Human naive CD8 T cells down-regulate expression of the WNT pathway transcription factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell factor-1) following antigen encounter in vitro and in vivo

Abstract The transcription factors lymphoid enhancer binding factor 1 (LEF1) and transcription factor 7 (TCF7) (T cell factor-1 (TCF-1)) are downstream effectors of the WNT signaling pathway, which is a critical regulator of T cell development in the thymus. In this study, we show that LEF1 and TCF7 (TCF-1) are not only expressed in thymocytes, but also in mature T cells. Our data demonstrate that Ag encounter in vivo and engagement of the TCR or IL-15 receptor in vitro leads to the down-regulation of LEF1 and TCF7 (TCF-1) expression in human naive CD8 T cells. We further show that resting T cells preferentially express inhibitory LEF1 and TCF7 (TCF-1) isoforms and that T cell activation changes the isoform balance in favor of stimulatory TCF7 (TCF-1) isoforms. Altogether, our study suggests that proteins involved in the WNT signaling pathway not only regulate T cell development, but also peripheral T cell differentiation.</jats:p

Nondestructive Evaluation of Rigid Pavements Using Road Rater Deflections [1986]

Dynamic deflections have been used to determine in-place structural conditions of rigid pavements, based on modifications of principles and experience with the structural evaluation of flexible pavements. Details of the use of elastic layer theory to simulate deflection measurements associated with loadings for the Kentucky Road Rater are presented. Included is an illustration of the use of field deflection measurements to back calculate in-place moduli. The procedures are generally iterative and involve matching measured deflections with theoretical deflections. Elastic layer principles have been used to simulate deflections only at the mid slab position. Relationships regarding deflections at other locations on the slab currently involve empirical analyses. Evaluations involving the effects of pavement temperature, time of day, season, etc. are still empirical. In summary, major aspects of this report will be twofold. One will be related to procedures and principles applied to the use of deflections and layer elastic theory to estimate effective parameters representative of existing in-place pavement conditions. The second will be related to the application of deflection measurements and evaluation methodologies to determine appropriate recommendations of rehabilitation strategies and scheduling for rigid pavements

Nondestructive Evaluation of Rigid Pavements Using Road Rater Deflections [1984]

Road Rater deflections have been used to determine in-place structural conditions of rigid and composite pavements, based on modifications of principles and experience with the structural evaluation of flexible pavements. Details of the use of elastic layer theory to simulate deflection measurements associated with loadings for the Kentucky Road Rater are presented. Included is an illustration of the use of field deflection measurements to back calculate\u27 in-place moduli. The procedures are generally iterative and involve matching measured deflections with theoretical deflections. Elastic layer principles have been used to simulate deflections only at the midslab position. Relationships regarding deflections at other locations on the slab currently involve empirical analyses. Evaluations involving the effects of pavement temperature, time of day, season, etc. are still empirical. In summary, major aspects of this paper will be twofold. One will be related to procedures and principles applied to the use of deflections and layer elastic theory to estimate effective parameters representative of existing in-place pavement conditions. The second will be related to the application of deflection measurements and evaluation methodologies to determine appropriate recommendations of rehabilitation strategies and scheduling for rigid pavements

Pavement Thickness Designs Utilizing Low-Strength (Pozzolanic) Base and Subbase Materials

This paper presents information whereby laboratory test data for pozzolanic base and subbase materials may be combined with elastic layer theory and a limiting strain criterion to determine thickness designs equivalent to conventional asphaltic concrete and crushed stone pavement structures. A summary of laboratory testing in Kentucky also is presented. An example thickness design determination is presented and includes an economic comparison of alternative designs with the conventional asphaltic – crushed stone thickness design

Evaluation of Full-Depth Asphaltic Concrete Pavements

This study was initiated to verify a newly-developed set of design curves for full-depth asphaltic concrete pavements. Quality control during construction was checked using nuclear density testers, Benkelman beams, and a Road Rater. During the course of this study, an analysis system was developed to interpret the dynamic deflections as measured by the Road Rater and was confirmed by elastic theory. The thickness design curves were verified within the accuracy of construction variations. Rut depths measured in 1979 were analyzed in terms of potential rut depth resulting from consolidation under traffic due to lack of obtaining 100-percent of Marshall density during compaction immediately after paving. Potential rutting was calculated as the decimal equivalent of the quantity of 100 percent minus percent compaction times the layer thickness and the results accumulated from the surface downward. Advances in technology under this study have led to greater advances under succeeding studies. Traffic was monitored using automatic traffic counters, manual classification/volume counts, and weigh-in-motion scales installed in the pavement

Aspidoscelis laredoensis and A. gularis hybridization.

13 pages : illustrations (some color) ; 26 cm.Karyotypes and allozyme data for 32 genetic loci overwhelmingly support the conclusion that Aspidoscelis laredoensis is a diploid all-female species that had a hybrid origin between A. gularis x A. sexlineatus. Comparisons of allozymes in individuals representing three mother-to-daughter generations raised in the laboratory suggest that they reproduce by parthenogenetic cloning. In addition to two previously described morphotypes (pattern classes A and B) that occur in southern Texas, we report the existence of three all-female clonal lineages based on allozymes. Individuals of at least one of these lineages occasionally hybridize in nature with males of A. gularis, producing viable and healthy triploid offspring that can grow to adulthood, one of which herself produced an offspring in the laboratory and could have represented a new, clonal triploid species. The possibility exists that cloned offspring of triploid hybrids are present in South Texas and/or northern Mexico, awaiting discovery. These would represent a new species that would appear to be very similar to A. laredoensis

Laboratory Evaluations of Stabilized Flue Gas Desulfurization Sludge (Scrubber Sludge) and Aggregate Mixtures

The Kentucky Transportation Research Program has completed a laboratory study involving the use of flue gas desulfurization sludge (scrubber sludge) for potential application as a highway subbase and/or embankment material. Scrubber sludge is a waste produet formed when fly ash (and other residue) is combined with a lime dust slurry filter cake and stabilized with quicklime (calcium oxide). Samples of stockpiled (field) sludge and dry sludge components were obtained from the Robert Reid Station (Big Rivers Electric Corporation) in Sebree, Kentuclty. Dry sludge components (fly ash, filter cake, and quicklime) were uaed to prepare sludge samples in the laboratory, allowing a higher degree of quality control for compariaon purposes. Mixtures for testing included scrubber sludge, scrubber sludge with pond ash (bottom ash), and scrubber sludge with dense graded limestone aggregate (DGA). One objective of laboratory analyses was the determination of optimum mixture proportions. A mixture of 20-percent scrubber sludge and 80-percent pond ash was determined to be the optimum design mix. That mixture showed significant strength gain with curing and had a static-chord modulus of elasticity approximately 118 times the compressive strength. Strength and modulus tests indicated that mixtures of scrubber sludge and pond ash were superior to mixtures of scrubber sludge and DGA. The scope of the study, however, did not permit complete explanation of these observations. An economic study showed that scrubber sludge with pond ash can be used economically as a highway subbase material, especially on low-fatigue roads, by partially replacing more expensive pavement layers. Triaxial tests and computer simulations indicated that scrubber sludge could be used as an embankment material in some applications. However, this would be economical only if suitable fill material was not available at or near the fill site

Global Emergency Medicine: A Review of the Literature From 2012

Objectives The Global Emergency Medicine Literature Review ( GEMLR ) conducts an annual search of peer‐reviewed and grey literature relevant to global emergency medicine ( EM ) to identify, review, and disseminate the most important new research in this field to a worldwide audience of academics and clinical practitioners. Methods This year, our search identified 4,818 articles written in six languages. These articles were distributed among 20 reviewers for initial screening based on their relevance to the field of global EM . Two additional reviewers searched and screened the grey literature. A total of 224 articles were deemed appropriate by at least one reviewer and were approved by their editor for formal scoring of overall quality and importance. Results Of the 224 articles that met our predetermined inclusion criteria, 56% were categorized as Emergency Care in Resource‐limited Settings, 18% as EM development, and 26% as Disaster and Humanitarian Response. A total of 28 articles received scores of 16 or higher and were selected for formal summary and critique. Inter‐rater reliability for two reviewers using our scoring system was good, with an intraclass correlation coefficient of 0.625 (95% confidence interval = 0.512 to 0.711). Conclusions In 2012 there were more disaster and humanitarian response articles than in previous years. As in prior years, the majority of articles addressed the acute management of infectious diseases or the care of vulnerable populations such as children and pregnant women. Resumen Medicina de Urgencias y Emergencias Global: Una Revisión de la Literatura de 2012 Objetivos La revisión de la literatura publicada en Medicina de Urgencias y Emergencias ( MUE ) global comporta una búsqueda anual de los trabajos relevantes para la MUE global, tanto publicados tras revisión por pares como corresponedientes a literatura gris. La finalidad es identificar, revisar y diseminar las investigaciones novedosas más importantes en este campoa médicos clínicos y universitarios de todo el mundo. Metodología Este año, nuestra búsqueda identificó 4.818 artículos escritos en seis lenguas. Estos artículos se distribuyeron entre 20 revisores para el despistaje inicial basándose en su relevancia para el campo de la MUE global. Dos revisores adicionales buscaron y filtraron la literatura gris. Un total de 224 artículos se consideraron apropiados por al menos un revisor, y se aprobaron por su editor para la puntuación formal de la calidad e importancia totales. Resultados De los 224 artículos que cumplieron nuestros criterios de inclusión predeterminados, un 56% se clasificaron como atención de urgencias y emergencias en ámbitos de recursos limitados, un 18% como desarrollo de la MUE y un 26% como catástrofes y respuesta humanitaria. Un total de 28 artículos recibieron una puntuación de 16 o más y se seleccionaron para el resumen y la crítica formal. La fiabilidad interobservador para los 2 revisores usando nuestro sistema de puntuación fue buena, con un coeficiente de correlación intraclase de 0,625 ( IC 95% = 0,512 a 0,711). Conclusiones En 2012 hubo más artículos sobre catástrofes y respuesta humanitaria que en años anteriores. Como en los años previos, la mayoría de los artículos valoraron el manejo agudo de enfermedades infecciosas o la atención de poblaciones vulnerables como los niños y las mujeres embarazadas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99685/1/acem12173.pd

CpG oligodeoxyribonucleotides protect mice from Burkholderia pseudomallei but not Francisella tularensis Schu S4 aerosols

Studies have shown that CpG oligodeoxyribonucleotides (ODN) protect mice from various bacterial pathogens, including Burkholderia pseudomallei and Francisella tularensis live vaccine strain (LVS), when administered before parenteral challenge. Given the potential to develop CpG ODN as a pre-treatment for multiple bacterial biological warfare agents, we examined survival, histopathology, and cytokine data from CpG ODN-treated C57BL/6 mice to determine whether previously-reported protection extended to aerosolized B. pseudomallei 1026b and highly virulent F. tularensis Schu S4 infections. We found that, although CpG ODN protected mice from aerosolized B. pseudomallei challenges, the immunostimulant failed to benefit the animals exposed to F. tularensis Schu S4 aerosols. Our results, which contrast with earlier F. tularensis LVS studies, highlight potential differences in Francisella species pathogenesis and underscore the need to evaluate immunotherapies against human pathogenic species

E. coli O157 on Scottish cattle farms: evidence of local spread and persistence using repeat cross-sectional data

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Escherichia coli (E. coli) O157 is a virulent zoonotic strain of enterohaemorrhagic E. coli. In Scotland (1998-2008) the annual reported rate of human infection is 4.4 per 100,000 population which is consistently higher than other regions of the UK and abroad. Cattle are the primary reservoir. Thus understanding infection dynamics in cattle is paramount to reducing human infections.&lt;p&gt;&lt;/p&gt; A large database was created for farms sampled in two cross-sectional surveys carried out in Scotland (1998 - 2004). A statistical model was generated to identify risk factors for the presence of E. coli O157 on farms. Specific hypotheses were tested regarding the presence of E. coli O157 on local farms and the farms previous status. Pulsed-field gel electrophoresis (PFGE) profiles were further examined to ascertain whether local spread or persistence of strains could be inferred.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The presence of an E. coli O157 positive local farm (average distance: 5.96km) in the Highlands, North East and South West, farm size and the number of cattle moved onto the farm 8 weeks prior to sampling were significant risk factors for the presence of E. coli O157 on farms. Previous status of a farm was not a significant predictor of current status (p = 0.398). Farms within the same sampling cluster were significantly more likely to be the same PFGE type (p &#60; 0.001), implicating spread of strains between local farms. Isolates with identical PFGE types were observed to persist across the two surveys, including 3 that were identified on the same farm, suggesting an environmental reservoir. PFGE types that were persistent were more likely to have been observed in human clinical infections in Scotland (p &#60; 0.001) from the same time frame.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The results of this study demonstrate the spread of E. coli O157 between local farms and highlight the potential link between persistent cattle strains and human clinical infections in Scotland. This novel insight into the epidemiology of Scottish E. coli O157 paves the way for future research into the mechanisms of transmission which should help with the design of control measures to reduce E. coli O157 from livestock-related sources