Granulocyte macrophage colony stimulating factor improves mucosal repair in a mouse model of acute colitis (P278)

Background and Aims: Granulocyte-macrophage colonystimulating factor (GM-CSF), a cytokine modulating the number and function of innate immune cells, has been shown to provide symptomatic benefit in some patients with Crohn's disease (CD). Since, it becomes widely appreciated that a timely and spatially regulated action of innate immune cells is critical for tissue regeneration, we tested whether GM-CSF therapy may favours intestinal mucosal repair in the acute mouse model of dextran sulfate sodium (DSS)-induced colitis. Methods: Mice treated with GM-CSF or saline were exposed for 7 days to DSS to induce colitis. On day 5, 7 and 10, mice were subjected to colonoscopy or sacrificed for evaluation of inflammatory reaction and mucosal healing. Results: GM-CSF therapy prevented body weight loss, diarrhea, dampened inflammatory reactions and ameliorated mucosal damages. Mucosal repair improvement in GM-CSF-treated mice was observed from day 7 on both by colonoscopy (ulceration score 1.2}0.3 (GM-CSF-treated) vs 3.1}0.5 (untreated), p = 0.01) and histological analysis (percentage of reepithelialized ulcers 55%}4% (GM-CSF-treated) vs 18%}13% (untreated), p = 0.01). GM-CSF therapy can still improve the colitis when hematopoietic, but not non-hematopoietic cells, are responsive to GM-CSF, as shown in WT→GM-CSFRKO chimeras. Lastly, we observed that GM-CSF-induced promotion of wound healing is associated with a modification of the cellular composition of DSS-induced colonic inflammatory infiltrate, characterized by the reduction of neutrophil numbers and early accumulation of CD11b+Gr1lo myeloid cells. Conclusion: Our study shows that GM-CSF therapy accelerates the complex program leading to tissue repair during acute colitis and suggests that GM-CSF promotion of mucosal repair might contribute to the symptomatic benefits of GM-CSF therapy observed in some CD patients.

Identification-commitment inventory (ICI-Model): confirmatory factor analysis and construct validity

The aim of this study is to confirm the factorial structure of the Identification-Commitment Inventory (ICI) developed within the frame of the Human System Audit (HSA) (Quijano et al. in Revist Psicol Soc Apl 10(2):27-61, 2000; Pap Psicól Revist Col Of Psicó 29:92-106, 2008). Commitment and identification are understood by the HSA at an individual level as part of the quality of human processes and resources in an organization; and therefore as antecedents of important organizational outcomes, such as personnel turnover intentions, organizational citizenship behavior, etc. (Meyer et al. in J Org Behav 27:665-683, 2006). The theoretical integrative model which underlies ICI Quijano et al. (2000) was tested in a sample (N = 625) of workers in a Spanish public hospital. Confirmatory factor analysis through structural equation modeling was performed. Elliptical least square solution was chosen as estimator procedure on account of non-normal distribution of the variables. The results confirm the goodness of fit of an integrative model, which underlies the relation between Commitment and Identification, although each one is operatively different.

Analytic evaluation of three-phase short circuit demagnetization and hysteresis loss risk in rotor-surface-magnet Permanent-Magnet Synchronous Machines

Permanent magnet synchronous machines (PMSM) have become widely used in applications because of high efficiency compared to synchronous machines with exciting winding or to induction motors. This feature of PMSM is achieved through the using the permanent magnets (PM) as the main excitation source. The magnetic properties of the PM have significant influence on all the PMSM characteristics. Recent observations of the PM material properties when used in rotating machines revealed that in all PMSMs the magnets do not necessarily operate in the second quadrant of the demagnetization curve which makes the magnets prone to hysteresis losses. Moreover, still no good analytical approach has not been derived for the magnetic flux density distribution along the PM during the different short circuits faults. The main task of this thesis is to derive simple analytical tool which can predict magnetic flux density distribution along the rotor-surface mounted PM in two cases: during normal operating mode and in the worst moment of time from the PM’s point of view of the three phase symmetrical short circuit. The surface mounted PMSMs were selected because of their prevalence and relatively simple construction. The proposed model is based on the combination of two theories: the theory of the magnetic circuit and space vector theory. The comparison of the results in case of the normal operating mode obtained from finite element software with the results calculated with the proposed model shows good accuracy of model in the parts of the PM which are most of all prone to hysteresis losses. The comparison of the results for three phase symmetrical short circuit revealed significant inaccuracy of the proposed model compared with results from finite element software. The analysis of the inaccuracy reasons was provided. The impact on the model of the Carter factor theory and assumption that air have permeability of the PM were analyzed. The propositions for the further model development are presented.

Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1α expression

Hypoxia-inducible factor-1α (HIF-1α) is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each): sham-operated (group S), hindlimb ischemia-reperfusion (group IR), and ischemic postconditioning (group IPO). Each group was divided into subgroups (n=6) according to reperfusion time: immediate (0 h, T0), 1 h (T1), 3 h (T3), 6 h (T6), 12 h (T12), and 24 h (T24). In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T0-T24), serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01). In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01), and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury-triggered inflammatory response.

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.

A five factor model of grief : a q-methodological study /

Q-methodology permitted 41 people to communicate their perspective of grief. In an attempt to clarify the research to date and to allow those who have experienced this human journey to direct the scientists, 80 statements were chosen to present to the participants based on the research from academic and counselling sources. Five different perspectives emerged from the Q-sorts and factor analysis. Each perspective was valuable for the understanding of different groups of mourners. They were interpreted using questionnaire data and interview information. They are as follows: Factor 1- Growth Optimism; Factor 2 - Schema Destruction and Negative Affect; Factor 3- Identification with the Deceased Person; Factor 4- Intact World view with High Clarity and High Social Support; Factor 5- Schema Destruction with High Preoccupation and Attention to Emotion. Some people grow in the face of grief, others hold on to essentially the same schemas and others are devastated by their loss. The different perspectives reported herein supply clues to the sources of these differing outcomes. From examination of Factor 1, it appears that a healthy living relationship helps substantially in the event of loss. An orientation toward emotions that encourages clarity, exemplified by Factor 4, without hyper-vigilance to emotion may be helpful as well. Strategies for maintaining schematic representations of the world with little alteration include: identification with the values of the deceased person, as in Factor 3 and reliance on social support and/or God as demonstrated by Factor 4. When the relationship had painful periods, social support may be accessed to benefit some mourners. When the person's frame of reference or higher order schemas are assaulted by the events of loss, the people most at risk for traumatic grief seem to be those with difficult relationships as indicated by Factor 5 individuals. When low social support, high attention to emotion with low clarity and little belief that feelings can be altered for the better are also attributes of the mourner devastating grief can result. In the end, there are groups of people who are forced to endure the entire process of schema destruction and devastation. Some appear to recover in part and others appear to stay in a form of purgatory for many years. The results of this study suggest that, those who experience devastating grief may be in the minority. In the future interventions could be more specifically addressed if these perspectives are replicated in a larger, more detailed study.

A Semi-Parametric Factor Model for Interest Rates.

Understanding the dynamics of interest rates and the term structure has important implications for issues as diverse as real economic activity, monetary policy, pricing of interest rate derivative securities and public debt financing. Our paper follows a longstanding tradition of using factor models of interest rates but proposes a semi-parametric procedure to model interest rates.

Factor Analysis of a Large DSGE Model

We study the workings of the factor analysis of high-dimensional data using artificial series generated from a large, multi-sector dynamic stochastic general equilibrium (DSGE) model. The objective is to use the DSGE model as a laboratory that allow us to shed some light on the practical benefits and limitations of using factor analysis techniques on economic data. We explain in what sense the artificial data can be thought of having a factor structure, study the theoretical and finite sample properties of the principal components estimates of the factor space, investigate the substantive reason(s) for the good performance of di¤usion index forecasts, and assess the quality of the factor analysis of highly dissagregated data. In all our exercises, we explain the precise relationship between the factors and the basic macroeconomic shocks postulated by the model.

The effects of administration of a nuclear factor kappa-B inhibitor on pulmonary endothelial dysfunction after cardiopulmonary bypass: impact on oxygenation and hemodynamics and development of therapeutic and preventive modalities in a porcine model

Introduction: La circulation extracorporelle (CEC) peut entraîner une dysfonction endothéliale pulmonaire et l’hypertension pulmonaire. Le SN50 agit au niveau de la signalisation cellulaire pour prévenir ces réactions à la CEC et pourrait renverser la dysfonction endothéliale pulmonaire post-CEC sans effets néfastes sur l’hémodynamie. Méthodes: Quatre groups de porcs ont reçu un parmi quatre traîtements avant de subir 90 minutes de CEC et 60 minutes de reperfusion: (1) milrinone nébulisé; (2) sildenafil nébulisé; (3) placebo nébulisé; et (4) SN-50 intraveineux. Un monitoring hémodynamique invasif a été utilisé. La réactivité vasculaire des artères pulmonaires de deuxième ordre a été évaluée face à l’acétylcholine et la bradykinine. Résultats: Le sildénafil produit une augmentation significative de la pression de l’artère pulmonaire (PAP) moyenne à 60 minutes de reperfusion par rapport au début de la chirurgie. Les relaxations dépendantes de l’endothélium face à la bradykinine étaient meilleurs dans les groupes milrinone et SN-50 et surtout dans le groupe sildénafil par rapport au groupe placébo. Le SN-50 produisait de moins bonnes relaxations dépendantes de l’endothélium face à l’acétylcholine que les autres traitements incluant placébo. Conclusion: Le sildénafil prévient mieux la dysfonction endothéliale pulmonaire que les autres traitements. Les bénéfices du SN-50 sont possiblement sous-estimés vu que la dose n’a pas pu être ajustée à la durée de CEC. Le sildenafil inhalé mérite une étude plus importante chez l’humain et le SN-50 dans un model de CEC animal.

The use of the bi-factor model to test the uni-dimensionality of a battery of reasoning tests

Resumen tomado de la publicación

The retrieval of ice water content from radar reflectivity factor and temperature and its use in evaluating a mesoscale model

Ice clouds are an important yet largely unvalidated component of weather forecasting and climate models, but radar offers the potential to provide the necessary data to evaluate them. First in this paper, coordinated aircraft in situ measurements and scans by a 3-GHz radar are presented, demonstrating that, for stratiform midlatitude ice clouds, radar reflectivity in the Rayleigh-scattering regime may be reliably calculated from aircraft size spectra if the "Brown and Francis" mass-size relationship is used. The comparisons spanned radar reflectivity values from -15 to +20 dBZ, ice water contents (IWCs) from 0.01 to 0.4 g m(-3), and median volumetric diameters between 0.2 and 3 mm. In mixed-phase conditions the agreement is much poorer because of the higher-density ice particles present. A large midlatitude aircraft dataset is then used to derive expressions that relate radar reflectivity and temperature to ice water content and visible extinction coefficient. The analysis is an advance over previous work in several ways: the retrievals vary smoothly with both input parameters, different relationships are derived for the common radar frequencies of 3, 35, and 94 GHz, and the problem of retrieving the long-term mean and the horizontal variance of ice cloud parameters is considered separately. It is shown that the dependence on temperature arises because of the temperature dependence of the number concentration "intercept parameter" rather than mean particle size. A comparison is presented of ice water content derived from scanning 3-GHz radar with the values held in the Met Office mesoscale forecast model, for eight precipitating cases spanning 39 h over Southern England. It is found that the model predicted mean I WC to within 10% of the observations at temperatures between -30 degrees and - 10 degrees C but tended to underestimate it by around a factor of 2 at colder temperatures.

The competition–performance relation: a meta-analytic review and test of the opposing processes model of competition and performance

What is the relation between competition and performance? The present research addresses this important multidisciplinary question by conducting a meta-analysis of existing empirical work and by proposing a new conceptual model—the opposing processes model of competition and performance. This model was tested by conducting an additional meta-analysis and 3 new empirical studies. The first meta-analysis revealed that there is no noteworthy relation between competition and performance. The second meta-analysis showed, in accord with the opposing processes model, that the absence of a direct effect is the result of inconsistent mediation via achievement goals: Competition prompts performance-approach goals which, in turn, facilitate performance; and competition also prompts performance-avoidance goals which, in turn, undermine performance. These same direct and mediational findings were also observed in the 3 new empirical studies (using 3 different conceptualizations of competition and attending to numerous control variables). Our findings provide both interpretational clarity regarding past research and conceptual guidance regarding future research on the competition–performance relation.

Ixolaris, a tissue factor inhibitor, blocks primary tumor growth and angiogenesis in a glioblastoma model

Background: The expression levels of the clotting initiator protein Tissue Factor (TF) correlate with vessel density and the histological malignancy grade of glioma patients. Increased procoagulant tonus in high grade tumors (glioblastomas) also indicates a potential role for TF in progression of this disease, and suggests that anticoagulants could be used as adjuvants for its treatment. Objectives: We hypothesized that blocking of TF activity with the tick anticoagulant Ixolaris might interfere with glioblastoma progression. Methods and results: TF was identified in U87-MG cells by flow-cytometric and functional assays (extrinsic tenase). In addition, flow-cytometric analysis demonstrated the exposure of phosphatidylserine in the surface of U87-MG cells, which supported the assembly of intrinsic tenase (FIXa/FVIIIa/FX) and prothrombinase (FVa/FXa/prothrombin) complexes, accounting for the production of FXa and thrombin, respectively. Ixolaris effectively blocked the in vitro TF-dependent procoagulant activity of the U87-MG human glioblastoma cell line and attenuated multimolecular coagulation complexes assembly. Notably, Ixolaris inhibited the in vivo tumorigenic potential of U87-MG cells in nude mice, without observable bleeding. This inhibitory effect of Ixolaris on tumor growth was associated with downregulation of VEGF and reduced tumor vascularization. Conclusion: Our results suggest that Ixolaris might be a promising agent for anti-tumor therapy in humans.

Proposal of a Transmission Line Model Based on Lumped Elements: An Analytic Solution

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

On high Q(2) behavior of the pion form factor for transitions gamma*gamma -> pi(0) and gamma*gamma* -> pi(0) within the nonlocal quark-pion model

The behavior of the transition pion form factor for processes gamma (*)gamma --> pi(0) and gamma (*)gamma (*) --> pi(0) at large values of space-like photon momenta is estimated within the nonlocal covariant quark-pion model. It is shown that, in general, the coefficient of the leading asymptotic term depends dynamically on the ratio of the constituent quark mass and the average virtuality of quarks in the vacuum and kinematically on the ratio of photon virtualities. The kinematic dependence of the transition form factor allows us to obtain the relation between the pion light-cone distribution amplitude and the quark-pion vertex function. The dynamic dependence indicates that the transition form factor gamma (*)gamma -->, pi(0) at high momentum transfers is very sensitive to the nonlocality size of nonperturbative fluctuations in the QCD vacuum. (C) 2000 Elsevier B.V. B.V. All rights reserved.