Aplicación de Métodos Meshless al Análisis de Problemas de Autovalores

La presente Tesis Doctoral aborda la aplicación de métodos meshless, o métodos sin malla, a problemas de autovalores, fundamentalmente vibraciones libres y pandeo. En particular, el estudio se centra en aspectos tales como los procedimientos para la resolución numérica del problema de autovalores con estos métodos, el coste computacional y la viabilidad de la utilización de matrices de masa o matrices de rigidez geométrica no consistentes. Además, se acomete en detalle el análisis del error, con el objetivo de determinar sus principales fuentes y obtener claves que permitan la aceleración de la convergencia. Aunque en la actualidad existe una amplia variedad de métodos meshless en apariencia independientes entre sí, se han analizado las diferentes relaciones entre ellos, deduciéndose que el método Element-Free Galerkin Method [Método Galerkin Sin Elementos] (EFGM) es representativo de un amplio grupo de los mismos. Por ello se ha empleado como referencia en este análisis. Muchas de las fuentes de error de un método sin malla provienen de su algoritmo de interpolación o aproximación. En el caso del EFGM ese algoritmo es conocido como Moving Least Squares [Mínimos Cuadrados Móviles] (MLS), caso particular del Generalized Moving Least Squares [Mínimos Cuadrados Móviles Generalizados] (GMLS). La formulación de estos algoritmos indica que la precisión de los mismos se basa en los siguientes factores: orden de la base polinómica p(x), características de la función de peso w(x) y forma y tamaño del soporte de definición de esa función. Se ha analizado la contribución individual de cada factor mediante su reducción a un único parámetro cuantificable, así como las interacciones entre ellos tanto en distribuciones regulares de nodos como en irregulares. El estudio se extiende a una serie de problemas estructurales uni y bidimensionales de referencia, y tiene en cuenta el error no sólo en el cálculo de autovalores (frecuencias propias o carga de pandeo, según el caso), sino también en términos de autovectores. This Doctoral Thesis deals with the application of meshless methods to eigenvalue problems, particularly free vibrations and buckling. The analysis is focused on aspects such as the numerical solving of the problem, computational cost and the feasibility of the use of non-consistent mass or geometric stiffness matrices. Furthermore, the analysis of the error is also considered, with the aim of identifying its main sources and obtaining the key factors that enable a faster convergence of a given problem. Although currently a wide variety of apparently independent meshless methods can be found in the literature, the relationships among them have been analyzed. The outcome of this assessment is that all those methods can be grouped in only a limited amount of categories, and that the Element-Free Galerkin Method (EFGM) is representative of the most important one. Therefore, the EFGM has been selected as a reference for the numerical analyses. Many of the error sources of a meshless method are contributed by its interpolation/approximation algorithm. In the EFGM, such algorithm is known as Moving Least Squares (MLS), a particular case of the Generalized Moving Least Squares (GMLS). The accuracy of the MLS is based on the following factors: order of the polynomial basis p(x), features of the weight function w(x), and shape and size of the support domain of this weight function. The individual contribution of each of these factors, along with the interactions among them, has been studied in both regular and irregular arrangement of nodes, by means of a reduction of each contribution to a one single quantifiable parameter. This assessment is applied to a range of both one- and two-dimensional benchmarking cases, and includes not only the error in terms of eigenvalues (natural frequencies or buckling load), but also of eigenvectors

Transient acoustic response in car cabins with localization of reflections

Due to its small size and the restrictions on source and listener positions, the design of sound reproduction systems for car cabins is particularly cumbersome. In the present project the measurement of the impulse response between a single loudspeaker and a listener position, with special emphasis on the directional characteristics, will be examined. The propagation paths inside a car are very short, meaning that it is very difficult for the existing commercial measurement systems to resolve the different reflections arriving to the listener. This paper propose a first approach of an algorithm based on time difference of arrival along a measurement technique aiming at finding the reflections and their direction of arrival to the listener. To this end a circular microphone array at a known position is employed, along with Maximum-Length Sequences (MLS) measurement technique. The results are processed so as to extract the directional properties, demonstrate the physical limitations that can influence or prevent this detection in practice. Measurements were carried out in a free-field environment (anechoic chamber) making use of different panels closer around the microphone array. RESUMEN. El diseño de sistemas de reproducción de audio para cabinas de coche es especialmente complicado debido al reducido tamaño del espacio y las restricciones de los altavoces y posiciones de escucha de los ocupantes. En el presente proyecto, se examinan mediciones de la respuesta al impulso entre un altavoz y una posición de escucha con especial énfasis en las características direccionales. Los caminos de propagación de las ondas sonoras dentro de un coche son muy cortos, lo que hace difícil para los instrumentos de medida existentes en el mercado determinar las direcciones de llegada de las diferentes reflexiones que llegan a una posición de escucha. Este trabajo propone una primera aproximación de un algoritmo, basado en las diferencias temporales de llegada de una onda a diferentes puntos de medida, y una particular técnica de medida de la respuesta al impulso para obtener las direcciones de llegada de reflexiones a una posición de escucha. Para ello, se emplea una matriz circular de micrófonos en una posición conocida junto con la técnica de medida MLS (Maximum Length Sequence). Los resultados obtenidos son procesados para extraer la dirección de llegada de las reflexiones acústicas y encontrar las limitaciones que influyan en la detección de dichas reflexiones. Las mediciones se llevan a cabo en un entorno de campo libre y utilizando diferentes superficies reflectantes alrededor de la matriz de micrófonos.

Un método de diferencias finitas generalizadas para simular la actividad eléctrica de un tejido cardiaco

Una evolución del método de diferencias finitas ha sido el desarrollo del método de diferencias finitas generalizadas (MDFG) que se puede aplicar a mallas irregulares o nubes de puntos. En este método se emplea una expansión en serie de Taylor junto con una aproximación por mínimos cuadrados móviles (MCM). De ese modo, las fórmulas explícitas de diferencias para nubes irregulares de puntos se pueden obtener fácilmente usando el método de Cholesky. El MDFG-MCM es un método sin malla que emplea únicamente puntos. Una contribución de esta Tesis es la aplicación del MDFG-MCM al caso de la modelización de problemas anisótropos elípticos de conductividad eléctrica incluyendo el caso de tejidos reales cuando la dirección de las fibras no es fija, sino que varía a lo largo del tejido. En esta Tesis también se muestra la extensión del método de diferencias finitas generalizadas a la solución explícita de ecuaciones parabólicas anisótropas. El método explícito incluye la formulación de un límite de estabilidad para el caso de nubes irregulares de nodos que es fácilmente calculable. Además se presenta una nueva solución analítica para una ecuación parabólica anisótropa y el MDFG-MCM explícito se aplica al caso de problemas parabólicos anisótropos de conductividad eléctrica. La evidente dificultad de realizar mediciones directas en electrocardiología ha motivado un gran interés en la simulación numérica de modelos cardiacos. La contribución más importante de esta Tesis es la aplicación de un esquema explícito con el MDFG-MCM al caso de la modelización monodominio de problemas de conductividad eléctrica. En esta Tesis presentamos un algoritmo altamente eficiente, exacto y condicionalmente estable para resolver el modelo monodominio, que describe la actividad eléctrica del corazón. El modelo consiste en una ecuación en derivadas parciales parabólica anisótropa (EDP) que está acoplada con un sistema de ecuaciones diferenciales ordinarias (EDOs) que describen las reacciones electroquímicas en las células cardiacas. El sistema resultante es difícil de resolver numéricamente debido a su complejidad. Proponemos un método basado en una separación de operadores y un método sin malla para resolver la EDP junto a un método de Runge-Kutta para resolver el sistema de EDOs de la membrana y las corrientes iónicas. ABSTRACT An evolution of the method of finite differences has been the development of generalized finite difference (GFD) method that can be applied to irregular grids or clouds of points. In this method a Taylor series expansion is used together with a moving least squares (MLS) approximation. Then, the explicit difference formulae for irregular clouds of points can be easily obtained using a simple Cholesky method. The MLS-GFD is a mesh-free method using only points. A contribution of this Thesis is the application of the MLS-GFDM to the case of modelling elliptic anisotropic electrical conductivity problems including the case of real tissues when the fiber direction is not fixed, but varies throughout the tissue. In this Thesis the extension of the generalized finite difference method to the explicit solution of parabolic anisotropic equations is also given. The explicit method includes a stability limit formulated for the case of irregular clouds of nodes that can be easily calculated. Also a new analytical solution for homogeneous parabolic anisotropic equation has been presented and an explicit MLS- GFDM has been applied to the case of parabolic anisotropic electrical conductivity problems. The obvious difficulty of performing direct measurements in electrocardiology has motivated wide interest in the numerical simulation of cardiac models. The main contribution of this Thesis is the application of an explicit scheme based in the MLS-GFDM to the case of modelling monodomain electrical conductivity problems using operator splitting including the case of anisotropic real tissues. In this Thesis we present a highly efficient, accurate and conditionally stable algorithm to solve a monodomain model, which describes the electrical activity in the heart. The model consists of a parabolic anisotropic partial differential equation (PDE), which is coupled to systems of ordinary differential equations (ODEs) describing electrochemical reactions in the cardiac cells. The resulting system is challenging to solve numerically, because of its complexity. We propose a method based on operator splitting and a meshless method for solving the PDE together with a Runge-Kutta method for solving the system of ODE’s for the membrane and ionic currents.

Estudio comparativo de los parámetros acústicos de la norma UNE-EN ISO 3382-1 medidos con fuente puntual y con el sistema de refuerzo sonoro en salas de cine

El objetivo principal de este trabajo fin de máster es la obtención de los parámetros acústicos, que especifica la norma UNE-EN ISO 3382-1, con una fuente omnidireccional y con cada uno de los canales del sistema de refuerzo sonoro (Izquierdo, Central, Derecho, Surround Izquierdo y Surround Derecho) en una sala de cine, así como la comparación de los resultados. La sala estudiada es la sala 6 de Kinepolis, que está situada en Pozuelo de Alarcón (Madrid). Es una sala de gran tamaño (8800 m3) que cuenta con 706 butacas. Tras un estudio de la situación actual en la investigación de acústica de salas, se han realizado las mediciones de la respuesta al impulso con las distintas fuentes y con dos tipos de señal: Secuencias de Máxima Longitud (Maximum Length Sequence - MLS) y barridos sinusoidales. Además, se ha creado un modelo virtual de la sala con el software EASE (Enhanced Acoustic Simulator for Engineers). Los tiempos de reverberación son bastante bajos (aproximadamente 0,6 s en frecuencias medias) y los parámetros subjetivos indican gran definición y claridad. C80 es mayor a 10 dB para casi todas las bandas de frecuencia y D50 es superior a 0,8. Con los datos obtenidos de las mediciones y la simulación se ha realizado un estudio comparativo en el que se incluye información acerca de cómo varían los parámetros acústicos en función del tipo de fuente utilizada, la fiabilidad del modelo creado o la calidad acústica de la sala. Además, presenta la posibilidad de realizar la medición de algunos de los parámetros acústicos con los altavoces del sistema de refuerzo sonoro, teniendo en cuenta las mejoras de los parámetros subjetivos con los altavoces de pantalla. ABSTRACT. The main objective of this Master's Dissertation is to measured some acoustic parameters, which are specified in UNE-EN ISO 3382-1, with an omnidirectional source and each channel sound reinforcement system (Left, Center, right, Surround Left and Surround Right) in a movie theater, and the comparison of results. The analyzed room is Kinepolis' room 6, which is placed in Pozuelo de Alarcón (Madrid). It is a large room (8800 m3) which has 706 seats. After the state of the art in room acoustics research, room's impulse responses have been measured with two types of signal: Maximum Length Sequence (MLS) and Logarithmic Frequency Sine Sweep. In addition, a virtual model of the room has been created with EASE software (Enhanced Acoustic Simulator for Engineers). Reverberation times are quite low (about 0.6 s at mid frequencies) and subjective parameters indicate high definition and clarity. C80 is greater than 10 dB for almost all frequency bands and D50 is greater than 0.8. The data obtained from both the measurements and the simulation has been analyzed in order to include a comparative study with information about the acoustic parameters variation depending on the type of acoustic source, the reliability of the model created or the acoustic quality of the room. Furthermore, it presents the possibility of measuring some acoustical parameters with sound reinforcement system, taking into account improvements in subjective parameters when you are measuring with screen channels.

Análisis de la precisión en la medida del tiempo de reverberación y de los parámetros asociados

El trabajo fin de master “Análisis de la precisión en la medida del tiempo de reverberación y de los parámetros asociados” tiene como objetivo primordial la evaluación de los parámetros y métodos utilizados para la obtención de estos, a través del tiempo de reverberación, tanto de forma global, conjunto de todos los métodos, como cada uno de ellos por separado. Un objetivo secundario es la evaluación de la incertidumbre en función del método de medición usado. Para realizarlo, se van a aprovechar las mediciones realizadas para llevar a cabo el proyecto fin de carrera [1], donde se medía el tiempo de reverberación en dos recintos diferentes usando el método del ruido interrumpido y el método de la respuesta impulsiva integrada con señales distintas. Las señales que han sido utilizadas han sido señales impulsivas de explosión de globos, disparo de pistola, claquetas y, a través de procesado digital, señales periódicas pseudoaleatorias MLS y barridos de tonos puros. La evaluación que se realizará a cada parámetro ha sido extraída de la norma UNE 89002 [2], [3]y [4]. Se determinará si existen valores aberrantes tanto por el método de Grubbs como el de Cochran, e interesará conocer la veracidad, precisión, repetibilidad y reproducibilidad de los resultados obtenidos. Los parámetros que han sido estudiados y evaluados son el tiempo de reverberación con caída de 10 dB, (T10), con caída de 15 dB (T15), con caída de 20 dB (T20), con caída de 30 dB (T30), el tiempo de la caída temprana (EDT), el tiempo final (Ts), claridad (C20, C30, C50 y C80) y definición (D50 y D80). Dependiendo de si el parámetro hace referencia al recinto o si varía en función de la relación entre la posición de fuente y micrófono, su estudio estará sujeto a un procedimiento diferente de evaluación. ABSTRACT. The master thesis called “Analysis of the accuracy in measuring the reverberation time and the associated parameters” has as the main aim the assessment of parameters and methods used to obtain these through reverberation time, both working overall, set of all methods, as each of them separately. A secondary objective is to evaluate the uncertainty depending on the measurement method used. To do this, measurements of [1] will be used, where they were carried on in two different spaces using the interrupted noise method and the method of impulse response integrated with several signals. The signals that have been used are impulsive signals such as balloon burst, gunshot, slates and, through digital processing, periodic pseudorandom signal MLS and swept pure tone. The assessment that will be made to each parameter has been extracted from the UNE 89002 [2], [3] and [4]. It will determine whether there are aberrant values both through Grubbs method and Cochran method, to say so, if a value is inconsistent with the rest of the set. In addition, it is interesting to know the truthfulness, accuracy, repeatability and reproducibility of results obtained from the first part of this rule. The parameters that are going to be evaluated are reverberation time with 10 dB decay, (T10), with 15 dB decay (T15), with 20 dB decay (T20), with 30 dB decay (T30), the Early Decay Time (EDT), the final time (Ts), clarity (C20, C30, C50 y C80) and definition (D50 y D80). Depending on whether the parameter refers to the space or if it varies depending on the relationship between source and microphone positions, the study will be related to a different evaluation procedure.

Faye Tull Carter

Faye Tull Carter obtained a Bachelor’s of Science Degree in Home Economics from Lincoln University in 1938. She also received a graduate degree from Teacher’s College, Columbia University in New York. After graduation, Carter accepted the position as Library Assistant at Lincoln University Laboratory School. Upon receiving a Master’s degree in Library Science (MLS) from Case Western Reserve University in Cleveland, Ohio, Carter was appointed the Librarian at Lincoln University Laboratory High School. She was later transferred to the University library, Inman E. Page Library, where she remained until her retirement in 1989. During her years of service, Carter was promoted to the level of Assistant Professor. She taught courses in Library Science and Children’s Literature. Carter’s duties at Inman E. Page Library included creating displays, arranging picture collections and organizing the research material for teachers and students in the Education Department. She also established the Children and Young Adult Literature Collection.

Unique molecular surface features of in vivo tolerized T cells

Differential expression of surface markers can frequently be used to distinguish functional subsets of T cells, yet a surface phenotype unique to T cells induced into an anergic state has not been described. Here, we report that CD4 T cells rendered anergic in vivo by superantigen can be identified by loss of the 6C10 T cell marker. Inoculation of Vβ8.1 T cell antigen receptor (TCR) transgenic mice with a Vβ8.1-reactive minor lymphocyte-stimulating superantigen (Mls-1a) induces tolerance to Mls-1a by clonal anergy. CD4 lymph node T cells from Mls-1a inoculated transgenic mice enriched for the 6C10− phenotype neither proliferate nor produce interleukin-2 upon TCR engagement, whereas 6C10+ CD4 T cells retain responsiveness. Analysis of T cell memory markers demonstrate that 6C10− T cells remain 3G11hi but express heterogeneous levels of CD45RB, CD62L, CD44, and the CD69 early activation marker, suggesting that T cells at various degrees of activation can be functionally anergic. These studies demonstrate that anergic T cells can be purified based on 6C10 expression permitting examination of issues concerning biochemical and biological features specific to T cell anergy.

Type 2 diabetes: Evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs

We are conducting a genome scan at an average resolution of 10 centimorgans (cM) for type 2 diabetes susceptibility genes in 716 affected sib pairs from 477 Finnish families. To date, our best evidence for linkage is on chromosome 20 with potentially separable peaks located on both the long and short arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, x̂ = 19.5 cM) under an additive model, whereas the weighted MLS was 2.06 on 20q (x̂ = 57 cM, recurrence risk, λ̂s = 1.25, P = 0.009). Weighted logarithm of odds scores of 2.00 (x̂ = 69.5 cM, P = 0.010) and 1.92 (x̂ = 18.5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibships with extreme mean values of diabetes-related quantitative traits yielded sets of families who contributed disproportionately to the peaks. Two-hour glucose levels in offspring of diabetic individuals gave a MLS of 2.12 (P = 0.0018) at 9.5 cM. Evidence from this and other studies suggests at least two diabetes-susceptibility genes on chromosome 20. We have also screened the gene for maturity-onset diabetes of the young 1, hepatic nuclear factor 4-a (HNF-4α) in 64 affected sibships with evidence for high chromosomal sharing at its location on chromosome 20q. We found no evidence that sequence changes in this gene accounted for the linkage results we observed.

Aod1, the immunoregulatory locus controlling abrogation of tolerance in neonatal thymectomy-induced autoimmune ovarian dysgenesis, maps to mouse chromosome 16.

Mice thymectomized at three days of age (D3Tx) develop during adulthood a variety of organ-specific autoimmune diseases, including autoimmune ovarian dysgenesis (AOD). The phenotypic spectrum of AOD is characterized by the development of anti-ovarian autoantibodies, oophoritis, and atrophy. The D3Tx model of AOD is unique in that disease induction depends exclusively on perturbation of the normal developing immune system, is T-cell-mediated, and is strain specific. For example, D3Tx A/J mice are highly susceptible to AOD, whereas C57BL/6J mice are resistant. After D3Tx, self ovarian antigens, expressed at physiological levels, trigger an autoimmune response capable of eliciting disease. The D3Tx model provides, therefore, the opportunity to focus on the mechanisms of self-tolerance that are relevant to disease pathogenesis. Previous studies indicate that the principal mechanisms involved in AOD susceptibility are genetically controlled and govern developmental processes associated with the induction and maintenance of peripheral tolerance. We report here the mapping of the Aod1 locus to mouse chromosome 16 within a region encoding several loci of immunologic relevance, including scid, Igl1, VpreB, Igll, Igl1r, Mtv6 (Mls-3), Ly-7, Ifnar, and Ifgt.

Encapsulação de colecalciferol (vitamina D3) por spray chilling

A indústria de alimentos está constantemente desenvolvendo produtos que fornecem, além de nutrientes, benefícios adicionais à saúde, tais como os enriquecidos com vitaminas. A vitamina D3 (colecalciferol) é sintetizada na pele durante a exposição da luz solar, controla a homeostase de cálcio e fósforo, metabolismo ósseo, pressão arterial e reabsorção renal de cálcio. O processo de microencapsulação vem sendo bastante aplicado em alimentos e um dos objetivos principais é o controle da liberação do agente ativo no momento e local desejado. A tecnologia de spray chilling é interessante para a microencapsulação de vitaminas lipossolúveis. O objetivo deste trabalho foi microencapsular vitamina D3, utilizando o método de spray chilling para a produção das micropartículas lipídicas sólidas (MLS). Para produção das MLS utilizou-se gordura vegetal com ponto de fusão em torno de 48 °C como carreador. Três tratamentos foram estabelecidos: sem aditivos (T1), com adição de 1% de cera de abelha (T2) e com 1% de lecitina de soja (T3). As micropartículas foram caracterizadas quanto à morfologia por microscopia eletrônica de varredura, tamanho médio por difração a laser, espectroscopia no infravermelho por transformada de Fourier (FTIR) e foi analisada a estabilidade da vitamina D3 durante o armazenamento a 10 e 25 °C, por meio de quantificações periódicas em cromatografia líquida de alta eficiência (CLAE). As micropartículas obtidas foram esféricas, semelhantes morfologicamente e com distribuição monocaudal de partículas. O tamanho médio das partículas variou em função dos seus ingredientes, sendo que as micropartículas produzidas apenas com vitamina e gordura foram menores em relação às demais (83,0% < 100 µm). A espectroscopia na região do infravermelho (FTIR) demonstrou que não ocorreu interação entre os ingredientes. A estabilidade da vitamina D3 encapsulada foi satisfatória ao longo de 65 dias com valores superiores a 87% para os três tratamentos e a temperatura apresentou influência na estabilidade. As MLS produzidas com cera apresentaram melhores resultados de estabilidade de vitamina D3 com valores de 90,18 ± 2,23 % após 65 dias de estocagem. Esses resultados são promissores e demostram a viabilidade da técnica de spray chilling na produção de MLS carregadas de vitamina D3, possibilitando uma futura aplicação em alimentos.

Aspects physionomiques de la végétation halo résistante et halophile du Nord et du Sud de l’Algérie occidentale

On se propose, à travers cette étude de cartographier la végétation halo résistante et halophile de deux zones de l’Algérie occidentale l’une au Nord (région de Hammam Boughrara) et l’autre au Sud (région du Chott El-Gharbi). Une comparaison de ces deux zones d’un point de vue physionomique a été menée, afin de mettre en évidence la diversité phytoécologique de ces peuplements. Les données bioclimatiques montrent que les zones d’étude sont toutes deux caractérisées par une longue période de sécheresse estivale variant de 6 à 7 mois. D’un autre côté, l’approche édaphique montre une texture limono-sableuse à sableuse aussi bien au Nord qu’au Sud. Par contre la salinité est nettement plus accentuée au Sud atteignant 1350 μ.S/cm. La carte physionomique de la végétation de la zone nord fait apparaitre la dominance de formations pures à Tamarix gallica L. (27,13%) ou à Atriplex halimus L. (37,99%), et de formations en mosaïques, où les deux genres se trouvent mêlés (16,87%). Au niveau de la zone sud deux grandes unités physionomiques se distinguent: les groupements à Salsola vermiculata L. (24 %) et les groupements à Lygeum spartum L. (6 %). Les groupements à Artemisia herba– alba Asso. occupent par contre de petites surfaces (2 %) de qualité moyenne à médiocre. Les peuplements à Arthrocnemum glaucum (Del.) Ung. quant à eux, se répartissent tout autour de la daya du Chott El-Gharbi, où la salinité est à son maximum, en constituant un tapis végétal assez dense (1 %).

Uso de señales pseudoaleatorias en aplicaciones para el estudio de la dinámica de vibraciones

El estudio de la propagación de una perturbación en un medio elástico es un contenido de relevancia en una carrera técnica. En los laboratorios docentes no es fácil llevar a cabo experimentos en los que el alumnado visualice fácilmente la dinámica de vibraciones. Además, la ejecución de prácticas demostrativas de análisis modal exige la utilización de configuraciones en las que son necesarios dispositivos excitadores como los Shaker o los martillos de impacto. En este trabajo se presenta una metodología experimental basada en la utilización de señales pseudoaleatorias tipo MLS (Maximum Length Sequence) y actuadores de tipo electrodinámico, de fácil acceso al profesorado, en aplicaciones para el estudio de la dinámica de vibraciones y que ha sido ensayada con éxito en diferentes titulaciones. La base experimental sobre la que se proponen las aplicaciones consiste en barras y estructuras tipo “L” construidas a partir de piedra arenisca tipo Bateig.

Lack of association between genetic markers on chromosome 16q22-Q24 and type 1 diabetes in Russian affected families

Aim To evaluate whether the T1D susceptibility locus on chromosome 16q contributes to the genetic susceptibility to T1D in Russian patients. Method Thirteen microsatellite markers, spanning a 47-centimorgan genomic region on 16q22-q24 were evaluated for linkage to T1D in 98 Russian multiplex families. Multipoint logarithm of odds (LOD) ratio (MLS) and nonparametric LOD (NPL) values were computed for each marker, using GENEHUNTER 2.1 software. Four microsatellites (D16S422, D16S504, D16S3037, and D16S3098) and 6 biallelic markers in 2 positional candidate genes, ICSBP1 and NQO1, were additionally tested for association with T1D in 114 simplex families, using transmission disequilibrium test (TDT). Results A peak of linkage (MLS = 1.35, NPL = 0.91) was shown for marker D16S750, but this was not significant (P = 0.18). The subsequent linkage analysis in the subset of 46 multiplex families carrying a common risk HLA-DR4 haplotype increased peak MLS and NPL values to 1.77 and 1.22, respectively, but showed no significant linkage (P = 0.11) to T1D in the 16q22-q24 genomic region. TDT analysis failed to find significant association between these markers and disease, even after the conditioning for the predisposing HLA-DR4 haplotype. Conclusion Our results did not support the evidence for the susceptibility locus to T1D on chromosome 16q22-24 in the Russian family data set. The lack of association could reflect genetic heterogeneity of type 1 diabetes in diverse ethnic groups.

Genomewide linkage study in 1,176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26

Endometriosis is a common gynecological disease that affects up to 10% of women in their reproductive years. It causes pelvic pain, severe dysmenorrhea, and subfertility. The disease is defined as the presence of tissue resembling endometrium in sites outside the uterus. Its cause remains uncertain despite 150 years of hypothesis-driven research, and thus the therapeutic options are limited. Disease predisposition is inherited as a complex genetic trait, which provides an alternative route to understanding the disease. We seek to identify susceptibility loci, using a positional-cloning approach that starts with linkage analysis to identify genomic regions likely to harbor these genes. We conducted a linkage study of 1,176 families ( 931 from an Australian group and 245 from a U. K. group), each with at least two members-mainly affected sister pairs-with surgically diagnosed disease. We have identified a region of significant linkage on chromosome 10q26 ( maximum LOD score [MLS] of 3.09; genomewide P = .047) and another region of suggestive linkage on chromosome 20p13 MLS p 2.09). Minor peaks with MLS > 1.0) were found on chromosomes 2, 6, 7, 8, 12, 14, 15, and 17. This is the first report of linkage to a major locus for endometriosis. The findings will facilitate discovery of novel positional genetic variants that influence the risk of developing this debilitating disease. Greater understanding of the aberrant cellular and molecular mechanisms involved in the etiology and pathophysiology of endometriosis should lead to better diagnostic methods and targeted treatments.