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Mécanismes d'immunosuppression induits par la tumeur chez les patients porteurs de mélanomeFourcade, Julien 05 July 2012 (has links)
Les lymphocytes T cytotoxiques (CTLs) présents au niveau des tumeurs reconnaissent des antigènes présentés par les cellules cancéreuses, mais ne parviennent pas à induire le rejet de ces tumeurs chez les patients cancéreux. Cette observation a amené les immunologistes à étudier les différents mécanismes d'immunosuppression induits par les tumeurs qui permettent aux cellules cancéreuses d'échapper à la reconnaissance et à la destruction immunitaires. L'un des mécanismes contribuant à la résistance des tumeurs aux réponses immunitaires est le recrutement de lymphocytes T CD4+ régulateurs (Tregs). Les Tregs s'accumulent au niveau des sites tumoraux et jouent un rôle important dans la suppression des réponses immunitaires dirigées contre les cellules tumorales. Dans ce travail de thèse, nous rapportons que des épitopes tumoraux dérivés des protéines NY-ESO-1 et TRAG-3 stimulent à la fois des lymphocytes T CD4+ auxiliaires (Th) et des Tregs chez des patients porteurs de mélanome. Grâce à une analyse clonotypique, nous démontrons que, contrairement aux cellules CD4+ Th, les TCR des Tregs dirigés contre NY-ESO-1 et TRAG-3 sont retrouvés à la fois dans le répertoire des Tregs naturels (CD4+CD25high) et dans celui des cellules T CD4+ classiques/Th (CD4+CD25-), au niveau des PBMCs des patients. Cette observation suggère que le recrutement des Tregs spécifiques d'antigènes tumoraux se fait en partie par la conversion des cellules T CD4+ classiques suite à leur stimulation chronique par des antigènes de tumeurs. / Cytotoxic T lymphocytes (CTLs) present in tumors recognize tumor antigens presented by cancer cells but fail to induce tumor rejection in patients. This observation has led immunologists to study the different mechanisms of tumor-induced immunosuppression that allow cancer cells to escape from recognition and destruction by the immune system. One of the mechanisms contributing to tumor resistance to immune responses is the recruitment of CD4+ regulatory T cells (Tregs). Tregs accumulate at tumor sites and play an important role in suppressing immune responses against tumor cells. In this thesis, we report that tumor epitopes derived from the proteins NY-ESO-1 and TRAG-3 stimulate both CD4+ T helper cells (Th) and Tregs in patients with metastatic melanoma. Through clonotypic analysis, we show that, within PBMCs of melanoma patients, tumor antigen-specific Tregs, but not Th cells, share a common TCR usage with naturally-occuring Tregs (CD4+CD25high) and Th cells (CD4+CD25-), suggesting that their recruitment occurs through the peripheral conversion of CD4+CD25- T cells upon chronic antigen exposure. The second part of this thesis consists of the study of inhibitory receptors expressed by CTLs directed against tumor antigens which, upon engagement by their ligands presented on the surface of tumor cells, activate negative regulatory pathways. Here, we report that tumor-induced CTLs directed against a peptide derived from NY-ESO-1 in melanoma patients upregulate the expression of the inhibitory receptors PD-1, Tim-3 and BTLA. Additionaly, the co-expression of PD-1 with Tim-3 and/or BTLA defines populations of dysfunctional tumor antigen-specific CTLs.
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Direito penal e prevenção criminal: as experiências de São Paulo e Nova Iorque / Criminal law and criminal prevention: the measures implemented in the São Paulo and New YorkVilardi, Rodrigo Garcia 29 May 2014 (has links)
A presente tese tem por objetivo investigar a relação entre o Direito Penal e a prevenção criminal, especialmente, no que se refere à possibilidade de construção de uma Política Criminal, fundada em conhecimentos produzidos pela Criminologia, que seja consentânea com os princípios e garantias do Direito Penal. No primeiro capítulo é apresentada a premissa de que a missão única e exclusiva do Direito Penal em um Estado Democrático de Direito deve ser a de proteger bens jurídicos que sejam valiosos para a preservação de uma determinada sociedade. Essa missão atribuída ao Direito Penal deve considerar os relevantes argumentos apresentados durante os debates realizados no âmbito das teorias da pena. Neste sentido, em que pese a existência de relevantes posicionamentos agnósticos e retributivos em relação à sanção e ao próprio Direito Penal, o conceito de prevenção criminal limitada ainda se apresenta como o mais apto a equacionar os desafios inerentes ao ius puniendi, assim como fundamentálo. Mais do que um sistema teórico complexo, no segundo capítulo visa-se demonstrar como este conceito pode ser viabilizado a partir da construção de uma Política Criminal que, não limitada às respostas jurídico-penais, resulte da relação dialética entre os conhecimentos produzidos no âmbito da Criminologia Crítica e da Criminologia Tradicional. Sob esta perspectiva, a ideia apresentada por Winfried Hassemer de substituição de uma prevenção normativa por uma prevenção organizacional pode subsidiar a construção dessa Política Criminal. Para exemplificar esta hipótese teórica, no terceiro capítulo analisam-se medidas implementadas na cidade de Nova Iorque com a finalidade de enfrentar o problema do Motor Vehicle Theft e que tiveram resultados positivos e consentâneos com o conceito de prevenção organizacional em contraposição com as ações de prevenção criminal desenvolvidas no âmbito dos furtos e roubos de veículos na cidade de São Paulo os quais, por sua vez, focaram em simples alterações de normas, exclusivamente, sob o aspecto de uma prevenção normativa. A distinção de resultados confirma a hipótese de que estudos criminológicos, fundados no conceito de prevenção organizacional, podem subsidiar a construção de uma Política Criminal que previna crimes sem desconsiderar os princípios informadores de um Direito Penal Mínimo. / This doctoral thesis aims to investigate the relationship between Criminal Law and crime prevention, especially with regard to the possibility of building a Criminal Policy founded on knowledge produced in the context of Criminology, which is consistent with the principles and guarantees of Criminal Law. The premise that the sole and exclusive mission of the Criminal Law in a Democratic State of Law must be to protect the legal interests which are valuable for the preservation of a given society is presented in the first chapter. This mission, assigned to Criminal Law, should consider the relevant arguments presented during the discussions held with respect to the \"theories of punishment\". Accordingly, despite the existence of relevant agnostic and retributive positions in relation to sanction and Criminal Law itself, the concept of \"limited crime prevention\" is still presented as the most apt to equate the challenges of ius puniendi, as well as ground it. More than a complex theoretical system, in the second chapter, we aim to demonstrate how this concept may be made possible through the construction of a Criminal Policy which, not limited to legal and criminal responses, results from the dialectical relationship between the knowledge produced within Critical Criminology and Traditional Criminology. From this perspective, the idea presented by Winfried Hassemer of replacing a \"normative prevention\" by an \"organizational prevention\" may subsidize the construction of Criminal Policy. To illustrate this theoretical hypothesis, in the third chapter, we analyze measures implemented in the City of New York in order to address the problem of Motor Vehicle Theft and which had positive results, consistent with the concept of \"organizational prevention\", as opposed to the actions developed under the crime prevention of thefts and motor vehicle thefts in the City of São Paulo, which focused on simple changes in rules and only under the aspect of a \"normative prevention\". The distinction of results confirms the hypothesis that criminological studies, based on the concept of \"organizational prevention\", may support the construction of a Criminal Policy that prevents crimes without disregarding the informing principles of Minimum Criminal Law.
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Direito penal e prevenção criminal: as experiências de São Paulo e Nova Iorque / Criminal law and criminal prevention: the measures implemented in the São Paulo and New YorkRodrigo Garcia Vilardi 29 May 2014 (has links)
A presente tese tem por objetivo investigar a relação entre o Direito Penal e a prevenção criminal, especialmente, no que se refere à possibilidade de construção de uma Política Criminal, fundada em conhecimentos produzidos pela Criminologia, que seja consentânea com os princípios e garantias do Direito Penal. No primeiro capítulo é apresentada a premissa de que a missão única e exclusiva do Direito Penal em um Estado Democrático de Direito deve ser a de proteger bens jurídicos que sejam valiosos para a preservação de uma determinada sociedade. Essa missão atribuída ao Direito Penal deve considerar os relevantes argumentos apresentados durante os debates realizados no âmbito das teorias da pena. Neste sentido, em que pese a existência de relevantes posicionamentos agnósticos e retributivos em relação à sanção e ao próprio Direito Penal, o conceito de prevenção criminal limitada ainda se apresenta como o mais apto a equacionar os desafios inerentes ao ius puniendi, assim como fundamentálo. Mais do que um sistema teórico complexo, no segundo capítulo visa-se demonstrar como este conceito pode ser viabilizado a partir da construção de uma Política Criminal que, não limitada às respostas jurídico-penais, resulte da relação dialética entre os conhecimentos produzidos no âmbito da Criminologia Crítica e da Criminologia Tradicional. Sob esta perspectiva, a ideia apresentada por Winfried Hassemer de substituição de uma prevenção normativa por uma prevenção organizacional pode subsidiar a construção dessa Política Criminal. Para exemplificar esta hipótese teórica, no terceiro capítulo analisam-se medidas implementadas na cidade de Nova Iorque com a finalidade de enfrentar o problema do Motor Vehicle Theft e que tiveram resultados positivos e consentâneos com o conceito de prevenção organizacional em contraposição com as ações de prevenção criminal desenvolvidas no âmbito dos furtos e roubos de veículos na cidade de São Paulo os quais, por sua vez, focaram em simples alterações de normas, exclusivamente, sob o aspecto de uma prevenção normativa. A distinção de resultados confirma a hipótese de que estudos criminológicos, fundados no conceito de prevenção organizacional, podem subsidiar a construção de uma Política Criminal que previna crimes sem desconsiderar os princípios informadores de um Direito Penal Mínimo. / This doctoral thesis aims to investigate the relationship between Criminal Law and crime prevention, especially with regard to the possibility of building a Criminal Policy founded on knowledge produced in the context of Criminology, which is consistent with the principles and guarantees of Criminal Law. The premise that the sole and exclusive mission of the Criminal Law in a Democratic State of Law must be to protect the legal interests which are valuable for the preservation of a given society is presented in the first chapter. This mission, assigned to Criminal Law, should consider the relevant arguments presented during the discussions held with respect to the \"theories of punishment\". Accordingly, despite the existence of relevant agnostic and retributive positions in relation to sanction and Criminal Law itself, the concept of \"limited crime prevention\" is still presented as the most apt to equate the challenges of ius puniendi, as well as ground it. More than a complex theoretical system, in the second chapter, we aim to demonstrate how this concept may be made possible through the construction of a Criminal Policy which, not limited to legal and criminal responses, results from the dialectical relationship between the knowledge produced within Critical Criminology and Traditional Criminology. From this perspective, the idea presented by Winfried Hassemer of replacing a \"normative prevention\" by an \"organizational prevention\" may subsidize the construction of Criminal Policy. To illustrate this theoretical hypothesis, in the third chapter, we analyze measures implemented in the City of New York in order to address the problem of Motor Vehicle Theft and which had positive results, consistent with the concept of \"organizational prevention\", as opposed to the actions developed under the crime prevention of thefts and motor vehicle thefts in the City of São Paulo, which focused on simple changes in rules and only under the aspect of a \"normative prevention\". The distinction of results confirms the hypothesis that criminological studies, based on the concept of \"organizational prevention\", may support the construction of a Criminal Policy that prevents crimes without disregarding the informing principles of Minimum Criminal Law.
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Är det lagligt att länka? : En upphovsrättslig undersökning och värdering av EU-domstolens hantering av länkar, särskilt i förhållande till ny publik-rekvisitet / The Legality of Linking : An Assessment of the Copyright Protection of Hyperlinks According to the CJEU, Focusing on its Usage of the New Public CriterionPremfors, Alida January 2020 (has links)
Enligt infosoc-direktivets artikel 3 har upphovsmän en ensamrätt att överföra sina verk till allmänheten. EU-domstolen har i en rad mål nått slutsatsen att publiceringen av länkar som leder till ett verk utgör en överföring av verket till allmänheten. När en länk leder till ett lagligen uppladdat verk, som tillgängliggjorts gratis, är den emellertid att betrakta som tillåten och kräver inte upphovsmannens samtycke. Detta beror på att länken under dessa omständigheter inte anses ha tillgängliggjort verket för en ny publik. Kravet på att en överföring, för att höra till ensamrätten, måste ske till en ny publik framgår inte av infosoc-direktivets lydelse. Rekvisitet har utvecklats i praxis, med åberopande av framförallt internationell rätt. Denna uppsats syftar till att undersöka hur länkar hanteras av EU-domstolen, samt om domstolens praxis till sin metod respektive till sina resultat är lämplig. Min slutsats är att ny publik-rekvisitet saknar stöd i såväl infosoc-direktivet som internationell rätt, och att det till och med i vissa delar framstår som svårförenligt med dessa rättskällor. Genom en praxisgenomgång når jag slutsatsen att ny publik-rekvisitet har tillämpats på ett anmärkningsvärt inkonsekvent sätt, och att detta antagligen kan förklaras med en ändamålshänsyn som inte uttalats i domskälen. Generellt framstår ny publik-rekvisitet som ett verktyg EU-domstolen använt då de velat nå slutsatsen att ett visst agerande antingen ska vara tillåtet eller ej, och stöd för detta saknats i rättskällorna. När det kommer till länkar har alltså ny publik-rekvisitet använts för att motivera att dessa ska vara tillåtna. Utifrån en avvägning mellan upphovsmannens intressen och intresset av informations- och yttrandefrihet anser jag att EU-domstolens inställning som huvudregel är befogad. Jag anser dock att det finns vissa omständigheter som i det specifika fallet skulle kunna motivera att en viss länkningsåtgärd bör betraktas som ett intrång. Särskilt ser jag att sådana situationer skulle kunna komma att uppstå då material inbäddas i vinstsyfte på ett sätt som konkurrerar med upphovsmannens tillgängliggörande av verket. Utifrån EU-domstolens hittills avlagda praxis framstår det som svårt att beakta dessa omständigheter inom ramen för ny publik-rekvisitets tillämpning. Sammantaget når jag slutsatsen att ny publik-rekvisitet inte utgör ett effektivt och lämpligt verktyg för att dra gränsen mellan tillåtna och otillåtna överföringar till allmänheten. Länkar hade kunnat hanteras på ett nyanserat sätt där majoriteten, men inte alla, tillåts även utan ny publik-rekvisitet. Om inte annat bör ny publik-rekvisitet omdefinieras så att det kan leda till lämpliga resultat även med en konsekvent tillämpning, och så det går att förena med övrig upphovsrättslig reglering. / According to Article 3 in the InfoSoc Directive, the creator of a creative work owns the exclusive right to communicate his work to the public. The CJEU has made it clear that the act of hyperlinking to a webpage where a work has been uploaded constitutes communication to the public. However, when a link leads to a creative work that has been uploaded freely and legally, the act of linking does not constitute a copyright infringement. This is motivated by the notion that a link under those circumstances does not communicate the work to a new public. The perception that a communication, to constitute an infringement, must be made to a new public is not based on the writings in the InfoSoc Directive. The criterion is developed by the CJEU, referring primarily to international law. This essay is an investigation of whether and under which circumstances linking constitutes a copyright infringement according to the CJEU. The approach chosen by the court is evaluated, considering both the suitability of its methods and its results. My conclusion is that the new public criterion lacks support in superior legal sources. To some degree, the criterion even appears discordant with both union and international law. Looking at the CJEU rulings, I reach the conclusion that the new public criterion has been used and defined in a remarkably inconsistent manner, and that this is probably due to an application of the criterion in accordance with a desired outcome. The new public criterion is, inter alia, used to support that the act of linking does not constitute an infringement. With consideration for both the interests of the rightsholder and the freedom of expression, I deem it suitable to let most links fall without the scope of the creator’s exclusive right. There are, however, circumstances under which I think it could be suitable to let a specific link fall within the rights of the creator. Such a situation could be at hand when imbedded links are used for profit by an actor in direct competition with the rightsholder. The rulings by the CJEU do not, as of yet, open up for such circumstances to be taken into consideration when applying the new public criterion. In conclusion, I believe that the new public criterion does not constitute an effective or suitable tool for drawing the line between lawful and unlawful communications to the public. Links can be handled in a nuanced way where the majority, but not all, are allowed – without the new public criterion. If nothing else, the new public criterion should be redefined so that it can lead to suitable results with a consistent definition, and to make it reconcilable with international and union copyright law.
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Place Identity in Ny Ellebjerg : A study of the place identity transformation of a post-industrial neighbourhood.Valentin Rasmussen, Sofie January 2022 (has links)
This research investigates two neighbourhoods around the train and S-train Ny Ellebjerg in South of Valby, which is a part of Copenhagen. The area, which is a post-industrial area, includes several old factory buildings renovated as office- and workspaces. The research aims to investigate the identity transformation in the area and the influence of the recent development plans in the identity. Therefore, the research questions are: How has the place identity of Ny Ellebjerg changed from being industrial to a densely built neighbourhood and what do the plans indicate for the future? How has the development plans and local plans contributed to the place identity transformation of the Ny Ellebjerg area? The thesis will answer these questions with a triangulation between a content analysis on the involved development plans, local plans and municipal plans, and expert interviews as well as walk-along interviews with residents from the area. The findings of the thesis showed that identity of Ny Ellebjerg has changed from being mainly industrial into a city environment inspired by the forms of the industrial constructions, but with a lot of the buildings perceived as very similar to other areas standardized architecture. The plans for the future indicate that it is necessary to plan with more focus on the residents living in the area. The findings of this thesis showed connections between the wish to preserve the area and turn it into a post-modern, post-industrial area with close ties to its past. The aims of the local plan were not realised fully, since the Følager development was only half built and much of the green areas shown in the illustrations was also found to have not been made, due to it not being directly stated in units in the plans.
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Tethered balloon measurements during Arctic spring conditions in Ny-Ålesund in the framework of HALO-(AC)3Lonardi, M., Ehrlich, A., Müller, J., Saavedra Garfias, P., Wendisch, M. 08 December 2023 (has links)
The tethered balloon system BELUGA (BalloonbornE moduLar Utility for
profilinG the lower Atmosphere) was operated in spring 2022 at the AWIPEV research
station (Ny-Ålesund, Svalbard). In-situ profiles of thermodynamic parameters, thermalinfrared
radiation, aerosol particle concentrations, and turbulence, were measured and
analyzed. Additionally, samples of ice-nucleating particles were collected at various
heights. In combination with previous BELUGA datasets, measurements from this
campaign provide a solid base for studying the vertical profiles of the radiative energy
budget and heating rates in different atmospheric states in the Arctic lower troposphere.
Here, example thermal-infrared radiation profiles are presented for a period of persisting
cloudless conditions related to a series of marine cold air outbreaks in late March/early
April. Measurements in clouds are analyzed for a developing cloud observed on 6 May
and display the impact of cloudiness on radiation profiles. / Das Fesselballonsystem BELUGA (BalloonbornE moduLar Utility
for profilinG the lowerAtmosphere) wurde im Frühjahr 2022 an der Forschungsstation
AWIPEVStation (Ny-Ålesund, Svalbard) eingesetzt. In-situ-Profile von thermodynamischen
Parametern, terrestrische Strahlung, Aerosolpartikelkonzentrationen und Turbulenz
wurden gemessen und ausgewertet. Zusätzlich wurden in verschiedenen Höhen Proben
von eiskeimbildenden Partikeln gesammelt. In Kombination mit früheren BELUGA
Messungen zu anderen Jahreszeiten und an anderen arktischen Messstandorten bieten die
Messungen in Ny-Ålesund eine Grundlage fürweitereUntersuchungen des Strahlungsenergiehaushalts
und des Einflusses vonWolken auf atmosphärische Heizraten. Profile der
Strahlungsbilanz werden für eine anhaltende Kälteperiode zwischen Ende März bis Anfang
April 2022 vorgestellt. Über diesen Zeitraum herrschten vor allem wolkenlose
Bedingungen. Weitere Beobachtungen unter einer sich entwickelnden Wolkendecke am
6. Mai 2022 zeigen den Einfluss der Bewölkung auf die Strahlungsprofile.
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It's a Match! : En kvalitativ studie om attityder och behovstillfredsställelse utifrån användningen av mobilapplikationen Tinder.Alm, Mathilda, Kullberg, William January 2015 (has links)
Syftet med denna undersökning var att ta reda på vilka attityder kring mobilapplikationen Tinder det fanns hos tio unga människor samt om det uppkommit nya behov i och med denna nya teknik där man sveper mellan olika människor. För att få fram ett resultat utfördes tio kvalitativa intervjuer med människor i åldrarna 18-30. Teorierna som kompletterade det insamlande materialet var uses & gratifications teorin som bland annat belyser hur publiken använder medier och vad de får ut av användningen, samt Castells teori om nätverkssamhället där teknologin och dess utveckling spelar stor roll för hur vi använder oss av medier och kommunikation på distans. De kvalitativa intervjuade visade att användningen av applikationen inte var i nätdejtingssyfte. Respondenterna använde snarare applikationen för att bland annat tillfredsställa ett emotionellt behov där ett bekräftelsesökande visade sig vara större än viljan att kommunicera med människor. Även ett avkopplingsbehov existerade, där respondenterna använde applikationen i brist på något annat att göra. Många av Tinders funktioner förstärkte dessa behov, bland annat det utseendebaserade användningsområdet samt applikationens enkelhet i sig.
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Spectroscopic studies of the tropospheric boundary layerNorton, Emily G. January 2006 (has links)
This thesis presents a development to the technique of rotational Raman lidar by, incorporating an imaging spectrometer in conjunction with a clocking CCD detection system. This allowed the rotational Raman spectra of nitrogen and oxygen to be simultaneously recorded as a function of altitude. The rotational Raman spectra were uses to calculate temperature profiles. Recording the complete band envelopes of the rotational Raman spectra removed the need for an external reference, such as a radiosonde. Results are presented from measurements made in Cambridge in chapter 4 and Ny-Alesund in chapter 6. Chapter 7 presents some conventional lidar backscatter measurements made using a PMT in Birmingham during the winter part of the pollution in the Urban Midlands Area (PUMA) campaign. These measurements were used to determine the cloud base and the planetarty boundary layer height. Two automated algorithms were tested at retrieving the PBL height, the inflection point method and the centroid method.
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Nya utmanare – nya strategier? : Etablerade partier bemöter ny konkurrensStröm, Anna January 2016 (has links)
The purpose of this study is to examine the strategic choice of mainstream parties in relation to the competition of voters posed by a niche party and their most important issue, in this case radicalist rightwing populists and the migration issue. The study uses a comparative approach to examine the mainstream parties Social Democrats and Moderates reaction to the niche parties New Democracy 1991-1994 and Sweden Democrats 2010-2015. Using Meguid´s PSO-theory and by performing an qualitative analyse of the parties rhetoric and political suggestions in the parliamentary debates as well as in government bills and reservations in committee reports, the study aims to describe mainstream parties position on the issue and if and how they change position and strategy. The results of the study shows that both mainstream parties over all applies an adversarial strategy, aiming to maintain distance to the niche party and its position but with time and due to changes in the political environment, changes in position and strategy takes place and the mainstream parties applies a slightly more accommodative strategy.
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Lokalt, lojalt och betalt : En kvalitativ studie av Mittmedias lansering av nyhetsapplikationerAhlberg, Rasmus, Boström, Isak January 2016 (has links)
Problemformulering och syfte: Lokaltidningarnas pappersupplagor minskar i Sverige. De digitala plattformarna blir allt viktigare för mediehusen när människor i allt större utsträckning övergår till att konsumera medier via sina mobiltelefoner. En naturlig del i utvecklingen blir att medierna följer samma väg, för att på det viset också i fortsättningen nå ut till sin publik, och på längre sikt säkra och stärka sin ekonomi. Syftet med vår studie är att undersöka varför svenska lokalmedier väljer att implementera nya tekniker och det gör vi genom att i en fallstudie följa mediekoncernen Mittmedias satsning på mobila och digitala plattformar när koncernen lanserar nyhetsapplikationer och push-notiser under hösten 2015. Vi studerar hur lanseringen förbereds, vilka strategier och drivkrafter som är inblandade och hur lanseringen genomförs på fyra olika redaktioner inom Mittmedia. Metod och material: Vi inleder med att studera och själva använda test-versionerna av applikationerna och deltar på Mittmedias förberedande möten. Vi genomför sedan kvalitativa och semistrukturerade samtalsintervjuer med digitalchefer på respektive redaktion som ingår i undersökningen, samt den redaktionellt utvecklingsansvarige på Mittmedia. Intervjuerna genomförs dels i samband med att nyhetsapplikationerna släpps ut till allmänheten, dels några veckor senare i uppföljande syfte. Huvudresultat: Vi kommer fram till tre nyckelord: Lokalt, lojalt och betalt, som tillsammans sammanfattar det breda spektrumet i lanseringen.
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