Written in response to a current gap in academic and industry based literature, this thesis was written on the topic of Trade Based Money Laundering (TBML) and risk assessment, within the banking context. Despite the increased use of TBML, most academic descriptions of money laundering have used the cash based model of placement and integration of large cash deposits acquired from criminal activity, which are then merged into legitimate pre-existing funds. However, there are a significant number of examples to show that cash transferred into goods and then shipped to other countries can be easier to move and less conspicuous or traceable than simple cash based deposits. One of the main challenges for detecting shipping based laundering techniques is that they involve a number of agencies sharing data and information, in order to catch the criminals. Simple banking checks may not always elicit the required information without verification from either customs or law enforcement agencies. The research sought to identify the current challenges and issues facing risk assessment professionals in the banking sector and to identify gaps in the current systems being used. The data collected included interviews and survey information taken from professionals working on AML risk assessment in banking and financial institutions from across the globe. In addition to the description of different money laundering schemes, much of the current academic discussion on money laundering in banking has focused on the regulation requirements for financial institutions to stop money laundering activity, but there has been little empirical guidance on how regulation can be adapted and implemented at the individual banking level. This research accessed a number of legal cases available in the public domain, which were analysed to see how and where some of the larger banks have failed to implement current anti-money laundering controls and to consider how this could impact on the detection of TBML activity. This research uses an Agency theory model to look at the pressures banks are under to manage client’s accounts efficiently, versus the requirements of outside regulation to undertake extensive checks on business transactions and accounts. Finally, the researcher proposed a simple risk matrix approach that developed the current thinking of client behaviour and transaction monitoring risk analysis associated with cash based laundering, to develop a four-point risk model that added geography and third party behaviour, to account for shipping and trade based laundering activity.

Acute myeloid leukemia (AML) is the second most common type of leukemia and accounts for 80% of adult acute leukemia cases and is characterized by the accumulation of poorly or undifferentiated myeloid blast cells. Standard treatment includes chemotherapy, which if unsuccessful, is followed by more rigorous chemotherapy as well as stem cell transplantation. Considering most patients are over the age of 45, these more rigorous therapies are not always possible, and as such, new therapies must be developed. Furthermore, AML patients harboring a chromosomal rearrangement involving Multiple Lineage Leukemia (MLL) that results in the expression of an MLL fusion protein exhibit far worse prognoses than patients without. In recent years, Danio rerio (zebrafish) has emerged as a powerful model organism for investigating human blood malignancies due to the conservation of hematopoiesis between humans and zebrafish. The first objective of this study was to develop a transient transgenic AML model in zebrafish, and the second objective was to determine if co-treatment with two medications currently in human trials for AML, Venetoclax and Flavopiridol, would be more effective than using either drug individually. In order to develop a transient transgenic AML model, we first developed a DNA construct encoding a known mixed lineage leukemia (MLL) fusion protein associated with human AML, MLL-ENL, driven by the zebrafish lysozyme C (lyz) promoter, which drives myeloid specific expression in zebrafish. We then microinjected single-cell zebrafish embryos with DNA encoding lyz driven MLL-ENL along with transposase mRNA to facilitate the genomic integration of MLL-ENL. Injected embryos were first tested for MLL-ENL expression, and subsequently tested for AML phenotypic characteristics, via whole mount in-situ hybridization (WISH) at 72 hours post fertilization (hpf). First, WISH analysis utilizing a human MLL riboprobe verified MLL-ENL expression in injected embryos, and WISH analysis utilizing the same MLL riboprobe revealed an expansion and clustering of MLL positive cells in injected embryos, characteristic of an AML phenotype. Embryos injected with MLL-ENL DNA were then treated with either DMSO (vehicle), 200 nanomolar (nM) Venetoclax, 200 nM Flavopiridol, or 200 nM Venetoclax and 200 nM Flavopiridol from 24 hpf to 72 hpf. MLL WISH analysis of injected and treated embryos revealed a reduction in MLL positive cells in both Venetoclax treated embryos and Flavopiridol treated embryos, and an even greater reduction in MLL positive cells in embryos treated with both Venetoclax and Flavopiridol, compared to controls. Although further analysis is required to be confident, these data suggest that we successfully developed an AML transient transgenic model in zebrafish. Furthermore, these data suggest that Venetoclax and Flavopiridol co-treatment could yield better outcomes for AML patients than treatment with either drug individually.

The goal of this study was to identify novel drug repurposing opportunities in cancer by utilizing the off-target profiles of clinically relevant kinase inhibitors. This was based on the observation that the global target profiles of compounds are largely ignored and that many compounds have activity that cannot be explained by their cognate target alone. Additionally, by utilizing clinically relevant compounds, any results would hold a high potential for eventual clinical implementation. We utilized a systems pharmacology approach utilizing cell viability-based drug screening to identify compounds with beneficial off-target activity and then using chemical and phosphoproteomics in order to elucidate the mechanisms of action of these compounds. We found that tivantinib has off-target activity in NSCLC cells through inhibition of GSK3. Based on tivantinib’s ability to inhibit GSK3, we hypothesized that tivantinib would therefore have activity in acute myeloid leukemia (AML). We found that tivantinib had potent activity in AML through inhibition of GSK3. We also identified a highly synergistic combination with ABT-199 by drug synergy screening which was effective in HL60 cells and patient derived AML cells. We also found that the anaplastic lymphoma kinase (ALK) inhibitor, ceritinib, had activity across several ALK-negative lung cancer cell lines. We utilized integrated functional proteomics to identify the new targets and network-wide signaling effects. Combining pharmacological inhibitors and RNA interference revealed a polypharmacology mechanism involving the noncanonical targets IGF1R, FAK1, RSK1 and RSK2. Mutating the downstream signaling hub YB1 protected cells from ceritinib. Consistent with YB1 signaling being known to cause taxol resistance, combination of ceritinib with paclitaxel displayed strong synergy, particularly in cells expressing high FAK autophosphorylation, which we show to be prevalent in lung cancer. Together, we present a systems chemical biology platform for elucidating multikinase inhibitor mechanisms, synergistic drug combinations, mechanistic biomarker candidates and identifying novel drug repurposing opportunities.

<p>Syftet med undersökningen är att beskriva och öka insikten om enhetschefernas dubbla roll och deras arbetssituation då det gäller tillämpningen av arbetsmiljölagen och socialtjänstlagen och hur de hanterar denna dubbla roll.</p><p>De forskningsfrågor som vi har sökt svar till är:</p><p>• Vad styr och vad består enhetschefernas arbete av?</p><p>• Hur ser enhetscheferna på sin dubbla roll gentemot arbetsmiljölagen och socialtjänstlagen?</p><p>• Hur hanterar enhetscheferna motsättningar mellan arbetsmiljölagen och socialtjänstlagen?</p><p>Studien är en kvalitativ intervjustudie där sex enhetschefer inom äldreomsorgen har intervjuats. Analysen har skett genom kodning som gav de kategorier och teman som resultatet redovisas under.</p><p>Resultatet visar på att socialtjänstlagen och arbetsmiljölagen styr enhetschefernas arbete och att lagarna genomsyrar hela verksamheten då de används som ett medel och redskap för att nå en lösning på motsättningar. Hanteringen av socialtjänstlagen och arbetsmiljölagen ses av enhetscheferna och organisationen som en självklar del i arbetet och de upplever överlag inte hanteringen som ett problem. De svårigheter som uppkommer är i den gråzon som finns mellan olika lagar och dessa svårigheter har de ansvaret för att lösa. Resultatet visar tydligt på att enhetscheferna är fokuserade på HUR de ska genomföra uppdraget och lösa svårigheterna och inte på VAD de ska göra. Motsättningar löses genom ett samarbete mellan berörda parter och det är enhetscheferna som har den samordnande rollen. Socialtjänstlagen och arbetsmiljölagen ses som två jämbördiga lagar men socialtjänstlagen prioriteras i tillämpningen eftersom brukaren måste få sina behov tillgodosedda.</p> / <p>The purpose of this research is to describe and gain a deeper insight in the dual role of the unit managers and their practical work situations in terms of applying and managing the work environment act as well as the social services act and possible oppositions between the two.</p><p>The following research questions have been formulated for the subject:</p><p>• Which are the tasks and responsibilities of the unit managers and which factors determine these?</p><p>• What is the opinion of the unit managers, in terms of their dual role, towards the work environment act as well as the social services act?</p><p>• How is the opposition in the work environment act and the social services act dealt with by the unit managers?</p><p>The research is of qualitative nature based on an interview study in which six unit managers within the geriatric care participated. In order to analyze the outcome a coding system was used, which resulted in the different categories and themes under which the outcome is presented. The outcome of the research indicates that the work environment act and the social services act are the base for the work of the unit managers, the laws permeate the whole unit as they are used as tools in order to reach solutions to oppositions. The unit managers consider the management of the two acts as a natural task in their work and they do not, in general, perceive the management of the acts as problematic. The possible problematic and difficult areas are the issues, which can be said to be in the grey zone between different acts, and it is the responsibility of the unit managers to solve these difficulties. The outcome of the research is strongly showing that the unit managers are focused on HOW the task should be performed and difficulties solved rather then WHAT they should be doing. Oppositions are solved through cooperation between the involved parties and it is the unit managers who have the coordinating role. The work environment act and the social services act are regarded equally important but nevertheless the latter is prioritized in practice since it is necessary to fulfill the needs of the users.</p>

Syftet med undersökningen är att beskriva och öka insikten om enhetschefernas dubbla roll och deras arbetssituation då det gäller tillämpningen av arbetsmiljölagen och socialtjänstlagen och hur de hanterar denna dubbla roll. De forskningsfrågor som vi har sökt svar till är: • Vad styr och vad består enhetschefernas arbete av? • Hur ser enhetscheferna på sin dubbla roll gentemot arbetsmiljölagen och socialtjänstlagen? • Hur hanterar enhetscheferna motsättningar mellan arbetsmiljölagen och socialtjänstlagen? Studien är en kvalitativ intervjustudie där sex enhetschefer inom äldreomsorgen har intervjuats. Analysen har skett genom kodning som gav de kategorier och teman som resultatet redovisas under. Resultatet visar på att socialtjänstlagen och arbetsmiljölagen styr enhetschefernas arbete och att lagarna genomsyrar hela verksamheten då de används som ett medel och redskap för att nå en lösning på motsättningar. Hanteringen av socialtjänstlagen och arbetsmiljölagen ses av enhetscheferna och organisationen som en självklar del i arbetet och de upplever överlag inte hanteringen som ett problem. De svårigheter som uppkommer är i den gråzon som finns mellan olika lagar och dessa svårigheter har de ansvaret för att lösa. Resultatet visar tydligt på att enhetscheferna är fokuserade på HUR de ska genomföra uppdraget och lösa svårigheterna och inte på VAD de ska göra. Motsättningar löses genom ett samarbete mellan berörda parter och det är enhetscheferna som har den samordnande rollen. Socialtjänstlagen och arbetsmiljölagen ses som två jämbördiga lagar men socialtjänstlagen prioriteras i tillämpningen eftersom brukaren måste få sina behov tillgodosedda. / The purpose of this research is to describe and gain a deeper insight in the dual role of the unit managers and their practical work situations in terms of applying and managing the work environment act as well as the social services act and possible oppositions between the two. The following research questions have been formulated for the subject: • Which are the tasks and responsibilities of the unit managers and which factors determine these? • What is the opinion of the unit managers, in terms of their dual role, towards the work environment act as well as the social services act? • How is the opposition in the work environment act and the social services act dealt with by the unit managers? The research is of qualitative nature based on an interview study in which six unit managers within the geriatric care participated. In order to analyze the outcome a coding system was used, which resulted in the different categories and themes under which the outcome is presented. The outcome of the research indicates that the work environment act and the social services act are the base for the work of the unit managers, the laws permeate the whole unit as they are used as tools in order to reach solutions to oppositions. The unit managers consider the management of the two acts as a natural task in their work and they do not, in general, perceive the management of the acts as problematic. The possible problematic and difficult areas are the issues, which can be said to be in the grey zone between different acts, and it is the responsibility of the unit managers to solve these difficulties. The outcome of the research is strongly showing that the unit managers are focused on HOW the task should be performed and difficulties solved rather then WHAT they should be doing. Oppositions are solved through cooperation between the involved parties and it is the unit managers who have the coordinating role. The work environment act and the social services act are regarded equally important but nevertheless the latter is prioritized in practice since it is necessary to fulfill the needs of the users.

Colony-stimulating factor 1 receptor (CSF1R, Fms) is an integral transmembrane glycoprotein with tyrosine specific protein kinase activity that it is found on the mononuclear phagocytes to promote their survival, proliferation and differentiation. Colony-stimulating factor 1 (CSF-1), also known as M-CSF, is a protein ligand that acts on the CSF1R. There is a variable association of Fms with the stem cell marker CD34 on acute myeloid leukemia (AML) cells and this suggests different structures of the AML hierarchy in different patients. Mouse stromal cells (MS-5) were transduced with a plasmid containing human CSF-1 because mouse CSF-1 is inactive on human CSF1R. Results show that AML cells cultured with CSF-1-expressing stroma had a much better growth and survival than the control stroma, suggesting that CSF-1 might be a stimulating factor for the growth of leukemic stem cells.

The FMS-like tyrosine kinase 3- internal tandem duplication (FLT3/ITD) aberration is common in acute myeloid leukemia (AML) and associated with poor patient outcome. Inhibitors targeting FLT3/ITD are in development, but clinical responses are transient. This project focussed on elucidating molecular signalling consequences of FLT3/ITD inhibition, to identify rational drug combinations for future development. A Multicolour Phospho Flow Cytometry (MPFC) assay was developed to assess signalling events downstream of FLT3/ITD in primary patient samples, focusing on alterations in ERK, STAT5, Akt, and S6. STAT5 signalling appeared to be important exclusively in FLT3/ITD samples. MPFC accurately predicted the presence of FLT3/ITD, inhibitor sensitivity and the initial positive clinical response of a trial patient receiving a FLT3/ITD inhibitor. PI3K pathway upregulation was observed in a Sorafenib-resistant FLT3/ITD cell line established to study resistance mechanisms of FLT3 inhibition. Further, combination FLT3 and PI3K inhibition demonstrated synergy, suggesting potential clinical relevance to this therapeutic strategy.

The FMS-like tyrosine kinase 3- internal tandem duplication (FLT3/ITD) aberration is common in acute myeloid leukemia (AML) and associated with poor patient outcome. Inhibitors targeting FLT3/ITD are in development, but clinical responses are transient. This project focussed on elucidating molecular signalling consequences of FLT3/ITD inhibition, to identify rational drug combinations for future development. A Multicolour Phospho Flow Cytometry (MPFC) assay was developed to assess signalling events downstream of FLT3/ITD in primary patient samples, focusing on alterations in ERK, STAT5, Akt, and S6. STAT5 signalling appeared to be important exclusively in FLT3/ITD samples. MPFC accurately predicted the presence of FLT3/ITD, inhibitor sensitivity and the initial positive clinical response of a trial patient receiving a FLT3/ITD inhibitor. PI3K pathway upregulation was observed in a Sorafenib-resistant FLT3/ITD cell line established to study resistance mechanisms of FLT3 inhibition. Further, combination FLT3 and PI3K inhibition demonstrated synergy, suggesting potential clinical relevance to this therapeutic strategy.

The paper examines the approach taken by Russian government to control money laundering by creating the preventive framework which has undergone significant changes over the past six years. With respect to the prevention of money laundering, the discussion involves a review of international standards and norms which constitute the global AML regime. Recognizing the need for adding the domestic dimension to the studies of international regimes with the help of two-level game theory, the paper further analyzes the preventive pillar of the domestic AML regime in Russia in comparison with the global standards. It concludes that the federal law, which is the cornerstone of the domestic AML regime, as well as institutional framework created in Russia, both formally comply with the international norms. The analyses of the practical implementation of the AML legislation in the financial institutions focus on legislative base for the regulated, behavioral patterns of the banks in the AML prevention, and the conflicts and debates, lately emerged within the domestic AML regime. This paper aims to show how new regulations have influenced both domestic AML regime and its main actors. The paper concludes that the existent domestic regime lacks interaction and communication between its actors which leads to the breach of the main principle and goal of a regime – cooperation. The paper argues that the representatives of banking community in Russia could play the role of epistemic community proposed by the cognitive theory of international regimes. Given the functions of epistemic community it could foster better understanding of the context and purposes of the AML regime, thus, decreasing uncertainty and facilitating cooperation between the parties. The paper will conclude with the recommendations on the future research about how risk-based approach to banking regulation of the AML prevention rather than traditional rule-based compliance method can be effective.

<p>The paper examines the approach taken by Russian government to control money laundering by creating the preventive framework which has undergone significant changes over the past six years. With respect to the prevention of money laundering, the discussion involves a review of international standards and norms which constitute the global AML regime. Recognizing the need for adding the domestic dimension to the studies of international regimes with the help of two-level game theory, the paper further analyzes the preventive pillar of the domestic AML regime in Russia in comparison with the global standards. It concludes that the federal law, which is the cornerstone of the domestic AML regime, as well as institutional framework created in Russia, both formally comply with the international norms.</p><p>The analyses of the practical implementation of the AML legislation in the financial institutions focus on legislative base for the regulated, behavioral patterns of the banks in the AML prevention, and the conflicts and debates, lately emerged within the domestic AML regime. This paper aims to show how new regulations have influenced both domestic AML regime and its main actors. The paper concludes that the existent domestic regime lacks interaction and communication between its actors which leads to the breach of the main principle and goal of a regime – cooperation.</p><p>The paper argues that the representatives of banking community in Russia could play the role of epistemic community proposed by the cognitive theory of international regimes. Given the functions of epistemic community it could foster better understanding of the context and purposes of the AML regime, thus, decreasing uncertainty and facilitating cooperation between the parties. The paper will conclude with the recommendations on the future research about how risk-based approach to banking regulation of the AML prevention rather than traditional rule-based compliance method can be effective.</p>