FAM-MDR: a flexible family-based multifactor dimensionality reduction technique to detect epistasis using related individuals

We propose a novel multifactor dimensionality reduction method for epistasis detection in small or extended pedigrees, FAM-MDR. It combines features of the Genome-wide Rapid Association using Mixed Model And Regression approach (GRAMMAR) with Model-Based MDR (MB-MDR). We focus on continuous traits, although the method is general and can be used for outcomes of any type, including binary and censored traits. When comparing FAM-MDR with Pedigree-based Generalized MDR (PGMDR), which is a generalization of Multifactor Dimensionality Reduction (MDR) to continuous traits and related individuals, FAM-MDR was found to outperform PGMDR in terms of power, in most of the considered simulated scenarios. Additional simulations revealed that PGMDR does not appropriately deal with multiple testing and consequently gives rise to overly optimistic results. FAM-MDR adequately deals with multiple testing in epistasis screens and is in contrast rather conservative, by construction. Furthermore, simulations show that correcting for lower order (main) effects is of utmost importance when claiming epistasis. As Type 2 Diabetes Mellitus (T2DM) is a complex phenotype likely influenced by gene-gene interactions, we applied FAM-MDR to examine data on glucose area-under-the-curve (GAUC), an endophenotype of T2DM for which multiple independent genetic associations have been observed, in the Amish Family Diabetes Study (AFDS). This application reveals that FAM-MDR makes more efficient use of the available data than PGMDR and can deal with multi-generational pedigrees more easily. In conclusion, we have validated FAM-MDR and compared it to PGMDR, the current state-of-the-art MDR method for family data, using both simulations and a practical dataset. FAM-MDR is found to outperform PGMDR in that it handles the multiple testing issue more correctly, has increased power, and efficiently uses all available information.

Implantació d'un sistema SCADA en una cèl·lula flexible de fabricació

La Universitat de Vic disposa, entre altres equips, d’una cèl·lula flexible de fabricació, del fabricant Festo, que simula un procés de formació de palets amb els productes que es disposen en un magatzem intermedi. Aquesta cèl·lula està composta de quatre estacions de muntatge diferenciades (càrrega de palets, càrrega de plaques, magatzem intermedi i transport). Cada una disposa d'un PLC SIEMENS S7-300 per la seva automatització, i tots aquests es troben interconnectats amb una xarxa industrial Profibus. L'objectiu d'aquest projecte és implantar el sistema SCADA Vijeo Citect pel control i supervisió de l'estació magatzem d'aquesta cèl·lula flexible de fabricació, establint també un intercanvi de dades entre l'SCADA i el Microsoft Access, per poder ser utilitzat per la docència. Aquest projecte s'ha desenvolupat en cinc fases diferents: 1. La primera fase s'ha dedicat a l'automatització pròpiament de l'estació magatzem a partir de l'autòmat programable Siemens S7-300 i complint amb les necessitats plantejades. 2. En la segona fase s'ha programat i establert la comunicació per l'intercanvi de dades (lectura i escriptura) entre el sistema SCADA Vijeo Citect i la base de dades de Microsoft Access. 3. En la tercera fase s'ha elaborat i programat l'entorn gràfic de supervisió i control del procés a partir del sistema SCADA Vijeo Citect. 4. En la quarta fase s'ha instal·lat un OPC Server en el PC i s'ha establert la comunicació entre el PLC i el sistema SCADA. 5. Finalment s'ha anat revisant i depurant les diferents programacions i comunicacions per tal de que el sistema funcioni com a un conjunt.

Qui utilise les crèches en Suisse ? : logiques sociales du recours aux structures d'accueil collectif pour la petite enfance

Depuis quelque temps, de plus en plus de spécialistes de la politique sociale préconisent une stratégie d'investissement social dans laquelle les crèches joueraient un rôle majeur. Cette stratégie vise à prévenir les exclusions sociales par la promotion de l'égalité des chances et de l'accès à l'emploi en vue d'un allègement des dépenses de protection sociale passive. Outre qu'elles permettent aux familles d'avoir deux revenus, les crèches ont en effet l'avantage de réduire les écarts au niveau des compétences cognitives et linguistiques entre les enfants venant de différents milieux sociaux. Mais le succès d'une telle stratégie présuppose que certains publics cibles recourent effectivement aux crèches, à savoir les ménages disposant d'un faible revenu ou/et de niveau de formation, ainsi que les familles issues de l'immigration. Or, des analyses statistiques sur la base de l'Enquête suisse sur la population active (ESPA) de 2008 montrent que, pour les familles en Suisse, les chances d'utiliser une crèche augmentent avec le niveau de formation des parents. Concernant plus particulièrement le niveau de formation des mères, ce phénomène n'est d'ailleurs que partiellement conditionné par le taux d'activité supérieur de celles ayant accompli une formation de degré tertiaire. En outre, certaines populations d'immigrés dont l'intégration dans la société suisse est réputée difficile sont peu disposées à recourir aux crèches. Les immigrés de première génération de quasiment toutes les origines fortement représentées en Suisse ont en revanche plus de chances que les parents d'origine suisse de faire appel au service d'une crèche à raison d'au moins 4 jours/semaine, ce qui peut influer négativement sur le comportement de l'enfant. Ce dernier résultat semble paradoxal mais montre qu'une migration rend plus difficile l'organisation d'une garde informelle comme solution complémentaire à la crèche. En synthèse, la présente étude attire l'attention sur le fait que les atouts pédagogiques et socialisants des crèches reviennent avant tout aux enfants de parents d'origine suisse ou venant de pays culturellement proches et ayant un niveau de formation supérieur. Telle que conçue actuellement, l'offre de crèches en Suisse ne semble guère opérer comme un instrument efficace de l'investissement social. Immer mehr Experten der Sozialpolitik empfehlen eine ,,Strategie der sozialen Investitionen", die den Kindertagesstätten (bzw. Kinderkrippen) eine wichtige Rolle zuschreibt. Ziel dieser Strategie ist es, durch Förderung von Chancengleichheit und Arbeitsmarktpartizipation sozialen Ausgrenzungen vorzubeugen, um Einsparungen im Bereich der passiven Sozialleistungen zu ermöglichen. Krippen haben einerseits den Vorteil, dass sie es den Familien ermöglichen, zwei Einkommen zu erzielen. Andererseits tragen sie zur Minderung von kognitiven und sprachlichen Fähigkeitsunterschieden zwischen Vorschulkindern aus verschiedenen sozialen Milieus bei. Der Erfolg dieser Strategie setzt jedoch voraus, dass gewisse Zielgruppen tatsächlich Krippen nutzen, nämlich bezüglich Einkommen und/oder Bildung benachteiligte Haushalte sowie Familien mit Migrationshintergrund. Die vorliegenden statistischen Analysen aufgrund der SAKE-Daten von 2008 (Schweizerische Arbeitskräfteerhebung) ergeben jedoch für die Schweiz, dass die Wahrscheinlichkeit, eine Krippe zu nutzen, mit dem Bildungsniveau der Eltern steigt. Was das Bildungsniveau der Mütter im Besonderen anbelangt, ist dieses Phänomen nur teilweise bedingt durch den tendenziell höheren Beschäftigungsgrad der besser Ausgebildeten. Zudem haben einige Migrantengruppen, deren Integration in die Schweizer Gesellschaft als besonders schwierig betrachtet wird, eine bedeutend tiefere Benützungswahrscheinlichkeit als Eltern Schweizer Herkunft. Für fast alle in der Schweiz stark vertretenen Migranten erster Generation ist dennoch das statistische Risiko grösser, die Krippe während mindestens 4 Tagen/Woche zu nutzen, was einen negativen Einfluss auf das Verhalten des Kindes haben kann. Dieses scheinbar paradoxe Ergebnis ist darauf zurückzuführen, dass ein Migrationshintergrund das Organisieren von krippenergänzenden Betreuungslösungen informeller Art meist erschwert. Gesamthaft zeigt die vorliegende Studie auf, dass die positiven pädagogischen und sozialisierenden Effekte der Krippen in erster Linie Kindern zugutekommen, deren Eltern eine höhere Ausbildung haben, Schweizer Herkunft sind oder aus einem kulturell nahestehenden Land kommen. So wie es gegenwärtig eingerichtet ist, scheint das Krippenangebot in der Schweiz kaum als effizientes Instrument sozialer Investitionen zu wirken.

Development of Non-Petroleum Based Binders for Use in Flexible Pavements, TR-594, 2010

Most bituminous adhesives or binders that are used for pavement materials are derived primarily from fossil fuels. With petroleum oil reserves becoming depleted and the drive to establish a bio-based economy, there is a push to produce binders from alternative sources, particularly from biorenewable resources. However, until now, no research has studied the applicability of utilizing bio-oils as a bitumen replacement (100% replacement) in the pavement industry. The main objective of this research was to test various properties of bio-oils in order to determine the applicability of using bio-oils as binders in the pavement industry. The overall conclusions about the applicability of using bio-oils as bio-binders in the pavement industry can be summarized as follows: 1. Bio-oils cannot be used as bio-binders/pavement materials without any heat pre-treatment/upgrading procedure. 2. Current testing standards and specifications, especially Superpave procedures, should be modified to comply with the properties of bio-binders. 3. The temperature range of the viscous behavior for bio-oils may be lower than that of bitumen binders by about 30°–40° C. 4. The rheological properties of the unmodified bio-binders vary in comparison to bitumen binders, but the rheological properties of these modified bio-binders change significantly upon adding polymer modifiers. 5. The high-temperature performance grade for the developed bio-binders may not vary significantly from that of the bitumen binders, but the low-temperature performance grade may vary significantly

Scale Effects in Hydraulic Model Tests of Rock Protected Structures, HR-119, 1970

A laboratory investigation was undertaken to determine the limiting model Reynolds number above which the scour behavior of rock protected structures can be reproduced in hydraulic models scaled according to the Froude criterion. A submerged jet was passed over an initially full scour pocket containing uniform glass spheres and the rate of scour was measured as a function of time. The dimensions of the scour pocket and jet and the particle diameters were varied as needed to maintain strict geometric similarity. For each of two different Froude numbers the Reynolds number was varied over a wide range. The normalized scour rate was found to be practically independent of the Reynolds number, R, (based on the jet velocity and particle diameter) at values of R above about 2.5 x 10^3, and to decrease with Rat smaller values. A grid placed in the jet was found to have a very strong effect on the scour rate. In an attempt to explain the effect of R on the scour behavior, turbulent pressure and velocity fluctuations were measured in air flows and water flows, respectively, over rigid scour pockets having the same geometry as those formed in the scour experiments. The normalized spectra of the fluctuations were found to be nearly independent of R, but the flow pattern was found to be very sensitive to the inlet condition, the jet deflecting upward or downward in a not wholly explainable manner. This indicates that scour behavior can be modeled only if the approach flow is also accurately modeled.

Investigation of Uplift Failures in Flexible Pipe Culverts, HR-306, 1990

This study was precipitated by several failures of flexible pipe culverts due to apparent inlet floatation. A survey of Iowa County Engineers revealed 31 culvert failures on pipes greater than 72" diameter in eight Iowa counties within the past five years. No special hydrologic, topography, and geotechnical environments appeared to be more susceptible to failure. However, most failures seemed to be on pipes flowing in inlet control. Geographically, most of the failures were in the southern and western sections of Iowa. The forces acting on a culvert pipe are quantified. A worst case scenario, where the pipe is completely plugged, is evaluated to determine the magnitude of forces that must be resisted by a tie down or headwall. Concrete headwalls or slope collars are recommended for most pipes over 4 feet in diameter.

Field Instrumentation, Testing, and Long-Term Monitoring of High-Mast Lighting Towers in the State of Iowa, TR-518, 2006

As a result of the collapse of a 140 foot high-mast lighting tower in Sioux City, Iowa in November of 2003, a thorough investigation into the behavior and design of these tall, yet relatively flexible structures was undertaken. Extensive work regarding the root cause of this failure was carried out by Robert Dexter of The University of Minnesota. Furthermore, a statewide inspection of all the high-mast towers in Iowa revealed fatigue cracks and loose anchor bolts on other existing structures. The current study was proposed to examine the static and dynamic behavior of a variety of towers in the State of Iowa utilizing field testing, specifically long-term monitoring and load testing. This report presents the results and conclusions from this project. The field work for this project was divided into two phases. Phase 1 of the project was conducted in October 2004 and focused on the dynamic properties of ten different towers in Clear Lake, Ames, and Des Moines, Iowa. Of those ten, two were also instrumented to obtain stress distributions at various details and were included in a 12 month long-term monitoring study. Phase 2 of this investigation was conducted in May of 2005, in Sioux City, Iowa, and focused on determining the static and dynamic behavior of a tower similar to the one that collapsed in November 2003. Identical tests were performed on a similar tower which was retrofitted with a more substantial replacement bottom section in order to assess the effect of the retrofit. A third tower with different details was dynamically load tested to determine its dynamic characteristics, similar to the Phase 1 testing. Based on the dynamic load tests, the modal frequencies of the towers fall within the same range. Also, the damping ratios are significantly lower in the higher modes than the values suggested in the AASHTO and CAN/CSA specifications. The comparatively higher damping ratios in the first mode may be due to aerodynamic damping. These low damping ratios in combination with poor fatigue details contribute to the accumulation of a large number of damage-causing cycles. As predicted, the stresses in the original Sioux City tower are much greater than the stresses in the retrofitted towers at Sioux City. Additionally, it was found that poor installation practices which often lead to loose anchor bolts and out-of-level leveling nuts can cause high localized stresses in the towers, which can accelerate fatigue damage.

Improved Methods for Determining Wind Loads on Highway Sign and Traffic-Signal Structures, TR-559, 2007

The main objective of the proposed study is to use Computational Fluid Dynamics (CFD) tools to determine the wind loads by accurate numerical simulations of air flow characteristics around large highway sign structures under severe wind speeds conditions. Fully three-dimensional Reynolds- Averaged Navier-Stokes (RANS) simulations are used to estimate the total force on different panels, as well as the actual pressure distribution on the front and back faces of the panels. In particular, the present study investigates the effects of aspect ratio and sign spacing for regular panels, the effect of sign depth for the dynamic message signs that are now being used on Iowa highways, the effect induced by the presence of back-to-back signs, the effect of the presence of add-on exit signs, and the effect of the presence of trucks underneath the signs potentially creating “wind tunnel” effect.

Reflective Crack Mitigation Guide for Flexible Pavements, TR-641, 2015

Reflective cracks form in pavements when hot-mix asphalt (HMA) overlays are placed over jointed and/or severely cracked rigid and flexible pavements. In the first part of the research, survival analysis was conducted to identify the most appropriate rehabilitation method for composite pavements and to evaluate the influence of different factors on reflective crack development. Four rehabilitation methods, including mill and fill, overlay, heater scarification (SCR), and rubblization, were analyzed using three performance indicators: reflective cracking, international roughness index (IRI), and pavement condition index (PCI). It was found that rubblization can significantly retard reflective cracking development compared to the other three methods. No significant difference for PCI was seen among the four rehabilitation methods. Heater scarification showed the lowest survival probability for both reflective cracking and IRI, while an overlay resulted in the poorest overall pavement condition based on PCI. In addition, traffic level was found not to be a significant factor for reflective cracking development. An increase in overlay thickness can significantly delay the propagation of reflective cracking for all four treatments. Soil types in rubblization pavement sites were assessed, and no close relationship was found between rubblized pavement performance and subgrade soil condition. In the second part of the research, the study objective was to evaluate the modulus and performance of four reflective cracking treatments: full rubblization, modified rubblization, crack and seat, and rock interlayer. A total of 16 pavement sites were tested by the surface wave method (SWM), and in the first four sites both falling weight deflectometer (FWD) and SWM were conducted for a preliminary analysis. The SWM gave close concrete layer moduli compared to the FWD moduli on a conventional composite pavement. However, the SWM provided higher moduli for the rubblized concrete layer. After the preliminary analysis, another 12 pavement sites were tested by the SWM. The results showed that the crack and seat method provided the highest moduli, followed by the modified rubblization method. The full rubblization and the rock interlayer methods gave similar, but lower, moduli. Pavement performance surveys were also conducted during the field study. In general, none of the pavement sites had rutting problems. The conventional composite pavement site had the largest amount of reflective cracking. A moderate amount of reflective cracking was observed for the two pavement sites with full rubblization. Pavements with the rock interlayer and modified rubblization treatments had much less reflective cracking. It is recommended that use of the modified rubblization and rock interlayer treatments for reflective cracking mitigation are best.

Development of Non-Petroleum-Based Binders for Use in Flexible Pavements – Phase II, TR-650, 2015

Bio-binders can be utilized as asphalt modifiers, extenders, and replacements for conventional asphalt in bituminous binders. From the rheology results of Phase I of this project, it was found that the bio-binders tested had good performance, similar to conventional asphalt, except at low temperatures. Phase II of this project addresses this shortcoming and evaluates the Superpave performance of laboratory mixes produced with the enhanced bio-binders. The main objective of this research was to develop a bio-binder capable of replacing conventional asphalt in flexible pavements by incorporating ground tire rubber (GTR) into bio-oil derived from fast pyrolysis of agriculture and forestry residues. The chemical compatibility of the new bio-binder with GTR was assessed, and the low-temperature performance of the bio-binders was enhanced by the use of GTR. The newly developed binder, which consisted of 80 percent conventional binder and 20 percent rubber-modified bio-oil (85 percent bio-oil with 15 percent GTR), was used to produce mixes at two different air void contents, 4 and 7 percent. The laboratory performance test results showed that the performance of the newly developed bio-binder mixes is as good as or better than conventional asphalt mixes for fatigue cracking, rutting resistance, moisture sensitivity, and low-temperature cracking. These results need to be validated in field projects in order to demonstrate adequate performance for this innovative and sustainable technology for flexible pavements.

Evaluation of the Need for Longitudinal Median Joints in Bridge Decks on Dual Structures, TR-661, 2015

The primary objective of this project was to determine the effect of bridge width on deck cracking in bridges. Other parameters, such as bridge skew, girder spacing and type, abutment type, pier type, and number of bridge spans, were also studied. To achieve the above objectives, one bridge was selected for live-load and long-term testing. The data obtained from both field tests were used to calibrate a three-dimensional (3D) finite element model (FEM). Three different types of loading—live loading, thermal loading, and shrinkage loading—were applied. The predicted crack pattern from the FEM was compared to the crack pattern from bridge inspection results. A parametric study was conducted using the calibrated FEM. The general conclusions/recommendations are as follows: -- Longitudinal and diagonal cracking in the deck near the abutment on an integral abutment bridge is due to the temperature differences between the abutment and the deck. Although not likely to induce cracking, shrinkage of the deck concrete may further exacerbate cracks developed from thermal effects. -- Based upon a limited review of bridges in the Iowa DOT inventory, it appears that, regardless of bridge width, longitudinal and diagonal cracks are prevalent in integral abutment bridges but not in bridges with stub abutments. -- The parametric study results show that bridge width and skew have minimal effect on the strain in the deck bridge resulting from restrained thermal expansion. -- Pier type, girder type, girder spacing, and number of spans also appear to have no influence on the level of restrained thermal expansion strain in the deck near the abutment.

Organisations paysannes, confréries islamiques et structures étatiques dans le processus de transformation au Sénégal: deux études de village au Sine-Saloum

EHESS/CNRS, Programme de recherches interdisciplinaires sur le monde musulman périphérique

Crystal structures of two closely related but antigenically distinct HLA-A2/melanocyte-melanoma tumor-antigen peptide complexes.

We have determined high-resolution crystal structures of the complexes of HLA-A2 molecules with two modified immunodominant peptides from the melanoma tumor-associated protein Melan-A/Melanoma Ag recognized by T cells-1. The two peptides, a decamer and nonamer with overlapping sequences (ELAGIGILTV and ALGIGILTV), are modified in the second residue to increase their affinity for HLA-A2. The modified decamer is more immunogenic than the natural peptide and a candidate for peptide-based melanoma immunotherapy. The crystal structures at 1.8 and 2.15 A resolution define the differences in binding modes of the modified peptides, including different clusters of water molecules that appear to stabilize the peptide-HLA interaction. The structures suggest both how the wild-type peptides would bind and how three categories of cytotoxic T lymphocytes with differing fine specificity might recognize the two peptides.