DYNAMICS OF TRAPPED POLARITONS INSTRESSED GaAs QUANTUMWELL-MICROCAVITY STRUCTURES:EXPERIMENTS AND NUMERICAL SIMULATIONS

Microcavity polaritons have been studied for a decade and a half. Soon after their discovery they were proposed as candidates for the observation of BEC in a solid. In consideration of this possibility, microcavity polaritons have been studied experimentally, analytically, and numerically. Most of the numerical studies have been qualitative. This thesis continues that analysis and for the first time fits experimentally obtained distributions with that obtained by numerical simulations.For this thesis, experiments were performed on a GaAs quantum well-microcavity structure. Excitations of this structure are manifested as polaritons when the quantum well excitons are strongly coupled to the cavity mode. The experimental study of these polaritons provides interesting results. The experiments where the polariton density is the highest show that there is accumulation of polaritons in the low energy states near $k=0$. Below this high density it is seen that the distribution becomes flat and maintains that shape as density is decreased. Neither the high density nor the low density data has a thermalized distribution. Can the accumulation at high density be explained with Boson statistics? What can explain the flat, nonthermalized distribution at low densities. To answer these questions a numerical model was developed. The model has shown that the distribuition functions from the experiments can be numerically simulated. The model has shown that the accumulation at $k=0$ is due to Boson statistics. Through the model, an explanation as to why the distribution curves are flat is also provided. This thesis is presented as follows. An introduction to microcavity polaritons and to our experimental system is presented in chapter 1. Chapter 2 describes the scattering processes that regulate the dynamics of the polaritons and the equations that are used in the model. Chapter 3 gives a review of previous numerical models on microcavity polaritons. Chapter 4 describes the experimental techniques used to acquire the data while chapter 5 compares the data with that given by the simulation. Chapter 6 then discusses directions for continued research

Identification of Small Molecule Inhibitors of Pseudomonas aeruginosa Exoenzyme S Using a Yeast Phenotypic Screen

Pseudomonas aeruginosa is an opportunistic human pathogen that is a key factor in the mortality of cystic fibrosis patients, and infection represents an increased threat for human health worldwide. Because resistance of Pseudomonas aeruginosa to antibiotics is increasing, new inhibitors of pharmacologically validated targets of this bacterium are needed. Here we demonstrate that a cell-based yeast phenotypic assay, combined with a large-scale inhibitor screen, identified small molecule inhibitors that can suppress the toxicity caused by heterologous expression of selected Pseudomonas aeruginosa ORFs. We identified the first small molecule inhibitor of Exoenzyme S (ExoS), a toxin involved in Type III secretion. We show that this inhibitor, exosin, modulates ExoS ADP-ribosyltransferase activity in vitro, suggesting the inhibition is direct. Moreover, exosin and two of its analogues display a significant protective effect against Pseudomonas infection in vivo. Furthermore, because the assay was performed in yeast, we were able to demonstrate that several yeast homologues of the known human ExoS targets are likely ADP-ribosylated by the toxin. For example, using an in vitro enzymatic assay, we demonstrate that yeast Ras2p is directly modified by ExoS. Lastly, by surveying a collection of yeast deletion mutants, we identified Bmh1p, a yeast homologue of the human FAS, as an ExoS cofactor, revealing that portions of the bacterial toxin mode of action are conserved from yeast to human. Taken together, our integrated cell-based, chemical-genetic approach demonstrates that such screens can augment traditional drug screening approaches and facilitate the discovery of new compounds against a broad range of human pathogens

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

The relationship between methamphetamine and alcohol use in a community sample of methamphetamine users.

While methamphetamine (MA) and alcohol are often used in combination, little is known about the pattern of co-use between these substances. The goal of the present study is to examine the relationship between MA use and alcohol use in a community sample of non-treatment seeking regular MA users.Participants completed a face-to-face assessment battery, which included a diagnostic interview for MA dependence and the timeline follow-back interview for both alcohol and MA use over the past 30 days. Sixty regular MA and alcohol users supplied data for 1800 person-days.Compared with non-drinking days, drinking days and binge drinking days increased the odds of same day MA use by 4.22 and 4.50 times, respectively (p's<0.0001). Further, binge drinking incrementally increased risk for MA use above and beyond the effects of drinking itself (p<0.0001). Lagged models revealed previous day MA use to predict following day MA use (p<0.0001), yet, after controlling for this relationship, neither previous day alcohol use nor previous day binge drinking predicted following-day MA use. Finally, the effect of binge drinking on MA use was stronger among individuals with lower MA dependence severity or higher alcohol problem severity (p's<0.05).These results suggest that alcohol and MA are co-used in predictable patterns, and in particular, that binge drinking may be incrementally associated with the likelihood of MA use. Future studies are needed to explore the temporal relationship between alcohol and MA use within a given episode

The relationship between methamphetamine and alcohol use in a community sample of methamphetamine users.

While methamphetamine (MA) and alcohol are often used in combination, little is known about the pattern of co-use between these substances. The goal of the present study is to examine the relationship between MA use and alcohol use in a community sample of non-treatment seeking regular MA users.Participants completed a face-to-face assessment battery, which included a diagnostic interview for MA dependence and the timeline follow-back interview for both alcohol and MA use over the past 30 days. Sixty regular MA and alcohol users supplied data for 1800 person-days.Compared with non-drinking days, drinking days and binge drinking days increased the odds of same day MA use by 4.22 and 4.50 times, respectively (p's<0.0001). Further, binge drinking incrementally increased risk for MA use above and beyond the effects of drinking itself (p<0.0001). Lagged models revealed previous day MA use to predict following day MA use (p<0.0001), yet, after controlling for this relationship, neither previous day alcohol use nor previous day binge drinking predicted following-day MA use. Finally, the effect of binge drinking on MA use was stronger among individuals with lower MA dependence severity or higher alcohol problem severity (p's<0.05).These results suggest that alcohol and MA are co-used in predictable patterns, and in particular, that binge drinking may be incrementally associated with the likelihood of MA use. Future studies are needed to explore the temporal relationship between alcohol and MA use within a given episode

L’enseignement et l’apprentissage de l’écrit académique à l’aide de corpus numériques

L’exploitation des corpus à des fins didactiques demeurent un vaste terrain d’étude. Ce numéro offre une collection de 6 articles d’étude de cas en milieu universitaire s’appuyant sur de solides bases théoriques. La richesse linguistique étudiée (français, anglais, allemand) apporte une ouverture exceptionnelle dans le cadre de la didactique des langues étrangères. Ce recueil d’articles, qui s’inscrit dans les traditions croisées de la linguistique, des langues de spécialité, de l’informatique et des sciences de l’éducation, offre l’occasion de présenter des applications pertinentes de la linguistique de corpus par des spécialistes et leur réception par les utilisateurs. REMERCIEMENTS Ont été sollicités pour évaluer les articles de ce numéro thématique : Dominique Bétrix Köhler, Alex Boulton, Claire Chaplier, Jeanne-Marie Debaisieux, Nadia Yassine-Diab, Mamadou Dramé, Françoise Dufour, Sylviane Granger, Francis Grossmann, Alice Henderson, Jean-Marc Mangiante, Luis Meneses, Alain Polguère, Fanny Rinck, Jean-Pascal Simon, Élodie Vargas

Mitosis-specific MPM-2 phosphorylation of DNA topoisomerase IIα is regulated directly by protein phosphatase 2A

Recent results suggest a role for topoIIα (topoisomerase IIα) in the fine-tuning of mitotic entry. Mitotic entry is accompanied by the formation of specific phosphoepitopes such as MPM-2 (mitotic protein monoclonal 2) that are believed to control mitotic processes. Surprisingly, the MPM-2 kinase of topoIIα was identified as protein kinase CK2, otherwise known as a constitutive interphase kinase. This suggested the existence of alternative pathways for the creation of mitotic phosphoepitopes, different from the classical pathway where the substrate is phosphorylated by a mitotic kinase. In the present paper, we report that topoIIα is co-localized with both CK2 and PP2A (protein phosphatase 2A) during interphase. Simultaneous incubation of purified topoIIα with CK2 and PP2A had minimal influence on the total phosphorylation levels of topoIIα, but resulted in complete disappearance of the MPM-2 phosphoepitope owing to opposite sequence preferences of CK2 and PP2A. Accordingly, short-term exposure of interphase cells to okadaic acid, a selective PP2A inhibitor, was accompanied by the specific appearance of the MPM-2 phosphoepitope on topoIIα. During early mitosis, PP2A was translocated from the nucleus, while CK2 remained in the nucleus until pro-metaphase thus permitting the formation of the MPM-2 phosphoepitope. These results underline the importance of protein phosphatases as an alternative way of creating cell-cycle-specific phosphoepitopes