1862-11-19 Lucy Feyler sends fragment of goodbye note from her brother Henderson Feyler

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Tumour Cell Generation of Inducible Regulatory T-Cells in Multiple Myeloma Is Contact-Dependent and Antigen-Presenting Cell-Independent

Regulatory T-cells (TReg cells) are increased in patients with multiple myeloma (MM). We investigated whether MM cells could generate and/or expand TReg cells as a method of immuno-surveillance avoidance. In an in vitro model, CD4+CD25-FoxP3- T-cells co-cultured with malignant plasma cells (primary MM cells and cell lines) induced a significant generation of CD4+CD25+FoxP3+ inducible TReg cells (tTReg cells; p<0.0001), in a contact-dependent manner. tTReg cells were polyclonal, demonstrated a suppressive phenotype and phenotypically, demonstrated increased FoxP3 (p = 0.0001), increased GITR (p<0.0001), increased PD1 (p = 0.003) and decreased CD62L (p = 0.007) expression compared with naturally occurring TReg cells. FACS-sorted tTReg cells differentiated into FoxP+IL-17+ and FoxP3-IL-17+ CD4+ cells upon TCR-mediated stimulation. Blocking experiments with anti-ICOS-L MoAb resulted in a significant inhibition of tTReg cell generation whereas both IL-10 & TGFβ blockade did not. MM tumour cells can directly generate functional TReg cells in a contact-dependent manner, mediated by ICOS/ICOS-L. These features suggest that tumour generation of TReg cells may contribute to evasion of immune surveillance by the host

Adultery and the Rumor Mill: les bourgeois de Molinchart and El gran galeoto

This article seeks to challenge interpretations of the adultery plot as a subversive current in nineteenth-century literature by examining two texts that are often dismissed by contemporary critics: Les bourgeois de Molinchart (1854), a novel by the French writer Champfleury (the pseudonym of Jules Husson), and El gran Galeoto (1881), a play by the Spanish playwright Jos, Echegaray. In each of these works, the rumor of the adultery precedes and to a large extent precipitates the infidelity at the end of the work. In committing adultery, therefore, the protagonists are not rising up against social norms so much as capitulating to the expectations of society, enacting a plot that has been projected upon them. The essay compares and contrasts the treatment of the rumor mill in the two works and examines the literary strategies that the writers use to undercut a transgressive reading of the infidelity plot

Genetic Polymorphisms of CYP2E1, GSTP1, NQO1 and MPO and the Risk of Nasopharyngeal Carcinoma in a Han Chinese Population of Southern China

<p>Abstract</p> <p>Background</p> <p>Southern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a case-control study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China.</p> <p>Methods</p> <p>Five single nucleotide polymorphisms (SNPs) of <it>CYP2E1</it>-rs2031920, <it>CYP2E1</it>-rs6413432, <it>GSTP1</it>-rs947894, <it>MPO</it>-rs2333227 and <it>NQO1</it>-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 controls (phase I cohort). Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). To confirm our results, sixteen tag SNPs for <it>GSTP1</it>, <it>MPO</it>, <it>NQO1 </it>(which 100% covered these genes), and 4 functional SNPs of <it>CYP2E1 </it>were genotyped in another cohort of 213 NPC cases and 230 controls (phase II cohort).</p> <p>Results</p> <p>No significant associations in NPC risk were observed for the five polymorphisms tested in the phase I cohort. In an additional stratified analysis for phase I, there was no significant association between cases and controls in NPC high risk population (EBV/IgA/VCA positive population). Analysis of 14 tagging SNPs within the same genes in an independent phase II cohort were in agreement with no SNPs significantly associated with NPC.</p> <p>Conclusions</p> <p>Our results suggest that polymorphism of <it>CYP2E1</it>, <it>GSTP1</it>, <it>MPO </it>and <it>NQO1 </it>genes does not contribute to overall NPC risk in a Han Chinese in southern China.</p

Menopausal Status Modifies Breast Cancer Risk Associated with the Myeloperoxidase (MPO) G463A Polymorphism in Caucasian Women: A Meta-Analysis

BACKGROUND: Breast cancer susceptibility may be modulated partly through polymorphisms in oxidative enzymes, one of which is myeloperoxidase (MPO). Association of the low transcription activity variant allele A in the G463A polymorphism has been investigated for its association with breast cancer risk, considering the modifying effects of menopausal status and antioxidant intake levels of cases and controls. METHODOLOGY/PRINCIPAL FINDINGS: To obtain a more precise estimate of association using the odds ratio (OR), we performed a meta-analysis of 2,975 cases and 3,427 controls from three published articles of Caucasian populations living in the United States. Heterogeneity among studies was tested and sensitivity analysis was applied. The lower transcriptional activity AA genotype of MPO in the pre-menopausal population showed significantly reduced risk (OR 0.56-0.57, p = 0.03) in contrast to their post-menopausal counterparts which showed non-significant increased risk (OR 1.14; p = 0.34-0.36). High intake of antioxidants (OR 0.67-0.86, p = 0.04-0.05) and carotenoids (OR 0.68-0.86, p = 0.03-0.05) conferred significant protection in the women. Stratified by menopausal status, this effect was observed in pre-menopausal women especially those whose antioxidant intake was high (OR 0.42-0.69, p = 0.04). In post-menopausal women, effect of low intake elicited susceptibility (OR 1.19-1.67, p = 0.07-0.17) to breast cancer. CONCLUSIONS/SIGNIFICANCE: Based on a homogeneous Caucasian population, the MPO G463A polymorphism places post-menopausal women at risk for breast cancer, where this effect is modified by diet

Relationship between cyclooxygenase 8473T>C polymorphism and the risk of lung cancer: a case-control study

BACKGROUND: Cyclooxygenase-2 (COX-2) plays an important role in the development of lung cancer. DNA sequence variations in the COX-2 gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to lung cancer. To test this hypothesis, we investigated the association between the 8473T>C polymorphism in the 3'-untranslated region of the COX-2 gene and the risk of lung cancer in a Korean population. METHODS: The COX-2 genotypes were determined using PCR-based primer-introduced restriction analysis in 582 lung cancer patients and in 582 healthy controls that were frequency-matched for age and gender. RESULTS: The distribution of the COX-2 8473T>C genotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by the tumor histology, the combined 8473 TC + CC genotype was associated with a significantly decreased risk of adenocarcinoma as compared with the 8473 TT genotype (adjusted OR = 0.64; 95% CI = 0.46–0.90, P = 0.01). On the stratification analysis, the protective effect of the combined 8473 TC + CC genotype against adenocarcinoma was statistically significant in the males, older individuals and ever-smokers (adjusted OR = 0.59; 95% CI = 0.39–0.91, P = 0.02; adjusted OR = 0.55; 95% CI = 0.33–0.93, P = 0.03; and adjusted OR = 0.57; 95% CI = 0.37–0.87, P = 0.01, respectively). CONCLUSION: These findings suggest that the COX-2 8473T>C polymorphism could be used as a marker for the genetic susceptibility to adenocarcinoma of the lung

Observations de géographie physique dans le Ténéré, région du Tafassasset, entre Ahaggar, Aïr, Tibesti et Tchad

Feyler . Observations de géographie physique dans le Ténéré, région du Tafassasset, entre Ahaggar, Aïr, Tibesti et Tchad. In: Bulletin de l'Association de géographes français, N°89, 12e année, juin 1935. pp. 91-95

Estimation and supervision of the risks of the financial conglomerates

Les mutations structurelles au sein de l'industrie financière sont nombreuses, protéiformes et complexes. L'analyse de leurs conséquences, particulièrement en matière de stabilité financière, s'avère cruciale. Notre travail se concentre sur l'une de ces transformations, à savoir l'émergence et le développement de la conglomération financière, qui a pour singularité d'entremêler diversification et globalisation, et qui, à notre sens, a été relativement peu étudié. Notre objectif est donc de contribuer à combler cette insuffisance. Nous avons articulé notre réflexion autour de trois axes : l'appréhension pratique de la conglomération financière, ses implications en termes de risque, et ses incidences en matière de dispositif prudentiel, et plus particulièrement en termes d'architecture de surveillance. Nous proposons de pallier l'absence de données dédiées spécifiquement à ce mouvement en utilisant des données relatives aux opérations de fusions-acquisitions. Alors qu'il est impossible d'affirmer de manière univoque si ces groupes sont plus ou moins risqués que leurs homologues individuels et susceptibles d'exposer la sphère financière à des risques exacerbés et/ou nouveaux, nous explicitons les éléments à même d'engendrer un profil de risque plus élevé, soulignons l'importance d'adopter une perspective globale du niveau de risque encouru et démontrons l'incidence pernicieuse de la stratégie de diversification sur la probabilité de risque systémique. Enfin, nous montrons à l'aide d'un Probit Multinomial que la conglomération financière est un facteur explicatif aux cotés des facteurs traditionnellement mis en avant de l'unification des autorités nationales de surveillance.The arisen structural changes, and still current, within the financial industry are especially numerous, multiple and complex. The analysis of their consequences, particularly on financial stability, turns out crucial. Our work concentrates on one of these transformations, the emergence and the development of the financial conglomeration, which has for peculiarity to mix diversification and globalization, and which in our sense was rarely studied. Our objective is to contribute to fill this lack. We articulated our reflection around three axes: the practice apprehension of the financial conglomeration, its implications in terms on risk exposure, and its incidences in prudential plan, more particularly in terms on architecture of the financial supervision. We suggest mitigating the absence of data dedicated specifically to this movement by using data relative to the operations of mergers & acquisitions. While it seems impossible to assert in a unambiguous way if these groups are more or less risked that their counterparts individual and susceptible to expose the financial sphere to aggravated and\or new risks, we clarify elements to engender a higher risk profile, underline the importance to adopt a global perspective towards this level of incurred risk and demonstrate the pernicious incidence of the strategy of diversification on the probability of systematic risk. Finally, we show by means of a Probit Multinomial that the financial conglomeration is an explanatory factor in the highly-rated of factors traditionally advanced by the unification of the national authorities of supervision

Les équivoques de la mémoire dans l’avant-dernier chapitre de L’Éducation sentimentale de Gustave Flaubert : mémoire salvatrice ou mémoire trompeuse ?

On sait que l’Éducation sentimentale (de 1869) offre la particularité de comporter, en quelque sorte, deux fins superposées : le sixième chapitre de la troisième partie, qui pourrait clore harmonieusement un ensemble tripartite, (un roman en trois parties comprenant chacune six chapitres) : autrement dit, le récit de la dernière visite de Mme Arnoux à Frédéric Moreau et les adieux des deux héros ; un septième et dernier chapitre, conçu, à l’origine, comme un épilogue, et ..