On the etiology of Crohn disease.

Crohn disease (CD) is a chronic, panenteric intestinal inflammatory disease. Its etiology is unknown. Analogous to the tuberculoid and lepromatous forms of leprosy, CD may have two clinical manifestations. One is aggressive and fistulizing (perforating), and the other is contained, indolent, and obstructive (nonperforating) [Gi]-berts, E. C. A. M., Greenstein, A. J., Katsel, P., Harpaz, N. & Greenstein, R. J. (1994) Proc. Natl. Acad. Sci. USA 91, 12721-127241. The etiology, if infections, may be due to Mycobacterium paratuberculosis. We employed reverse transcription PCR using M. paratuberculosis subspecies-specific primers (IS 900) on total RNA from 12 ileal mucosal specimens (CD, n = 8; controls, n = 4, 2 with ulcerative colitis and 2 with colonic cancer). As a negative control, we used Myobacterium avium DNA, originally cultured from the drinking water of a major city in the United States. cDNA sequence analysis shows that all eight cases of Crohn's disease and both samples from the patients with ulcerative colitis contained M. paratuberculosis RNA. Additionally, the M. avium control has the DNA sequence of M. paratuberculosis. We demonstrate the DNA sequence of M. paratuberculosis from mucosal specimens from humans with CD. The potable water supply may be a reservoir of infection. Although M. paratuberculosis signal in CD has been previously reported, a cause and effect relationship has not been established. In part, this is due to conflicting data from studies with empirical antimycobacterial therapy. We conclude that clinical trials with anti-M. paratuberculosis therapy are indicated in patients with CD who have been stratified into the aggressive (perforating) and contained (nonperforating) forms.

Differential distribution of two ATP-gated channels (P2X receptors) determined by immunocytochemistry.

Several P2X receptor subunits were recently cloned; of these, one was cloned from the rat vas deferens (P2X1) and another from pheochromocytoma (PC12) cells differentiated with nerve growth factor (P2X2). Peptides corresponding to the C-terminal portions of the predicted receptor proteins (P2X1 391-399 and P2X2 460-472) were used to generate antisera in rabbits. The specificities of antisera were determined by staining human embryonic kidney cells stably transfected with either P2X1 or P2X2 receptors and by absorption controls with the cognate peptides. In the vas deferens and the ileal submucosa, P2X1 immunoreactivity (ir) was restricted to smooth muscle, whereas P2X2-ir was restricted to neurons and their processes. Chromaffin cells of the adrenal medulla and PC12 cells contained both P2X1- and P2X2-ir. P2X1-ir was also found in smooth muscle cells of the bladder, cardiac myocytes, and nerve fibers and terminals in the superficial dorsal horn of the spinal cord. In contrast, P2X2-ir was observed in scattered cells of the anterior pituitary, neurons in the hypothalamic arcuate and paraventricular nuclei, and catecholaminergic neurons in the olfactory bulb, the substantia nigra, ventral tegmental area, and locus coeruleus. A plexus of nerve fibers and terminals in the nucleus of the solitary tract contained P2X2-ir. This staining disappeared after nodose ganglionectomy, consistent with a presynaptic function. The location of the P2X1 subunit in smooth muscle is consistent with its role as a postjunctional receptor in autonomic transmission, while in neurons, these receptors appear in both postsynaptic and presynaptic locations.

Transgenic mice that overexpress the human trefoil peptide pS2 have an increased resistance to intestinal damage.

pS2 is a member of the trefoil peptide family, all of which are overexpressed at sites of gastrointestinal injury. We hypothesized that they are important in stimulating mucosal repair. To test this idea, we have produced a transgenic mice strain that expresses human pS2 (hpS2) specifically within the jejunum and examined the effect of this overexpression on proliferation and susceptibility to indomethacin-induced damage. A transgenic mouse was produced by microinjecting fertilized oocytes with a 1.7-kb construct consisting of rat intestinal fatty acid binding protein promoter (positions -1178 to +28) linked to full-length (490 bp) hpS2 cDNA. Screening for positive animals was by Southern blot analysis. Distribution of hpS2 expression was determined by using Northern and Western blot analyses and immunohistochemical staining. Proliferation of the intestinal mucosa was determined by assessing the crypt cell production rate. Differences in susceptibility to intestinal damage were analyzed in animals that had received indomethacin (85 mg/kg s.c.) 0-30 h previously. Expression of hpS2 was limited to the enterocytes of the villi within the jejunum. In the nondamaged intestine, villus height and crypt cell production rate were similar in transgenic and negative (control) litter mates. However, there was a marked difference in the amount of damage caused by indomethacin in control and transgenic animals in the jejunum (30% reduction in villus height in controls vs. 12% reduction in transgenic animals, P < 0.01) but the damage sustained in the non-hpS2-expressing ileal region was similar in control and transgenic animals. These studies support the hypothesis that trefoil peptides are important in stimulating gastrointestinal repair.

Efeito do cobre como adição interfacial no sistema tribológico pino X disco.

O presente trabalho de mestrado teve como meta realizar um estudo do comportamento do cobre particulado em ensaios tribológicos do tipo pino contra disco. O cobre é atualmente utilizado em até 15% em massa das pastilhas de freios automotivos e tal utilização é responsável pela emissão de até 70% do cobre particulado presente no ar. Devido ao caráter carcinogênico do cobre, se faz necessária sua substituição. Foram realizados ensaios tribológicos pino disco com adição de diferentes meios interfaciais. Foram utilizados pares tribológicos aço/aço, em ensaios a seco de pino contra disco com adição de meio interfacial nanoparticulado de óxido de ferro, grafite e de cobre metálico em diferentes granulometrias (400 m, 20 m e 50 nm). Após os ensaios, amostras das superfícies de pinos e discos para cada uma das adições de cobre, bem como para a condição sem adição de meio interfacial, foram caracterizadas utilizando técnicas de microscopia eletrônica de varredura, de forma a entender o comportamento das partículas de cobre e sua contribuição para o coeficiente de atrito. As adições de cobre obtiveram os maiores coeficientes de atrito, e entre elas os coeficientes de atrito foram mais altos durante todos os ensaios para a adição de 50 nm, seguido de 20 m e 400 m. A análise das superfícies tribológicas em MEV mostrou heterogeneidade das superfícies ensaiadas em relação à presença de debris oxidados e camadas compactas. Observou-se a presença de cobre apenas nas superfícies ensaiadas com adição dos cobres de 50 nm e 20 m. A presença de um filme óxido compacto e contínuo foi observada apenas nas superfícies tribológicas ensaiadas sem adição de meio interfacial e com adição de cobre a 400 m.

Isolamento de vibrios potencialmente patogênicos em moluscos bivalves

Neste estudo, 26 amostras de ostras (Crassostrea gigas) comercializadas na cidade de São Paulo e em alguns pontos do litoral de São Paulo, e 36 amostras de mexilhões (Perna perna) colhidas mensalmente em 3 pontos do litoral de Ubatuba - SP, foram submetidas à pesquisa de vibrios potencialmente patogênicos. As amostras desses moluscos eram submetidas a enriquecimento em água peptonada alcalina sem cloreto de sódio e com 1 por cento de cloreto de sódio, e GSTB. O isolamento foi realizado em ágar TCBS. Colônias sacarose positivas e negativas, sugestivas de espécies de Vibrio foram identificadas presuntivamente em meio de ágar ferro de Kligler, sendo confirmadas através de provas bioqufmicas complementares. Uma parte das amostras de vibrios potencialmente patogênicos isoladas foi submetida ao teste de Dean e teste de alça ligada em íleo de coelhos. Os vibrios potencialmente patogênicos encontrados em amostras de ostras foram V. alginolyticus (81 por cento ), V.parahaemolyticus (77 por cento ), V. cholerae não 0:1 (31 por cento ), V. fluvialis (27 por cento ), V. furnissii (19 por cento ), V. mimicus (12 por cento ) e V. vulnificus (12 por cento ) e em amostras de mexilhões foram V. alginolyticus(97 por cento ), V. parahaemolyticus(75 por cento ), V. fluvialis (47 por cento ), V. vulnificus (11 por cento ), V. cholerae não 0:1 (6 por cento ), V. furnissii (6 por cento ) e V. mimicus (6 por cento ). Observou-se acúmulo de fluido em alça ligada de íleo de coelho entre 0,25 e 0,49 ml/cm em 6,9 por cento das amostras, entre 0,5 e 0,99 ml/cm em 15,6 por cento e maior ou igual a 1 ml/cm em 15,1 por cento , e/ou intestino de camundongos lactentes (Teste de Dean) em 26,6 por cento das amostras testadas, confirmando o elevado potencial desses microrganismos em causar gastrenterite. Verificou-se ausência de variação sazonal e também, de correlação entre os vibrios potencialmente patogênicos isolados e os indicadores de contaminação fecal, confirmando que a presença desses microrganismos ocorre de forma autóctone e que, as condições climáticas foram favoráveis à sobrevivência dessas espécies em todas as épocas do ano. Considerando-se os resultados obtidos no presente estudo e o fato de que ostras e mexilhões são habitualmente ingeridos crus ou insuficientemente cozidos, pode-se concluir que sua ingestão constitui-se em um determinado grau de risco para a saúde do consumidor.

State Transformation and the European Integration Project. Lessons from the financial crisis and the Greek paradigm. CEPS Special Report No. 130/February 2016

The financial crisis that erupted in the eurozone not only affected the EU’s financial governance mechanisms, but also the very nature of state sovereignty and balances in the relations of member states; thus, the actual inequalities between the member states hidden behind their institutional equality have deteriorated. This transformation is recorded in the case law of the Court of Justice of the European Union and the member states’ constitutional courts, particularly in those at the heart of the crisis, with Greece as the most prominent example. It is the issue of public debt (sovereign debt) of the EU member states that particularly reflects the influence of the crisis on state sovereignty as well as the intensely transnational (intergovernmental) character of European integration, which under these circumstances takes the form of a continuous, tough negotiation. The historical connection between public debt (sovereign debt) and state sovereignty has re-emerged because of the financial crisis. This development has affected not only the European institutions, but also, at the member state level, the actual institutional content of the rule of law (especially judicial review) and the welfare state in its essence, as the great social and political acquis of 20th century Europe. From this perspective, the way that the Greek courts have dealt with the gradual waves of fiscal austerity measures and structural reforms from 2010 to 2015 is characteristic. The effect of the financial crisis on the sovereignty of the member states and on the pace of European integration also has an impact on European foreign and security policy, and the correlations between the political forces at both the national and European level, thus producing even more intense pressures on European social democracy. In light of the experience of the financial crisis, the final question is whether the nation state (given the large real inequalities among the EU member states) currently functions as a brake or as an engine for future European integration.

Maastricht 2.0 - Proposed reform of EU sovereign debt rules. Policy Brief #2012/05

The European Union’s regulations governing sovereign debt are based on the principle of equal treatment of all member states. The recommendations we make here concerning changes in European Union sovereign-debt reduction rules take account of national particularities, but are by no means arbitrary in nature. According to the calculations we present here, such reformed regulations would do far more to promote economic growth than would be the case under the Fiscal Compact’s European debt brake. By 2030, real gains in growth will amount to more than 450 billion euros more than the outcome that would presumably be obtained under the European debt brake.

Sustainability and solidarity – basic ideas of new financial structures. Policy Brief #2012/07

Federal financial structures which include fiscal equalization between the states are and will remain to be indispensable. Such structures are required to equalize the significant regional economic differences which exist within the federal republic and to ensure sufficient funding for the responsibilities of the public sector across the nation. The current federal financial structures have a number of structural flaws which regard both the criteria for tax distribution, the design of the debt brake and the role of municipalities. The financial structures will have to be revised beginning in 2020. The objective is to consolidate in the long term the budgets of federation, state and municipal governments and to safe-guard a modern welfare state.

Results of Minicars RSV crash avoidance tests conducted in West Germany.

National Highway Traffic Safety Administration, Washington, D.C.

Development of proposed height standards and tolerances for light-post traffic barriers. Interim report.

Federal Highway Administration, Office of Research, Development and Technology, Washington, D.C.

The development and evaluation of a prototype grade severity rating system. Final report.

Federal Highway Administration, Washington, D.C.

Tri-level study: modification. Task 1: final report on potential benefits of various improvements in vehicle systems in preventing accidents or reducing their severity. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Collision avoidance radar braking systems investigation - phase III study. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Collision avoidance radar braking systems investigation - phase III study, technical report. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Validation of the reduction of rear-end collisions by a high-mounted auxiliary stoplamp. Final report.

National Highway Traffic Safety Administration, Washington, D.C.