Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease.

Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD)1, 2. These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case–control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer’s disease in seven independent case–control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer’s disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer’s disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer’s disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

A generalized fuzzy linguistic model for predicting component concentrations in an optical gas sensing system

Motivated by environmental protection concerns, monitoring the flue gas of thermal power plant is now often mandatory due to the need to ensure that emission levels stay within safe limits. Optical based gas sensing systems are increasingly employed for this purpose, with regression techniques used to relate gas optical absorption spectra to the concentrations of specific gas components of interest (NO_x, SO₂ etc.). Accurately predicting gas concentrations from absorption spectra remains a challenging problem due to the presence of nonlinearities in the relationships and the high-dimensional and correlated nature of the spectral data. This article proposes a generalized fuzzy linguistic model (GFLM) to address this challenge. The GFLM is made up of a series of “If-Then” fuzzy rules. The absorption spectra are input variables in the rule antecedent. The rule consequent is a general nonlinear polynomial function of the absorption spectra. Model parameters are estimated using least squares and gradient descent optimization algorithms. The performance of GFLM is compared with other traditional prediction models, such as partial least squares, support vector machines, multilayer perceptron neural networks and radial basis function networks, for two real flue gas spectral datasets: one from a coal-fired power plant and one from a gas-fired power plant. The experimental results show that the generalized fuzzy linguistic model has good predictive ability, and is competitive with alternative approaches, while having the added advantage of providing an interpretable model.

Spatio-temporal coverage optimization of sensor networks

Les réseaux de capteurs sont formés d’un ensemble de dispositifs capables de prendre individuellement des mesures d’un environnement particulier et d’échanger de l’information afin d’obtenir une représentation de haut niveau sur les activités en cours dans la zone d’intérêt. Une telle détection distribuée, avec de nombreux appareils situés à proximité des phénomènes d’intérêt, est pertinente dans des domaines tels que la surveillance, l’agriculture, l’observation environnementale, la surveillance industrielle, etc. Nous proposons dans cette thèse plusieurs approches pour effectuer l’optimisation des opérations spatio-temporelles de ces dispositifs, en déterminant où les placer dans l’environnement et comment les contrôler au fil du temps afin de détecter les cibles mobiles d’intérêt. La première nouveauté consiste en un modèle de détection réaliste représentant la couverture d’un réseau de capteurs dans son environnement. Nous proposons pour cela un modèle 3D probabiliste de la capacité de détection d’un capteur sur ses abords. Ce modèle inègre également de l’information sur l’environnement grâce à l’évaluation de la visibilité selon le champ de vision. À partir de ce modèle de détection, l’optimisation spatiale est effectuée par la recherche du meilleur emplacement et l’orientation de chaque capteur du réseau. Pour ce faire, nous proposons un nouvel algorithme basé sur la descente du gradient qui a été favorablement comparée avec d’autres méthodes génériques d’optimisation «boites noires» sous l’aspect de la couverture du terrain, tout en étant plus efficace en terme de calculs. Une fois que les capteurs placés dans l’environnement, l’optimisation temporelle consiste à bien couvrir un groupe de cibles mobiles dans l’environnement. D’abord, on effectue la prédiction de la position future des cibles mobiles détectées par les capteurs. La prédiction se fait soit à l’aide de l’historique des autres cibles qui ont traversé le même environnement (prédiction à long terme), ou seulement en utilisant les déplacements précédents de la même cible (prédiction à court terme). Nous proposons de nouveaux algorithmes dans chaque catégorie qui performent mieux ou produits des résultats comparables par rapport aux méthodes existantes. Une fois que les futurs emplacements de cibles sont prédits, les paramètres des capteurs sont optimisés afin que les cibles soient correctement couvertes pendant un certain temps, selon les prédictions. À cet effet, nous proposons une méthode heuristique pour faire un contrôle de capteurs, qui se base sur les prévisions probabilistes de trajectoire des cibles et également sur la couverture probabiliste des capteurs des cibles. Et pour terminer, les méthodes d’optimisation spatiales et temporelles proposées ont été intégrées et appliquées avec succès, ce qui démontre une approche complète et efficace pour l’optimisation spatio-temporelle des réseaux de capteurs.

Feminista Frequencies: Tuning In to Chicana Radio Activism in the Pacific Northwest, 1975-1990

Thesis (Ph.D.)--University of Washington, 2016-06

Revising Devotion: the role of wooden sculptures in affecting painting and devotion in the Late Medieval period in Italy (XII-XV century)

Thesis (Ph.D.)--University of Washington, 2016-06

Identidade, memória e narrativas na dança de São Gonçalo do povoado Mussuca (SE)

This study deals with the participation of the dance of São Gonçalo of the Mussuca town/SE, in the process of construction of the ethnic identity among this social group. The Mussuca is a grouping recognized as afro-descendents, linked with black enslaved people in the valley of the Cotinguiba region. The collective memory functions as a drive of this linking with the past and if it makes to elaborate narratives on this descent. The objective of this study was to investigate the ways the rite went through to constitute itself as an element of ethnic representation. Internal and external agents had been identified who had participated in different contexts. By means of an ethnographic work we ve reached some aspects of the local structure social which demonstrated the contradictions through the social relations of the group. This process of ethnic autorecognition presents the kinship and the space question as definers of the social arrangements which establish its ethnic boundaries

Surgical technique to avoid bladder flap formation during cesarean section

Cesarean section (CS) is now the most common major surgical procedure performed on women worldwide. A CS can be performed by either suturing or not suturing of the visceral peritoneum. Creation of the bladder flap is an integral step of the standard cesarean section. The bladder flap is made by superficially incising and dissecting the peritoneal lining to separate the urinary bladder from the lower uterine segment. It’s still debated whether the formation of bladder flap is advantageous or not. If the uterine incision is made slightly above the vesicouterine peritoneal fold, the loose connective tissue between the uterus and the urinary bladder allows spontaneous descent of the bladder. Evidence on the role of the bladder flap in cesarean section is very limited. At present, it remains to be established whether there is any advantage in dissecting the bladder from the lower uterine segment during cesarean section.

Coupled CFD Shape Optimization for aerodynamic profiles

The present document deals with the optimization of shape of aerodynamic profiles -- The objective is to reduce the drag coefficient on a given profile without penalising the lift coefficient -- A set of control points defining the geometry are passed and parameterized as a B-Spline curve -- These points are modified automatically by means of CFD analysis -- A given shape is defined by an user and a valid volumetric CFD domain is constructed from this planar data and a set of user-defined parameters -- The construction process involves the usage of 2D and 3D meshing algorithms that were coupled into own- code -- The volume of air surrounding the airfoil and mesh quality are also parametrically defined -- Some standard NACA profiles were used by obtaining first its control points in order to test the algorithm -- Navier-Stokes equations were solved for turbulent, steady-state ow of compressible uids using the k-epsilon model and SIMPLE algorithm -- In order to obtain data for the optimization process an utility to extract drag and lift data from the CFD simulation was added -- After a simulation is run drag and lift data are passed to the optimization process -- A gradient-based method using the steepest descent was implemented in order to define the magnitude and direction of the displacement of each control point -- The control points and other parameters defined as the design variables are iteratively modified in order to achieve an optimum -- Preliminary results on conceptual examples show a decrease in drag and a change in geometry that obeys to aerodynamic behavior principles

On the reduction theory of binary forms

Cremona developed a reduction theory for binary forms of degree 3 and 4 with integer coefficients, the motivation in the case of quartics being to improve 2-descent algorithms for elliptic curves over Q. In this paper we extend some of these results to forms of higher degree. One application of this is to the study of hyperelliptic curves.

Saúde hunana e ambiental: estudo com trabalhadores agricultores da ilha dos marinheiros

Este estudo apresenta uma relação entre o trabalho agrícola familiar e a saúde humana e ambiental em um cenário insular com características rurais, tendo-se como objetivo geral, analisar a sustentabilidade da relação socioambiental do trabalho de agricultores moradores da Ilha dos Marinheiros. Os objetivos específicos foram: Caracterizar a sustentabilidade do trabalho agrícola familiar na Ilha dos Marinheiros; Identificar como os trabalhadores agricultores da Ilha dos Marinheiros significam a sua saúde e atuam para mantê-la; Compreender como os trabalhadores agricultores identificam os impactos positivos e negativos do trabalho agrícola familiar desencadeados no ambiente e a conservação da saúde ambiental. Trata-se de uma pesquisa exploratória, descritiva, transversal com desenho de método misto com estruturação [QUAL + quan]. Foi realizada na Ilha dos Marinheiros, Rio Grande, Brasil, com 129 trabalhadores agricultores entre março a outubro de 2013, utilizando-se entrevista com aplicação individual de um questionário semiestruturado, gravado, previamente elaborado e testado. Também foram utilizados dados secundários referentes à constituição geográfica, cultural e econômica da Ilha. A organização dos dados qualitativos ocorreu a partir da transcrição dos dados oriundos das entrevistas no Microsoft Word, seguido da Análise de Conteúdo por temas com auxílio do Software Nvivo10. Para ambos os processos de análise utilizou-se o apoio teórico na racionalidade cultural de Enrique Leff. A organização dos dados quantitativos se fez pela codificação dos dados e digitação no software Statistical Package for the Social Sciences, 21.0, seguido da análise estatística descritiva e Teste Qui-quadrado de Pearson, com o p-valor <0,05 como significância estatística. Foram asseguradas as exigências éticas e científicas preconizadas nas pesquisas com seres humanos, mediante Resolução 466/2012 e aprovação do macroprojeto pelo Comitê de Ética da Universidade Federal do Rio Grande sob parecer 026/2013. Teve-se 78 trabalhadores agricultores do sexo masculino com idade média de (55,33±14,27), e 51 do sexo feminino, com idade média de (54,68±11,08). Predominou a descendência portuguesa 106 (84,8%), a maioria 100 (77,52%) com ensino fundamental incompleto, média de 2,53 integrantes no domicílio e renda familiar média de (1.648,39±947,72) para uma média de 2,58 dependentes desta. Os participantes atuavam em média há 40,56 anos, por (8,51± 3,10) horas diárias de trabalho em suas propriedades com média de 12,49 hectares. A atividade que mais exerciam e que eram mais auxiliados foi colher os produtos agrícolas, predominando o sexo masculino nesta função. O desenvolvimento do trabalho era conduzido mais pelos homens e de forma diária 83 (64,34%), seguido dos filhos 33 (25,58%) também diariamente 24 (18,60%). Quanto à saúde humana, esta foi concebida como boa, regular e ruim, com ações que convergem à continuidade do exercício laboral e adesão aos serviços de saúde mínima anualmente. Já os impactos positivos do trabalho no ambiente incidiram na conservação do trabalho como uma riqueza, o que exige atenção quanto ao uso dos agrotóxicos frente aos impactos negativos desencadeados ao ambiente em uma perspectiva sustentável à vida humana e não humana. O estudo fornece subsídios 6 contributivos à prática argumentativa do Enfermeiro à saúde ocupacional na agricultura familiar sob uma perspectiva sustentável ao ambiente.

Monadic Parsing in Haskell

This paper is a tutorial on defining recursive descent parsers in Haskell. In the spirit of one-stop shopping, the paper combines material from three areas into a single source. The three areas are functional parsers, the use of monads to structure functional programs, and the use of special syntax for monadic programs in Haskell. More specifically, the paper shows how to define monadic parsers using do notation in Haskell. The paper is targeted at the level of a good undergraduate student who is familiar with Haskell, and has completed a grammars and parsing course. Some knowledge of functional parsers would be useful, but no experience with monads is assumed.

Hybrid Variable Neighborhood HyperHeuristics for Exam Timetabling Problems

This paper presents our work on analysing the high level search within a graph based hyperheuristic. The graph based hyperheuristic solves the problem at a higher level by searching through permutations of graph heuristics rather than the actual solutions. The heuristic permutations are then used to construct the solutions. Variable Neighborhood Search, Steepest Descent, Iterated Local Search and Tabu Search are compared. An analysis of their performance within the high level search space of heuristics is also carried out. Experimental results on benchmark exam timetabling problems demonstrate the simplicity and efficiency of this hyperheuristic approach. They also indicate that the choice of the high level search methodology is not crucial and the high level search should explore the heuristic search space as widely as possible within a limited searching time. This simple and general graph based hyperheuristic may be applied to a range of timetabling and optimisation problems.

Ophthalmic findings in albinism

Purpose: Albinism is a rare genetic disorder of melanin production, which can affect only eyes or simultaneously eyes and skin/hair, resulting respectively in ocular (OA) or oculocutaneous albinism (OCA). Through of a case report of a child with OCA we pretend review ophthalmological manifestations of albinism. Case Report: A girl of West African descent was referenced to our appointment for ophthalmological evaluation of oculocutaneous albinism. Visual acuity was 20/310 OD e 20/630 OS by teller cards. In biomicroscopy, iris hypopigmentation and transillumination was visible, allowing to see spiral vessels and other iris details. Fundoscopy showed a denser and complex choroidal circulation due to lack of pigment in retinal pigment epithelium. Foveal hypoplasia was assumed because foveal pit is not apparent and vessels become less respectful of normal arcade and transverse the macula. Results: Melanin plays an important role in the development of the optic system and it’s absence leads to diverse ocular manifestations, such as: iris hypopigmentation and transillumination , reducted pigmentation of retinal pigment epithelium cells, photoreceptor rod cell deficits, foveal hypoplasia, optic nerve hypoplasia and misrouting of optic nerve at the chiasm, with temporal retina fibers inappropriately routed contralaterally instead of ipsilaterally. Photophobia, nystagmus, reduced visual acuity, color impairment and strabismus are other manifestations usually seen in albinism. Conclusion: Ophthalmologists must be familiar with the specific visual manifestations and needs of these patients. It is essential to correct refractive error to optimize visual acuity. Patients should also be advised to wear tinted glasses and sunblock. In more severely affected children they may benefit of low vision consultation and specialized low vision aids like telescopes.

Hybrid Variable Neighborhood HyperHeuristics for Exam Timetabling Problems

This paper presents our work on analysing the high level search within a graph based hyperheuristic. The graph based hyperheuristic solves the problem at a higher level by searching through permutations of graph heuristics rather than the actual solutions. The heuristic permutations are then used to construct the solutions. Variable Neighborhood Search, Steepest Descent, Iterated Local Search and Tabu Search are compared. An analysis of their performance within the high level search space of heuristics is also carried out. Experimental results on benchmark exam timetabling problems demonstrate the simplicity and efficiency of this hyperheuristic approach. They also indicate that the choice of the high level search methodology is not crucial and the high level search should explore the heuristic search space as widely as possible within a limited searching time. This simple and general graph based hyperheuristic may be applied to a range of timetabling and optimisation problems.

Photochemistry and transport of tropospheric ozone and its precursors in urban and remote environments

Tropospheric ozone (O3) adversely affects human health, reduces crop yields, and contributes to climate forcing. To limit these effects, the processes controlling O3 abundance as well as that of its precursor molecules must be fully characterized. Here, I examine three facets of O3 production, both in heavily polluted and remote environments. First, using in situ observations from the DISCOVER-AQ field campaign in the Baltimore/Washington region, I evaluate the emissions of the O3 precursors CO and NOx (NOx = NO + NO2) in the National Emissions Inventory (NEI). I find that CO/NOx emissions ratios derived from observations are 21% higher than those predicted by the NEI. Comparisons to output from the CMAQ model suggest that CO in the NEI is accurate within 15 ± 11%, while NOx emissions are overestimated by 51-70%, likely due to errors in mobile sources. These results imply that ambient ozone concentrations will respond more efficiently to NOx controls than current models suggest. I then investigate the source of high O3 and low H2O structures in the Tropical Western Pacific (TWP). A combination of in situ observations, satellite data, and models show that the high O3 results from photochemical production in biomass burning plumes from fires in tropical Southeast Asia and Central Africa; the low relative humidity results from large-scale descent in the tropics. Because these structures have frequently been attributed to mid-latitude pollution, biomass burning in the tropics likely contributes more to the radiative forcing of climate than previously believed. Finally, I evaluate the processes controlling formaldehyde (HCHO) in the TWP. Convective transport of near surface HCHO leads to a 33% increase in upper tropospheric HCHO mixing ratios; convection also likely increases upper tropospheric CH3OOH to ~230 pptv, enough to maintain background HCHO at ~75 pptv. The long-range transport of polluted air, with NO four times the convectively controlled background, intensifies the conversion of HO2 to OH, increasing OH by a factor of 1.4. Comparisons between the global chemistry model CAM-Chem and observations show that consistent underestimates of HCHO by CAM-Chem throughout the troposphere result from underestimates in both NO and acetaldehyde.