Varicella zoster virus (VZV) is an alpha herpes virus that causes primary infection with varicella (chicken pox), establishes latency in ganglia and may later reactivate as herpes zoster (shingles). Innate immune effectors are thought to control initial viral replication, but it is the adaptive immune system, involving T cells that mediates eventual control of viraemia and the associated clinical disease. Although both CD4⁺ and CD8⁺ T cells mediate viral clearance during acute illness, memory responses are dominated by CD4⁺ T cells. We tested the hypothesis that the paucity in memory CD8⁺ T cell effectors is partly attributed to immune evasion mechanisms that are mounted by VZV. We confirmed that VZV readily down regulates cell surface HLA-A and HLA-C but spares HLA-B onVZV infected keratinocytes and VZV infected Mewo cells. Analysis of intracellular HLA protein expression and gene transcription showed global down regulation of all HLA subtypes. Further analysis showed that VZV inhibits IFN-γ mediated up regulation of HLA expression and augments IFN-γ mediated up regulation of HLA-E and CD71 expression. Furthermore, we show that acute VZV infection lowers the frequency of circulating peripheral blood myeloid dendritic cells (mDC), reduces the expression of the DC activation marker HLA-DR and impairs inflammatory cytokine secretion in blood DC populations. Inhibition of DC cytokine secretion was found to be dependent on viral replication as irradiated virus resulted only in mild inhibition of IFN-α and TNF-α secretion. Lastly, we observed that VZV infection results in increased expression of host peptides, including MHC derived leader sequences that potentially bind to HLA-E. Cell surface HLA-E is known to be a ligand for the natural killer (NK) cell inhibitory receptor CD94/ NKG2A identifying a novel mechanism of viral immune escape from NK cell surveillance. In conclusion, our data reiterates the fact that VZV targets different aspects of antigen presentation to evade the immune system with implications for pathogenesis and approaches to improved vaccination and treatment.

Σύμφωνα με έρευνες που πραγματοποιήθηκαν τα τελευταία χρόνια, παρατηρείται μια αύξηση της φοροδιαφυγής όχι μόνο σε παγκόσμιο επίπεδο αλλά και στον ελληνικό χώρο. Το γεγονός αυτό δείχνει τη δυσαρέσκεια και τη δυσκολία των εταιριών να ανταπεξέλθουν στους υπάρχοντες φορολογικούς νόμους αλλά και την επιδίωξης τους να αυξήσουν τα κέρδη τους με όχι νόμιμο όμως τρόπο. Στην παρούσα εργασία γίνεται ανάλυση του φορολογικού συστήματος στην Ελλάδα και των κινήτρων που ωθούν τις επιχειρήσεις στη φοροδιαφυγή, ενώ διερευνάται η σχέση ανάμεσα στους φορολογικούς ελέγχους χρήσεως και σε άλλα στοιχεία χρηματοοικονομικών καταστάσεων των εταιριών. Βασιζόμενοι σε εμπειρική έρευνα σε ευρύ δείγμα επιχειρήσεων για την τριετία 2008-2010 οδηγούμαστε στο συμπέρασμα ότι το ύψος της φοροδιαφυγής που επικρατεί στην Ελλάδα έχει μεγάλες διαστάσεις και συνδέεται με συγκεκριμένα εταιρικά χαρακτηριστικά. / According to surveys carried out in recent years, there is an increase in tax evasion not only globally but also in the Greek area. This indicates dissatisfaction and difficulty for companies to cope in existing tax laws and the pursuit to increase their profits with no legitimate way though.

Peatlands cover approximately 2-3% of the world’s land area yet represent approximately a third of the worlds estimated total soil carbon pool. They therefore play an important role in regulating global atmospheric CO2 and CH4 concentrations, and even minor changes in their ability to store carbon could potentially have significant effects on global climate change. Much previous research has focussed primarily on land-atmosphere fluxes. Where aquatic fluxes have been considered, they are often in isolation from the rest of the catchment and usually focus on downstream losses, ignoring evasion (degassing) from the water surface. However, as peatland streams have been repeatedly shown to be highly supersaturated in both CO2 and CH4 with respect to the atmosphere, they potentially represent an important pathway for catchment GHG losses. This study aimed to a) create a complete GHG and carbon budget for Auchencorth Moss catchment, Scotland, linking both terrestrial and aquatic fluxes, and b) understand what controls and drives individual fluxes within this budget. This understanding was further developed by a short study of C exchange at the peat-aquatic interface at Mer Bleue peatland, Canada. Significant variability in soil-atmosphere fluxes of both CH4 and N2O emissions was evident at Auchencorth Moss; coefficients of variation across 21 field chambers were 300% and 410% for CH4 and N2O, respectively. Both in situ chamber measurements and a separate mesocosm study illustrated the importance of vegetation in controlling CH4 emissions. In contrast to many previous studies, CH4 emissions were lower and uptake greater where aerenchymous vegetation was present. Water table depth was also an important driver of variability in CH4 emissions, although the effect was only evident during either periods of extreme drawdown or when the water table was consistently near or above the peat surface. Significant pulses in both CH4 and N2O emissions were observed in response to fluctuations in water table depth. Despite the variability in CH4 and N2O emissions and the uncertainty in up-scaled estimates, their contribution to the total GHG and carbon budgets was minor. Concentrations of dissolved CO2 in peatland drainage waters ranged from a mean of 2.88 ± 0.09 mg C L-1 in the Black Burn, Scotland, to a mean of 7.64 ± 0.80 mg C L-1 in water draining Mer Bleue, Canada. Using non-dispersive infra-red (NDIR) CO2 sensors with a 10-minute measurement frequency, significant temporal variability was observed in aquatic CO2 concentrations at the 2 contrasting field sites. However, the drivers of this variability differed significantly. At Mer Bleue, Canada, biological activity in the water column led to clear diurnal cycles, whereas in the Black Burn draining Auchencorth Moss, dilution due to discharge was the primary driver. The NDIR sensor data also showed differences in soil-stream connectivity both between the sites (connectivity was weak at Mer Bleue) and across the range of conditions measured at Auchencorth Moss i.e. connectivity increased during periods of stormflow. Compiling the results from both the terrestrial and aquatic systems at Auchencorth Moss indicated that the catchment was functioning as a net sink for GHGs (382 kg CO2-eq ha-1 yr-1) and a net source of carbon (143 kg C ha-1 yr-1). The greatest flux of GHGs was via net ecosystem exchange (NEE). Terrestrial emissions of CH4 and N2O combined returned only ~5% of CO2-equivalents captured by NEE to the atmosphere, whereas evasion of CO2, CH4 and N2O from the stream surface returned ~40%. The budgets clearly show the importance of aquatic fluxes at Auchencorth Moss and highlight the potential for significant error in source/sink strength calculations if they are omitted. Furthermore, the process based understanding of soil-stream connectivity suggests the aquatic flux pathway may play an increasingly important role in the source-sink function of peatlands under future management and climate change scenarios.

In North America, Borrelia burgdorferi is the primary causative agent of Lymedisease which is a growing health concern. The ability of B. burgdorferi to maintain chronic infection indicates that they are capable of immune evasion. A distinguishing characteristic of B. burgdorferi is the large number of sequences encoding predicted or known lipoproteins, including outer surface protein F (OspF). This study analyzes the specificity of the humoral immune response to B. burgdorferi B3 IMI OspF proteins during murine and human infection. Immunoblot analyses revealed a temporal expression of OspF proteins during infection and mapped the immunodominant epitopes which lie within the variable domains. To determine if OspF-related proteins are produced by other isolates, immunoblot analyses were performed using sera collected from mice and humans infected with diverse B. burgdorferi strains. Differences in the immunoreactivity profile to OspF proteins were seen among the infection sera tested. To identify the molecular basis of these differences, the ospF gene was isolated from several strains, sequenced and evolutionary analyses were conducted. These analyses revealed that OspF proteins show little diversity despite the separate geographic locations from which isolates originated. The high degree of OspF protein conservation seen in isolates from two distinct regions emphasizes the potential for OpsF proteins as vaccinogens or in serodiagnostic assays. Altogether, this study demonstrates the potential contribution of OspF proteins to immune evasion through its temporal expression during infection which may play specific roles at different stages of infection. Studies are underway to determine if inactivation of ospF genes through allelic exchange mutagenesis impacts on the pathogenicity of the Lyme disease spirochetes.

This thesis deals with the legal aspects of the fight against tax evasion with a particular focus on current legal instruments within the Czech legal order. The thesis is divided into five parts. The first part of the thesis defines the concept of tax evasion, compares the concepts of tax avoidance and tax evasion in the foreign literature. The term tax evasion does not have a legal definition in the Czech legal order and different views of the meaning of this term can be found. This thesis works with tax evasion as an illegal arrangement aiming at minimizing one's tax liability, as well as acting towards circumventing tax legislation. The second part also summarizes the knowledge about BEPS and its influence on the state budget, competition and society. The third part is devoted to selected specific legal instruments in the fight against BEPS, namely the institute of abuse of law, transfer pricing rules, low capitalization, international cooperation and double tax treaties. These tools are described in detail and their current form is analyzed. The work also expresses the author's personal opinion on these tools, which he considers to be very conservative. Similarly, the instruments introduced into the Czech legal system with the implementation of the ATAD Directive are analyzed. The last part of...

Abstract The South African Revenue Service (‘SARS’) and National Treasury has in the recent past identified various areas of tax in which taxpayers have been avoiding tax by arranging their affairs in a certain way. An area which SARS and National Treasury sees as being a danger to the South African tax base is the utilisation of trusts by individuals. This was made evident in the 2013 National Budget Speech by way of a passing high-level comment on how SARS proposes to mitigate the risk that trusts pose to the South African tax base. This research evaluates whether trusts do in fact pose a valid risk to erode the tax base and whether they are as ‘deadly’ as they are made out to be. A discussion of the taxation of local trusts is included in this paper and it continues by analysing the various antiavoidance provisions contained in the Income Tax Act. In addition, this paper discusses the proposed amendments to be made to the current tax regime as well as the revised tax return format for trusts and the supposed purpose thereof. The paper concludes on the validity of the concern raised by both SARS and National Treasury in respect of trusts being used as vehicles to erode the South African tax base.

A research report submitted to the Faculty of Commerce, Law and Management, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Commerce (specialising in Taxation) Johannesburg, 2017 / As a result of a weakening and slow global economy and rising debt, many foreign governments are finding it difficult to implement strategies to ensure continued inclusive and sustainable growth. It is based on this troubling perspective of global uncertainty that tax authorities worldwide have unanimously persisted in their fight against tax evasion through the under-declaration of income from foreign assets, the illegal movement of money abroad, the misapplication and / or manipulation of transfer pricing legislation and mistreatments of tax treaties. The G20 Leaders together with the Organisation for Economic Co-operation and Development (“OECD”) have developed standards such as the Common Reporting Standard (“CRS”) for the Automatic Exchange of Information (“AEOI”) between tax authorities to enhance the sharing of information and transparency of information between tax authorities worldwide. South Africa has pledged to implement the CRS and automatically share tax information with other jurisdictions on an annual basis in the fight against tax evasion and avoidance. Of significance, in terms of timing for South African tax residents, is that South Africa has undertaken to be one of the early adopters of the CRS and committed to commence the first exchange of information from 2017. In light of the standards and actions coming into place, it has become clear that before long the likelihood of the South African Revenue Services (“SARS”) and the South African Reserve Bank (“SARB”) detecting tax evasion and avoidance is increasingly high. Based on this, non-compliant taxpayers have a limited timeframe to manoeuvre freely in and what may be their last opportunity to voluntarily disclose these assets and the income derived therefrom to SARS and SARB without facing heavier penalties and possible criminal prosecution. / MT 2018

A research report submitted to the Faculty of Commerce, Law and Management, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Commerce (Specialising in Taxation) Johannesburg, 2017 / Trusts are an essential tool for estate planning. The interest in trust structures by taxpayers has increased over the years and the South African Revenue Services (‘SARS’) and National Treasury (‘NT’) have placed trusts on their agenda due to their perceived tax avoidance resulting from the use of trust structures. Section 7C was introduced into the Income Tax Act 58 of 1962 (as amended) (‘the Act’) in order to curb the avoidance of estate duty. However, the work undertaken by SARS and NT over the years and the insertion of this section in the Act, created an impression that there is avoidance of taxation through the use of trust structures. This study will interrogate the provisions of s 7C in order to determine the effectiveness of this section in curbing the avoidance of estate duty and/or tax through the use of trust structures. The well thought out manner in which this section was drafted and the existence of other tax provisions in the Act which pertain to trusts and the funding mechanisms of trusts suggest that this new inclusion is a convenient and easy manner to monitor the abuse by SARS and NT and subsequently curb the perceived abuse. The interplay of this section with ss 7 and 31 of the Act indicate a risk of unintended double taxation. This and the circumvention options that taxpayers may embark on are matters that may render the section ineffective, although it is evidenced that this section closes that last door that remained open for taxpayers in respect of funding a trust. Key Words: Tax avoidance, estate duty avoidance, National Treasury, SARS, National Budget Speech, Davis Tax Committee Reports on estate duty, Interest-free and low interest loans, Affected Transactions (s 31), Donor attribution rules (s 7), Donations and donations tax, Double taxation. / GR2018

A leptospirose é uma zoonose de distribuição mundial, com maior incidência nas regiões tropicais. As bactérias que causam a doença pertencem ao gênero Leptospira, família Leptospiracea e ordem Spirochaetales. A leptospirose é mantida na natureza pela colonização persistente dos túbulos renais proximais dos animais portadores. Uma estratégia adotada por estas espiroquetas para sobreviver à ação do sistema imune inato do hospedeiro é a capacidade que possuem de interagir com os reguladores do sistema complemento Fator H (FH) e proteína de ligação a C4b (C4BP). O sistema complemento é um componente vital da imunidade inata, uma vez que desempenha um papel crucial na defesa do hospedeiro, particularmente contra bactérias Gram-negativas. Dados recentes gerados por nosso grupo mostraram que C4BP interage com a proteína de superfície LcpA de Leptospira. Com cerca de 20 kDa, essa proteína é capaz de se ligar a C4BP purificado ou solúvel no soro de maneira dose-dependente. Uma vez ligado à proteína, C4BP permanece funcional agindo como cofator de Fator I na clivagem de C4b. O presente estudo teve como principal objetivo avaliar a interação da proteína LcpA com FH humano, principal regulador solúvel da via alternativa do sistema complemento. A proteína LcpA e suas porções N-Terminal, Intermediária e CTerminal recombinantes foram purificadas por cromatografia de afinidade a metal a partir da fração insolúvel. A interação dessas proteínas com FH foi avaliada por dois métodos distintos: ELISA e Western blot com overlay. Os resultados indicaram que a porção C-Terminal da proteína LcpA é responsável pela interação com FH. Curiosamente, C4BP também se liga a esse domínio da proteína. Uma vez que esses dois reguladores solúveis do sistema complemento interagem com o mesmo segmento da LcpA, realizaram-se, a seguir, ensaios de competição com o objetivo de avaliar se ambos compartilhariam os mesmos sítios de interação. Os dados mostraram que FH e C4BP devem se ligar a sequências distintas desta proteína. Com o objetivo de se avaliar a funcionalidade de FH ligado à LcpA, realizou-se um ensaio para investigar sua atividade de co-fator de Fator I na clivagem de C3b. Produtos de degradação de 46 kDa e 43 kDa da cadeia α' de C3b foram detectados, indicando que FH permanece funcional. Em se tratando de uma proteína com funções relacionadas ao processo de evasão ao sistema imune inato, decidiu-se realizar ensaios de desafio em modelo de hamster com a finalidade de se avaliar seu potencial imunoprotetor. Os três ensaios realizados indicaram que a proteína não é capaz de conferir proteção. Os ensaios de ELISA visando à avaliação dos títulos de anticorpos mostraram que LcpA não é imunogênica, fato que explica os resultados dos ensaios de desafio observados. Portanto, embora interaja com moléculas do hospedeiro e pareça contribuir para o processo de evasão ao sistema imune inato, essa proteína de membrana não se mostrou promissora como candidato vacinal contra leptospirose. / Leptospirosis is a zoonosis of global distribution, with higher incidence in tropical areas. The bacteria that cause the disease belong to the genus Leptospira, family Leptospiracea and order Spirochaetales. Leptospirosis is maintained in nature by persistent colonization of proximal renal tubules of carrier animals. One strategy adopted by these spirochetes to escape from host´s innate immune system is the ability to interact with the complement regulators Factor H (FH) and C4b Binding Protein (C4BP). The complement system is a vital component of the innate immune system, being crucial for host´s defense, particularly against Gram-negative bacteria. According to our recent published data, C4BP interacts with the leptospiral surface protein LcpA. This 20 kDa outer membrane protein binds both purified and serum C4BP in a dose-dependent manner. Once bound, C4BP remains functional acting as a cofactor for Factor I in the cleavage of C4b. In the present study we evaluated the interaction of LcpA with human FH, the main soluble regulator of the alternative pathway of complement. The intact protein as well as its N-terminal, intermediate and C-terminal portions were purified by metal-affinity chromatography from the insoluble pellet. The interaction of these proteins with FH was evaluated by two distinct methods: ELISA and Western blot overlay. Our results indicate that the C-terminal domain of LcpA mediates interaction with FH, and also with C4BP. Since both complement regulators interact with the same fragment of LcpA, we next performed competition assays to assess if they would share binding sites. According to our data, FH and C4BP have distinct binding sites on LcpA. Cofactor activity of FH bound to immobilized LcpA was confirmed by detecting the C3b α' chain cleavage fragments of 46 and 43 kDa upon incubation with Factor I, thus indicating that it remains functionally active. Given the LcpA´s role in host´s innate immune evasion, we also evaluated its vaccine potential in a hamster model. Data from three challenge assays indicated that the protein can not afford protection. Low ELISA antibody titers of hamsters immunized with LcpA were observed, which strongly suggests that this protein is not immunogenic. In conclusion, LcpA interacts with host´s molecules and seems to contribute to the bacterial immune evasion. Nevertheless, this outer membrane protein is not a promising vaccine candidate against leptospirosis.

Several successful pathogens evade host defenses resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory oral bone loss and systemic inflammation manifested as atherosclerosis. The pathogenic mechanisms contributing to P. gingivalis evasion of host immunity and chronic inflammation are not well defined. P. gingivalis evades host immunity at Toll-like receptor (TLR)-4 through expression of an atypical lipopolysaccharide (LPS) that contains lipid A species that exhibit TLR4 agonist or antagonist activity or fail to activate TLR4. By utilizing a series of P. gingivalis lipid A mutants we demonstrated that expression of antagonist lipid A structures resulted in weak induction of proinflammatory mediators. Moreover, expression of antagonist lipid A failed to activate the inflammasome, which correlated with increased bacterial survival in macrophages. Oral infection of atherosclerotic prone apolipoprotein E (ApoE) deficient mice with the antagonist lipid A strain resulted in vascular inflammation characterized by macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain expressing exclusively agonist lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11 dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE deficient mice infected with the agonist lipid A strain exhibited diminished vascular inflammation. Notably, the ability of P. gingivalis to induce local inflammatory oral bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. We next investigated the role of TLRs and lipid A on bacterial trafficking by the autophagic pathway. Originally characterized as a cell autonomous pathway for recycling damaged organelles and proteins, autophagy is now recognized to play a critical role in innate defense and release of the proinflammatory cytokine interleukin (IL)-1β. We demonstrated that P. gingivalis suppresses the autophagic pathway in macrophages for pathogen survival and intercepts autophagy-mediated IL-1β release. P. gingivalis-mediated suppression of autophagy was independent of lipid A expression but partially dependent on TLR2 signaling. Collectively, our results indicate that P. gingivalis evasion of innate immunity plays a role in chronic inflammation.