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Earnings management and accounting fraud are detrimental to the integrity of financial reporting, and more worryingly, are pervasive. Furthermore, there is often a grey area in which individuals regularly question whether or not specified accounting methods are strictly legal and permitted, or an underhanded abuse of GAAP-granted flexibility. In response, recently there has been an uprising of legislation attempting to curb the incidence of both these events, but there is still question as to whether or not these attempts are effective, or even wholly necessary. This piece examines methods of accounting manipulation through an analysis of cases, and then analyzes the effects on companies of attempts at both regulation and prevention.

MexCD-OprJ is an RND-type multidrug efflux pump present in P. aeruginosa and is capable of exporting, and as such providing resistance to, several clinically important antimicrobials including fluoroquinolones, cephems, macrolides, and several biocides including chlorhexidine (CHX). Expression of mexCD-oprJ is negatively regulated by NfxB, a LacI-type repressor. The promoter region of mexCD-oprJ was identified and included two inverted repeat operator sites, B1 and B2, both of which are required in order for NfxB to bind, thereby repressing mexCD-oprJ. NfxB oligomerizes into a tetramer in solution and likely functions as a dimer of NfxB homodimers. In addition to being derepressed by loss of NfxB, MexCD-OprJ is inducible by a variety of non-antibiotic membrane-damaging agents (MDAs) such as CHX. A homologue of NfxB, PA4596, was found to be induced in response to CHX-promoted envelope stress in an AlgU-dependent manner and is directly repressed by NfxB. Loss of PA4596 resulted in increased resistance to the biocide CHX, shown to be a result of increased CHX-dependent expression of mexCD-oprJ. Susceptibility to CHX was restored upon expression of PA4596 from the plasmid pAK1900 as was decreased expression of mexCD-oprJ in the presence of CHX, indicating that PA4596 contributes to mexCD-oprJ repression in the presence of CHX. PA4596 was found to form oligomers in solution, likely dimers and tetramers. In the absence of NfxB, PA4596 is unable to contribute to repression of mexCD-oprJ. However, NfxB and PA4596 interact and together form a repressor capable of regulating mexCD-oprJ expression. Screening of transposon mutants for increased resistance to erythromycin potentially indicative of increased mexCD-oprJ expression lead to the identification of several novel genes including PA0479, cupA3, faoA, PA3259, mucD, and clpA whose loss generated a multidrug resistance profile consistent with increased production of MexCD-OprJ. However, further studies are required to determine how each of these genes may be affecting expression of mexCD-oprJ. / Thesis (Ph.D, Microbiology & Immunology) -- Queen's University, 2013-06-12 12:07:28.67

In this study it is argued that quality of health is predominantly influenced by health behaviour and health-risk behaviour. Self-regulation as an important factor in health and health-risk behaviour was operationalised by three phases, namely goal establishment, goal execution and self-reflection and adjustment. In addition, mindfulness is an important metacognitive skill applied throughout the process of self-regulation. The lack of research on self-regulation and health behaviour, especially with reference to South African youth and young adolescents is surprising. Health programmes seem to pay insufficient attention to the enhancement of self-regulatory skills in preventing health risk behaviour. Another limitation is the lack of qualitative data regarding self-regulation research. 'This study aims to explore the self-regulation of health-related goals in a group of young adults. Insight to this process could contribute to the development of more appropriate health promoting programmes. A qualitative research design with content analysis as data analysis technique was applied. An availability sample of 92 participants, aged between 18 and 30, completed self-compiled questionnaires on health-risk behaviour and self-regulation. Results indicate a high prevalence of health risk behaviour, supporting other South African findings. Various differences were found between participants engaging in high risk behaviour and those with low risk behaviour with reference to the phases and processes of self-regulation. The high risk group's goal setting seems to be problematic as it does not address identified high risk behaviours. This may be as a result of insufficient mindfulness in that they are ignorant of their health risk behaviour and its implication or alternatively, that they attempt to avoid the risk of failure. In addition, the high risk group is more dependent on external motivation regarding health-related goals and is, therefore, more influenced by controlled regulation. In contrast, the low risk group more often relies on individual personal resources as a source of motivation for their health related goals. Furthermore, the high risk group experiences regulatory non-fit as 'their actions were more often inappropriate. No major differences were found between the groups concerning stumbling blocks and self-observation. Participants in the high risk group evaluate their performance less favourably and are more likely to experience negative emotions in the face of failure compared to participants in the low risk group. When taking the whole self-regulation process into account, it can thus be concluded that participants of the high risk group have poor self-regulation in relation to participants in the low risk group. In general, the findings of this study support the findings of other researchers, confirming the importance of self-regulation in health and health-risk behaviour. The main implication is that there should be a much stronger emphasis on self-regulatory skills in health promotion and illness prevention programmes. Certain limitations of this study were also taken into account. Future studies should consider the role of individuals' risk perceptions with regard to the goal establishment phases as well as the manner in which individuals deal with stumbling blocks in the action phase. Finally, the way in which self-regulation as a dynamic process should be accurately assessed is still not clear. As this study is one of the first to explore self-regulation from a qualitative perspective, future studies could shed more light on the usefulness of other qualitative and even mixed method designs. / Thesis (M.A. (Clinical Psychology))--North-West University, Potchefstroom Campus, 2007.

The proliferation of regional trading agreements around the world has changed the landscape of international trade law from a multi-polar system anchored in the nationstate to one where there are groups of closely-knit sovereign nations. They are usually drawn along geographical lines and are conducting trade with one another in a myriad of ways. This craze for trade deals is sure to give rise to disputes that are an inescapable outcome of the bilateral, regional and international agreements that contain the will of these nations to engage in greater co-operation with one another. As such, it has become necessary to design reliable dispute settlement mechanisms for the settlement of trade related disputes for the effective functioning of the trading agreements. Dispute settlement systems have progressed from being unsophisticated and diplomacy oriented as typified by that of the GATT to the highly legalized adjudication based mechanism that is the crowning glory of the WTO. This trend has been followed by other trading organizations that have modified their dispute settlement mechanisms to become more legalistic. CARICOM is a reborn regional trading bloc in the Caribbean and in lock step with the trend of other trading clubs has augmented its dispute settlement mechanism with a long awaited regional court and other non-binding alternative dispute resolution methods to avert legal clashes. This thesis examines the progress of the CARICOM dispute settlement mechanism from its originally diplomatic procedures to its enhanced legalistic system. A standing judicial institution in CARICOM is a coming of age for this region and its jurisprudence now referred to as CARICOM law. These significant legal advances raise many normative questions about the adequacy of the dispute settlement institutions and whether the rules and processes are clearly defined to enable nascent CARICOM law to be the primary tool by which there can be effective regulation of CARICOM integration. In order to answer these questions this thesis reviews the dispute settlement mechanisms of the WTO and the EU as the natural ‘parents’ of the CARICOM dispute settlement system.

<p>Diversity of T cell receptors (TCR) and immunoglobulins (Ig) is generated by V(D)J recombination of antigen receptor (AgR) loci. The Tcra-Tcrd locus is of particular interest because it displays a nested organization of Tcrd and Tcra gene segments and V(D)J recombination follows an intricate developmental program to assemble both TCRδ and TCRα repertoires. However, the mechanisms that dictate the developmental regulation of V(D)J recombination of the Tcra-Tcrd locus remain unclear. </p><p>We have previously shown that CCCTC-binding factor (CTCF) regulates Tcra gene transcription and rearrangement through organizing chromatin looping between CTCF- binding elements (CBEs). This study is one of many showing that CTCF functions as a chromatin organizer and transcriptional regulator genome-wide. However, detailed understanding of the impact of specific CBEs is needed to fully comprehend the biological function of CTCF and how CTCF influences the generation of the TCR repertoire during thymocyte development. Thus, we generated several mouse models with genetically modified CBEs to gain insight into the CTCF-dependent regulation of the Tcra-Tcrd locus. We revealed a CTCF-dependent chromatin interaction network at the Tcra-Tcrd locus in double-negative thymocytes. Disruption of a discrete chromatin loop encompassing Dδ, Jδ and Cδ gene segments allowed a single Vδ segment to frequently contact and rearrange to diversity and joining gene segments and dominate the adult TCRδ repertoire. Disruption of this loop also narrowed the TCRα repertoire, which, we believe, followed as a consequence of the restricted TCRδ repertoire. Hence, a single CTCF-mediated chromatin loop directly regulates TCRδ diversity and indirectly regulates TCRα diversity. In addition, we showed that insertion of an ectopic CBE can modify chromatin interactions and disrupt the rearrangement of particular Vδ gene segments. Finally, we investigated the role of YY1 in early T cell development by conditionally deleting YY1 in developing thymocytes. We found that early ablation of YY1 caused severe developmental defects in the DN compartment due to a dramatic increase in DN thymocyte apoptosis. Furthermore, late ablation of YY1 resulted in increased apoptosis of DP thymocytes and a restricted TCRα repertoire. Mechanistically, we showed that p53 was upregulated in both DN and DP YY1-deficient thymocytes. Eliminating p53 in YY1-deficient thymocytes rescued the survival and developmental defects, indicating that these YY1-dependent defects were p53-mediated. We conclude that YY1 is required to maintain cell viability during thymocyte development by thwarting the accumulation of p53.</p><p>Overall, this thesis work has shown that CTCF-dependent looping provides a central framework for lineage- and developmental stage-specific regulation of Tcra-Tcrd gene expression and rearrangements. In addition, we identified YY1 as a novel regulator of thymocyte viability.</p> / Dissertation

One of the major challenges facing clinicians is how to effectively manage excessive host immune response to pathogenic insults resulting in sepsis. This is demonstrated by the fact that despite over half-century research efforts, sepsis and its spectrum of diseases (severe sepsis and septic shock) are still associated with poor clinical outcome. Currently, sepsis is a leading cause of death in intensive care units. The immune system protects the host against pathogens and is therefore armed with an arsenal of deadly ammunitions (including chemicals, cells and proteins) necessary for the elimination of microbes. It is therefore paramount that the immune system must develop mechanisms necessary to prevent destruction of the host it is designed to protect. A good example of such a mechanism is found in the subset of lymphocytes known as regulatory T cells (Tregs). There is unequivocal experimental evidence of the role of Tregs in the maintenance of immune homeostasis and self tolerance and aberrant Treg function has been linked with several inflammatory diseases. Since sepsis is a disease marked by a hyper-inflammatory state, I investigated the possible role of Tregs in dampening sepsis-induced excessive inflammation. Using a murine model of lipopolysaccharide (LPS) infusion and bacterial infection, I show that Tregs are essential for survival during sepsis because their depletion leads to acute death to an otherwise non-lethal dose of LPS. This enhanced susceptibility to LPS following Treg depletion was also observed using live E. coli infection. Next, I probed the mechanism by which Tregs protect against LPS challenge. I found that defective Treg function leads to exaggerated activity of two immune cells – CD4+ effector T cells and neutrophils in response to LPS, leading to severe inflammatory response. Hence, this work successfully illustrates the critical role of Tregs in regulating other immune cells and the catastrophic consequences of defective Treg function during an immune response. Overall, this work highlights the significant role of Tregs in the regulation of bacteria associated inflammatory processes. The findings hold implications for the successful management of sepsis and have potential for use in development of adequate therapeutic intervention for sepsis. / October 2016

This thesis examines the roles of endothermy and body size in the thermal biology of solitary bees (Hymenoptera: Apoidea) within the species Anthophora plumipes (Anthophoridae) Amegilla sapiens (Anthophoridae) and Creightonellafrontalis (Megachilidae), within the genus Anthophora, and over the Apoidea as a whole. The effects of body size, climate and sexual interactions on the biology of Anthophora plumipes were investigated in Oxford between 1987 and 1989. Both ambient temperature and body size had a significant effect on females' ability to forage, what time they initiated foraging in the morning, and the type and mass of provisions collected. The behaviour of males was also strongly dependent on ambient temperature, which affected not only when they emerged from their nest tunnels, but also how long they spent basking, when and where they fed, and whether they showed courtship behaviour. The activity patterns and behaviour of male and female A. plumipes over time were shown to correlate with a complex array of factors. Activity patterns of females depended on the quality of floral resources available at foraging sites, body mass, ambient temperature, the position of the female in her nest-provisioning cycle, and levels of male interference at foraging sites. Male behaviour not only depended on body size and ambient temperature, but also on which other bees (particularly male and female conspecifics) were encountered while patrolling food sources and at the nest site. Endothermy in bees is much more widespread than previously thought, and warm-up before flight was present to some degree in all the species examined. Levels of thermoregulation achieved, however, varied considerably between species. Warm-up rates in bees, and thoracic temperatures in free and tethered flight, are shown to depend on ambient temperature and body mass within a species (for temperate and tropical examples), across members of the genus Anthophora and across the Apoidea as a whole. The persistence of these relationships over a range of comparative levels suggests that they are of fundamental importance. The form of these relationships differs between families in the Apoidea, and significant patterns only emerge when a comparative technique controlling for phylogeny is applied. Furthermore, body temperatures may also depend, in at least some cases, on sex and there may be differences within a group of related species between provisioning and parasitic forms. The interaction of all these factors is complex, and the predictive value of a variable such as body mass does not always emerge unless sophisticated techniques are used to control for other variables. The errors associated with two common methods in the measurement of insect body temperatures have often been loosely discussed but rarely quantified. This thesis examines (a) the magnitude and possible effects of errors in 'grab-and-stab' measurement of body temperature, and (b) the errors in measurement of body temperature using fixed sensors linked by thermally conducting leads to measuring devices. In neither case do the demonstrated errors preclude use of the technique, but care with interpretation is required. In both cases, measurement of thoracic temperature in small bees involves the largest errors, and this is the most serious obstacle to comparisons of endothermic and thermoregulatory abilities over the full range of body sizes found in the Apoidea.

Acid-base regulation is vital for animals and while the inorganic carbon system largely determines body fluid pH, another potentially valuable acid-base pair is ammonia (NH4+/NH3). This study focuses on the American horseshoe crab (Limulus polyphemus), a phylogenetically ancient marine chelicerate with no published studies on its acid-base physiology. Physiological and molecular analyses indicate that Na+/K+-ATPase, Rhesus-protein (Rh), and carbonic anhydrase (CA) are involved in acid-base homeostasis and/or ammonia regulation. This likely occurs in the book gills, which consist of ultrastructurally distinct regions. The ventral half-lamella is ion-leaky and displayed high Rh-protein, cytoplasmic CA, and hyperpolarization-activated cyclic nucleotide-gated K+ channel mRNA expression levels, suggesting a specialization in facilitated CO2 and/or ammonia diffusion compared to the dorsal half-lamella. During hypercapnia acclimation, hemolymph acid-base status exhibited a compensated respiratory acidosis accompanied with signs of metabolic depression. Ammonia influx associated with high environmental ammonia acclimation was successfully counteracted, but induced modifications in acid-base homeostasis. / October 2016