Yrkeskategorin personlig assistans uppkom 1994 genom assistansreformen. Yrketsyftar till att främja jämlika levnadsvillkor och delaktighet i samhällslivet förmänniskor med funktionshinder. Yrket kan upplevas som svårt då den personligaassistenten dras mellan två lagrum; brukarens självbestämmande kontra den egnaarbetsmiljön. Syftet med studien var att undersöka hur personliga assistenter,anställda av Halmstad kommun, upplever sitt yrke då yrkeskategorin är starktpåverkad av brukarens lagstadgade rättigheter. Studien genomfördes genomvägledning av följande frågeställningar: Hur beskriver assistenter sin relation till brukare ochvad har relationen för betydelse för assistentens upplevelse av arbetet? Hur upplever assistenter attderas arbetsrättsliga behov tillgodoses? Hur upplever assistenterna att brukarnas socialrättsligabehov tillgodoses? Denna studie var uppdragsbaserad och ämnet valdes utifrån behovfrån socialförvaltningen i Halmstad kommun. Studien genomfördes med hjälp av enkvalitativ undersökning med inspiration av grundad teori som metod.Datainsamlingen utfördes genom sju stycken semistrukturerade intervjuer. Urvaletavgränsades till personliga assistenter anställda av socialförvaltningen i Halmstadkommun. Med inspiration av grundad teori togs en faktisk teori fram. Denna teorivisar att yrkeskategorin vilar på ett trepartsförhållande där brukare, arbetsgivare ochassistent deltar. Teorin kan ge förklaring på vad arbetsgivaren kan göra för att skapabättre arbetsförhållanden för assistenten och vidare förbättra relationen mellanassistent och brukare. Då tidigare forskning indikerar att det finns en kunskapsluckainom denna yrkeskategori var valet av metod relevant för att synliggöra möjligamodeller och teorier för yrkeskategorin. Den framtagna teorin kan vara till nytta föratt bättre förstå vad som påverkar medarbetarna inom denna yrkeskategori. / The professional category of personal assistance arose in 1994 through the personalassistance reform. The profession aims to promote equal living conditions andparticipation in the social life, for people with disabilities. The profession can be perceivedas difficult, since the personal assistant is drawn between two law fields; the client’s selfdetermination versus their working environment. The purpose of the study was toinvestigate how personal assistant employees, at the municipality of Halmstad, experiencetheir profession. This is of interest since this professional category is strongly influencedby the client’s self-determination, integrity and freedom of choice. The study was carriedout with guidance of the following questions: How do assistants describe their relationship withclients and what does this relationship mean for how the assistants’ feel about their employments? How doassistants feel that their labour law needs are met? How do the assistants feel that the social law needs ofthe clients are met? This study was assignment-based and the subject was chosen based onneeds from the social administration in Halmstad municipality. The study was conductedusing a qualitative study and inspired by grounded theory as a method. The data collectionwas carried out through seven semi-structured interviews. The selection was limited topersonal assistant employees within the social services in Halmstad municipality. Withinspiration from a grounded theory as a tool of work, an actual theory was developed.This theory shows that the professional category is based on a tripartite relationship inwhich the client, employer and assistant participate. The theory can explain what theemployer can do to create better working conditions for the assistant and further improvethe relationship between the assistant and the client. Previous research indicates that thereis a knowledge gap in this professional category. Therefore, choosing method basedtheory as a working tool was relevant for visualizing possible models and theories withinthis professional category. The presented theory can be useful to better understand theaffects the employees can experience within this professional category.

Pengar utgör en grundläggande pelare i samhället och är en avgörande faktor i individens vardagliga liv. Finansiella institut bär ett samhällsansvar kring de finansiella medel som är i cirkulation. Vilket även medför regulatoriska krav som finansiella institut behöver följa för att få bedriva sin verksamhet. Finansiella institut behöver bland annat förhålla sig till lag (2017:630) om åtgärder mot penningtvätt och finansiering av terrorism vilket utgör grunden för arbetet med penningtvätt. Artificiell intelligens har blivit vanligare att integrera i sin verksamhet och finansiella institut är inget undantag. Det förekommer däremot fortfarande utmaningar för finansiella institut trots det regulatoriska systemet som finns på plats. Studien syftar därför till att undersöka möjligheterna AI kan medföra för användarna i AML-processen inom finansiella institut. Studien avser att besvara frågeställningen genom en kvalitativ forskningsansats med en narrativ litteraturstudie samt empirisk insamling gjord med semistrukturerade intervjuer. Den empiriska insamlingen tyder på återkommande områden som konkretiserar både möjligheter och utmaningar med att nyttja AI i AML-processen hos finansiella institut. Studiens resultat visar att möjligheterna för användarna i AML processen mynnar ut i tre områden som är följande: AI för kompetensutveckling, AI som analysverktyg och AI som sammanställningsverktyg. / Money forms a fundamental pillar of the society and is a decisive factor in the everyday life of an individual. Financial institutions bear a societal responsibility regarding the financial funds that are in circulation. Which also entails regulatory requirements that financial institutions need to follow in order to conduct their business. Financial institutions need to comply with, among other things, Act (2017:630) on measures against money laundering and the financing of terrorism, which forms the foundation for the work against money laundering. Artificial intelligence has become more frequent to integrate into businesses and financial institutions are no exception. There are still challenges for financial institutions despite the regulatory system in place. The study therefore aims to investigate the possibilities AI can bring to the users in the AML process within financial institutions. The study intends to answer the question through a qualitative research approach with a narrative literature study and an empirical collection made with semi-structured interviews. The empirical collection indicates recurring areas that concretize both the opportunities and challenges of using AI in the AML process of financial institutions. The result of the study shows that the possibilities for the users within the AML process boils down to three areas which are as follows: AI for competence development, AI as an analysis tool and AI as complementary tool.

As financial crime increases, banks face greater challenges in preventing money laundering.Since it is the employees of the Anti-Money Laundering (AML)-departments who play acrucial role in combating money laundering, this study will examine their attitudes andprofessional role. The study uses a qualitative method, where semi-structured interviewswere used for data collection. To continuously revise and further develop, an inductiveexploratory approach has been used. The study's theoretical framework is based oninstitutional theory, profession theory and theory of legitimacy, which together helped tocreate an analysis of the collected data. The results of the study indicate that the AMLdepartment is not only a recipient of external regulations but also plays an active role in thebank's ethical obligations. It also appears that employees' motivation is not primarily drivenby compliance with laws and regulations. Instead, the motivation lies in contributingpositively to society. The contribution to society strengthens the professional identity ofthe professional role. In their day-to-day work, AML-staff face significant challenges relatedto bank secrecy, which limit the possibilities for information exchange between banks andthus make it difficult to effectively combat money laundering.

Background: Children with Down syndrome (DS) have increased risk for developing AML (DS-AMKL), and they usually experience severe therapy-related toxicities compared to non DS-AMKL. Refractory/ relapsed disease has very poor outcome, and patients would benefit from novel, less toxic, therapeutic strategies that overcome resistance. Relapse/resistance are linked to cancer stem cells with high aldehyde dehydrogenase (ALDH) activity. The purpose of the present work was to study less toxic alternative therapeutic agents for relapsed/refractory DS-AMKL. Methods: Fourteen AML cell lines including the DS-AMKL CMY and CMK from relapsed/refractory AML were used. Cytarabine (Ara-C), bortezomib (BTZ), disulfiram/copper (DSF/Cu2+) were evaluated for cytotoxicity, depletion of ALDH-positive cells, and resistance. BTZ-resistant CMY and CMK variants were generated by continuous BTZ treatment. Cell viability was assessed using CellTiter-Glo((R)), ALDH activity by ALDELUOR(TM), and proteasome inhibition by western blot of ubiquitinated proteins and the Proteasome-Glo(TM) Chymotrypsin-Like (CT-like) assay, apoptosis by Annexin V Fluos/Propidium iodide staining, and mutations were detected using PCR, cloning and sequencing. Results: Ara-C-resistant AML cell lines were sensitive to BTZ and DSF/Cu2+. The Ara-C-resistant DS-AMKL CMY cells had a high percentage of ALDHbright "stem-like" populations that may underlie Ara-C resistance. One percent of these cells were still resistant to BTZ but sensitive to DSF/Cu2+. To understand the mechanism of BTZ resistance, BTZ resistant (CMY-BR) and (CMK-BR) were generated. A novel mutation PSMB5 Q62P underlied BTZ resistance, and was associated with an overexpression of the beta 5 proteasome subunit. BTZ-resistance conferred increased resistance toAra-C due to G1 arrest in the CMY-BR cells, which protected the cells from S-phase damage by Ara-C. CMY-BR and CMK-BR cells were cross-resistant to CFZ and MG-132 but sensitive to DSF/Cu2+. In this setting, DSF/Cu2+ induced apoptosis and proteasome inhibition independent of CT-like activity inhibition. Conclusions: We provide evidence that DSF/Cu2+ overcomes Ara-C and BTZ resistance in cell lines from DS-AMKL patients. A novel mutation underlying BTZ resistance was detected that may identify BTZ-resistant patients, who may not benefit from treatment with CFZ or Ara-C, but may be responsive to DSF/Cu2+. Our findings support the clinical development of DSF/Cu2+ as a less toxic efficacious treatment approach in patients with relapsed/refractory DS-AMKL.

Money laundering and terrorist financing are serious problems that may not only disrupt the stability and reputation of financial institutions, but also affect a wide range of individuals. Therefore, this kind of conduct can be punished as a crime, including the active involvement of banks in money laundering. However, the diploma thesis focuses mainly on preventive measures introduced by the provisions of administrative law. The role of a well-functioning banking system is essential for the effective suppression of money laundering and financing of terrorism. Banks are the most frequent reporters of suspicious transactions and the bank services are used by wide range of persons. The role of banks is mainly determined by their designation as obliged entities by the Act no. 253/2008 Coll., on certain measures against the legalization of proceeds of crime and terrorist financing. The obligations arising out of this act are put into context with the Czech Banking Act and with regulations governing payments and implementation of international sanctions, including directly applicable laws of the European Union. The importance of the bank services is also caused by the regulation of cash payments. In connection with the activities of banks, the thesis reflects selected changes that will be introduced by...

Un des mécanismes d’évasion des cellules tumorales au système immunitaire fait intervenir la famille des molécules de type B7. Ces molécules de costimulation ont aussi un rôle dans les mécanismes de tolérance immunitaire. La molécule B7-H1 (PD-L1 ou CD274) inhibe directement les lymphocytes T cytotoxiques (CTL) et est fortement exprimée à la surface de nombreux types de cellules tumorales. Les mécanismes de régulation de son expression ne sont pas bien connus. Il existe une augmentation d’expression de cette molécule après stimulation par l’IFNγ et récemment les ligands des Toll-Like-Receptor (TLR) 2, 4 et 9 ont été impliqués dans sa régulation au niveau du myélome multiple. L’implication possible des TLR dans l’expression de B7-H1 suggère un rôle possible de pathogènes dans l’échappement des tumeurs au système immunitaireIl n’existe aucune donnée dans la littérature sur l’expression des TLR au niveau des cellules blastiques de patients atteints de leucémies aigues myéloblastique (LAM). Nous avons dans un premier temps étudié l’expression des TLR dans les LAM et l’inductibilité de l’expression de la molécule B7-H1 par les ligands des TLR en cytométrie en flux. Nos résultats montrent que les TLR sont exprimés dans les LAM, avec une grande variabilité suivant les patients. On observe une augmentation significative de l’expression de B7-H1 après stimulation par le LPS (ligand TLR4) alors qu’elle n’est pas significative pour les autres ligands (PGN et ODN). Comme dans les tumeurs solides et le myélome multiple, l’expression de B7-H1 est augmentée par l’IFN γ. Des tests de lyse CTL sont en cours afin de confirmer le rôle fonctionnel de cette expression de B7-H1 via les TLR dans les LAM.Une autre partie de l’étude a été réalisée sur deux lignées murines leucémiques : DA1-3B et WEHI-3B, afin de disposer de modèles expérimentaux d’expression de B7-H1. On retrouve sur ces deux modèles l’augmentation d’expression de B7-H1 après stimulation par l’IFN γ et les ligands des TLR. L’utilisation de différents inhibiteurs chimiques des voies de signalisation suggère le rôle des voies MEK/ERK et de la voie JAK/STAT dans l’expression de cette molécule. La voie PI3kinase/Akt semble au contraire jouer un rôle inhibiteur. Le travail se poursuit avec la transfection de transdominants négatifs des différentes voies et de mutants constitutivement actifs. L’objectif à terme est de tester des stratégies d’immunothérapies des LAM par blocage pharmacologique de l’expression de B7-H1. / B7-H1 (PD-L1) is a B7-related protein that inhibits T-cell responses. B7-H1 participates in the immunoescape of cancer cells and is also involved in the long-term persistence of leukemic cells in a mouse model. B7-H1 can be constitutively expressed by cancer cells but is also induced by various stimuli. We therefore examined the constitutive and inducible expression of B7-H1 and the consequences of expression in human acute myeloid leukemia (AML). We analyzed B7-H1 expression in a cohort of 79 patients with AML. Blast cells were also studied after incubation with interferon-gamma or TLR ligands. Functionality was evaluated by cytotoxic T-cell activity against blast cells. Expression of B7-H1 at diagnosis was high in 18% of patients. Expression of toll-like receptors (TLR) 2, 4, and 9 was detected in one-third of AML samples. Expression of TLR2 and TLR4 ligands or IFN- induced by B7-H1 was found to protect AML cells from CTL-mediated lysis. Spontaneous B7-H1 expression was also found to be enhanced at relapse in some patients. MEK inhibitors including UO126 and AZD6244 reduced B7-H1 expression and restored CTL-mediated lysis of blast cells. In AML, B7-H1 expression by blasts represents a possible immune escape mechanism. The inducibility of B7-H1 expression by IFN- or TLR ligands suggests that various stimuli, either produced during the immune response against leukemia cells or released by infectious microorganisms, could protect leukemic cells from T-cells. The efficacy of MEK inhibitors against B7-H1-mediated inhibition of CTLs suggests a possible cancer immunotherapy strategy using targeted drugs.

La tumorigenèse est un processus complexe provoqué par l'accumulation d'altérations génétiques contribuant à la transformation progressive d'une cellule normale en une cellule cancéreuse. Les travaux menés en hématologie ont permis d'identifier de nombreux mécanismes de signalisation impliqués dans des processus cellulaires clés comme la prolifération, la différenciation et la survie cellulaire, particulièrement au niveau des cellules souches hématopoïétiques (CSH). Parmi ces mécanismes, ceux déclenchés par les récepteurs à activité tyrosine kinase comme c-KIT ou FLT-3 ont été largement décrits au cours de ces dernières années. PTK7 est un récepteur tyrosine kinase de la famille des pseudokinases impliqué dans le développement embryonnaire qui joue un rôle important dans la polarité planaire. Le gène humain initialement cloné à partir de cellules de cancer du côlon code pour une protéine surexprimée dans de nombreuses tumeurs malignes. Nous avons confirmé sa surexpression dans les leucémies aiguës myéloïdes humaines et démontré que cet évènement représente un facteur indépendant de mauvais pronostic, en modulant la réponse aux agents cytotoxiques. Afin de mieux comprendre le rôle de PTK7 dans l'hématopoïèse physiologique, mon projet a consisté à générer une souris déficiente pour cette protéine et à étudier sa fonction dans la biologie des CSH. J'ai montré que les cellules déficientes pour PTK7 présentent un défaut de domiciliation vers la moelle osseuse. Ce travail contribue à mettre en évidence le rôle des protéines de la polarité dans le système hématopoïétique et, plus particulièrement, dans la biologie des CSH. / Tumorigenesis is a multiple step process resulting from accumulation of genetic alterations leading to progressive transformation of normal cells into tumoral cells. Many signaling pathways have been described as key processes implicated in cell proliferation, cell differentiation and cell survival, in particular in mature hematotopoietic cells and hematopoietic stem cells (HSCs). Among these signaling pathways, those controlled by tyrosine kinase receptors such as c-KIT or FLT-3 have been extensively described during the last two decades.PTK7 is a pseudokinase receptor of the tyrosine kinase receptor family involved in embryonic development and described for its role in planar cell polarity. The human gene has been initially cloned from colon carcinoma cells and is frequently overexpressed in solid tumors. We described PTK7 overexpression in acute myeloid leukemia and demonstrated that it represents an independent poor prognosis factor acting as a modulator of the chemotherapeutic response.To better understand the physiological role of PTK7 in the hematopoietic system, my project consisted in the generation of a PTK7 deficient mouse model, and in the study of its function, in particular in HSC biology. My work demonstrated that PTK7 deficient HSCs have a general homing defect and poorly colonize hematopoietic organs including the bone marrow. This work contributes to a better understanding of PTK7 functions and, more generally, sheds light on the role of cell polarity proteins in the biology of HSCs.

Faculty of Science School of Molecular Medicine and Haematology Masters Dissertation / Studies on the development of drug resistance in several cancer types, including acute myeloid leukaemia (AML), have implicated the PI3-kinase pathway. This pathway phosphorylates Akt resulting in the activation of proteins involved in cell survival. The aim of this study is to determine the role that Akt plays in urvival and the relationship between Akt, IKK and IkB in HL-60 cells. This study demonstrated that etoposide caused apoptosis in HL-60 cells, which was slightly increased when the PI3-kinase pathway was inhibited by LY294002. Stimulation with PDGF resulted in cell proliferation and increased Akt, IKK and IkB phosphorylation. Although pre-treatment with LY294002 decreased the amount of Phospho-Akt, phosphorylation of IKK and IkB still occurred. Therefore additional pathways must be involved in IkB regulation in HL-60 cells. Akt mRNA transcription was decreased when the cells were pretreated with LY294002 and either PDGF or etoposide. In conclusion, the PI3-kinase pathway plays a minor role in the survival of HL-60 cells and Akt substrates other than IKK are mediating this survival.

Les Leucémies Aigües Myéloïdes (LAM) sont des hémopathies malignes hétérogènes de mauvais pronostic qui se caractérisent par une expansion clonale de progéniteurs immatures. De nombreuses dérégulations de voies de signalisation sont retrouvées dans les cellules leucémiques et leur confèrent un avantage de prolifération et de survie. La voie de signalisation mTORC1, qui contrôle la traduction protéique, l’autophagie et plusieurs voies métaboliques, est ainsi constitutivement activée dans les cellules leucémiques. La reprogrammation métabolique notamment via « l’effet Warburg » est un phénomène bien décrit dans les cellules cancéreuses. L’augmentation de l’utilisation de la glycolyse, confère aux cellules tumorales un avantage de survie en favorisant une production rapide d’ATP et d’intermédiaires métaboliques nécessaires pour les biosynthèses de nucléotides, d’acides-aminés et de lipides. C’est donc dans ce contexte que j’ai étudié le métabolisme du glucose dans les cellules de LAM et l’implication de la voie de signalisation mTORC1 dans la dérégulation de ce métabolisme. J’ai tout d’abord identifié par une étude transcriptomique dans la lignée leucémique MOLM-14 que la signalisation mTORC1 contrôle plusieurs voies métaboliques notamment celles permettant l’utilisation du glucose. Ceci a été vérifié dans plusieurs lignées de LAM puisque l’inhibition ou la sur-activation de mTORC1 entrainent respectivement une diminution ou une augmentation de la consommation de glucose et de la production de lactate. De façon intéressante, le niveau d’activation de la voie mTORC1 détermine la sensibilité des cellules leucémiques à l’inhibition de la glycolyse. En effet, lorsque mTORC1 est activé, le blocage de la glycolyse induit de l’autophagie et l’apoptose des cellules leucémiques. A l’inverse, le blocage de mTORC1 induit une reprogrammation métabolique des cellules leucémiques qui utilisent alors principalement la phosphorylation oxydative pour produire l’ATP dont elles ont besoin. Leur survie devient alors indépendante du glucose. A l’inverse des cellules primaires de LAM, les cellules hématopoïétiques immatures normales CD34+ sont moins sensibles au blocage de la glycolyse. Le ciblage du métabolisme du glucose pourrait donc constituer une stratégie thérapeutique intéressante dans les LAM. Je me suis ensuite intéressée aux effets anti-leucémiques induits par l’inhibition de la voie des pentoses phosphates (PP) et plus particulièrement au ciblage de la G6PD (glucose-6-phosphate déshydrogénase) par le composé le 6-aminonicotinamide (6-AN). En effet, une étude de flux métabolique a permis de mettre en évidence qu’une proportion importante de glucose est dirigé vers la voie des PP, laissant suggérer que l’addiction des cellules leucémiques au glucose pourrait être liée à une utilisation augmentée de cette voie annexe. J’ai alors observé que le 6-AN induit une cytotoxicité in-vitro y compris dans les cellules primaires de patients, sans avoir d’effets sur les cellules hématopoïétiques normales et in-vivo dans un modèle de xénogreffe de la lignée MOLM-14 chez la souris NUDE. Cette étude a donc permis de montrer que l’activation constitutive de mTORC1 rend la survie des cellules de LAM dépendante de la glycolyse et crée une sensibilité spécifique à l’inhibition de la G6PD. La dérégulation de la signalisation mTORC1 étant quasi-constante dans les LAM, cibler la G6PD pourrait donc représenter une stratégie thérapeutique intéressante. / Acute Myeloid Leukemia (AML) are heterogeneous hematological diseases with poor prognosis characterized by a clonal expansion of immature progenitors. Many deregulation of signaling pathways are found in leukemic cells and give them an advantage of proliferation and survival. The MTORC1 signaling pathway, which controls protein translation, autophagy and several metabolic pathways, is constitutively activated in leukemic cells. Metabolic reprogramming in particular the "Warburg effect" is a phenomenon well described in cancer cells. High rate of glycolysis has been considered to give tumour cells advantages through rapid production of ATP and intermediates for the synthesis of nucleotides, amino acids, and lipids. In this context, I studied glucose metabolism in AML cells and the involvement of the mTORC1 signaling pathway in the deregulation of this metabolism. First, I identified by a transcriptomic analysis in the MOLM-14 cell line that mTORC1 signaling controls several metabolic pathways including those for glucose utilization. This has been verified in several AML cell lines, since inhibition or over-activation of mTORC1 respectively induces a decrease or an increase in glucose consumption and lactate production. Interestingly, the level of activation of the mTORC1 signaling pathway determines the sensitivity of AML cells to the inhibition of glycolysis. Indeed, when mTORC1 is activated, the blockade of glycolysis induces autophagy and apoptosis of leukemic cells. Conversely, blocking mTORC1 induces metabolic reprogramming of leukemic cells, which then mainly use oxidative phosphorylation to produce ATP for their needs. AML cell survival become independent of glucose. Unlike primary AML cells, survival of normal immature hematopoietic cells CD34+ is only barely affected by the blockade of glycolysis. Thus, targeting the glucose metabolism may constitute an attractive therapeutic strategy in AML. I then investigated the anti-leukemic activity induced by the inhibition of the pentose phosphate pathway (PPP) and more particularly by the specific blockade of G6PD (glucose 6-phosphate dehydrogenase) with the 6-aminonicotinamide (6- AN) compound. Indeed, a metabolic flux analysis demonstrated that a significant proportion of glucose was directed towards the PPP. This result suggested that the addiction of leukemic cells toward glucose might be related to an increased use of PPP. I then observed that the 6-AN induced in vitro cytotoxicity including in primary AML cells from patients without effect on normal immature hematopoietic cells CD34+ and in vivo in a xenograft model of MOLM-14 cell line in the NUDE mouse. This study therefore demonstrated that the constitutive activation of mTORC1 makes AML cells survival dependent on glycolysis, and creates a specific vulnerability to the inhibition of G6PD. Given that deregulation of the mTORC1 signaling pathway is almost constant in AML, targeting G6PD may therefore represent an interesting therapeutic strategy.

The Legal Regulation of Banking Activities Abstract The subject of this diploma thesis is the legal regulation of the activities of banks. Emphasis is placed on newly regulated areas and topical areas in respect to legislative changes. The primary aim of the thesis is to analyse areas related to the activities of banks and to assess the suitability and sufficiency or redundancy of the legal regulation of the selected areas in terms of the scope and depth of regulation. In this context, the work is complemented by proposals de lege ferenda. The first section is devoted to the subjects of banking regulation. Within this part, the term "bank" is defined, including the assessment of online banks. After that, supervisors, namely the Czech National Bank and the European Banking Authority, are presented together with an outline of their functions. The following section covers the general basis of the regulation of bank activities. The sources of regulation are described, and the objectives and reasons for and against regulation are outlined. A description of processes for entering and exiting the banking sector are included, with a more detailed analysis of procedures for obtaining a banking license. The third section contains an analysis of the selected obligations of banks arising from the legislation regulating...