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Progress versus Pseudoprogress beim Lungenkarzinom unter Immuntherapie / Progress versus pseudoprogress in lung cancer under immunotherapySchiwitza, Annett Jenny 31 December 1100 (has links)
No description available.
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Translanguaging in the English classroom : A study examining young learners’ attitudes and perceptions of translanguaging in the English classroom.Harris, Krystal January 2021 (has links)
Many studies show that language learners see the benefits of using their first language in order to learn second or subsequent languages, while they also see some disadvantages. This reflects dominant ideas in language learning about the importance of keeping languages separate. The present study examines translanguaging, a strategy in which learners are encouraged to use their entire linguistic repertoires during language learning. To this aim, data are examined from Swedish learners (n= 168) in grades 7-9 to investigate their attitudes and perceptions towards translanguaging in the EFL classroom, and to shed light on the roles of age and proficiency in constraining them. The data was collected by means of a questionnaire and a proficiency test in order to measure the participants’ proficiency in English. Unlike the mixed views reported in previous studies, the learners investigated here had a positive view of translanguaging and perceived it as beneficial to their learning. Furthermore, the findings suggest that learners often used Swedish for specific functions, especially explaining grammar and vocabulary, clarifying tasks and instructions, comparing the languages and asking questions. This was even more so for low proficiency learners, who used translanguaging more for both practical and social purposes. On the other hand, higher proficiency learners used less Swedish and viewed translanguaging as less helpful. These learners also reported that their teachers used more Swedish in the classroom compared with their less proficient peers. It was also found that learners showed a greater tendency to use translanguaging with increasing age, although this might have been due to differences between teachers and their individual practices. / Många studier visar att elever ser fördelarna med att använda sitt förstaspråk för att lära sig andra eller efterföljande språk, medan de också ser några nackdelar. Detta återspeglar dominerande idéer i språkinlärningen om vikten av att hålla språken åtskilda. I den här studien undersöks transspråkande (translanguaging), en strategi där eleven uppmuntras att använda hela sin språkliga repertoar under språkinlärningen. För detta ändamål undersöks data från svenska elever (n = 168) i årskurs 7-9 för att undersöka deras attityder och uppfattningar kring transspråkande i det EFL-klassrummet och för att belysa hur faktorerna ålder och färdighet påverkar dem. Uppgifterna samlades in med hjälp av en enkät och ett färdighetstest för att mäta deltagarnas färdigheter på engelska. Till skillnad från de blandade åsikter som rapporterats i tidigare studier hade de studenter som undersöktes i denna studien en positiv syn på transspråkande och uppfattade det som fördelaktigt för deras lärande. Dessutom tyder resultaten på att eleverna ofta använde svenska för specifika funktioner; särskilt att förklara grammatik och nya ord, klargöra uppgifter och instruktioner, jämföra språk och ställa frågor. Detta var ännu mer för elever med låg färdighet, som använde transspråkande mer för både praktiska och sociala ändamål. Å andra sidan använde elever med högre kompetens mindre svenska och betraktade transspråkande som mindre användbart. Dessa elever rapporterade också att deras lärare använde mer svenska i klassrummet jämfört med sina kamrater med lägre färdighet. Studien pekar också på att eleverna visade en större tendens att använda transspråkande med ökande ålder, även om detta kan ha berott på skillnader mellan lärare och deras individuella metoder.
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Volumes finis et solutions renormalisées, applications à des systèmes couplés. / Finite volumes and renormalized solutions : applications to coupled systemsLeclavier, Sarah 12 December 2017 (has links)
On s’intéresse dans cette thèse à montrer que la solution approchée, par la méthode des volumes finis, converge vers la solution renormalisée de problèmes elliptiques ou paraboliques à donnée L1. Dans la première partie nous étudions une équation de convection-diffusion ellliptique à donnée L1. En adaptant la stratégie développée pour les solutions renormaliséesà la méthode des volumes finis, nous montrons que la solution approchée converge vers l’unique solution renormalisée.Dans la deuxième partie nous nous intéressons à un problème parabolique nonlinéaire à donnée L1. En utilisant une version discrète de résultats de compacité classiques, nous montrons que les résultats obtenues dans le cas elliptique restentvrais dans le cas parabolique. Dans la troisième partie nous montrons des résultats similaires pour une équationparabolique doublement non-linéaire à donnée L1. Le caractère doublement nonlinéaire de l’équation crée des difficultés supplémentaires par rapport à la partie précédente, notamment car la règle de dérivation en chaîne ne s’applique pas dansle cas discret. Enfin, dans la quatrième partie, nous utilisons les résultats établis précédemment pour étudier un système de type thermoviscoélasticité. Nous montrons que la solution approchée, obtenue par un schéma éléments finis-volumes finis, converge vers une solution faible-renormalisée du système. / In this thesis we are interested in proving that the approximate solution, obtained by the finite volume method, converges to the unique renormalized solution of elliptic and parabolic equations with L1 data. In the first part we study an elliptic convection-diffusion equation with L1 data. Mixing the strategy developed for renormalized solution and the finite volume method,we prove that the approximate solution converges to the unique renormalized solution. In the second part we investigate a nonlinear parabolic equation with L1 data. Using a discrete version of classical compactness results, we show that the results obtaines previously in the elliptic case hold true in the parabolic case. In the third part we prove similar results for a doubly nonlinear parabolic equation with L1 data. The doubly nonlinear character of the equation makes new difficulties with respect to the previous part, especially since the chain rule formula does not apply in the discrete case. Finaly, in the fourth part we use the results established previously to investigate a system of thermoviscoelasticity kind. We show that the approximate solution,obtaines by finite element-finite volume scheme, converges to a weak-renormalized solution of the system.
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Exploiting DNA Repair Vulnerabilities to Modulate Anti-Cancer Immunity : a Study of the Immunological Potential of PARP inhibitors / Exploiter les défauts de réparation de l’ADN pour moduler l’immunité anti-cancéreuse : une étude du potentiel immunologique des inhibiteurs de PARPChabanon, Roman 31 January 2019 (has links)
Les inhibiteurs de poly(ADP-ribose) polymérase (PARPi) ciblent sélectivement les cellules porteuses de défauts des voies de réparation de l’ADN tels que les mutations de BRCA1/2 et les défauts d’ERCC1. Sur le plan clinique, plusieurs PARPi ont été approuvés pour le traitement des cancers BRCA-mutés ou platine-sensibles du sein et de l’ovaire, et des essais cliniques sont en cours pour évaluer l’efficacité des PARPi dans le cancer bronchique non-à-petites cellules (CBNPC) platine-sensible. Alors que les PARPi ont un fort potentiel thérapeutique dans les cancers comportant des défauts de réparation de l’ADN, de plus en plus d’essais cliniques évaluent également l’efficacité de ces médicaments en combinaison avec les « inhibiteurs d’immune checkpoints » (ICI) dans diverses populations de patients. Dans ce contexte, il est essentiel de mieux comprendre comment les PARPi modulent la réponse immunitaire anti-tumorale, et d’étudier le potentiel immunologique inhérent de ces médicaments.Dans cette étude, nous avons établi que les cellules de CBNPC déficientes en ERCC1 expriment fortement la signature interféron (IFN) de type I, et que les tumeurs de CBNPC ayant une faible expression d’ERCC1 ont un infiltrat lymphocytaire renforcé. En utilisant des lignées cellulaires isogéniques et des xénogreffes dérivées de patients, nous avons montré que plusieurs PARPi, notamment l’olaparib et le rucaparib, ont des propriétés immunomodulatrices dans les modèles de CBNPC ERCC1-déficients et de cancers du sein triple-négatifs (CSTN) BRCA1-mutés. D’un point de vue mécanistique, les PARPi génèrent des fragments d’ADN cytoplasmiques ayant les caractéristiques de micronoyaux ; ceux-ci activent la voie cGAS/STING et déclenchent une réponse IFN de type I, associée à la sécrétion de la cytokine CCL5. De manière importante, ces effets sont largement diminués dans les cellules de CSTN BRCA1-révertantes et les cellules de CBNPC ré-exprimant ERCC1, ce qui suggère que les défauts de réparation de l’ADN amplifient les phénotypes immunitaires associés au traitement par PARPi. En outre, ces effets sont totalement abrogés dans les cellules de CSTN PARP1-neutralisées, ce qui confirme que les phénotypes observés dépendent d’un effet spécifique des PARPi sur leur cible.Au-delà de leur potentiel d’activation d’une immunité spécifique des cellules cancéreuses via cGAS/STING et la signalisation IFN de type I, nous avons également constaté que les PARPi potentialisent les effets inducteurs de l‘IFN de type II sur l’expression de PD-L1 dans des lignées cellulaires et cellules tumorales fraîches de patients CBNPC, surtout en présence de défauts d’ERCC1. De plus, nous avons montré que certains PARPi, utilisés à des concentrations létales, activent de manière indépendante les éléments moléculaires clés de la mort cellulaire immunogénique, dont l’exposition de la calréticuline à la surface des cellules cancéreuses, la sécrétion d’ATP et le relargage d’HMGB1 en grandes quantités dans le milieu extracellulaire.Dans l’ensemble, ces données précliniques suggèrent que les PARPi ont des propriétés immunomodulatrices intrinsèques qui participent à l’activation de réponses immunitaires anti-tumorales ; ce potentiel pourrait être exploité cliniquement en combinaison avec les ICI dans des populations adéquatement sélectionnées au plan moléculaire. / Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as BRCA1/2 mutations or ERCC1 defects. Clinically, several PARPi are currently approved for the treatment of BRCA-mutant or platinum-sensitive advanced ovarian and breast cancers, and ongoing clinical trials are investigating the efficacy of PARPi in platinum-sensitive Non-Small Cell Lung Cancer (NSCLC). While PARPi constitute potent targeted therapies for the treatment of DNA repair-deficient malignancies, an increasing number of clinical trials are also evaluating their efficacy in combination with immune checkpoint inhibitor (ICI) in various populations. In this context, it is of critical importance to better understand how PARPi might modulate immune responses against cancer, and to investigate the inherent immunological potential of these agents.In this study, we show that ERCC1-defective NSCLC cells exhibit an enhanced type I interferon (IFN) transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration in human NSCLC tumours. Using isogenic cell lines and patient-derived xenografts, we further demonstrate that several clinical PARPi, including olaparib and rucaparib, display cell-autonomous immunomodulatory properties in ERCC1-defective NSCLC and BRCA1-mutant triple-negative breast cancer (TNBC) models. Mechanistically, PARPi generate cytoplasmic chromatin fragments with micronuclei characteristics; this activates the cGAS/STING pathway and elicits downstream type I IFN signalling and CCL5 secretion. Importantly, these effects are suppressed in BRCA1-reverted TNBC cells and ERCC1-rescued NSCLC cells, suggesting that DNA repair defects exacerbate the innate immunity-related phenotypes triggered by PARPi. Similarly, these effects are totally abrogated in PARP1-null TNBC cells, supporting the on-target effect of PARPi in mediating such phenotypes. Besides this potential to activate tumour cell-autonomous immunity through cGAS/STING and type I IFN signalling, we also observed that PARPi synergize with type II IFN to induce PD-L1 expression in NSCLC cell lines and fresh patient tumour cells, especially in the ERCC1-deficient setting. Moreover, we show that lethal concentrations of some PARPi independently activate the key damage-associated molecular patterns dictating the immunogenicity of cancer cell death, including calreticulin exposure at the tumour cell surface, ATP secretion and HMGB1 release in the extracellular compartment.Together, these preclinical data suggest that PARPi have intrinsic immunomodulatory properties that activate anti-cancer immune responses; this could be exploited clinically in combination with ICI in appropriately molecularly-selected populations.
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Tikhonov regularization with oversmoothing penaltiesGerth, Daniel 21 December 2016 (has links)
In the last decade l1-regularization became a powerful and popular tool for the regularization of Inverse Problems. While in the early years sparse solution were in the focus of research, recently also the case that the coefficients of the exact solution decay sufficiently fast was under consideration. In this paper we seek to show that l1-regularization is applicable and leads to optimal convergence rates even when the exact solution does not belong to l1 but only to l2. This is a particular example of over-smoothing regularization, i.e., the penalty implies smoothness properties the exact solution does not fulfill. We will make some statements on convergence also in this general context.
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Utvärdering av biomarkörerna PD-L1 och calretinin i parade histologiska och cytologiska provmaterial från patienter med mesoteliom / Evaluation of the biomarkers PD-L1 and calretinin in paired histological and cytological specimen from patients with mesotheliomaAndersson, Anni January 2023 (has links)
Malignt mesoteliom är en ovanlig och aggressiv cancerform. Den är vanligast i pleura och kallas då pleuralt mesoteliom. Vanligaste orsaken till utveckling av pleuralt mesoteliom är exponering för asbest. Insjuknande patienter har dålig prognos och begränsade behandlingsmöjligheter. Röntgen kan i ett första stadie ge diagnos av sjukdomen. Oftast behövs också en biopsi tas för fastställande av diagnos. Även provtagning av pleuravätskan kan ge värdefull diagnostisk information. Immunhistokemi är en viktig tilläggsanalys för diagnos med biopsier och cellblock. Immunhistokemi innebär färgning med antikroppar. För pleuralt mesoteliom kan exempelvis antikropparna PD-L1 och calretinin användas för diagnostisering. I denna studie färgades 10 parade pleurabiopsier och cellblock från pleuravätska från patienter med malignt mesoteliom. Antikropparna PD-L1 och calretinin användes. Syftet var att utvärdera uttrycket av PD-L1 och calretinin. Alla infärgade glas undersöktes i ljusmikroskop. För PD-L1 ansågs enbart membranfärgning som positivt infärgad och för calretinin ansågs cytoplasmatisk och/eller kärnfärgning som positiv. Procentuellt antal positiva tumörceller undersöktes vid två cutoff värden, ≥1 % och ≥10 %. Procentuellt antal <1 % vid cutoff ≥1 % och procentuellt antal <10 % vid cutoff ≥10 % ansågs negativt. Detta gällde för båda antikropparna. Antal positiva och negativa biopsier samt cellblock och konkordansen redovisades. Overall percentage agreement (OPA), Cohen’s kappa (κ) och konfidensintervall (CI) beräknades också. Resultatet visade på lägre antal positiva färgningar för cellblocken jämfört med biopsierna för båda antikropparna. För konkordansen visades att den vara lika för PD-L1 och calretinin vid cutoff ≥1 % men högre för PD-L1 än för calretinin vid cutoff ≥10 %. / Malignant mesothelioma is a rare and aggressive cancer. It is most common in the pleura, called pleural mesothelioma. The most common reason for developing pleural mesothelioma is exposure to asbestosis. Patients that get sick have a poor prognosis and limited treatment options. X-ray can in a first stadium give diagnose of the disease. A biopsy is often necessary to confirm the diagnosis. Even sampling of pleural fluid can give valuable diagnostic information. Immunohistochemistry is a common additional analysis for diagnosis with biopsy and cell block. Immunohistochemistry implies staining with antibodies. For example, for pleural mesothelioma the antibodies PD-L1 and calretinin can be used for diagnosis. In this study 10 paired pleural biopsies and cell blocks from pleural fluid from patients with malign mesothelioma were immunostained. The study aimed to evaluate expression of PD-L1 and calretinin. All the stained glasses were evaluated by a light microscope. For PD-L1, only membranous staining was considered positive and for calretinin cytoplasmic and/or nuclear staining was considered positive. Percentage number of positive tumor cells were evaluated at two cutoff values, ≥1 % and ≥10 %. Percentage number <1 % at cutoff ≥1 % and percentage number <10 % at cutoff ≥10 % were considered negative. The same criteria were applied for both antibodies. The number of positive and negative biopsies as well as cell blocks and the concordance were reported. Overall percentage agreement (OPA), Cohen’s kappa (κ) and confidence interval (CI) was also calculated. Result showed lower number of positive staining for the cell blocks than for the biopsies for both antibodies. The concordance was shown to be equal for PD-L1 and calretinin at cutoff ≥1 % but higher for PD-L1 than for calretinin at cutoff ≥10 %.
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Språkvalet i engelskundervisningen : En studie om lärares språkval i engelskundervisningen i årskurs 4–6 / A study on teachers' choice of language in English teaching in grades 4–6Wessling Reisenhofer, Alexandra January 2022 (has links)
Lärare reflekterar ofta kring vilket språk av svenska och engelska som ska användas mest i engelskundervisningen. Syftet med detta examensarbete är att undersöka lärares val av språk i engelskundervisningen samt vad de ser för konsekvenser med att använda svenska respektive engelska under engelsklektionerna. Syftet är också att undersöka hur elever tänker kring språkvalet som lärare gör när de har engelska. I denna studie genomfördes tre semistrukturerade intervjuer med lärare, verksamma eller har varit verksamma i engelska i årskurs 4–6, samt en enkät, utdelad som en survey till elever i årskurs 6 (12 år) och besvarades av 20 elever. Slutsatsen av denna studie visar att lärare vill använda den mängden engelska som är möjligt, men att svenskan behöver användas som ett hjälpmedel, främst till svaga elever i engelska. Konsekvenser med att använda engelskan visar enligt resultatet att svaga elever får svårigheter att förstå vad som ska göras under engelsklektioner. Konsekvenser med att använda svenskan blir enligt lärare att eleverna tappar en del engelska och att de inte får öva på sina språkliga strategier. Majoriteten av eleverna i studien har bekräftat att de är nöjda med lärares språkval på engelsklektionerna. Många elever föredrar också att både svenskan och engelskan används. / Teachers often reflect on which language of Swedish and English should be used mostly in English teaching. The purpose of this thesis is to investigate teachers' choice of language in English teaching and what they see as consequences of using Swedish and English respectively during English lessons. The purpose is also to investigate how students think about the language choice that teachers make when they have English. In this study, three semi-structured interviews were conducted with teachers working or have been working in English in grades 4–6, as well as a questionnaire, distributed as a survey to students in grade 6 (12 years old) and answered by 20 students. The conclusion of this study shows that teachers want to use as much English as possible, but that Swedish needs to be used as an aid, mainly for weak students in English. Consequences of using English shows according to the results that weak students have difficulties in understanding what to do during English lessons. According to teachers, negative consequences of using Swedish are that the students lose some English and that they do not get to practice their linguistic strategies. The majority of the students in the study have confirmed that they are satisfied with the teachers' choice of language in the English lessons. Many students also prefer that both Swedish and English are used.
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"We live in Sweden; We use Swedish to understand" : A study on L1 functions and students' attitudes toward L1 use in a Swedish L2 English learning environmentPettersson, Johanna January 2024 (has links)
This study aims to explore Swedish upper secondary students’ attitudes toward first language (L1) use in a second language (L2) English learning environment. In addition, it aims to explore the functions of L1 use. Through a qualitative approach with both observations and interviews, a pattern of L1 use was noticed. The results corroborate prior research on student attitudes and show that students are positive toward L1 use. Swedish students tend to use their L1 through translanguaging and codeswitching as a tool for understanding, and as a way to establish relationships. In other words, L1 use needs to be considered a natural part of their L2 learning environment, even though they also understand the importance of exposure to and use of English in the classroom in order to become proficient in it. The students’ attitudes thus challenge the monolingual approach that is predominantly used in Swedish upper secondary schools today.
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Role of the L1 in FL classrooms: learner and teacher beliefs, attitudes, and practicesSamadi, Mohammad Rahim January 1900 (has links)
Master of Arts / Department of Modern Languages / Abby Franchitti / The role of first language (L1) has been controversial in foreign language (FL) learning and teaching. This study examines the relationship between L1 use and gender and level of education of EFL teachers as well as gender and EFL proficiency level of learners in an Afghan university setting. It also investigates the relationship between FL use and learner anxiety by learner gender and EFL proficiency level. The study hypothesized that female FL teachers use the L1 more than male teachers in FL classrooms. Second, low FL proficiency learners consider L1 use as necessary in FL classrooms. Third, low FL proficiency students experience more anxiety with the exclusive use of FL than higher level learners. Fourth, female learners experience more anxiety than male students with the exclusive use of FL by learners and teachers.
Twenty EFL teachers participated in the study by completing a 19-item questionnaire and sixty EFL learners by completing a 27-item questionnaire about their views towards L1/FL use and learner anxiety. The data, analyzed through SPSS software, included calculating frequencies and percentages, computing correlations, and conducting independent-samples t-tests to compare the mean difference between the variables.
The first hypothesis was not supported as male teachers reported using the L1 more than female teachers. The study also revealed that male teachers with BA and MA degrees used the L1 more than female teachers with BA degrees. In contrast, female teachers with MA degrees used the L1 more than male teachers with BA and MA degrees and also more than female teachers with BA degrees. The results supported hypothesis two. More elementary learners considered the use of L1 as necessary than intermediate and advanced students. The findings also supported hypotheses three and four. Elementary learners as well as female students experienced more anxiety with the exclusive use of FL than intermediate and advanced level students and male learners. The principal conclusion indicated a significant positive correlation between the exclusive use of FL and learner anxiety.
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L1 AND L2 DOCTORAL STUDENTS’ INTERTEXTUALITY AND ACADEMIC LITERACIES AT THE GCLR WEB SEMINARSAngay-Crowder, Tuba 13 May 2016 (has links)
The new world of academic discourse is complex and necessitates that L1 and L2 graduate students learn a multiplicity of texts, master intertextuality, and actively participate in emerging literacies or genres of their disciplines (Molle & Prior, 2008; Swales, 2004; Warren, 2013). Challenges arise about how doctoral students produce, interpret, and learn texts and genres, and how they act and react around text production in particular multicultural institutional contexts (Hyland, 2000; Prior, 2004). Little is known about how students, particularly those in higher education, establish intertextual connections among different modes of texts (e.g., written, oral, visual) for actively engaging in literacy (Belcher & Hirvela, 2008; Seloni, 2012).
The purpose of this study is to examine how L1 and L2 doctoral students use intertextual practices to create meaning and develop their academic literacies during the literacy events of Global Conversations and Literacy Research (GCLR) web seminars. Drawing upon microethnographic discourse analysis, more particularly the constructs of intertextuality (Bloome, & Carter, 2013), I investigate the following questions a) How are the L1 and L2 students engaged in intertextual practices in the literacy events of GCLR web seminars? b) How does the use of intertextuality contribute to L1 and L2 students’ academic literacies?
The participants are two L1 and two L2 doctoral students, who are also multilinguals, had different first languages (i.e., Korean, English, Chinese), and actively engaged in the GCLR web seminars. Data drew upon interviews, chat transcriptions, video recordings of the web seminars, and visuals. Data collection and analyses began in September 2014, and continued through November 2015. Microethnographic discourse analysis showed how participants constructed intertextual connections during the literacy events of the GCLR web seminars.
The findings show how L1 and L2 doctoral students used intertextuality to socialize into academic discourse, mediate discoursal identities, and develop cultural models. The study has implications for L1 and L2 pedagogy, multilingual’s learning, and research: Future research should investigate academic literacies with intertextual connections to oral, written, and online discourses. Educators and graduate students are encouraged to exploit the full potential of intertextuality through metacognition in emerging academic literacies and mediated discoursal identities.
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