An analysis of pitch and duration in material used to test L2 processing of words

The material reported on in this paper is part of a set of experiments in which the role of Information Structure on L2 processing of words is tested. Pitch and duration of 4 sets of experimental material in German and English are measured and analyzed in this paper. The well-known finding that accent boosts duration and pitch is confirmed. Syntactic and lexical means of marking focus, however, do not give the duration and the pitch of a word an extra boost

Focus accent, word length and position as cues to L1 and L2 word recognition

The present study examines native and nonnative perceptual processing of semantic information conveyed by prosodic prominence. Five groups of German learners of English each listened to one of 5 experimental conditions. Three conditions differed in place of focus accent in the sentence and two conditions were with spliced stimuli. The experiment condition was presented first in the learners’ L1 (German) and then in a similar set in the L2 (English). The effect of the accent condition and of the length and position of the target in the sentence was evaluated in a probe recognition task. In both the L1 and L2 tasks there was no significant effect in any of the five focus conditions. Target position and target word length had an effect in the L1 task. Word length did not affect accuracy rates in the L2 task. For probe recognition in the L2, word length and the position of the target interacted with the focus condition

Jonathan Boucher: Moderate Loyalist and Public Man

This inquiry began then, with an attempt to understand Jonathan Boucher, the Tory of Tories, the adversary of Locke and egalitarian principles, the spokesman for Filmer in America, and the divine rights advocate. The whole complex of Boucher\u27s life has been examined, with particular emphasis on the pre-Revolutionary years of crisis in Virginia and Maryland between 1765 and 1775, together with the milieu of the two colonies, in order to discover what factors may have contributed to Boucher\u27s High Tory role, if, indeed, he was a High Tory. And it has been an effort to understand all of the circumstances that caused Boucher to fail so dismally in halting the progress of rebellion. The intellectual biography of Boucher is the account of a thoroughly Americanized cleric, planter, and would-be patriot caught up in a bewildering collapse of civil and religious authority in Maryland. Torn by loyalty to Church and State of England and by his love for America, Boucher\u27s courage, integrity, and principles forced him into the life of an exile

Regards croisés sur la veille

La veille et la recherche d’informations, qu’elles soient sur et par le web ou non, sont des pratiques indispensables à de nombreux métiers : communication, marketing, RH, web... L’objectif de ce livre blanc est d’apporter, modestement, des visions et des méthodologies variées sur ces pratiques. Le constat de départ qui a amené à cet ouvrage est le suivant : la veille tout le monde en parle et en fait (ou presque), alors comment enrichir l’existant ? Les multiples apports qui constituent cette pratique et cette profession, qu’ils proviennent de la documentation, de l’intelligence économique ou encore du web, rendent riches les possibilités d’analyse. Nous avons donc pris le parti ici de ne pas viser l’exhaustivité (impossible de toute manière) mais de creuser certains aspects, certaines pratiques liées : cartographie, mind mapping, innovation, recrutement, qualification des sources... Et ce en faisant appel à des spécialistes de ces domaines et à des veilleurs professionnels. Pour ne pas être trop théorique et surtout ramener la veille à ce qu’elle est, à la fois une compétence et un métier à part entière, cet e-book propose aussi de nombreuses interviews de professionnels. Professionnels dont les activités de veille ne sont pas des tâches à plein temps, mais font partie de leurs activités quotidiennes. Et qui éclaireront sûrement, nous l’espérons, sous un angle très pragmatique certaines de vos interrogations. L’idée est de vous fournir une vision large : des trucs et astuces pour mener une veille quotidienne aux pratiques plus avancées. Ceci afin de montrer que si la veille est accessible à tous (surtout grâce aux outils web), elle peut aussi révéler certains aspects complexes à ne pas négliger. En parlant d’outils, vous remarquerez que l’accent n’a pas été porté sur eux. Plutôt que de faire une longue liste de tutoriaux, il nous a paru plus intéressant de se focaliser sur les méthodologies et les bonnes pratiques, la maîtrise des outils n’étant souvent qu’un moyen plus qu’un objectif à atteindre. Au final, ce livre blanc vise à la fois à élargir votre champ de vision, renforcer vos connaissances sur certains aspects, et vous donner quelques armes pour développer votre propre stratégie de veille. Cet objectif étant ambitieux, nous remercions les auteurs et interviewés pour le temps, l’énergie et la créativité qu’ils ont développé pour l’atteindre. Mais aussi la graphiste Morgane Maillard pour les créas qui mettent en valeur ce contenu

Impact of S-sulfocysteine on fragments and trisulfide bond linkages in monoclonal antibodies

The quality of recombinant proteins such as monoclonal antibodies produced using Chinese hamster ovary cell-based mammalian systems is dependent on many factors, including cell line, process and cell culture media. Due to these factors, the generated product is heterogeneous and may have chemically induced modifications or post-translational modifications that affect antibody stability, functionality and, in some cases, patient safety. This study demonstrates that S-sulfocysteine, a cysteine derivative, can increase the antibody specific productivity in different cell lines cultivated with different processes while minimizing trisulfide linkages in generated mAbs, mainly between heavy and light chain. The supplementation of a cell culture feed with S-sulfocysteine also proved to be useful to reduce the percentage of antibody fragments generated from the monoclonal antibody. Overall, this new component used in the upstream process allows a reduction of product heterogeneity

Impact of the Histidine‐Containing Phosphocarrier Protein HPr on Carbon Metabolism and Virulence in Staphylococcus aureus

Carbon catabolite repression (CCR) is a common mechanism pathogenic bacteria use to link central metabolism with virulence factor synthesis. In gram‐positive bacteria, catabolite control protein A (CcpA) and the histidine‐containing phosphocarrier protein HPr (encoded by ptsH) are the predominant mediators of CCR. In addition to modulating CcpA activity, HPr is essential for glucose import via the phosphotransferase system. While the regulatory functions of CcpA in Staphylococcus aureus are largely known, little is known about the function of HPr in CCR and infectivity. To address this knowledge gap, ptsH mutants were created in S. aureus that either lack the open reading frame or harbor a ptsH variant carrying a thymidine to guanosine mutation at position 136, and the effects of these mutations on growth and metabolism were assessed. Inactivation of ptsH altered bacterial physiology and decreased the ability of S. aureus to form a biofilm and cause infections in mice. These data demonstrate that HPr affects central metabolism and virulence in S. aureus independent of its influence on CcpA regulation

High prevalence and little awareness in patients with chronic inflammatory skin diseases and genital involvement

Background Genital involvement in patients with chronic inflammatory skin diseases is frequent, yet insufficiently acknowledged. Objective To evaluate the prevalence of genital symptoms in psoriasis and chronic urticaria patients, effects on quality of life, physician-patient relations and disease management. Patients and Methods 100 patients with psoriasis and 100 with chronic urticaria from our outpatient clinic, as well as 50 healthy controls were included. Data was collected using questionnaires developed by dermatological experts. Results Out of 250 subjects, 74 % had already experienced genital symptoms – 70 % of psoriasis patients and 58 % of urticaria patients. Seven out of ten even complained about recurrent genital involvement. 50 % of psoriasis and 41 % of urticaria patients reported an impact on quality of life. 41 % identified genital pruritus as the main symptom, with one out of three expecting a better management for this specific problem. Furthermore, 74 % complained about a lack of awareness among physicians: 79 % of urticaria patients and 58 % of psoriasis patients reported never having been questioned about genital symptoms by their physicians. Conclusions The majority of patients with psoriasis and chronic urticaria suffer from genital involvement and an impaired quality of life. Patient and physician reported outcomes should include genital symptoms as an influencing factor for quality of life

Melanoma Cells Treated with GGTI and IFN-γ Allow Murine Vaccination and Enhance Cytotoxic Response against Human Melanoma Cells

International audienceBACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I) and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298) stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL), we demonstrated that in vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC) revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i) activation of CD8 T lymphocytes (CD8+/CD69+); ii) proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+); iii) secretion of hIFN-gamma; and iv) anti-melanoma specific cytotoxic cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells

Endogenous Neurotrophins and Trk Signaling in Diffuse Large B Cell Lymphoma Cell Lines Are Involved in Sensitivity to Rituximab-Induced Apoptosis

International audienceBACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. Immunochemotherapy, a combination of rituximab to standard chemotherapy, has resulted in improved survival. However a substantial proportion of patients still fail to reach sustained remission. We have previously demonstrated that autocrine brain-derived neurotrophic factor (BDNF) production plays a function in human B cell survival, at least partly via sortilin expression. As neurotrophin receptor (Trks) signaling involved activation of survival pathways that are inhibited by rituximab, we speculated that neurotrophins may provide additional support for tumour cell survival and therapeutic resistance in DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used two DLBCL cell lines, SUDHL4 and SUDHL6, known to be respectively less and more sensitive to rituximab. We found by RT-PCR, western blotting, cytometry and confocal microscopy that both cell lines expressed, in normal culture conditions, BDNF and to a lesser extent NGF, as well as truncated TrkB and p75(NTR)/sortilin death neurotrophin receptors. Furthermore, BDNF secretion was detected in cell supernatants. NGF and BDNF production and Trk receptor expression, including TrkA, are regulated by apoptotic conditions (serum deprivation or rituximab exposure). Indeed, we show for the first time that rituximab exposure of DLBCL cell lines induces NGF secretion and that differences in rituximab sensitivity are associated with differential expression patterns of neurotrophins and their receptors (TrkA). Finally, these cells are sensitive to the Trk-inhibitor, K252a, as shown by the induction of apoptosis. Furthermore, K252a exhibits additive cytotoxic effects with rituximab. CONCLUSIONS/SIGNIFICANCE: Collectively, these data strongly suggest that a neurotrophin axis, such NGF/TrkA pathway, may contribute to malignant cell survival and rituximab resistance in DLBCL