Site-directed mutagenesis and structural modeling of Coq10p indicate the presence of a tunnel for coenzyme Q6 binding

Coq10p is a protein required for coenzyme Q function, but its specific role is still unknown. It is a member of the START domain superfamily that contains a hydrophobic tunnel implicated in the binding of lipophilic molecules. We used site-directed mutagenesis, statistical coupling analysis and molecular modeling to probe structural determinants in the Coq10p putative tunnel. Four point mutations were generated (coq10-K50E, coq10-L96S, coq10-E105K and coq10-K162D) and their biochemical properties analysed, as well as structural consequences. Our results show that all mutations impaired Coq10p function and together with molecular modeling indicate an important role for the Coq10p putative tunnel. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Gas-Phase Nucleophilic and Elimination Reactions in Simple Alkyl Nitrates

There has been increasing interest in the gas-phase reactivity of alkyl nitrates because of their well-known applications as explosives and because of then role in atmospheric and in marine processes This manuscript describes an experimental study by FT-ICR techniques of the gas-phase reactions of OH(-) and F(-) with methyl and ethyl Innate For methyl nitrate, the main reaction channel is found to be an elimination process promoted by abstraction of an a proton from the methyl group. Nucleophilic displacement of nitrate anion through an S(N)2 process at the carbon center Is also found to he an important reaction channel with methyl nitrate In ethyl nitrate, Ruination of NO(3)(-) is greatly enhanced and this is attributed to the ease of an E2-type elimination process promoted by proton abstraction at the beta position of the ethyl group. Theoretical calculations at the MP2/6-311+G(3df,2p)//MP2/6-31+G(d) level of theory ale consistent with the relative importance of the reaction channels and suggest that these reactions proceed through a double well potential The calculations also predict that nucleophilic attack by OH(-) at the nitrogen center (Sn2@N) is energetically the rueful ad pathway but experiments with (18)OH(-) showed no evidence for this channel. Single-point calculations reveal a strong preference for approach to the emboli center and may explain the lack of reactivity at the nitrogen center. Calculations were also carried out or NH(2)(-) and SH(-) to establish the reactivity pattern to provide a better understanding of environmentally relevant nitrate esters.

Spectroscopic and theoretical studies of some N,N-diethyl-2-[(4 `-substituted)phenylsulfonyl]acetamides

The analysis of the IR carbonyl band of the N,N-diethyl-2-[(4`-substituted)phenylsulfonyl]acetamides Et(2)NC(O)CH(2)S(O)(2)-C(6)H(4)-Y (Y = OMe 1, Me 2,1-13, Cl 4, Br 5, NO(2) 6) supported by B3LYP/6-31G(d,p) calculations for 3, indicated the existence of three pairs (anti and syn) of cis (c) and gauche (g(1) and g(2)) conformers in the gas phase, being the gauche conformers significantly more stable than the cis ones. The anti geometry is more stable than the syn one, for each pair of cis and gauche conformers. The summing up of the orbital (NBO analysis) and electrostatic interactions justifies quite well the populations and the v(CO) frequencies of the anti and syn pairs of c, g(1) and g(2) conformers. The IR higher carbonyl frequency component whose population is ca. 10%, in CCl(4), may be ascribed to the least stable and most polar cis conformer pair (in the gas phase) and the lower frequency component whose population is ca. 90%, to the summing up of the populations of the two most stable and least polar gauche conformer pairs (g(1) and g(2)) (in the gas phase). The reversal of the cis(c)/gauche (g(1) + g(2)) population ratio observed in chloroform ca. 60% (cis)/40% (gauche) and the occurrence of the most polar cis(c) conformer only, in acetonitrile, strongly suggests the coalescence of the two gauche components in a unique carbonyl band in solution. A further support to this rationalization is given by the single point PCM solvation model performed by HF/6-31G(d,p) method, which showed a progressive increase of the c/(g(1) + g(2)) ratio going from gas to CCl(4), to CHCl(3) and to CH(3)CN. X-ray single crystal analysis of 4 indicates that this compound assumes, in the solid state, the syn-clinal (gauche) conformation with respect to the [O=C-CH(2)-S] moiety, and the most stable anti geometry relative to the [C(O)N(CH(2)CH(3))(2)] fragment. In order to obtain larger energy gain from the crystal packing the molecules of 4 are linked in centrosymmetric dimers through two C-H center dot center dot center dot O interactions (C-H([O-Ph])center dot center dot center dot O([SO2])) forming a step ladder. (C) 2011 Elsevier B.V. All rights reserved.

Bounds on functionals of the distribution treatment effects

Bounds on the distribution function of the sum of two random variables with known marginal distributions obtained by Makarov (1981) can be used to bound the cumulative distribution function (c.d.f.) of individual treatment effects. Identification of the distribution of individual treatment effects is important for policy purposes if we are interested in functionals of that distribution, such as the proportion of individuals who gain from the treatment and the expected gain from the treatment for these individuals. Makarov bounds on the c.d.f. of the individual treatment effect distribution are pointwise sharp, i.e. they cannot be improved in any single point of the distribution. We show that the Makarov bounds are not uniformly sharp. Specifically, we show that the Makarov bounds on the region that contains the c.d.f. of the treatment effect distribution in two (or more) points can be improved, and we derive the smallest set for the c.d.f. of the treatment effect distribution in two (or more) points. An implication is that the Makarov bounds on a functional of the c.d.f. of the individual treatment effect distribution are not best possible.

Modos de ser e modos de viver : a trajetória dos estrangeiros em Natal/RN

This work aims to understand the trajectory of immigrants living in Natal / RN, between the years 1990 and 2009, their motivations for this change, their sociability relations, as well as the impact of this group in Natal and specifically, in the district of Ponta Negra, where most of them established their residences or work. Considering that the historical, political, economical and social environment where these immigrants are inserted, are different from that experienced by former immigrants who came to Brazil in the late nineteenth and early twentieth centuries, a period of mass migration, it was revealed that immigration studied in contemporary Natal constitutes a new configuration (Elias, 1994). This new configuration is represented by several characteristics that distinguish this contemporary immigration, as: the relationship established by these foreigners, both with their country of origin and the destination, the formation of social networks that offer support to newcomers and those already installed, the relations of sociability with locals and a new relationship of belonging with the space, since the possibility of coming and going from one country to the other, allows a (re)production of their original ?? social and economic life in the new space. The research methodology was based on the analysis of narrative interviews, in light of the theory of Schütze (1977) in order to understand the faces of this immigration. As theoretical support for the data analysis the theories of authors such as Norbert Elias, presentedin his work about the established and outsiders, Pierre Bourdieu, and his concept of habitus, distinction and style of life, Georg Simmel, and his study of life in the metropolis, his analysis of the foreigner and his theory of sociability, among others. This study attempted to give visibility to foreigners living in Natal, who experience the dynamics of the district of Ponta Negra and reconstruct their daily relations of sociability in this space. In fact, the presence of foreigners in this urban context allows for the construction of new configurations, both in terms of the physical space of the neighborhood, which has been modified by the touristification process and the real estate market, which is molded to meet this demand, but also in their social sphere, with regard to the relations established between foreign residents and locals. In seeking to characterize these migratory experiences it could be understood that the trajectories of each foreigner is part of a broader social structure, which cannot be evaluated neither disconnected from the contexts in which they operate, nor under a single point of view

Fractais e percolação na recuperação de Petróleo

The complex behavior of a wide variety of phenomena that are of interest to physicists, chemists, and engineers has been quantitatively characterized by using the ideas of fractal and multifractal distributions, which correspond in a unique way to the geometrical shape and dynamical properties of the systems under study. In this thesis we present the Space of Fractals and the methods of Hausdorff-Besicovitch, box-counting and Scaling to calculate the fractal dimension of a set. In this Thesis we investigate also percolation phenomena in multifractal objects that are built in a simple way. The central object of our analysis is a multifractal object that we call Qmf . In these objects the multifractality comes directly from the geometric tiling. We identify some differences between percolation in the proposed multifractals and in a regular lattice. There are basically two sources of these differences. The first is related to the coordination number, c, which changes along the multifractal. The second comes from the way the weight of each cell in the multifractal affects the percolation cluster. We use many samples of finite size lattices and draw the histogram of percolating lattices against site occupation probability p. Depending on a parameter, ρ, characterizing the multifractal and the lattice size, L, the histogram can have two peaks. We observe that the probability of occupation at the percolation threshold, pc, for the multifractal is lower than that for the square lattice. We compute the fractal dimension of the percolating cluster and the critical exponent β. Despite the topological differences, we find that the percolation in a multifractal support is in the same universality class as standard percolation. The area and the number of neighbors of the blocks of Qmf show a non-trivial behavior. A general view of the object Qmf shows an anisotropy. The value of pc is a function of ρ which is related to its anisotropy. We investigate the relation between pc and the average number of neighbors of the blocks as well as the anisotropy of Qmf. In this Thesis we study likewise the distribution of shortest paths in percolation systems at the percolation threshold in two dimensions (2D). We study paths from one given point to multiple other points. In oil recovery terminology, the given single point can be mapped to an injection well (injector) and the multiple other points to production wells (producers). In the previously standard case of one injection well and one production well separated by Euclidean distance r, the distribution of shortest paths l, P(l|r), shows a power-law behavior with exponent gl = 2.14 in 2D. Here we analyze the situation of one injector and an array A of producers. Symmetric arrays of producers lead to one peak in the distribution P(l|A), the probability that the shortest path between the injector and any of the producers is l, while the asymmetric configurations lead to several peaks in the distribution. We analyze configurations in which the injector is outside and inside the set of producers. The peak in P(l|A) for the symmetric arrays decays faster than for the standard case. For very long paths all the studied arrays exhibit a power-law behavior with exponent g ∼= gl.

Investigation on Surface Finishing of Components Ground with Lapping Kinematics: Lapgrinding Process

Over the last three decades, researchers have responded to the demands of industry to manufacture mechanical components with geometrical tolerance, dimensional tolerance, and surface finishing in nanometer levels. The new lapgrinding process developed in Brazil utilizes lapping kinematics and a flat grinding wheel dressed with a single-point diamond dresser in agreement with overlap factor (U(d)) theory. In the present work, the influences of different U(d) values on dressing (U(d) = 1, 3 e 5) and grain size of the grinding wheel made of silicon carbide (SiC = 800, 600 e 300 mesh) are analyzed on surface finishing of stainless steel AISI 420 flat workpieces submitted to the lapgrinding process. The best results, obtained after 10 minutes of machining, were: average surface roughness (Ra) 1.92 nm; 1.19 mu m flatness deviation of 25.4 mm diameter workpieces and mirrored surface finishing. Given the surface quality achieved, the lapgrinding process can be included among the ultra-precision finishing processes and, depending on the application, the steps of lapping followed by polishing can be replaced by the proposed abrasive process.

Surface finishing of flat pieces when submitted to lapping kinematics on abrasive disc dressed under several overlap factors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Paralelização em GPU da segmentação vascular com extração de Centerlines por Height Ridges

The vascular segmentation is important in diagnosing vascular diseases like stroke and is hampered by noise in the image and very thin vessels that can pass unnoticed. One way to accomplish the segmentation is extracting the centerline of the vessel with height ridges, which uses the intensity as features for segmentation. This process can take from seconds to minutes, depending on the current technology employed. In order to accelerate the segmentation method proposed by Aylward [Aylward & Bullitt 2002] we have adapted it to run in parallel using CUDA architecture. The performance of the segmentation method running on GPU is compared to both the same method running on CPU and the original Aylward s method running also in CPU. The improvemente of the new method over the original one is twofold: the starting point for the segmentation process is not a single point in the blood vessel but a volume, thereby making it easier for the user to segment a region of interest, and; the overall gain method was 873 times faster running on GPU and 150 times more fast running on the CPU than the original CPU in Aylward

Mutational analysis of Arabidopsis thaliana plant uncoupling mitochondrial protein

In this study, point mutations were introduced in plant uncoupling mitochondrial protein AtUCP1, a typical member of the plant uncoupling protein (UCP) gene subfamily, in amino acid residues Lys147, Arg155 and Tyr269, located inside the so-called UCP-signatures, and in two more residues, Cys28 and His83, specific for plant UCPs. The effects of amino acid replacements on AtUCP1 biochemical properties were examined using reconstituted proteoliposomes. Residue Arg155 appears to be crucial for AtUCP1 affinity to linoleic acid (LA) whereas His83 plays an important role in AtUCP1 transport activity. Residues Cys28, Lys147, and also Tyr269 are probably essential for correct protein function, as their substitutions affected either the AtUCP1 affinity to LA and its transport activity, or sensitivity to inhibitors (purine nucleotides). Interestingly, Cys28 substitution reduced ATP inhibitory effect on AtUCP1, while Tyr269Phe mutant exhibited 2.8-fold increase in sensitivity to ATP, in accordance with the reverse mutation Phe267Tyr of mammalian UCP1. (C) 2007 Elsevier B.V. All fights reserved.

Aspectos moleculares do câncer tiroideano

A proliferação da célula tiroideana normal é regulada por fatores de crescimento estimuladores e inibidores, que atuam através de seus receptores de membrana e, subseqüentemente, através de transdutores citoplasmáticos. Na glândula normal adulta, o equilíbrio de sinais é tal que a proliferação é mínima, enquanto nas neoplasias o crescimento resulta de um distúrbio irreversível desse equilíbrio. Apesar do número de moléculas envolvidas nesse processo ser grande, apenas um pequeno subgrupo parece estar envolvido na tumorigênese tiroideana. Tais proteínas são codificadas pelos genes RAS, RET, NTRK1 e TP53. O transdutor de sinais ras é ativado por mutações em ponto e constitui uma alteração genética precoce nos tumores com histologia folicular. Os genes dos receptores de crescimento RET e NTRK1 são alterados por rearranjos cromossômicos do tipo translocação ou inversão nos carcinomas papilares e por mutações em ponto nos medulares. As alterações do gene TP53, por sua vez, têm sido observadas em carcinomas tiroideanos pobremente diferenciados e na maioria dos indiferenciados, o que sugere sua participação na progressão dessas lesões. O modelo molecular da carcinogênese tiroideana, embora ainda incompleto, pode fornecer instrumentos importantes para o diagnóstico diferencial e para o desenvolvimento de novas técnicas terapêuticas nesse grupo de neoplasias.

Crystal structure of a lectin from Canavalia maritima (ConM) in complex with trehalose and maltose reveals relevant. mutation in ConA-like lectins

The crystal structure of Canavalia maritima lectin (ConM) complexed with trehalose and maltose revealed relevant point mutations in ConA-like lectins. ConM with the disaccharides and other ConA-like lectins complexed with carbohydrates demonstrated significant differences in the position of H-bonds. The main difference in the ConM structure is the replacement of Pro202 by Ser202, a residue that promotes the approximation of Tyr12 to the carbohydrate-binding site. The O-6' of the second glucose ring in maltose interacts with Tyr12, while in trehalose the interaction is established by the O-2' and Tyr12, explaining the higher affinity of ConM for disaccharides compared to monosaccharides. (c) 2006 Elsevier B.V. All rights reserved.

SrBi2Ta2O9 ferroelectric thick films prepared by electrophoretic deposition using aqueous suspension

SrBi2Ta2O9 ferroelectric thick films were prepared by electrophoretic deposition (EPD). For that, ceramic powders were prepared by chemical method in order to obtain compounds with chemical homogeneity. The polymeric precursor method was used for the synthesis of the SrBi2Ta2O9 powder. The crystallographic structure of the powder was examined by X-ray diffraction, and the surface area was determined by single point BET adsorption. The 0.03 vol.% suspension was formed by dispersing the powder in water using two different polymers as dispersants: an ester polyphosphate (C213) and an ammonium polyacrilate (Darvan 821-A). It was investigated the influence of the different dispersants in the surface properties of the powder by zeta potential measurements. The films were deposited on platinum-coated alumina and Pt/Ti/SiO2/Si substrates by a 4 mA constant current, for 10 min, using two parallel electrodes placed at a separation distance of 3 min in the suspension. Several cycles of deposition-drying of the deposit were carried out until reaching the desired thickness. After thermal treatment at temperatures ranging from 700 to 1000 degreesC, the films were characterized by X-ray diffraction and scanning electron microscopy for the microstructure observation. (C) 2003 Elsevier Ltd. All rights reserved.

Preparation of SrBi2Ta2O9 ferroelectric thick films by electrophoretic deposition using aqueous suspensions

SrBi2Ta2O9 ferroelectric thick films were prepared by electrophoretic deposition (EPD). For that, ceramic powders were prepared by chemical method in order to obtain compounds with chemical homogeneity. The polymeric precursor method was used for the synthesis of the SrBi2Ta2O9 powder. The crystallographic structure of the powder was examined by X-ray diffraction, and the surface area was determined by single point BET adsorption. The 0.03 vol% suspension was formed by dispersing the powder in water using two different polymers as dispersants: an ester polyphosphate (C213) and an ammonium polyacrilate (Darvan 821-A). The influence of the different dispersants on the powder surface properties were investigated by zeta potential measurements. The films were deposited on platinum-coated alumina and Pt/Ti/SiO2/Si substrates by electrophoretic deposition using a 4 mA constant current, for 10 min, with two parallel electrodes placed at a separation distance of 3 min in the suspension. Several cycles of deposition-drying of the deposit was carried out until the desired thickness was obtained. After thermal treatment at temperatures ranging from 700 to 1000degreesC, the films were characterized by X-ray diffraction and scanning electron microscopy.

Surface amorphization in diamond turning of silicon crystal investigated by transmission electron microscopy

Silicon crystal exhibits a ductile regime during machining prior to the onset of fracture when appropriate cutting conditions are applied. The present study shows that the ductile regime is a result of a phase transformation which is indirectly evidenced by the amorphous phase detected in the machined surface. Transmission electron microscopy (TEM) planar view studies were successfully performed on monocrystalline silicon (1 0 0) single point diamond turned. TEM electron diffraction patterns show that the machined surface presents diffuse rings along with traces of crystalline material. This is attributed to crystalline silicon immersed in an amorphous matrix. Furthermore, only diffuse rings in the diffraction patterns of the ductile chip are detected, indicating that it is totally amorphous. © 2000 Elsevier Science B.V. All rights reserved.