Development of triplet repeat primed PCR (TP-PCR) technique as a support of molecular test in Machado-Joseph disease

Dissertação de Mestrado, Ciências Biomédicas, 3 de Fevereiro de 2016, Universidade dos Açores.

TP perturbation of TN matrices and totally positive directions

Here, we define and consider (linear) TP-directions and TP-paths for a totally nonnegative matrix, in an effort to more deeply understand perturbation of a TN matrix to a TP matrix. We give circumstances in which a TP-direction exists and an example to show that they do not always exist. A strategy to give (nonlinear) TP-paths is given (and applied to this example). A long term goal is to understand the sparsest TP-perturbation for application to completion problems.

Estudio epidemiológico de úlceras por presión en tobillo-pie (UPP-TP) en el lesionado medular ingresado

Objetivo general: Determinar los indicadores de incidencia y prevalencia de úlceras por presión en tobillo-pie en lesionados medulares ingresados. Material y métodos: Ensayo clínico controlado de 549 lesionados medulares, durante 48 meses. Resultados: La incidencia promedio de pacientes con UPP-TP de todo el periodo estudiado fue de: 1"178 pac./mes. La incidencia promedio de UPP-TP de todo el periodo estudiado fue de: 1"789 UPP-TP/mes. La prevalencia promedio de pacientes con UPP-TP de todo el periodo estudiado, respecto al total de pacientes fue de: 7"75%. La prevalencia promedio de todo el periodo de las UPP-TP, respecto al total de UPP fue de: 39"28%. La prevalencia promedio de todo el periodo estudiado de las UPP-TP, respecto al total de heridas (UPP+Traumáticas) fue de: 24"39%. Todos los pacientes crónicos con UPP-TP presentaban LM completa, por tanto ningún pac. crónico incompleto presento UPP-TP. Un 39"66% (23 pac.) presentaron más de 1 lesión. El 47"72% de las UPP-TP se presentaron en talón y un 19"32 en maléolo ext, siendo respectivamente las zonas de mayor localización de las lesiones. Un 13"63% de las UPP-TP se presentaron en dedos a pesar de la no deambulación de estos y de los 6 pac. que tuvieron la lesión en 1º dedo 4 pac. padecieron onicocriptosis. En el 19"23% (5 pac.) de los pac. crónicos sus UPPTP presentaron estadio IV, 3 pac. la presentaron en su domicilio y 2 pac. en ULM. El 25"86% de los pac. cicatrizaron sus lesiones dentro del 1º mes. Conclusiones: Teniendo en cuenta que el 29"30% de los pacientes, la incidencia de su UPP-TP, tuvo origen en el domicilio habitual, que de estos el 94% eran crónicos con LM completa y que el 34"48% del total de pacientes afectos de UPP-TP del estudio fueron dados de alta a su domicilio sin la curación de su úlcera, es notoria la importancia del seguimiento domiciliario de proximidad, la educación sanitaria de pacientes y familiarescuidadores, así como el uso de guías clínicas preventivas en nuestra asistencia podológica, especialmente en pacientes con lesión medular completa.

Terutroban, A TP-receptor antagonist, reduces portal pressure in cirrhotic rats.

Increased production of vasoconstrictive prostanoids, such as thromboxane A2 (TXA2 ), contributes to endothelial dysfunction and increased hepatic vascular tone in cirrhosis. TXA2 induces vasoconstriction by way of activation of the thromboxane-A2 /prostaglandin-endoperoxide (TP) receptor. This study investigated whether terutroban, a specific TP receptor blocker, decreases hepatic vascular tone and portal pressure in rats with cirrhosis due to carbon tetrachloride (CCl4 ) or bile duct ligation (BDL). Hepatic and systemic hemodynamics, endothelial dysfunction, liver fibrosis, hepatic Rho-kinase activity (a marker of hepatic stellate cell contraction), and the endothelial nitric oxide synthase (eNOS) signaling pathway were measured in CCl4 and BDL cirrhotic rats treated with terutroban (30 mg/kg/day) or its vehicle for 2 weeks. Terutroban reduced portal pressure in both models without producing significant changes in portal blood flow, suggesting a reduction in hepatic vascular resistance. Terutroban did not significantly change arterial pressure in CCl4 -cirrhotic rats but decreased it significantly in BDL-cirrhotic rats. In livers from CCl4 and BDL-cirrhotic terutroban-treated rats, endothelial dysfunction was improved and Rho-kinase activity was significantly reduced. In CCl4 -cirrhotic rats, terutroban reduced liver fibrosis and decreased alpha smooth muscle actin (α-SMA), collagen-I, and transforming growth factor beta messenger RNA (mRNA) expression without significant changes in the eNOS pathway. In contrast, no change in liver fibrosis was observed in BDL-cirrhotic rats but an increase in the eNOS pathway. CONCLUSION: Our data indicate that TP-receptor blockade with terutroban decreases portal pressure in cirrhosis. This effect is due to decreased hepatic resistance, which in CCl4 -cirrhotic rats was linked to decreased hepatic fibrosis, but not in BDL rats, in which the main mediator appeared to be an enhanced eNOS-dependent vasodilatation, which was not liver-selective, as it was associated with decreased arterial pressure. The potential use of terutroban for portal hypertension requires further investigation.

Distribuição volumétrica de calda produzidas pelas pontas pulverização XR, TP e TJ sob diferentes condições operacionais

Foram avaliados os perfis de distribuição volumétrica das pontas de pulverização de jato plano "Extended Range" XR 8004, "Teejet" TP 8004 e "TwinJet" TJ60-8004, em mesa de teste construída segundo a norma ISO 5.682-1:1996, sendo as pontas de pulverização posicionadas a 30, 40 e 50 cm de altura da mesa coletora, submetidas à pressão de 200 e 300 kPa, e posicionadas com ângulos de 30 e 45º nos sentidos horário e anti-horário e na posição vertical (0º). As pontas TJ60-8004 foram analisadas nas mesmas alturas, porém somente na posição vertical. Avaliaram-se 10 unidades de cada tipo de ponta, instaladas isoladamente na mesa. A distribuição média do volume pulverizado, coletado nas provetas, foi inserida em programa computacional, que permitiu a simulação do perfil de distribuição de uma barra pulverizadora com 24 bicos, em espaçamentos variáveis, obtendo-se ao final o coeficiente de variação, o desvio-padrão e a média do volume. Os resultados mostraram que a uniformidade de distribuição é menos influenciada pela variação da altura da barra quando o espaçamento entre bicos é reduzido e que há necessidade de adequação do espaçamento quando se utiliza ângulo na barra pulverizadora.

Validación del Cuestionario de Creencias Centrales de los Trastornos de la Personalidad (CCE-TP) en población colombiana

Se construyó un cuestionario para evaluar creencias centrales asociadas con los trastornos de la personalidad, fundamentadas en el Modelo de la Terapia Cognitiva. Se realizó el análisis estructural y la validez de contenido de la prueba en población universitaria de la ciudad de Medellín, Colombia. La muestra fue representativa y elegida al azar a través de un procedimiento polietápico. Un número de 809 estudiantes universitarios contestaron el cuestionario de creencias centrales de los trastornos de la personalidad (CCE-TP). Se realizó un análisis factorial exploratorio de la prueba, reagrupándose los ítems en 14 factores (F) que representan el 61,3% de la varianza. F1: CCE-TP antisocial (8 ítems, a 0,839); F2: CCE-TP esquizotípico/límite (8 ítems, a 0,846); F3: CCE-TP histriónico/patrón seductor (6 ítems, a 0,833); F4: CCE-TP paranoide (6 ítems, a 0,836); F5: CCE-TP por evitación / autopercepción negativa (5 ítems, a 0,755); F6: CCE-TP por dependencia (5 ítems, a 0,797); F7: CCE-TP histriónico/ dependencia emocional (4 ítems, a 0,755); F8: CCETP obsesivo-compulsivo/perfeccionista (4 ítems, a 0,808); F9: CCE-TP por evitación/hipersensible (4 ítems, a 0,766); F10: CCE-TP obsesivo-compulsivo/ crítico frente a los demás (3 ítems, a 0,851); F11: CCE-TP narcisista (4 ítems, a 0,717); F12: CCE-TP pasivo-agresivo / temor a ser dominado (3 ítems, a 0,719); F13: CCE-TP pasivo-agresivo/crítico frente a la autoridad (3 ítems, a 0,685), y F14: CCE-TP esquizoide (2 ítems, a 0,774). El alfa de Cronbach de la prueba fue de 0,931.

Flavonoids inhibit the platelet TxA(2) signalling pathway and antagonize TxA(2) receptors (TP) in platelets and smooth muscle cells

What is already known about this subject center dot Flavonoids are largely recognized as potential inhibitors of platelet function, through nonspecific mechanisms such as antioxidant activity and/or inhibition of several enzymes and signalling proteins. center dot In addition, we, and few others, have shown that certain antiaggregant flavonoids may behave as specific TXA2 receptor (TP) ligands in platelets. center dot Whether flavonoids interact with TP isoforms in other cell types is not known, and direct evidence that flavonoid-TP interaction inhibits signalling downstream TP has not been shown. What this study adds center dot This study first demonstrates that certain flavonoids behave as ligands for both TP isoforms, not only in platelets, but also in human myometrium and in TP-transfected HEK 293T cells. center dot Differences in the effect of certain flavonoids in platelet signalling, induced by either U46619 or thrombin, suggest that abrogation of downstream TP signalling is related to their specific blockage of the TP, rather than to a nonspecific effect on tyrosine kinases or other signalling proteins. Flavonoids may affect platelet function by several mechanisms, including antagonism of TxA(2) receptors (TP). These TP are present in many tissues and modulate different signalling cascades. We explored whether flavonoids affect platelet TP signalling, and if they bind to TP expressed in other cell types. Platelets were treated with flavonoids, or other selected inhibitors, and then stimulated with U46619. Similar assays were performed in aspirinized platelets activated with thrombin. Effects on calcium release were analysed by fluorometry and changes in whole protein tyrosine phosphorylation and activation of ERK 1/2 by Western blot analysis. The binding of flavonoids to TP in platelets, human myometrium and TP alpha- and TP beta-transfected HEK 293T cells was explored using binding assays and the TP antagonist H-3-SQ29548. Apigenin, genistein, luteolin and quercetin impaired U46619-induced calcium mobilization in a concentration-dependent manner (IC50 10-30 mu M). These flavonoids caused a significant impairment of U46619-induced platelet tyrosine phosphorylation and of ERK 1/2 activation. By contrast, in aspirin-treated platelets all these flavonoids, except quercetin, displayed minor effects on thrombin-induced calcium mobilization, ERK 1/2 and total tyrosine phosphorylation. Finally, apigenin, genistein and luteolin inhibited by > 50% H-3-SQ29548 binding to different cell types. These data further suggest that flavonoids may inhibit platelet function by binding to TP and by subsequent abrogation of downstream signalling. Binding of these compounds to TP occurs in human myometrium and in TP-transfected HEK 293T cells and suggests that antagonism of TP might mediate the effects of flavonoids in different tissues.

Model car-exhaust catalyst studied by TPD and TP-RAIRS: Surface reactions of NO on clean and O-covered Ir{100}

The adsorption of NO on Ir{100} has been studied as a function of NO coverage and temperature using temperature programmed reflection absorption infrared spectroscopy (TP-RAIRS), low energy electron diffraction (LEED) and temperature programmed desorption (TPD). After saturating the clean (1 x 5)-reconstructed surface with NO at 95 K. two N-2, desorption peaks are observed upon heating. The first N-2 peak at 346 K results from the decomposition of bridge-bonded NO, and the second at 475 K from the decomposition of atop-bonded NO molecules. NO decomposition is proposed to be the rate limiting step for both N-2 desorption states. For high NO coverages on the (1 x 5) surface, the narrow width of the first N-2 desorption peak is indicative of an autocatalytic process for which the parallel formation of N2O appears to be the crucial step. When NO is adsorbed on the metastable unreconstructed (1 x 1) phase of clean Ir{100} N-2 desorption starts at lower temperatures, indicating that this surface modification is more reactive. When a high coverage of oxygen, near 0.5 ML, is pre-adsorbed on the surface, the decomposition of NO is inhibited and mainly desorption of intact NO is observed.

Distribuição volumétrica de calda produzidas pelas pontas pulverização XR, TP e TJ sob diferentes condições operacionais

Foram avaliados os perfis de distribuição volumétrica das pontas de pulverização de jato plano Extended Range XR 8004, Teejet TP 8004 e TwinJet TJ60-8004, em mesa de teste construída segundo a norma ISO 5.682-1:1996, sendo as pontas de pulverização posicionadas a 30, 40 e 50 cm de altura da mesa coletora, submetidas à pressão de 200 e 300 kPa, e posicionadas com ângulos de 30 e 45º nos sentidos horário e anti-horário e na posição vertical (0º). As pontas TJ60-8004 foram analisadas nas mesmas alturas, porém somente na posição vertical. Avaliaram-se 10 unidades de cada tipo de ponta, instaladas isoladamente na mesa. A distribuição média do volume pulverizado, coletado nas provetas, foi inserida em programa computacional, que permitiu a simulação do perfil de distribuição de uma barra pulverizadora com 24 bicos, em espaçamentos variáveis, obtendo-se ao final o coeficiente de variação, o desvio-padrão e a média do volume. Os resultados mostraram que a uniformidade de distribuição é menos influenciada pela variação da altura da barra quando o espaçamento entre bicos é reduzido e que há necessidade de adequação do espaçamento quando se utiliza ângulo na barra pulverizadora.

Synthesis and reactivity in salt metathesis reactions of trivalent [La(Tp(Me2))(2)X] (X = Cl, I) complexes: crystal structures of [La(Tp(Me2))(2)Cl] and [La(Tp(Me2))(2)(kappa(2)-pz(Me2))]

Reaction of LaX3(THF)(n) (X = Cl, 1) with two equiv. of K(Tp(Me2)) gave good yields of the bis-Tp complexes [La(Tp(Me2))(2)X] (X = Cl (1); I (3)). However, the formation of 1 and 3 is always accompanied by significant amounts of La(Tp(Me2))(2)(kappa(2)-pz(Me2)) ([pz(Me2)](-) = 3,5-dimethyl-pyrazolato) (2). The pyrazolato complex 2, which presumably arises from decomposition of the [Tp(Me2)](-) moiety during salt metathesis, was independently prepared in good yield from 1 and in situ generated [pz(Me2)](-). The solid-state structures of 1 and 2 were determined by single-crystal X-ray diffraction studies. Subsequent reactions of halogeno-Tp(Me2) complexes 1 and 3 with various alkali metal salts MR (M = Li, R = CH2SiMe3, Ph, N(SiMe3)(2); M = K, R = OAr) gave M(Tp(Me2)) as the major product. Alternatively, the mono-Tp bis(aryloxide) derivatives [Ln(Tp(Me2))(OC6H2-2,6-'Bu-4-Me)(2)] (Ln = La (4); Nd (5)) were obtained in high yields by salt metathesis of [Ln(OC6H2-2,6-'Bu-4-Me)(3)] with one equiv. of K(Tp(Me2)). (C) 2004 Elsevier Ltd. All rights reserved.

Linear low density polyethylene (LLDPE) from ethylene using Tp(Ms)NiCl (Tp(Ms) = hydridotris(3-mesitylpyrazol-1-yl)) and CP2ZrCl2 as a tandem catalyst system

Linear low density polyethylene (LLDPE) with different branching contents were prepared from ethylene, without the addition of alpha-olefin comonomer, using a combination of catalyst precursors {Tp(Ms)}NiCl (1) (Tp(Ms) = hydridotris(3-mesitylpyrazol-1-yl)) and Cp2ZrCl2 (2) activated with MAO/TMA (1:1) in toluene at 0degreesC and by varying the nickel loading mole fraction (x(Ni)). The polymerization results showed that the turnover frequencies are strongly dependent on the x(Ni) varying from 6.6 x 10(3) to 32.1 x 10(3) mol[C2H4]/mol[Zr] h. The C-13 NMR spectra of the copolymers showed that the branch contents of the polymers increase as the x(Ni) increase in the medium promoting the production of polymers with a wide range of melting point (T-m) (C) 2004 Elsevier B.V. All rights reserved.

Sensor eletro-óptico de tensões elevadas e sua viabilidade para implementação de TP óptico

Pós-graduação em Engenharia Elétrica - FEIS