Persistent enteric murine norovirus infection is associated with functionally suboptimal virus-specific CD8 T cell responses

Norovirus (NV) gastroenteritis is a major contributor to global morbidity and mortality, yet little is known about immune mechanisms leading to NV control. Previous studies using the murine norovirus (MNV) model have established a key role for T cells in MNV clearance. Despite these advances, important questions remain regarding the magnitude, location, and dynamics of the MNV-specific T cell response. To address these questions, we identified MNV-specific major histocompatibility complex (MHC) class I immunodominant epitopes using an overlapping peptide screen. One of these epitopes (amino acids 519 to 527 of open reading frame 2 [ORF2(519-527)]) was highly conserved among all NV genogroups. Using MHC class I peptide tetramers, we tracked MNV-specific CD8 T cells in lymphoid and mucosal sites during infection with two MNV strains with distinct biological behaviors, the acutely cleared strain CW3 and the persistent strain CR6. Here, we show that enteric MNV infection elicited robust T cell responses primarily in the intestinal mucosa and that MNV-specific CD8 T cells dynamically regulated the expression of surface molecules associated with activation, differentiation, and homing. Furthermore, compared to MNV-CW3 infection, chronic infection with MNV-CR6 resulted in fewer and less-functional CD8 T cells, and this difference was evident as early as day 8 postinfection. Finally, MNV-specific CD8 T cells were capable of reducing the viral load in persistently infected Rag1(−/−) mice, suggesting that these cells are a crucial component of NV immunity. Collectively, these data provide fundamental new insights into the adaptive immune response to two closely related NV strains with distinct biological behaviors and bring us closer to understanding the correlates of protective antiviral immunity in the intestine

On the character degree graph of finite groups

Given a finite group G, let cd (G) denote the set of degrees of the irreducible complex characters of G. The character degree graph of G is defined as the simple undirected graph whose vertices are the prime divisors of the numbers in cd (G) , two distinct vertices p and q being adjacent if and only if pq divides some number in cd (G). In this paper, we consider the complement of the character degree graph, and we characterize the finite groups for which this complement graph is not bipartite. This extends the analysis of Akhlaghi et al. (Proc Am Math Soc 146:1505\u20131513, 2018), where the solvable case was treated

Diagnostic accuracy of the primary care screener for affective disorder (PC-SAD) in primary care

Background: Depression goes often unrecognised and untreated in non-psychiatric medical settings. Screening has recently gained acceptance as a first step towards improving depression recognition and management. The Primary Care Screener for Affective Disorders (PC-SAD) is a self-administered questionnaire to screen for Major Depressive Disorder (MDD) and Dysthymic Disorder (Dys) which has a sophisticated scoring algorithm that confers several advantages. This study tested its performance against a ‘gold standard’ diagnostic interview in primary care. Methods: A total of 416 adults attending 13 urban general internal medicine primary care practices completed the PC-SAD. Of 409 who returned a valid PC-SAD, all those scoring positive (N=151) and a random sample (N=106) of those scoring negative were selected for a 3-month telephone follow-up assessment including the administration of the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I) by a psychiatrist who was masked to PC-SAD results. Results: Most selected patients (N=212) took part in the follow-up assessment. After adjustment for partial verification bias the sensitivity, specificity, positive and negative predictive value for MDD were 90%, 83%, 51%, and 98%. For Dys, the corresponding figures were 78%, 79%, 8%, and 88%. Conclusions: While some study limitations suggest caution in interpreting our results, this study corroborated the diagnostic validity of the PC-SAD, although the low PPV may limit its usefulness with regard to Dys. Given its good psychometric properties and the short average administration time, the PC-SAD might be the screening instrument of choice in settings where the technology for computer automated scoring is available

Кинетика восстановления железа при восстановительной плавке рудоугольных окатышей

Исследовано влияние интенсивности теплообмена на кинетику восстановления железа в процессе плавки рудоугольных окатышей. Показано, что с ростом интенсивности теплообмена повышается скорость восстановительных процессов. Вследствие роста коэффициента теплообмена увеличивается глубина восстановленного слоя окатыша, существенно изменяются его структура и химический состав образующейся металлической фазы.Досліджено вплив інтенсивності теплообміну на кінетику відновлення заліза в процесі плавки рудовугільних окатишів. Показано, що при зростанні інтенсивності теплообміну підвищується швидкість відновлювальних процесів. Внаслідок зростання коефіцієнту теплообміну збільшується глибина відновленого шару окатиша, суттєво змінюються його структура та хімічний склад металевої фази, що утворюється.Influence of intensity of heat exchange is investigational on kinetics reduction of iron in the process of melting ore-coal pellets. It is rotined that speed of reduction processes rises with growth of intensity of heat exchange. Because of growth of coefficient of heat exchange the depth of the recovered layer of pellet is increased, his structure and chemical composition of appearing metallic phase changes substantially

SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation

Salmonella enterica is a prominent bacterial pathogen with implications on human and animal health. Salmonella serovars could be classified as gastro-intestinal or extra-intestinal. Genome-wide comparisons revealed that extra-intestinal strains are closer relatives of gastro-intestinal strains than to each other indicating a parallel evolution of this trait. Given the complexity of the differences, a systems-level comparison could reveal key mechanisms enabling extra-intestinal serovars to cause systemic infections. Accordingly, in this work, we introduce a unique resource, SalmoNet, which combines manual curation, high-throughput data and computational predictions to provide an integrated network for Salmonella at the metabolic, transcriptional regulatory and protein-protein interaction levels. SalmoNet provides the networks separately for five gastro-intestinal and five extra-intestinal strains. As a multi-layered, multi-strain database containing experimental data, SalmoNet is the first dedicated network resource for Salmonella. It comprehensively contains interactions between proteins encoded in Salmonella pathogenicity islands, as well as regulatory mechanisms of metabolic processes with the option to zoom-in and analyze the interactions at specific loci in more detail. Application of SalmoNet is not limited to strain comparisons as it also provides a Salmonella resource for biochemical network modeling, host-pathogen interaction studies, drug discovery, experimental validation of novel interactions, uncovering new pathological mechanisms from emergent properties and epidemiological studies. SalmoNet is available at http://salmonet.org

The effector T cell response to influenza infection

Influenza virus infection induces a potent initial innate immune response, which serves to limit the extent of viral replication and virus spread. However, efficient (and eventual) viral clearance within the respiratory tract requires the subsequent activation, rapid proliferation, recruitment, and expression of effector activities by the adaptive immune system, consisting of antibody producing B cells and influenza-specific T lymphocytes with diverse functions. The ensuing effector activities of these T lymphocytes ultimately determine (along with antibodies) the capacity of the host to eliminate the viruses and the extent of tissue damage. In this review, we describe this effector T cell response to influenza virus infection. Based on information largely obtained in experimental settings (i.e., murine models), we will illustrate the factors regulating the induction of adaptive immune T cell responses to influenza, the effector activities displayed by these activated T cells, the mechanisms underlying the expression of these effector mechanisms, and the control of the activation/differentiation of these T cells, in situ, in the infected lungs

Essays in macroeconomics

Esta tesis consta de tres capítulos, cada uno de los cuales analiza temas relevantes en el campo de la Macroeconomía. La investigación realizada en los tres capítulos se basa en la metodología de los modelos dinámicos de equilibrio general. Los fundamentos microeconómicos se encuentran en el núcleo de este tipo de modelos, en los que los agentes forman sus expectativas sobre el futuro de manera racional. Esta metodología ha demostrado ser una herramienta poderosa para abordar un gran conjunto de problemas económicos. El primer capítulo, ``Risk Aversion, Entrepreneurship and Wealth Distribution'', explora el efecto de la heterogeneidad en la aversión al riesgo sobre el emprendimiento, el comportamiento del ahorro y la distribución de la riqueza. La distribución de la riqueza es uno de los temas más debatidos no solo en la política contemporánea, sino también en los medios de comunicación y en ámbitos académicos. En particular, la gran concentración de riqueza en la parte superior de la distribución, que se observa en muchas economías avanzadas, se ha situado en el centro del debate. La relevancia de este problema no se ha visto socavada a pesar de la dificultad que supone estimar los niveles de riqueza acumulada en manos de los hogares más ricos. Apoyado por razones empíricas, el marco teórico para analizar la distribución de la riqueza debe incluir tanto el emprendimiento como la heterogeneidad de las preferencias. Con este objetivo, en el primer capítulo se desarrolla un modelo de elección ocupacional con agentes heterogéneos en el que los hogares varían en su aversión al riesgo, se enfrentan a perturbaciones idiosincrásicas no asegurables, tienen restricciones financieras y deben decidir si convertirse en trabajadores o en emprendedores. Esta decisión se basa en una combinación de la aversión al riesgo individual, las habilidades específicas en cada ocupación y los niveles de riqueza acumulados. Como resultado se obtiene que la aversión al riesgo tiene un efecto directo e indirecto en la decisión de ahorro y en la ocupación de los agentes. Por un lado, una mayor aversión al riesgo disuade a los agentes de convertirse en emprendedores y, por lo tanto, los ahorros destinados a superar las restricciones financieras son menores. Por otro lado, una mayor aversión al riesgo también conduce a un mayor ahorro por motivo de precaución que, indirectamente, atenúa las restricciones financieras y hace que la opción de convertirse en emprendedor sea más atractiva. En el modelo desarrollado, el último efecto domina, y los agentes con mayor aversión al riesgo acumulan mayores niveles de riqueza y también se convierten en emprendedores. La contribución más importante de este modelo es que permite desentrañar los efectos que la aversión al riesgo y las fricciones financieras tienen sobre el emprendimiento, que es un factor clave para explicar la desigualdad en la acumulación de la riqueza. El segundo capítulo se titula ``Long-term business relationships, bargaining and monetary policy'' y es un trabajo conjunto con Mirko Abbritti y Tommaso Trani. Su motivación se deriva de la creciente literatura empírica que documenta la importancia de las relaciones comerciales a largo plazo y los procesos de negociación sobre la rigidez de los precios y las dinámicas empresariales. Este artículo introduce relaciones comerciales entre empresas (B2B) a largo plazo y procesos de negociación de precios en un modelo monetario de equilibrio general dinámico estocástico (DSGE) estándar. El modelo se basa en dos suposiciones. Primero, tanto los productores mayoristas como los minoristas necesitan gastar recursos para formar nuevas relaciones comerciales. Segundo, una vez que se forma una relación comercial, el precio se establece en una negociación bilateral entre las empresas. El modelo proporciona un marco riguroso para estudiar el efecto de las relaciones comerciales a largo plazo y los procesos de negociación sobre la política monetaria y la dinámica del ciclo económico. Además, se demuestra que estas relaciones comerciales reducen tanto el papel de asignación de los precios intermedios como los efectos reales de las perturbaciones de la política monetaria. También encontramos que el modelo hace un gran trabajo al replicar los segundos momentos y las correlaciones cruzadas de los datos, y que mejora con respecto al modelo de referencia Neo Keynesiano en explicar dichos estadísticos. El tercer y último capítulo de esta tesis, ``On Staggered Prices and Optimal Inflation'', es coautoreado con uno de mis directores, Miguel Casares. En este artículo se calcula la tasa de inflación óptima en estado estacionario bajo dos especificaciones de rigidez de precios diferentes, Calvo (1983) y Taylor (1980), en un modelo con competencia monopolística. Encontramos que la tasa óptima de inflación en estado estacionario es siempre positiva. Este resultado es robusto a los cambios en el grado de rigidez de los precios. En ambos casos con rigidez de precios, la tasa de inflación óptima es aproximadamente igual al cociente entre la tasa de descuento y la elasticidad de Dixit-Stiglitz. Para calibraciones estándar, el coste de bienestar de la inflación es cuantitativamente pequeño, pero significativamente más alto si los precios son rígidos a la Calvo que si son rígidos a la Taylor.Fundación Banco Sabadell, Fundación Bancaria Caja Navarra y Universidad Pública de NavarraPrograma de Doctorado en Economía, Empresa y Derecho (RD 99/2011)Ekonomiako, Enpresako eta Zuzenbideko Doktoretza Programa (ED 99/2011

Measuring the nonlinear refractive index of graphene using the optical Kerr effect method

© 2016 Optical Society of America.By means of the ultrafast optical Kerr effect method coupled to optical heterodyne detection (OHD-OKE), we characterize the third-order nonlinear response of graphene and compare it to experimental values obtained by the Z-scan method on the same samples. From these measurements, we estimate a negative nonlinear refractive index for monolayer graphene, n2 = -1.1 × 10-13 m2/W. This is in contradiction to previously reported values, which leads us to compare our experimental measurements obtained by the OHD-OKE and the Z-scan method with theoretical and experimental values found in the literature and to discuss the discrepancies, taking into account parameters such as doping

Fibrotic remodeling of colonic tunica muscularis is associated with vascular network activation in ulcerative colitis

Intestinal fibrosis in inflammatory bowel disease is a dynamic, multifactorial process, which involve multiple cell types and interconnected events [1]. Angiogenesis is a hallmark of active gut disease and closely related to fibrogenetic processes. Endothelial cells and pericytes of neovessels have been found to be able to differentiate into fibroblasts and can be considered good candidates for fibrogenesis also in the intestinal tract [2]. This study was aimed to study whether the fibrotic processes occurring within the tunica muscularis of UC patients are associated with vascular remodeling. Full-thickness left colonic samples were obtained from patients with established, severe and pharmacologically unresponsive UC, who underwent bowel resection. Routine histology, histochemistry and immunohistochemistry were conducted in paraffin cross-sections. Collagen and elastic fiber distribution was evaluated within the tunica muscularis by both histochemical and immunohistochemical assays. The vascular network pattern was analyzed by revealing the expression of CD31, CD105 and nestin by immunofluorescence applied to laser confocal microscopy. A significant increase in collagen fibers and a decrease in elastin content were detected in the tonaca muscularis of UC inflamed colon, as compared with controls. In particular, enhanced collagen deposition were found at level of the longitudinal muscle and circular muscle layer, and in perivascular spaces. By contrast, elastic fiber pattern was significantly decreased throughout the whole muscle compartment. Increased blood vessel density was observed in the colonic tunica muscularis of UC samples compared with samples from healthy control individuals. In particular, the neovessels of inflamed colon showed the activation of both endothelial cells and pericytes, which overexpressed CD105 and nestin, respectively. A significant vascular remodelling (i.e., angiogenesis, endothelial proliferation and pericyte activation) has been observed in the fibrotic tunica muscularis of colon from UC patients. On the basis of the present findings, it is possible to argue that cells of newly formed vessels within the tunica muscularis may contribute to the UC-associated fibrosis by cell transition to mesenchymal phenotype