Genome instability quantified in constitutive tissues as well as putatively stable tumor tissue in hereditary non -polyposis colon cancer patients by small pool PCR

Microsatellite instability (MSI) is a hallmark of the mutator phenotype associated with Hereditary Non-Polyposis Colon Cancer (HNPCC). The MSI-High (MSI-H) HNPCC population has been well characterized, but the microsatellite low and stable (MSI-L/MSS) HNPCC population is much less understood. We hypothesize there are significant levels of MSI in HNPCC DNA classified as MSI-L/MSS, but no single variant allele makes up a sufficient population in the tumor DNA to be detected by standard analysis. Finding variants would suggest there is a mutator phenotype for the MSI-L/MSS HNPCC population that is distinct from the MSI-H HNPCC populations. This study quantified and compared MSI in HNPCC patients previously shown to be MSI-H, MSI-L/MSS and an MSI-H older, sporadic colorectal cancer patient. Small-pool Polymerase Chain Reactions (SP-PCRs) were conducted where the DNAs from each sample and controls are diluted into multiple pools, each containing approximately single genome equivalents. At least 100 alleles/sample were studied at six microsatellite loci. Mutant fragments were identified, quantified, and compared using Poisson statistics. Most of the variants were small deletions or insertions, with more mutants being deletions, as has been previously described in yeast and transgenic mice. SP-PCR, where most of the pools contained only 3 or less fragments, enabled identification of variants too infrequent to be detected by large pool PCR. Mutant fragments in positive control MSI-H tumor samples ranged from 0.26 to 0.68 in at least 4 of the 6 loci tested and were consistent with their MSI-H status. In the so called MSS tumors and constitutive tissues (normal colon tissue, and PBLs) of all the HNPCC patients, low, but significant levels of MSI were seen in at least two of the loci studied. This phenomenon was not seen in the sporadic MSI constitutive tissues nor the normal controls and suggests haploinsufficiency, gain-of-function, or a dominant/negative basis of the instability in HNPCC patients carrying germline mutations for tumor suppressor genes. A different frequency and spectrum of mutant fragments suggests a different genetic basis (other than a major mutation in MLH1 or MSH2) for disease in MSI-L and MSS HNPCC patients. ^

Work instability. Presentation of an empirical model about its psychological impact

Research on the impact that work instability has on workers has the limitation of assess the relations among different variables separately, without examining the possible mediation relationships that can exists between them. The aim of this article is to test a conceptual model of the mediating relations between the uneasiness due to work instability and the psychological impact, in the framework of interactive stress theory, conducting a Path Analysis. 191 workers participated on the study, with a mean age of 31 years-old (SD = 11). Results showed that the proposed model didn't fit to the data. Alternative models were explored, consistent with the original conceptual model and the empiric evidence. A new causal model is proposed, where Uneasiness due to Work Instability as an independent variable, Personal Strain and Personal Resources as intervenient variables, and Anger, Hopelessness, and Satisfaction as dependent ones. The theoretical and empirical importance of the resulting model is discussed.

Work instability perception in a sample of psychologists

Considering work instability as a contextual stressor we designed a specific instrument to assess how it is perceived by a group of psychologists: The Perceived Uneasiness in Work Instability - Psychologists Inventory (in Spanish, IMPIL-PS). The data were collected from a 44-subject sample, both male and female, residents of the City of Buenos Aires and Greater Buenos Aires. We present data referring to sample characteristics and the areas with the greatest impact of the stressor are indicated. Recent research on work instability as a contextual stressor point out its influence on subjects' performance and behaviour.

Work instability versus mental health

This contribution is part of a research on guidance and employment in La Plata , province of Buenos Aires (Argentina) undertaken jointly by the Chairs of Preventive Psychology and Vocational Guidance, both pertaining to the course of studies for Psychology at the National University of La Plata. This research is based on four axes, namely, education-work-social policies-health. This paper shall focus around the health axis, which is not provided with placement and employment services. Some unsystematical guidance experiences from the services of Adolescence and Mental Health are currently under way in the area. Research points to the existence of new demands of psychological treatment from a population ("the new poor") afraid of losing their jobs -or even unemployed- who was not in the habit of going to the public hospital. In the casuistry explored here, people afraid of losing their jobs present more psychosomatic complexities. Local population is also analysed and the said analysis is linked with several national and international research projects.

Work instability. Presentation of an empirical model about its psychological impact

Research on the impact that work instability has on workers has the limitation of assess the relations among different variables separately, without examining the possible mediation relationships that can exists between them. The aim of this article is to test a conceptual model of the mediating relations between the uneasiness due to work instability and the psychological impact, in the framework of interactive stress theory, conducting a Path Analysis. 191 workers participated on the study, with a mean age of 31 years-old (SD = 11). Results showed that the proposed model didn't fit to the data. Alternative models were explored, consistent with the original conceptual model and the empiric evidence. A new causal model is proposed, where Uneasiness due to Work Instability as an independent variable, Personal Strain and Personal Resources as intervenient variables, and Anger, Hopelessness, and Satisfaction as dependent ones. The theoretical and empirical importance of the resulting model is discussed.

Work instability perception in a sample of psychologists

Considering work instability as a contextual stressor we designed a specific instrument to assess how it is perceived by a group of psychologists: The Perceived Uneasiness in Work Instability - Psychologists Inventory (in Spanish, IMPIL-PS). The data were collected from a 44-subject sample, both male and female, residents of the City of Buenos Aires and Greater Buenos Aires. We present data referring to sample characteristics and the areas with the greatest impact of the stressor are indicated. Recent research on work instability as a contextual stressor point out its influence on subjects' performance and behaviour.

Work instability versus mental health

This contribution is part of a research on guidance and employment in La Plata , province of Buenos Aires (Argentina) undertaken jointly by the Chairs of Preventive Psychology and Vocational Guidance, both pertaining to the course of studies for Psychology at the National University of La Plata. This research is based on four axes, namely, education-work-social policies-health. This paper shall focus around the health axis, which is not provided with placement and employment services. Some unsystematical guidance experiences from the services of Adolescence and Mental Health are currently under way in the area. Research points to the existence of new demands of psychological treatment from a population ("the new poor") afraid of losing their jobs -or even unemployed- who was not in the habit of going to the public hospital. In the casuistry explored here, people afraid of losing their jobs present more psychosomatic complexities. Local population is also analysed and the said analysis is linked with several national and international research projects.

Work instability perception in a sample of psychologists

Considering work instability as a contextual stressor we designed a specific instrument to assess how it is perceived by a group of psychologists: The Perceived Uneasiness in Work Instability - Psychologists Inventory (in Spanish, IMPIL-PS). The data were collected from a 44-subject sample, both male and female, residents of the City of Buenos Aires and Greater Buenos Aires. We present data referring to sample characteristics and the areas with the greatest impact of the stressor are indicated. Recent research on work instability as a contextual stressor point out its influence on subjects' performance and behaviour.

Work instability. Presentation of an empirical model about its psychological impact

Research on the impact that work instability has on workers has the limitation of assess the relations among different variables separately, without examining the possible mediation relationships that can exists between them. The aim of this article is to test a conceptual model of the mediating relations between the uneasiness due to work instability and the psychological impact, in the framework of interactive stress theory, conducting a Path Analysis. 191 workers participated on the study, with a mean age of 31 years-old (SD = 11). Results showed that the proposed model didn't fit to the data. Alternative models were explored, consistent with the original conceptual model and the empiric evidence. A new causal model is proposed, where Uneasiness due to Work Instability as an independent variable, Personal Strain and Personal Resources as intervenient variables, and Anger, Hopelessness, and Satisfaction as dependent ones. The theoretical and empirical importance of the resulting model is discussed.

Work instability versus mental health

This contribution is part of a research on guidance and employment in La Plata , province of Buenos Aires (Argentina) undertaken jointly by the Chairs of Preventive Psychology and Vocational Guidance, both pertaining to the course of studies for Psychology at the National University of La Plata. This research is based on four axes, namely, education-work-social policies-health. This paper shall focus around the health axis, which is not provided with placement and employment services. Some unsystematical guidance experiences from the services of Adolescence and Mental Health are currently under way in the area. Research points to the existence of new demands of psychological treatment from a population ("the new poor") afraid of losing their jobs -or even unemployed- who was not in the habit of going to the public hospital. In the casuistry explored here, people afraid of losing their jobs present more psychosomatic complexities. Local population is also analysed and the said analysis is linked with several national and international research projects.

The urban middle class in the instability of new democracies

The recent revolts of the middle class in the national capitals of the Philippines and Thailand have raised a new question about democratic consolidation. Why would the urban middle class, which is expected to stabilize democracy, expel the democratically elected leaders through extra-constitutional action? This article seeks to explain such middle class deviation from democratic institutions through an examination of urban primacy and the change in the winning coalition. The authoritarian regime previously in power tended to give considerable favor to the primate city to prevent it revolting against the ruler, because it could have become a menace to his power. But after democratization the new administration shifts policy orientation from an urban to rural bias because it needs to garner support from rural voters to win elections. Such a shift dissatisfies the middle class in the primate city. In this article I take up the Philippines as a case study to examine this theory.

Electromagnetic Instability Studies in Fusion Plasmas Edge

Este trabajo esta dedicado al estudio de las estructuras macroscópicas conocidas en la literatura como filamentos o blobs que han sido observadas de manera universal en el borde de todo tipo de dispositivos de fusión por confinamiento magnético. Estos filamentos, celdas convectivas elongadas a lo largo de las líneas de campo que surgen en el plasma fuertemente turbulento que existe en este tipo de dispositivos, parecen dominar el transporte radial de partículas y energía en la región conocida como Scrape-off Layer, en la que las líneas de campo dejan de estar cerradas y el plasma es dirigido hacia la pared sólida que forma la cámara de vacío. Aunque el comportamiento y las leyes de escala de estas estructuras son relativamente bien conocidos, no existe aún una teoría generalmente aceptada acerca del mecanismo físico responsable de su formación, que constituye una de las principales incógnitas de la teoría de transporte del borde en plasmas de fusión y una cuestión de gran importancia práctica en el desarrollo de la siguiente generación de reactores de fusión (incluyendo dispositivos como ITER y DEMO), puesto que la eficiencia del confinamiento y la cantidad de energía depositadas en la pared dependen directamente de las características del transporte en el borde. El trabajo ha sido realizado desde una perspectiva eminentemente experimental, incluyendo la observación y el análisis de este tipo de estructuras en el stellarator tipo heliotrón LHD (un dispositivo de gran tamaño, capaz de generar plasmas de características cercanas a las necesarias en un reactor de fusión) y en el stellarator tipo heliac TJ-II (un dispositivo de medio tamaño, capaz de generar plasmas relativamente más fríos pero con una accesibilidad y disponibilidad de diagnósticos mayor). En particular, en LHD se observó la generación de filamentos durante las descargas realizadas en configuración de alta _ (alta presión cinética frente a magnética) mediante una cámara visible ultrarrápida, se caracterizó su comportamiento y se investigó, mediante el análisis estadístico y la comparación con modelos teóricos, el posible papel de la Criticalidad Autoorganizada en la formación de este tipo de estructuras. En TJ-II se diseñó y construyó una cabeza de sonda capaz de medir simultáneamente las fluctuaciones electrostáticas y electromagnéticas del plasma. Gracias a este nuevo diagnóstico se pudieron realizar experimentos con el fin de determinar la presencia de corriente paralela a través de los filamentos (un parámetro de gran importancia en su modelización) y relacionar los dos tipos de fluctuaciones por primera vez en un stellarator. Así mismo, también por primera vez en este tipo de dispositivo, fue posible realizar mediciones simultáneas de los tensores viscoso y magnético (Reynolds y Maxwell) de transporte de cantidad de movimiento. ABSTRACT This work has been devoted to the study of the macroscopic structures known in the literature as filaments or blobs, which have been observed universally in the edge of all kind of magnetic confinement fusion devices. These filaments, convective cells stretching along the magnetic field lines, arise from the highly turbulent plasma present in this kind of machines and seem to dominate radial transport of particles and energy in the region known as Scrapeoff Layer, in which field lines become open and plasma is directed towards the solid wall of the vacuum vessel. Although the behavior and scale laws of these structures are relatively well known, there is no generally accepted theory about the physical mechanism involved in their formation yet, which remains one of the main unsolved questions in the fusion plasmas edge transport theory and a matter of great practical importance for the development of the next generation of fusion reactors (including ITER and DEMO), since efficiency of confinement and the energy deposition levels on the wall are directly dependent of the characteristics of edge transport. This work has been realized mainly from an experimental perspective, including the observation and analysis of this kind of structures in the heliotron stellarator LHD (a large device capable of generating reactor-relevant plasma conditions) and in the heliac stellarator TJ-II (a medium-sized device, capable of relatively colder plasmas, but with greater ease of access and diagnostics availability). In particular, in LHD, the generation of filaments during high _ discharges (with high kinetic to magnetic pressure ratio) was observed by means of an ultrafast visible camera, and the behavior of this structures was characterized. Finally, the potential role of Self-Organized Criticality in the generation of filaments was investigated. In TJ-II, a probe head capable of measuring simultaneously electrostatic and electromagnetic fluctuations in the plasma was designed and built. Thanks to this new diagnostic, experiments were carried out in order to determine the presence of parallel current through filaments (one of the most important parameters in their modelization) and to related electromagnetic (EM) and electrostatic (ES) fluctuations for the first time in an stellarator. As well, also for the first time in this kind of device, measurements of the viscous and magnetic momentum transfer tensors (Reynolds and Maxwell) were performed.

Three-dimensional flow instability in a lid-driven isosceles triangular cavity

Linear three-dimensional modal instability of steady laminar two-dimensional states developing in a lid-driven cavity of isosceles triangular cross-section is investigated theoretically and experimentally for the case in which the equal sides form a rectangular corner. An asymmetric steady two-dimensional motion is driven by the steady motion of one of the equal sides. If the side moves away from the rectangular corner, a stationary three-dimensional instability is found. If the motion is directed towards the corner, the instability is oscillatory. The respective critical Reynolds numbers are identified both theoretically and experimentally. The neutral curves pertinent to the two configurations and the properties of the respective leading eigenmodes are documented and analogies to instabilities in rectangular lid-driven cavities are discussed.

Linear global instability of non-orthogonal incompressible swept attachment-line boundary layer flow

Instability of the orthogonal swept attachment line boundary layer has received attention by local1, 2 and global3–5 analysis methods over several decades, owing to the significance of this model to transition to turbulence on the surface of swept wings. However, substantially less attention has been paid to the problem of laminar flow instability in the non-orthogonal swept attachment-line boundary layer; only a local analysis framework has been employed to-date.6 The present contribution addresses this issue from a linear global (BiGlobal) instability analysis point of view in the incompressible regime. Direct numerical simulations have also been performed in order to verify the analysis results and unravel the limits of validity of the Dorrepaal basic flow7 model analyzed. Cross-validated results document the effect of the angle _ on the critical conditions identified by Hall et al.1 and show linear destabilization of the flow with decreasing AoA, up to a limit at which the assumptions of the Dorrepaal model become questionable. Finally, a simple extension of the extended G¨ortler-H¨ammerlin ODE-based polynomial model proposed by Theofilis et al.4 is presented for the non-orthogonal flow. In this model, the symmetries of the three-dimensional disturbances are broken by the non-orthogonal flow conditions. Temporal and spatial one-dimensional linear eigenvalue codes were developed, obtaining consistent results with BiGlobal stability analysis and DNS. Beyond the computational advantages presented by the ODE-based model, it allows us to understand the functional dependence of the three-dimensional disturbances in the non-orthogonal case as well as their connections with the disturbances of the orthogonal stability problem.

Effect of Aspect Ratio on the Three-Dimensional Global Instability Analysis of Incompressible Open Cavity Flows

The stability analysis of open cavity flows is a problem of great interest in the aeronautical industry. This type of flow can appear, for example, in landing gears or auxiliary power unit configurations. Open cavity flows is very sensitive to any change in the configuration, either physical (incoming boundary layer, Reynolds or Mach numbers) or geometrical (length to depth and length to width ratio). In this work, we have focused on the effect of geometry and of the Reynolds number on the stability properties of a threedimensional spanwise periodic cavity flow in the incompressible limit. To that end, BiGlobal analysis is used to investigate the instabilities in this configuration. The basic flow is obtained by the numerical integration of the Navier-Stokes equations with laminar boundary layers imposed upstream. The 3D perturbation, assumed to be periodic in the spanwise direction, is obtained as the solution of the global eigenvalue problem. A parametric study has been performed, analyzing the stability of the flow under variation of the Reynolds number, the L/D ratio of the cavity, and the spanwise wavenumber β. For consistency, multidomain high order numerical schemes have been used in all the computations, either basic flow or eigenvalue problems. The results allow to define the neutral curves in the range of L/D = 1 to L/D = 3. A scaling relating the frequency of the eigenmodes and the length to depth ratio is provided, based on the analysis results.