Neisseria gonorrhoeae is an obligate human pathogen that causes the common sexually- transmitted infection, gonorrhea. Gonococcal infections cause significant morbidity, particularly among women, as the organism ascends to the upper reproductive tract, resulting in pelvic inflammatory disease, ectopic pregnancy and infertility. Antibiotic resistance rates have risen dramatically, leading to severe restriction of treatment options for gonococcal disease. Gonococcal infections do not elicit protective immunity nor is there an effective vaccine to prevent the disease. Thus, further characterization of expression, function and regulation of surface antigens could lead to better treatment and prevention modalities in the future. N. gonorrhoeae express a repertoire of TonB-dependent transporters for the acquisition of iron. All of these transporters are under the transcriptional regulation of Fur. We investigated putative intracellular iron sources utilized by gonococci and the role that the TonB-dependent transporter, TdfF, played in this acquisition. We determined that ascorbate which could prevent ferritin degradation or withhold iron from gonococci, inhibited intracellular survival. The utilization of iron from the iron binding moiety 2, 5-DHBA of the putative mammalian siderophore was also examined. In this study we continued to investigate the regulation of TdfF and further investigate potential host-specific inducing molecules for TdfF expression. We investigated the regulation of tdfF expression and the role of MpeR, an AraC-like regulator, in tdfF expression. We determined that MpeR, interacted specifically with the DNA sequence upstream of fetA and activated FetA expression. We confirmed that the outer membrane transporter, FetA, allows gonococcal strain FA1090 to utilize the xenosiderophore, ferric-enterobactin, as an iron source. However, we further demonstrated that FetA has an extended range of substrates that encompasses other catecholate xenosiderophores, including ferric-salmochelin and the dimers and trimers of dihydroxybenzoylserine. We demonstrated that fetA is encoded as part of an iron-repressed, MpeR-activated operon, which putatively encodes other iron transport proteins. These iron transport proteins also play a role in xenosiderophore acquisition. We also identified genetic differences that may explain why some gonococcal strains are capable of xenosiderophore internalization in a TonB-dependent pathway and other strains are restricted to TonB-independent pathways. Interestingly, the chromosomal locus that codes for mpeR and tdfF is pathogen specific. Thus understanding more about the TonB-dependent transporter and AraC-like regulator may further elucidate the pathogenicity of N gonorrhoeae.

Research report presented to the SBL, Unisa, Midrand. / This report proposes to make a contribution in the area of governance by critically analyzing the governance structure of SNV (The Netherlands Development Organization) in implementing projects. This study is motivated by the scarcity of published documentation on corporate and project governance practices specific to the African and particularly Kenyan context which organisations interested in pursuing good governance and managerial practices can use as a reference point.

The aim of this diploma thesis called The dependent work is to assess a current legal regulation of the dependent work and consequences of its performance outside a labour law relationship. This practice that is also known as a so-called švarcsystém, i.e. the mutual relationship between two parties in which a natural person performs the dependent work for another natural person or legal entity on grounds of a commercial- law or civil law agreement and therefore outside a labour-law relationship, has been as of 1 January 2012 regarded as illegal work. The regulation of labour law in the Czech Republic has been significantly changed as of 1 January 2012, including amendments to Labour Code and Act on Employment. The amendment to the Labour Code changed a legal definition of the dependent work that is one of the main terms of the Czech labour law. The performance of the dependent work outside the labour law relationship has been regarded as the illegal work due to the amendment of the Act on Employment. In this diploma thesis the definition of the dependent work as well as of a related term, a dependent activity, is explained based on the current legal regulation as well as the decision-making practice of the Czech courts. These terms are crucial for regarding a certain activity as an illegal work....

Cardiac hypertrophy leading to heart failure remains a leading cause of morbidity and mortality in the 21st century despite major therapeutic advances. Improved understanding of novel molecular and cellular processes contributing to cardiac hypertrophy therefore continues to be important. Cyclin-dependent Kinase 9 (CDK9), part of a family of proteins controlling cell cycle and growth, has emerged as one such potential candidate over the last 5 years. CDK9 is the catalytic subunit of the CDK9/CyclinT complex and acts by phosphorylating the carboxy-terminal domain of RNA polymerase II. Hypertrophic signals, such as Endothelin-1 (ET-1) and phenylephrine, have been shown to cause CDK9 activation leading to a hypertrophic response in cultured mouse cardiomyocytes associated with reactivation of the foetal gene program. CDK9 also forms a complex with GATA4 to play a role in differentiation of mouse ES cells into cardiomyocytes. These findings suggest a specific role for CDK9 in controlling growth and differentiation of cardiomyocytes and merits further study in models where cardiomyocyte differentiation and proliferation are key contributors. In contrast to mammals, zebrafish retain a high cardiomyocyte proliferative capacity throughout their life span and can readily repair following injury. I have examined the role of CDK9 on global and cardiac development in the zebrafish embryo. I have also assessed the impact of CDK9 manipulation on response to ventricle injury using a laser-induced injury model developed and validated as part of my thesis. My findings confirm that normal growth of the embryonic ventricle is associated with a rapid increase in cardiomyocyte number, that was of 50% in the period 96-120 hpf, accompanied by increasing chamber trabeculation. This is also characterized by an increase in the gene expression of most of cardiac development relevant transcription factors, i.e. GATA4, 5 and 6, and MEF2c. The significant reduced cardiovascular function (14% of Ejection Fraction compared to 20% in controls) at 2 h post laser injury in the zebrafish embryonic heart promptly recovers at 24 hour post-laser, accompanied by acceleration of cardiomyocyte proliferation, that increased of 49% in injured ventricles compared to 20% in controls in the period 2-24 h post-laser. Pharmacological and genetic inhibition of CDK9 activity also significantly reduced cardiac growth, cardiomyocyte number, ventricle function and impairs functional recovery following laser injury. Conversely, genetic inhibition of LARP7, a CDK9 repressor, resulted in increased cardiomyocyte number and was associated with full functional and cellular recovery following laser-injury. In conclusion, I have provided evidence, in the zebrafish embryonic heart, that CDK9 plays an important role in cardiac growth and development and impacts significantly on cardiomyocyte proliferation. I have also shown that CDK9 manipulation significantly affects cellular and functional recovery following laser-induced injury. Further studies are required to further define the role of CDK9 and LARP7 in the heart and develop therapeutic strategies using this pathway that could contribute to cellular repair mechanisms in the adult mammalian heart.

The purpose of this study was to examine how professionals describe the interaction between psychiatry and addiction care when it comes to clients/patients  who suffer from comorbidity of substance abuse and diagnosed mental illness. In this study we posed the following questions: How do the care personnel within psychiatric treatment and substance abuse care describe the current state of the collaboration between them? Which pros and cons do the personnel within the two sectors describe regarding collaboration? Based on six interviews; three among professionals in psychiatry and three in addiction care, the overall result shows that the informants believe that the existing cooperation works well but can be developed. The study also shows that concerted individual plans (SIP) as a tool can generate positive results for clients/patients within both organizations. SIP is also an opportunity for the professionals to go beyond the current confidentiality that exists between the client/patient and organization and thus better able to collaborate around a client/patient. The conclusion is that cooperation can be favored or discriminated against by the staff's attitudes towards individuals who suffer from comorbidity, political decisions, maneuver and professional, personal experience and knowledge of each other's professions. / Syftet med denna studie var att undersöka hur yrkesverksamma inom psykiatrin och beroendevården beskriver samverkan mellan organisationerna angående personer som lider av samsjuklighet av missbruk och diagnostiserad psykisk ohälsa. Frågeställningarna var: Hur beskriver vårdpersonalen inom psykiatrin och beroendevården att samverkan fungerar? Vilka fördelar respektive nackdelar beskriver personalen inom de olika verksamheterna att det finns med samverkan? Utifrån sex intervjuer, tre bland anställda inom psykiatrin respektive tre i beroendevården, visar det övergripande resultatet att informanterna anser att den befintliga samverkan fungerar bra men kan utvecklas. Studien visar även att samordnade individuella planer (SIP) som verktyg kan generera positiva resultat för klienterna/patienterna inom de båda organisationerna. SIP är också en möjlighet för de professionella att få möjlighet att häva rådande tystnadsplikt som finns mellan klienten/patienten och organisationen och därigenom bättre kunna samverka kring en klient/patient. Slutsatsen är att samverkan kan gynnas eller missgynnas av personalens attityder gentemot individer som lider av samsjuklighet, politiska beslut, handlingsutrymmet samt yrke, personlig erfarenhet och kunskap om varandras professioner.

Programs are more distributed and concurrent today than ever before, and structural communications are at the core. Constructing and debugging such programs are hard due to the lack of formal specifications and verifications of concurrency. Recent advances in type systems allow us to specify the structures of communications as session types, thus enabling static type checking of the usages of communication channels against protocols. The soundness of session type systems implies communication fidelity and absence of deadlock. This work proposes to formalize multiparty dependent session types as an expressive and practical type discipline for enforcing communication protocols. The type system is formulated in the setting of multi-threaded λ-calculus with inspirations from multirole logic. It is sound, and it provides linearity and coherence guarantees entirely statically. The type system supports recursion and polymorphism. The formulation is particularly suitable for practical implementation, and this work provides such a runtime implementation.

M.Fam.Med. Faculty of Health Sciences, University of the Witwatersrand, 2009. / Worldwide, obesity prevalence is rapidly rising. Doctors have poor understanding of what patients experience and expect from them regarding weight-loss management. This qualitative study explored what obese patients with Non-insulin Dependent Diabetes Mellitus experience and expect from their primary care doctors concerning weight-loss management. Free attitude interviews were conducted with eight participating patients. The findings showed that doctors encouraged and counselled patients regarding weight-loss, mainly giving dietary advice, but did not routinely weigh them. Patients accepted responsibility for losing weight, trusted their doctors, valued their advice highly and did not want referrals to gymnasiums or dieticians. They expected doctors to advise them practically about exercise, diet and weight-loss goals, weigh them regularly and communicate effectively. They believed that doctor-patient relationships and interaction are important in weight-loss management, patients should be treated on an individual basis and the process should be empowering. Medical intervention costs were not problematic for this group. Generally patients were satisfied with their doctors but there were areas concerning patients’ expectations that primary care doctors should take cognisance of.

Students may engage in behavior during instruction that impacts the acquisition of skills. Intervening on student behavior using group contingencies may be more efficacious than other intervention methods. Directly programming for generalization of treatment effects may increase the durability of behavior change and further increase the efficacy of group contingencies. The current study examined the effect of a randomized dependent group contingency and programming common stimuli on levels of academic engagement and problem behavior for second-grade participants receiving small-group reading and writing instruction. The results showed that a randomized dependent group contingency increased the academic engagement of primary participants and several of the other participants during small-group instruction. The findings also showed that high levels of academic engagement were maintained when common stimuli were present and the dependent group contingency was withdrawn.

This literature review will discuss Zika virus and the salient research on antibody dependent enhancement and how this mechanism may lead to congenital defects. Specific objectives include: the mechanism of antibody dependent enhancement, Zika and dengue virus pathogenesis, placenta pathophysiology, and how changes in viral virulence may play a role the pathogenesis of neurologic congenital defects seen in infants infected with Zika virus in utero. While some cohort studies have examined the relationship between prior dengue immunity, Zika virus infection in pregnancy, and effects on neonatal outcomes further prospective studies using large cohorts and more detailed lab testing and imaging is essential to better understand this relationship. A proposed study enrolling a large cohort of women in the 6th- 8th week of pregnancy from Northeastern Brazil will seek to further describe what additional risk dengue immunity may pose in the context of Zika virus. This risk is essential to understand, as Zika and Dengue viruses co-circulate in many regions of the world. Furthermore, participants in the proposed study will undergo bi-weekly screening for Zika virus through laboratory and ultrasound testing until their delivery. Infants will then have full neurologic testing and MRI scanning for the following year after birth to characterize any congenital defects. Neonates born to mothers with prior dengue immunity who contract Zika virus during pregnancy will be compared to neonates not exposed to Zika virus in utero. This experiment will illuminate the associated risk and evidence of ADE occurring with prior dengue immunity and Zika virus infection during pregnancy. Results from this study will not only help define risks of congenital defects with Zika virus, it will inform vaccine research and elucidate challenges in the administration of the current tetravalent dengue vaccine.

Stroke is one of the leading causes of human death in the United States. The debilitating effects of an ischemic stroke are due to the fact that mammalian neurons are highly susceptible to hypoxia and subsequent oxygen reperfusion. From studies in Drosophila melanogaster, cGMP-dependent Protein Kinase (PKG) enzyme is thought to affect anoxia tolerance by modifying the electrical current through potassium ion channels. In this research, two animal models were employed: Drosophila melanogaster and mammalian neurons exposed to stroke-like conditions. First, in vivo studies using Drosophila were performed to further our knowledge about the differences between the naturally occurring variants of the Drosophila foraging gene, which shows different protein levels of PKG. Mitochondrial density and metabolic activity between two fly genotypes exposed to anoxia and reoxygenation were compared. It was found that flies with less enzyme potentially showed mitochondrial biogenesis and higher metabolic rates upon reoxygenation. Next, in vivo studies where PKG enzyme was activated pharmacologically were performed; it was found that the activation of the cGMP/PKG pathway led to neuroprotection upon anoxia and reoxygenation. Furthermore, this model was translated into the in vitro model using Drosophila cells. Instead of anoxia and reoxygenation, hypoxia mimetics and hydrogen peroxide were used to induce cellular injury. After showing the cGMP/PKG pathway activation-induced cell protection, the potential downstream targets of the molecular signaling as well as underlying biochemical changes were assessed. It was found that mitochondrial potassium ion channels were involved in the protective signaling and the signaling modulated metabolic function. Furthermore, it was found that acidosis protected Drosophila cells from cell death, metabolic disruption, and oxidative stress. Finally, this research was translated to a mammalian in vitro model of neuronal damage upon stroke-like conditions; there, it was demonstrated that the cGMP/PKG pathway activation in rat primary cortical neurons and human cortical neurons was protective from low oxygen and acute oxidative stress. The results of this study lead to a better understanding of molecular mechanisms taking place during low oxygen and oxidative stresses. Consequently, this knowledge may be used to identify potential therapeutic targets and treatments that may prevent detrimental neurological effects of an ischemic stroke in humans. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection