6 resultados para Praziquantel. Stability. Rheology. Schistosomiasis. Emulsified system
Resumo:
Over the last thirty years, there has been an increased demand for better management of public sector organisations (PSOs). This requires that they are answerable for the inputs that they are given but also for what they achieve with these inputs (Hood 1991; Hood 1995). It is suggested that this will improve the management of the organisation through better planning and control, and the achievement of greater accountability (Smith 1995). However, such a rational approach with clear goals and the means to measure achievement can cause difficulties for many PSOs. These difficulties include the distinctive nature of the public sector due to the political environment within which the public sector manager operates (Stewart and Walsh 1992) and the fact that PSOs will have many stakeholders, each of whom will have their own specific objectives based on their own perspective (Boyle 1995). This can
result in goal ambiguity which means that there is leeway in interpreting the results of the PSO. The National Asset Management Agency (NAMA) was set up to bring stability to the financial system by buying loans from the banks (which were in most cases, non-performing loans). The intention was to cleanse the banks of these loans so that they could return to their normal business of taking deposits and making loans. However, the legislation, also gave NAMA a wide range of other responsibilities including responsibility for facilitating credit in the economy and protecting the interests of taxpayers. In more recent times, NAMA has been given responsibility for building social housing. This wide-range of activities is a clear example of a PSO being given multiple goals which may conflict and is therefore likely to lead to goal ambiguity. This makes it very difficult to evaluate NAMA’s performance as they are attempting to meet numerous goals at the same time and also highlights the complexity of policy making in the public sector. The purpose of this paper is to examine how NAMA dealt with goal ambiguity. This will be done through a thematic analysis of its annual reports over the last five years. The paper’s will contribute to the ongoing debate about the evaluation of PSOs and the complex environment within which they operate which makes evaluation difficult as they are
answerable to multiple stakeholders who have different objectives and different criteria for measuring success.
Characterising granuloma regression and liver recovery in a murine model of schistosomiasis japonica
Resumo:
For hepatic schistosomiasis the egg-induced granulomatous response and the development of extensive fibrosis are the main pathologies. We used a Schistosoma japonicum-infected mouse model to characterise the multi-cellular pathways associated with the recovery from hepatic fibrosis following clearance of the infection with the anti-schistosomal drug, praziquantel. In the recovering liver splenomegaly, granuloma density and liver fibrosis were all reduced. Inflammatory cell infiltration into the liver was evident, and the numbers of neutrophils, eosinophils and macrophages were significantly decreased. Transcriptomic analysis revealed the up-regulation of fatty acid metabolism genes and the identification of Peroxisome proliferator activated receptor alpha as the upstream regulator of liver recovery. The aryl hydrocarbon receptor signalling pathway which regulates xenobiotic metabolism was also differentially up-regulated. These findings provide a better understanding of the mechanisms associated with the regression of hepatic schistosomiasis.
Resumo:
BACKGROUND: We report the use of an ex vivo precision cut liver slice (PCLS) mouse model for studying hepatic schistosomiasis. In this system, liver tissue is unfixed, unfrozen, and alive for maintenance in culture and subsequent molecular analysis.
METHODS AND FINDINGS: Using thick naive mouse liver tissue and sterile culture conditions, the addition of soluble egg antigen (SEA) derived from Schistosoma japonicum eggs, followed 4, 24 and 48 hrs time points. Tissue was collected for transcriptional analysis and supernatants collected to quantitate liver enzymes, cytokines and chemokines. No significant hepatotoxicity was demonstrated by supernatant liver enzymes due to the presence of SEA. A proinflammatory response was observed both at the transcriptional level and at the protein level by cytokine and chemokine bead assay. Key genes observed elevated transcription in response to the addition of SEA included: IL1-α and IL1-β, IL6, all associated with inflammation. The recruitment of antigen presenting cells was reflected in increases in transcription of CD40, CCL4 and CSF1. Indications of tissue remodeling were seen in elevated gene expression of various Matrix MetalloProteinases (MMP3, 9, 10, 13) and delayed increases in TIMP1. Collagen deposition was significantly reduced in the presence of SEA as shown in COL1A1 expression by qPCR after 24 hrs culture. Cytokine and chemokine analysis of the culture supernatants confirmed the elevation of proteins including IL6, CCL3, CCL4 and CXCL5.
CONCLUSIONS: This ex vivo model system for the synchronised delivery of parasite antigen to liver tissue provides an insight into the early phase of hepatic schistosomiasis, corresponding with the release of soluble proteins from dying schistosome eggs.
Resumo:
RNA ligases function pervasively across the three kingdoms of life for RNA repair, splicing and can be stress induced. The RtcB protein (also HSPC117, C22orf28, FAAP and D10Wsu52e) is one such conserved ligase, involved in tRNA and mRNA splicing. However, its physiological role is poorly described, especially in bacteria. We now show in Escherichia coli bacteria that the RtcR activated rtcAB genes function for ribosome homeostasis involving rRNA stability. Expression of rtcAB is activated by agents and genetic lesions which impair the translation apparatus or may cause oxidative damage in the cell. Rtc helps the cell to survive challenges to the translation apparatus, including ribosome targeting antibiotics. Further, loss of Rtc causes profound changes in chemotaxis and motility. Together, our data suggest that the Rtc system is part of a previously unrecognised adaptive response linking ribosome homeostasis with basic cell physiology and behaviour.
Resumo:
Wind generation in highly interconnected power networks creates local and centralised stability issues based on their proximity to conventional synchronous generators and load centres. This paper examines the large disturbance stability issues (i.e. rotor angle and voltage stability) in power networks with geographically distributed wind resources in the context of a number of dispatch scenarios based on profiles of historical wind generation for a real power network. Stability issues have been analysed using novel stability indices developed from dynamic characteristics of wind generation. The results of this study show that localised stability issues worsen when significant penetration of both conventional and wind generation is present due to their non-complementary characteristics. In contrast, network stability improves when either high penetration of wind and synchronous generation is present in the network. Therefore, network regions can be clustered into two distinct stability groups (i.e. superior stability and inferior stability regions). Network stability improves when a voltage control strategy is implemented at wind farms, however both stability clusters remain unchanged irrespective of change in the control strategy. Moreover, this study has shown that the enhanced fault ride-through (FRT) strategy for wind farms can improve both voltage and rotor angle stability locally, but only a marginal improvement is evident in neighbouring regions.
Resumo:
Future power systems are expected to integrate large-scale stochastic and intermittent generation and load due to reduced use of fossil fuel resources, including renewable energy sources (RES) and electric vehicles (EV). Inclusion of such resources poses challenges for the dynamic stability of synchronous transmission and distribution networks, not least in terms of generation where system inertia may not be wholly governed by large-scale generation but displaced by small-scale and localised generation. Energy storage systems (ESS) can limit the impact of dispersed and distributed generation by offering supporting reserve while accommodating large-scale EV connection; the latter (load) also participating in storage provision. In this paper, a local energy storage system (LESS) is proposed. The structure, requirement and optimal sizing of the LESS are discussed. Three operating modes are detailed, including: 1) storage pack management; 2) normal operation; and 3) contingency operation. The proposed LESS scheme is evaluated using simulation studies based on data obtained from the Northern Ireland regional and residential network.