The influence of type II cytokines in central tolerance

While the genetic elements of many autoimmune conditions have been established, many environmental factors remain a mystery. Exposure to certain infections has been implicated as a possible explanation for the significantly different autoimmune disease rates in developing versus industrialized countries. In this manner, type II cytokines have been shown to play a role in peripheral tolerance. The full impact of these type II cytokines in central tolerance and autoimmunity has still yet to be explored. In chapter II, the data indicate that IL-4 and IL-13, dominant type II cytokines, can indeed be found within the thymic microenvironment of healthy C57BL/6 mice. IL-4/IL-13 signaling in ETPs that express the IL-4Rα/IL-13Rα1 heteroreceptor (HR) drives these progenitors to yield thymic resident DCs. These DCs aid in negative selection and the prevention of experimental allergic encephalomyelitis (EAE). In chapter III, the data presented shows that, in contrast to the C57BL/6 strain, HR+ETPs from the type one diabetes (T1D) susceptible NOD strain give rise to T cells. Notably, the NOD thymus shows a dramatic reduction in the steady-state level of IL-4. Indeed, increasing the availability of this cytokine can rescue the lineage fate of HR+ETPs and provide a new pool of thymic DCs. Restoration of NOD HR+ETP lineage fate can improve negative selection, alter the TCRβ repertoire, and ultimately prevent T1D onset. Thus, microenviromental changes within the thymus may be implicated in fine-tuning the balance that dictates the negative selection of autoreactive cells. From this, one may envision that environmental induction of IL-4 and IL-13 may play a role in altering that balance and shifting the tables towards autoimmunity prevention.Includes bibliographical reference

Type II cytokines direct choices of early thymic progenitor lineage and influence negative selection of myelin-reactive T cells

Autoimmune diseases have been known for having a strong genetic component; however, there is growing indication that shows the environment also plays an important role. One way in which the environment plays a role is though influencing central tolerance via fine tuning of the thymic microenvironment. It has been shown that early thymic progenitors (ETPs) that express the heteroreceptor (HR), which are comprised of both IL-13R[alpha]1 and IL- 4R[alpha] chain, are directed toward the myeloid lineage and serve as antigen presenting cells (APCs). Due to the role of APCs in T cell negative selection, this research looks to investigate whether type II cytokines can determine ETP lineage choice and subsequently alter negative T cell selection. --Introduction.Funding: NIH grant, RO1 NS057194.Hannah Gavin (Undergraduate Student, University of Missouri School of Medicine at Columbia), Alexis Cattin-Roy (Molecular Microbiology and Immunology Department, University of Missouri Hospital, MO, 65201), Habib Zaghouani (Molecular Microbiology and Immunology Department, University of Missouri Hospital)

La société civile dans le débat politique au Mali

Cet article expose les problèmes relatifs à la définition du concept de « société civile » et sa transposition dans un contexte non occidental, au Mali. Le questionnement porte alors sur la place qu’occupe la « société civile » dans les discours des institutions internationales et dans leurs projets relatifs aux pays en cours de démocratisation. Nous verrons aussi la façon dont les hommes politiques maliens tentent d’intégrer la « vogue » du concept de société civile. Au-delà de ces discours, nous présenterons quelques pistes de travail qui soulignent les difficultés rencontrées dans la recherche d’une société civile autochtone. Nous verrons qu’une fois de plus le clientélisme, communautaire ou non, empêche la nette séparation entre le pouvoir, la chose publique et la sphère privée, pourtant nécessaire à l’émergence d’une société civile.“Civil Society” in Malian Political Debate. — Problems in defining “civil society” and transposing this concept to a non-Western context (Mali) are examined. What place does “civil society” have in the discourses of international institutions and their plans for countries undergoing democratization? Light is shed on the ways that Malian politicians try to adopt this voguish concept. Beyond the talk, attention is drawn to the difficulties encountered in the quest to find a “native civil society”. Once again, patronage, whether community-based or not, makes it impossible to clearly separate power, public goods and the private sphere—a separation necessary for “civil society” to emerge

Moseley, William G. & Gray, Leslie C. (eds.). – Hanging by a Thread

Cet ouvrage collectif composé de dix articles tente d’offrir un état des lieux des enjeux autour de la culture du coton en Afrique, à partir d’exemples répartis sur tout le continent. À travers ses différents contributeurs, le livre propose plusieurs approches qui empruntent à l’économie, l’anthropologie, l’agro-écologie ou encore à la géographie. « Hanging by a thread » (« tenu par un fil ») présente bien dans toute leur complexité les filières cotonnières africaines, tentant de ne négliger ..

Characterization of the Spatiotemporal Network in Prefrontal Cortex-Hippocampal Synchronization: The Role of the Thalamic Nucleus Reuniens and Delta Band 2-5 Hz Oscillations

Background: Schizophrenia is a devastating mental health illness in which our pharmacologic options do not treat the cognitive deficits that largely contribute to long-term disability. Problems with cognition likely arise from dysfunctional neural networks in which spatially distinct brain regions are unable to temporally coordinate electrical activity accurately. More specifically, the hippocampus (HC) normally achieves long-range, temporal coordination through generation of theta (4-8 Hz) oscillations by which the prefrontal cortex (PFC) can synchronize its activity. This synchronization occurs through direct HC-to-PFC monosynaptic projections, and disruptions in this pathway can replicate key features of schizophrenia. Although prior research has concentrated heavily on HC-to-PFC theta oscillatory synchronization, the neural network by which PFC exerts “top-down” influence back to HC is largely unknown for at least two reasons. For one, unlike direct HC-to-PFC projections, PFC-to-HC projections are indirect, mainly occurring through a synapse in the thalamic nucleus reunions (nRe). Secondly, the oscillatory band utilized by PFC to synchronize HC activity is largely unknown, although limited evidence suggests a 2-5 Hz oscillation as a potential candidate. The overall aim of this thesis was to characterize the circuitry by which PFC coordinates HC activity. We hypothesized PFC-to-HC synchronization occurs through a 2-5 Hz oscillation that is mediated through nRe. Methods: Local field potentials (LFPs) were recorded in PFC, HC, and nRe in normal rats (n= 15) under urethane anesthesia. The nucleus reticularis pontis oralis (RPO) was stimulated at five intensity levels to induce theta oscillations in HC. LFPs during RPO stimulation were extracted and underwent fast Fourier transform. Linear regression analysis (Pearson’s correlation coefficient, r) was performed to analyze the relationship between peak oscillatory frequency and power spectrum density in PFC and HC as a function of RPO stimulus intensity. Peak frequencies for theta and 2-5 Hz were identified in HC and PFC spectra, respectively, and spectral power at these frequencies were identified for each signal. Pairwise correlations were calculated between power spectrum density in PFC, HC, and nRe within the 2-5 Hz and theta bands to assess synchronization. Partial correlational analysis was performed between HC-PFC to statically remove the influence of nRe signal to characterize its role in PFC-HC synchronization. In the second set of experiments, LFPs were recorded in PFC and HC during local lidocaine in vivo inactivation of nRe (n=4 rats). Coherence between HC-PFC was calculated before and after lidocaine injections to assess influence of nRe. Results: As previously described, theta oscillations were the prominent signal in HC during RPO stimulation. In comparison, a narrow-band oscillation within the 2-5 Hz range (distinct from wide-band delta) dominated PFC signals at low RPO stimulus intensities. Oscillatory frequency increased linearly with RPO stimulus intensity for theta (r = 0.64, p<0.001) and 2-5 Hz (r =0.37, p<0.01) frequency bands. However, these two oscillations followed an opposite trend with respect to power density: theta power increased (r = 0.63, p <0.001), whereas 2-5 Hz power decreased (r = -0.60, p<0.001) with RPO stimulus intensity, suggesting a negative coupling between the two signals. PFC-HC signals were significantly correlated for both theta and 2-5 Hz oscillations in 7 out of the 15 rats (47%). For this subgroup, PFC-HC partial correlation, controlling for nRe signal, eliminated residual PFC-HC correlations for the 2-5 Hz oscillation (correlation r=0.81, partial correlation r=0.13, p<0.001), but had no significant effect on HC-PFC correlations for theta oscillation (correlation r=0.65, partial correlation r=0.61, p=0.53). PFC-HC coherence of 2-5 Hz oscillation significantly decreased after lidocaine injection (coherence pre-lidocaine 0.73, post-lidocaine 0.34, p<0.01), but had little effect on coherence for theta oscillation (coherence pre-lidocaine =0.52, post-lidocaine =0.48, p=0.19). Discussion: Our results support that HC-PFC synchronization occurs not only by previously reported HC theta rhythm, but also by a second narrow-band oscillation in the 2-5 Hz range that dominates PFC activity. Importantly, removal of nRe influence, either statistically (using partial correlation) or experimentally (by in vivo lidocaine inactivation) significantly reduces PFC-HC coupling within the 2-5 Hz band, but has minimal effect on HC-PFC theta coupling, suggesting that nRe mediates PFC-HC 2-5 Hz but not theta oscillatory synchronization. In summary, this thesis proposes a novel thalamo-cortical (nRe-PFC) network by which PFC-HC synchronization occurs through a 2-5 Hz oscillation that is mediated through nRe. In contrast, reciprocal HC-to-PFC synchronization occurs through the theta band via a direct, monosynaptic projection. This network is likely dynamic by which the strength of PFC-HC coupling between theta and 2-5 Hz oscillatory bands vary depending on RPO stimulation intensity level. In the future, continued elucidation of this neural network will likely offer a deeper understanding of the cognitive dysfunction in schizophrenia, and thus the potential for improved treatment options

Representing place and situation in an online social environment

Thesis (S.M.)--Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2000.Includes bibliographical references (leaves 61-66).This thesis presents work focused on the creation of a sociable space for communication online. Sociable communication requires the ability to converse with others using simple and meaningful mechanisms, supporting flexibility and expressiveness. Equally important is the ability for people to read the space they inhabit and make sense of it in socially significant ways, such as people watching to observe others' interests and interaction styles. A third key to sociable communication is emphasis on identity and embodiment, giving participants a strong sense of themselves and others through their online representations. These issues are approached through research in areas ranging from sociology to urban architecture, directed at finding bases for the design of capabilities that are useful and engaging in the context of computer support for distributed multiparty communication. The result of this research is Talking in Circles, a graphical audio conferencing environment that employs abstract graphics for representation and provides lightweight access to multiple expressive modes. This thesis discusses foundations for work towards sociable communication online as well as the design and implementation processes involved in the creation of the Talking in Circles system. User experiences with the system, lessons learned and directions for further research into sociable communication are then detailed.by Roy Alexis Rodenstein Kartofel.S.M

Estudio de tiempos y movimientos para aumentar la productividad en el área de producción de la distribuidora Vania S.R.L, Trujillo 2020

La presente investigación titulada: “Estudio de Tiempos y Movimientos para aumentar la Productividad en el Área de Producción de la distribuidora Vania S.R.L, Trujillo 2020” tuvo como objetivo principal la aplicación de una Técnica de medición del trabajo siendo este el Estudio de Tiempos y Movimientos para aumentar la productividad, con la finalidad de reducir el tiempo elevado que existen en las actividades para la entrega de pedidos. El Tipo de Investigación fue Aplicada y el Diseño de Investigación fue Experimental centrado en su condición Pre experimental en donde se tomó como muestra a los 13 operarios del Área de Producción, para su posterior análisis y contrastación de la Hipótesis planteada. La presente investigación comprendió el diagnostico actual, el desarrollo, la aplicación y evaluación del estudio, basada en el registro de los tiempos obtenidos a través de la observación en campo de cada una de las líneas de producción (panes, pasteles y kekes) datos obtenidos a través de una entrevista y encuesta, evaluación de indicadores, registro de las cantidades producidas en cada línea de producción, diagramas, muestreo del tiempo de los operarios (% labor y % de ocio), balanceo de líneas, simulación en software ProModel . Los resultados de la presente investigación indica que se logró mejorar la Productividad en el Área de Producción de cada una de sus líneas con el Estudio de Tiempos y Movimientos, dismuyendo sus tiempos de operaciones en un 21.9% e incrementando su capacidad de producción en un 13.9% en promedio en sus líneas y por ende sus indicadores tales como Eficiencia, Eficacia, Utilización aumentaron después de la aplicación. Se concluyó que la Aplicación del Estudio de Tiempos y Movimientos aumenta la productividad en el Área de producción de la Distribuidora Vania S.R.L

Why Chromatic Imaging Matters

During the last two decades, the first generation of beam combiners at the Very Large Telescope Interferometer has proved the importance of optical interferometry for high-angular resolution astrophysical studies in the near- and mid-infrared. With the advent of 4-beam combiners at the VLTI, the u-v coverage per pointing increases significantly, providing an opportunity to use reconstructed images as powerful scientific tools. Therefore, interferometric imaging is already a key feature of the new generation of VLTI instruments, as well as for other interferometric facilities like CHARA and JWST. It is thus imperative to account for the current image reconstruction capabilities and their expected evolutions in the coming years. Here, we present a general overview of the current situation of optical interferometric image reconstruction with a focus on new wavelength-dependent information, highlighting its main advantages and limitations. As an Appendix we include several cookbooks describing the usage and installation of several state-of-the art image reconstruction packages. To illustrate the current capabilities of the software available to the community, we recovered chromatic images, from simulated MATISSE data, using the MCMC software SQUEEZE. With these images, we aim at showing the importance of selecting good regularization functions and their impact on the reconstruction.Comment: Accepted for publication in Experimental Astronomy as part of the topical collection: Future of Optical-infrared Interferometry in Europ