The Ets-1 transcription factor controls the development and function of natural regulatory T cells

Regulatory T cells (T reg cells) constitute a population of CD4+ T cells that limits immune responses. The transcription factor Foxp3 is important for determining the development and function of T reg cells; however, the molecular mechanisms that trigger and maintain its expression remain incompletely understood. In this study, we show that mice deficient for the Ets-1 transcription factor (Ets-1−/−) developed T cell–mediated splenomegaly and systemic autoimmunity that can be blocked by functional wild-type T reg cells. Spleens of Ets-1−/− mice contained mostly activated T cells, including Th2-polarized CD4+ cells and had reduced percentages of T reg cells. Splenic and thymic Ets-1−/− T reg cells expressed low levels of Foxp3 and displayed the CD103 marker that characterizes antigen-experienced T reg cells. Thymic development of Ets-1−/− T reg cells appeared intrinsically altered as Foxp3-expressing cells differentiate poorly in mixed fetal liver reconstituted chimera and fetal thymic organ culture. Ets-1−/− T reg cells showed decreased in vitro suppression activity and did not protect Rag2−/− hosts from naive T cell–induced inflammatory bowel disease. Furthermore, in T reg cells, Ets-1 interacted with the Foxp3 intronic enhancer and was required for demethylation of this regulatory sequence. These data demonstrate that Ets-1 is required for the development of natural T reg cells and suggest a role for this transcription factor in the regulation of Foxp3 expression

Nutritional Status of Patients with End Stage Liver Disease: An Outpatient Assessment

Cirrhosis is the 12th leading cause of death in the United States. It is well documented end stage liver disease drives a patient to a catabolic state thus depleting them of essential nutrients. Malnutrition is often unrecognized and untreated in outpatients. Though BMI, nutritional intake, anthropometric measurements have been used in clinical trials, there still remains no standard nutritional assessment. The purpose of this dissertation was to (1) identify the incidence of malnutrition in patients with compensated and decompensated liver disease utilizing defined nutritional parameters (Subjective Global Assessment, anthropometric measurements, hand grip strength, and laboratory values) and (2) correlate with care (hospital visits, physician appointments, outcome and quality of life) secondary to viral hepatitis, metabolic and alcoholic liver disease. The conceptual framework underlying this study is derived from the literature based on the domains of liver function, nutrition, and malnutrition. Nutrition includes the chemical substances in food utilized by the body for growth, maintenance, and repair: the intake, digestion, and assimilation and utilization of nutrients for tissue maintenance and energy provision. There is no gold standard for proper nutritional assessment of patients diagnosed with liver disease; notably, the traditional assessment tools are invalid with end-stage liver disease. Ascites, edema, and diuretics cause fluctuations in weight and weight changes. Cirrhosis of the liver drives a patient to a catabolic state, thus depriving them of essential nutrients. Simple and easily applied methods are needed to identify the patients approaching the state of malnutrition. Study findings presented in three papers provides a major contribution in discriminating the nutritional parameters of different etiologies of cirrhosis leading to malnutrition

Strategy for the identification of micro-organisms producing food and feed products : bacteria producing food enzymes as study case

Recent European regulations require safety assessments of food enzymes (FE) before their commercialization. FE are mainly produced by micro-organisms, whose viable strains nor associated DNA can be present in the final products. Currently, no strategy targeting such impurities exists in enforcement laboratories. Therefore, a generic strategy of first line screening was developed to detect and identify, through PCR amplification and sequencing of the 16S-rRNA gene, the potential presence of FE producing bacteria in FE preparations. First, the specificity was verified using all microbial species reported to produce FE. Second, an in-house database, with 16S reference sequences from bacteria producing FE, was constructed for their fast identification through blast analysis. Third, the sensitivity was assessed on a spiked FE preparation. Finally, the applicability was verified using commercial FE preparations. Using straightforward PCR amplifications, Sanger sequencing and blast analysis, the proposed strategy was demonstrated to be convenient for implementation in enforcement laboratories

L'Inspection du Travail au féminin, 1878-1974. Itinéraires et statuts

rapport dactylographié à la DARES, 2 tomes; le 2e tome est un annuaire des Inspectrices du Travail, 1878-1974La loi de 1892 qui scelle la professionnalisation de l'Inspection du travail — avec un concours de recrutement national, la rémunération des inspecteurs et inspectrices par le Ministère — n'organise pas exactement le même métier pour les Inspecteurs que pour les Inspectrices. Si la rémunération est convenue identique (ce qui n'est pas le cas dans l'enseignement), par contre les lieux d'exercice diffèrent ; ainsi seuls les Inspecteurs peuvent visiter des ateliers comprenant une majorité d'hommes et/ou des machines et ce n'est qu'en 1932 qu'une épreuve technique est incluse dans leur concours. Lors des conflits et des arbitrages du Front populaire, l'activité des inspectrices montre qu'elles sont confinées dans des secteurs à main-d'œuvre très féminine et où dominent les petites entreprises. Par ailleurs, les femmes sont, par le texte de la loi de 1892, exclues de la promotion, puisque seuls les Inspecteurs peuvent accéder au grade d'Inspecteur divisionnaire, c'est-à-dire celui de la responsabilité et du commandement sur les autres. Jusqu'à la Seconde guerre mondiale, pour ces quelques dizaines d'inspectrices, les recrutements sont rares, les concours féminins s'ouvrent rarement (tous les six ou sept ans) et la concurrence y est rude. De fait, le recrutement est plus compétitif aux inspectrices qu'aux inspecteurs ; les centaines de candidates qui se présentent pour sont bien plus diplômées que leurs confrères et font même partie des « pionnières » pour l'acquisition des diplômes de l'enseignement supérieur. La hauteur de leurs diplômes correspond à celle des maris et des pères: une moitié de ces femmes sont filles et épouses d'industriels, de négociants, d'hommes des professions libérales où dominent les médecins. Si ces Inspectrices sont des femmes actives, elle ne travaillent donc pas par nécessité financière, ni par désœuvrement familial (elles sont mères de famille pour les deux tiers d'entre elles), mais bien par souci d'équité sociale et/ou de réalisation individuelle. À partir de 1946, avec la mise en place du Statut de la fonction publique et surtout de 1974, avec la mixité des concours de recrutements des fonctionnaires, des mutations égalitaires s'organisent. À partir de 1946, les circonscriptions deviennent mixtes, les Inspectrices peuvent organiser la mobilité géographique qui permet la promotion. Pourtant, même si les textes du Statut énoncent l'égalité, les Inspectrices n'accèdent toujours pas aux grades qui autorisent la prise décision et l'autorité sur les autres, en particulier comme directeur régional du travail : il faut attendre 1974 pour que leurs carrières commencent à être comparables à celles de leurs collègues masculins. 1974 est aussi la date de la fusion des corps de l'Inspection, avec l'intégration des Inspecteurs de l'Agriculture et des Transports, où les femmes étaient toujours interdites de concours de recrutement

Individualisierte Erinnerungen an NS-Zwangsarbeit: zum Wandel in Erinnerungskultur und Oral History

"In dem Text wird anhand von 84 lebensgeschichtlichen Interviews untersucht, wie ehemalige NS-Zwangsarbeitende im Kontext der jeweiligen Gesellschaftsordnungen, politischen Systeme und Erinnerungskulturen ihre Erfahrungen verarbeitet und gedeutet haben. Aufbauend auf vergleichenden empirischen Befunden, werden fachwissenschaftlich geprägte und gesellschaftlich gewachsene Verständnisse von Zwangsarbeit mit den subjektiven Blicken der Betroffenen kontrastiert und das Verhältnis von individualisierter und sozialer Erinnerung analysiert. Ehemalige Zwangsarbeitende mussten teilweise lebenslang um ihre Anerkennung als NS-Opfer kämpfen. Ihre Erzählungen bilden ein Widerlager zu gegenwärtigen Forschungstendenzen, nach denen der Nationalstaat als Referenzpunkt für Erinnerungen an Bedeutung verliere und Interviews nur von der Gegenwart der Erzählenden und den konkreten Umständen des Interviews geprägt seien. Die Erinnerungen an NS-Zwangsarbeit lassen sich nicht in ein eindeutiges Helden- oder Opferschema pressen, sondern ermöglichen Einblicke in die Fähigkeit, unter widrigsten Umständen in kleinräumigen Aushandlungsprozessen mit dem Kriegsalltag umzugehen. Dabei werden komplexe Verständnisse von Arbeit und heterogene Dimensionen des Zwangs erkennbar." (Autorenreferat

Computational Stylistics in Poetry, Prose, and Drama

The contributions in this edited volume approach poetry, narrative, and drama from the perspective of Computational Stylistics. They exemplify methods of computational textual analysis and explore the possibility of computational generation of literary texts. The volume presents a range of computational and Natural Language Processing applications to literary studies, such as motif detection, network analysis, machine learning, and deep learning

Modification of macroporous titanium tracheal implants with biodegradable structures: tracking in vivo integration for determination of optimal in situ epithelialization conditions.

Previously, we showed that macroporous titanium implants, colonized in vivo together with an epithelial graft, are viable options for tracheal replacement in sheep. To decrease the number of operating steps, biomaterial-based replacements for epithelial graft and intramuscular implantation were developed in the present study. Hybrid microporous PLLA/titanium tracheal implants were designed to decrease initial stenosis and provide a surface for epithelialization. They have been implanted in New Zealand white rabbits as tracheal substitutes and compared to intramuscular implantation samples. Moreover, a basement membrane like coating of the implant surface was also designed by Layer-by-Layer (LbL) method with collagen and alginate. The results showed that the commencement of stenosis can be prevented by the microporous PLLA. For determination of the optimum time point of epithelialization after implantation, HPLC analysis of blood samples, C-reactive protein (CRP), and Chromogranin A (CGA) analyses and histology were carried out. Following 3 weeks the implant would be ready for epithelialization with respect to the amount of tissue integration. Calcein-AM labeled epithelial cell seeding showed that after 3 weeks implant surfaces were suitable for their attachment. CRP readings were steady after an initial rise in the first week. Cross-linked collagen/alginate structures show nanofibrillarity and they form uniform films over the implant surfaces without damaging the microporosity of the PLLA body. Human respiratory epithelial cells proliferated and migrated on these surfaces which provided a better alternative to PLLA film surface. In conclusion, collagen/alginate LbL coated hybrid PLLA/titanium implants are viable options for tracheal replacement, together with in situ epithelialization.journal articleresearch support, non-u.s. gov't2012 Aug2012 03 02importe

EUS-Guided Pancreatic Cyst Ablation: a Clinical and Technical Review

Purpose of Review Pancreatic cystic lesions represent a growing public health dilemma, particularly as our population ages and cross-sectional imaging becomes more sensitive. Mucinous cysts carry a clinically significant risk of developing pancreatic cancer, which carries an extremely poor prognosis. Determining which cysts will develop cancer may be challenging, and surgical resection of the pancreas carries significant morbidity. The goal of this paper is to review the rationale for cyst ablation and discuss prior and current research on cyst ablation techniques and efficacy. Indications, contraindications, and factors related to optimal patient selection are outlined. Recent Findings Endoscopic ultrasound-guided chemoablation of pancreatic cysts has been performed in neoplastic cysts, with varying levels of efficacy. Safety concerns arose due to the risk of pancreatitis in alcohol-based treatments; however, the most recent data using a non-alcohol chemoablation cocktail suggests that ablation is effective without the need for alcohol, resulting in a significantly more favorable adverse event profile. Summary Endoscopic ultrasound-guided chemoablation of neoplastic pancreatic cysts is a promising, minimally invasive approach for treatment of cysts, with recent significant advances in safety and efficacy, suggesting that it should play a role in the treatment algorithm