriormente, se de facto a comunicação veiculada nos TACV, influencia a motivação dos colaboradores. Após as análises saiu a conclusão de que realmente a comunicação veiculada nos TACV é satisfatória e influencia a motivação dos colaboradores.

Comunicação interna como factor de motivação e promoção da qualidade de ensino – Estudo de caso, professores do Ensino Básico Integrado de Santa Cruz

Com este trabalho de investigação, cujo tema é « Comunicação interna como factor de motivação e promoção da qualidade de ensino no concelho de Santa Cruz - estudo de caso, Professores do EBI de Santa Cruz ». Pretende-se analisar a motivação dos professores e o contributo do Relações Públicas (RP) na promoção da qualidade do ensino no concelho para o alcance da qualidade de ensino em Cabo Verde há tanto almejada e indispensável nos dias actuais. Hoje em dia muitas organizações devem preocupar-se mais com a existência de uma excelente Comunicação Interna para motivar, eliminando assim as incertezas e as ambiguidades e produzindo um clima de confiança e segurança dentro delas para manter-se motivado os colaboradores e melhor garantir o profissionalismo por parte destes. O RP, enquanto profissional de comunicação, contribui para que tudo isso aconteça. Metodologicamente trata-se de um estudo quantitativo e exploratório que tem como objecto os professores do 2º ano, da 1ª fase. A recolha de dados foi efectuada através de autopreenchimento por parte dos professores e decorreu entre os meses de Junho e Julho de 2012. O trabalho descrito foi realizado através da aplicação de inquérito por questionário, elaborado em coerência com os objectivos preconizados. Os dados foram tratados através do programa SPSS, versão 15.0, e a análise de dados foi efectuada utilizando as técnicas estatísticas.