Fine mapping and functional analysis of the multiple sclerosis risk gene CD6

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (Pmax(T) permutation=161024). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naı¨ve cells, P = 0.0001; CD8+ naı¨ve cells, P,0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells.

PLP 238/2013 : alteração das exigências do art. 14 da LRF para desonerações de receitas públicas : necessidade de tratamento equânime

A presente Nota Técnica, apresentada por solicitação do Deputado JOÃO DADO, SISCONOF 274/2013, visa apresentar análise do Projeto de Lei Complementar nº 238/2013, no qual o Poder Executivo propõe alterações das exigências para concessão de desonerações tributárias presentes no art. 14 da Lei Complementar nº 101/2000, Lei de Responsabilidade Fiscal – LRF, dentre outras propostas

Análisis de las publicaciones del personal docente e investigador de las facultades españolas de Bellas Artes

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Análise do veto ao art. 118 da Lei nº 13.080, de 2 de janeiro 2015 (LDO 2015), que determina ao Poder Executivo a criação de “Cadastro de Obras Públicas”

Visa a atender à Solicitação de Trabalho nº 17/2015-CONOF, por meio da qual o Deputado Pauderney Avelino solicita a esta Consultoria que elabore nota técnica acerca do veto ao art. 118 da Lei 13.080, de 2 de janeiro 2015 (LDO 2015), que determinava ao Poder Executivo a criação de “Cadastro de Obras Públicas”

Análise das Portarias Interministeriais nº 221 e 222 : Execução das programações decorrentes de Emendas Individuais em 2015 : Orçamento Impositivo - art. 56 da LDO 2015 –Lei nº 13.080, de 2/1/2015

Analisa as disposições contidas nas Portarias Interministeriais nºs 221 e 222, editadas em 18 de junho último pelo Governo Federal. Essas portarias regulamentam procedimentos preparatórios à execução de emendas individuais da Lei Orçamentária Anual (LOA) de 2015, sujeitas ao regime de execução obrigatória (“orçamento impositivo”), instituído na Lei de Diretrizes Orçamentárias de 2015 (LDO 2015 – Lei 13.080/2015) e, posteriormente, na Emenda Constitucional 86.

Fine interference fringes formed in high-order harmonic spectra generated by infrared driving laser pulses

We experimentally investigate the high-order harmonic generation in argon gas using a driving laser pulse at a center wavelength of 1240 nm. High-contrast fine interference fringes could be observed in the harmonic spectra near the propagation axis, which is attributed to the interference between long and short quantum paths. We also systematically examine the variation of the interference fringe pattern with increasing energy of the driving pulse and with different phase-matching conditions.

The Art of Madness

The nineteenth century was not an entirely kind time for the female artist. Coming of age as the 1800’s bridged into its latter half, literary artists Elizabeth Stuart Phelps Ward, Charlotte Perkins Gilman, and Kate Chopin were all well aware of their uncharitable culture. Equipped with firm feminist bents and creative visions, each of three women produced a seminal work – The Story of Avis, “The Yellow Wallpaper,” and The Awakening, respectively – taking that atmosphere to task. In these stories, each of the three women produces a female protagonist who struggles for having been born simultaneously an artist and a woman. The writers pit their women’s desires against the restrictive latitude of their time and show how such conditions drive women to madness, as a result of which they are forced to either escape into the blind mind of insanity or deal daily with their pain and inescapable societal condemnation. In an age where “hysteria” was a frequent hit in the vernacular, Phelps, Gilman and Chopin use art and literature as mediums to show that, indeed, there is a method behind the madness.

Experimental and theoretical developments in extended x-ray absorption fine structure (EXAFS) spectroscopy

To obtain accurate information from a structural tool it is necessary to have an understanding of the physical principles which govern the interaction between the probe and the sample under investigation. In this thesis a detailed study of the physical basis for Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy is presented. A single scattering formalism of EXAFS is introduced which allows a rigorous treatment of the central atom potential. A final state interaction formalism of EXAFS is also discussed. Multiple scattering processes are shown to be significant for systems of certain geometries. The standard single scattering EXAFS analysis produces erroneous results if the data contain a large multiple scattering contribution. The effect of thermal vibrations on such multiple scattering paths is also discussed. From symmetry considerations it is shown that only certain normal modes contribute to the Debye-Waller factor for a particular scattering path. Furthermore, changes in the scattering angles induced by thermal vibrations produces additional EXAFS components called modification factors. These factors are shown to be small for most systems.

A study of the physical basis for the determination of structural information from EXAFS data is also presented. An objective method of determining the background absorption and the threshold energy is discussed and involves Gaussian functions. In addition, a scheme to determine the nature of the scattering atom in EXAFS experiments is introduced. This scheme is based on the fact that the phase intercept is a measure of the type of scattering atom. A method to determine bond distances is also discussed and does not require the use of model compounds or calculated phase shifts. The physical basis for this method is the absence of a linear term in the scattering phases. Therefore, it is possible to separate these phases from the linear term containing the distance information in the total phase.

Palladium-Catalyzed Decarboxylative and Decarbonylative Transformations in the Synthesis of Fine and Commodity Chemicals

Decarboxylation and decarbonylation are important reactions in synthetic organic chemistry, transforming readily available carboxylic acids and their derivatives into various products through loss of carbon dioxide or carbon monoxide. In the past few decades, palladium-catalyzed decarboxylative and decarbonylative reactions experienced tremendous growth due to the excellent catalytic activity of palladium. Development of new reactions in this category for fine and commodity chemical synthesis continues to draw attention from the chemistry community.

The Stoltz laboratory has established a palladium-catalyzed enantioselective decarboxylative allylic alkylation of β-keto esters for the synthesis of α-quaternary ketones since 2005. Recently, we extended this chemistry to lactams due to the ubiquity and importance of nitrogen-containing heterocycles. A wide variety of α-quaternary and tetrasubstituted α-tertiary lactams were obtained in excellent yields and exceptional enantioselectivities using our palladium-catalyzed decarboxylative allylic alkylation chemistry. Enantioenriched α-quaternary carbonyl compounds are versatile building blocks that can be further elaborated to intercept synthetic intermediates en route to many classical natural products. Thus our chemistry enables catalytic asymmetric formal synthesis of these complex molecules.

In addition to fine chemicals, we became interested in commodity chemical synthesis using renewable feedstocks. In collaboration with the Grubbs group, we developed a palladium-catalyzed decarbonylative dehydration reaction that converts abundant and inexpensive fatty acids into value-added linear alpha olefins. The chemistry proceeds under relatively mild conditions, requires very low catalyst loading, tolerates a variety of functional groups, and is easily performed on a large scale. An additional advantage of this chemistry is that it provides access to expensive odd-numbered alpha olefins.

Finally, combining features of both projects, we applied a small-scale decarbonylative dehydration reaction to the synthesis of α-vinyl carbonyl compounds. Direct α-vinylation is challenging, and asymmetric vinylations are rare. Taking advantage of our decarbonylative dehydration chemistry, we were able to transform enantioenriched δ-oxocarboxylic acids into quaternary α-vinyl carbonyl compounds in good yields with complete retention of stereochemistry. Our explorations culminated in the catalytic enantioselective total synthesis of (–)-aspewentin B, a terpenoid natural product featuring a quaternary α-vinyl ketone. Both decarboxylative and decarbonylative chemistries found application in the late stage of the total synthesis.

Infiltration of fine and coarse sand into an open-work gravel bed

The siltation of an experimental gravel bed, with three grades of sand moving in suspension and as bedload, was examined. The rate of infiltration of sand into the void space of the gravel was determined under differing conditions of discharge, water depth, and velocity (jointly expressed as variation in the Froude Number) and suspended sediment concentration. The downstream reduction in siltation from the point source was also examined.

Microoptical research in Shanghai Institute of Optics and Fine Mechanics

This paper summarized the recent research results of Changhe Zhou's group of Information Optics Lab in Shanghai Institute of Optics and Fine Mechanics (SIOM). The first is about the Talbot self-imaging research. We have found the symmetry rule, the regular-rearranged neighboring phase difference rule and the prime-number decamping rule, which is briefly summarized in a recent educational publication of Optics and Photonics News, pp.46-50, November 2004. The second is about four novel microoptical gratings designed and fabricated in SIOM. The third is about the design and fabrication of novel supperresolution phase plates for beam shaping and possible use in optical storage. The fourth is to develop novel femtosecond laser information processing techniques by incorporating microoptical elements, for example, use of a pair of reflective Dammann gratings for splitting the femtosecond laser pulses. The most attractive feature of this approach is that the conventional beam splitter is avoided. The conventional beam splitter would introduce the unequal dispersion due to the broadband spectrum of ultrashort laser pulses, which will affect the splitting result. We implemented the Dammann splitting apparatus by using two-layered reflective Dammann gratings, which generates the almost same array without angular dispersion. We believe that our device is highly interesting for splitting femtosecond laser pulses.