Glucocorticoids have long been used in the treatment of acute lymphoblastic leukaemia due to their ability to cause cell cycle arrest and apoptosis of lymphoid cells. However, some patients do not respond to glucocorticoid treatment and the majority, who initially respond, may relapse upon prolonged hormone treatment. The inefficiency of the treatment is mainly attributed to the gradual loss of the cellular sensitivity to glucocorticoid-induced apoptosis. Therefore, the need to understand the molecular mechanisms of resistance/ sensitivity of acute lymphoblastic leukaemia cells to glucocorticoid-induced apoptosis is of vital importance, as this will help to develop better prognostic outcomes and improve glucocorticoids therapy. Several mechanisms have been proposed to explain the evasion of glucocorticoid mediated apoptosis in resistant cells. These include post-translational modifications of GR especially phosphorylation which modulates the GR transcriptional activity, and GR mediated signalling thereby affecting gene expression and hence the balance between pro- and anti-apoptotic Bcl-2 family members. In addition the concentration of components of the energy metabolism pathways (i.e. oxidative phosphorylation and glycolysis) and ROS generation are altered in the acute lymphoblastic leukaemia cells. The hypothesis that differentially phosphorylated GR in the resistant versus sensitive ALL cells modulate GR transcriptional activity and target selectively resulting in diverse pro- or anti-apoptotic Bcl-2 family members' gene expression in the two cell lines was tested. Furthermore, in a similar manner, the possibility that differential GR phosphorylation diversely affected gene expression of GR transcriptional target genes that are components of cellular energy production pathways in resistant versus sensitive cells, altering energy and ROS production levels in distinct ways in the two cell lines was explored. GR was found to be predominantly phosphorylated at S211 in the glucocorticoid-sensitive CEM C7-14, and at S226 in the glucocorticoid-resistant CEM C1-15 cells. Differential GR phosphorylation is presumably an indication of dominant p38 MAPK activity in CEM C7-14 and JNK kinase activity in CEM C1-15, which could lead to adverse gene expression of some pro- and anti-apoptotic Bcl-2 family members and particularly Mcl-1, in the two cell lines. Furthermore, differential GR phosphorylation at S211 and S226 in CEM C7-14 and CEM C1-15 affected the gene expression of the Cytochrome C Oxidase assembly factors Surf-1 and SCO2 as well as the nuclear encoded Cytochrome C Oxidase subunit COX-Va and the mitochondrial encoded COX-I, COX-II and COX-III. This effect was more pronounced in the glucocorticoid-sensitive CEM C7-14 cells, probably due to the fact that GR was predominantly phosphorylated at S211 and hence transcriptionally active in these cells. Moreover, in comparison to the resistant CEM C1-15 cells, the CEM C7-14 cells exhibited higher levels of ROS, increased number of active mitochondria and up-regulated glycolysis upon inhibition of oxidative phosphorylation. Glucocorticoids further reduced ROS levels in the CEM C1-15 cells, and increased the NADH/ NAD+ ratio. In conclusion results presented in this thesis provide evidence that differential GR phosphorylation in resistant versus sensitive to glucocorticoid induced apoptosis cells plays essential role in the regulation of programmed cell death and energy metabolism pathways, offering a potential explanation for the molecular events that determine resistance/sensitivity to glucocorticoid-induced apoptosis in ALL cells.

In this Thesis I focus on the ensuring of the energy safety in the Czech republic.Further more I deal with a size of the resources, energy utilization, energy legislation and energy forecasting.

The problems of lack of potable water, food and electrical power in and around the desert environment are analysed and their solutions based on the utilisation of indigenous renewable energy resources are evaluated in the current research. Self-contained, decentralised solar energy powered processes are devised in the research results as means to attain the objectives of supplying electrical power, potable water and food to the communities living in the deserts in environmentally sustainable manner. Needs analysis of desert community, a questionnaire survey, desert energy model utilisation scenarios, solar potential assessment and environmental emissions reduction strategy are used as means of analysis in the current research. A potential assessment of a desert site Islamkot, at Thar is carried out to demonstrate the capability of available solar potential to meet the energy needs of underground pumping, desalination of aquifer water potable water, cultivation of wheat, rice and pulses and domestic power consumption. The needs analysis estimates the amounts of electrical power needs of potable water desalination, agricultural commodities cultivation and electrical power needs per person per day, which can be scale up for any number of communities living in and around the deserts. The results reveals that indigenous solar potential capability can be used to produce the required amounts of electrical power to meet the water, wheat, rice, pulses, electrical power, drinking, non-drinking and cultivation water needs of the desert communities in environmentally sustainable manner. The research results are practicable and can be implemented to meet the energy needs of isolated communities living in and around the deserts in the long run. However, sustainable efforts would be required to encourage stakeholders to initiate a process of small, medium and large scale solar power utilization in and around the deserts.

System specifications and testing model for increasing the rated power output, rotor diameter, hub height, and maximum tip speed of horizontal axis wind turbines is designed and implemented on the system advisor model simulator. Its performance is tested on offshore wind turbine’s direct-drive and single stage-low speed generators. Although this simulator produces impressive results, it has some limitations in the operation of wind turbines. The terrain and topography of wind turbines are not considered in the simulation process. It also does not assess the electrical transients and physical stress of wind turbine components. Despite its limitations, four large offshore wind turbines and wind farms have been successfully simulated. It is found that the 9 MW, 10 MW, 11 MW and their respective wind farms generate more energy and better capacity factor on the direct-drive than single stage-low speed generator. Furthermore, a rectangular layout of 20 wind turbines considerably impacted the excellent performance of this generator on the wind farms. Another notable outcome of the study is that higher system specifications do not always generate feasible results for wind turbines despite favourable weather conditions. For the Vestas 8 MW wind turbine, the viable percentages for increasing the size of its rated power output, rotor diameter, hub height and maximum tip speed is only 12.5%, 25% and 37.5%. The viability of these three upgrades has been confirmed by suitable graphs of power curves and feasible energy production results. Thus, these percentages confirm an 8 MW wind turbine’s attainable design limits for generating realistic energy production and capacity factor. On the contrary, a 50% increase in the above four system specifications yielded unviable capacity factor and energy production results. This is because this upgrade is too high to work successfully on the current wind turbine technology. Furthermore, the shape of the power curve from the 50% specifications is not the typical curve for wind turbines. It has been observed that increasing the value of maximum tip speed beyond 143 m/s and the rotor diameter beyond 246 m give rise to an unusual power curve. Concerning wind speed for high energy production, an average daily minimum and maximum wind speed of 4.58 m/s and 15.08 m/s yielded good results. Given the prevailing trend of designing large wind turbines, findings in this study are particularly helpful in understanding how capacity factor, energy production and energy losses are affected by the size of system specifications. Not only that, but these findings also have fundamental concepts that can be used to optimize the design of large offshore wind turbines. The study is equally valuable for determining suitable weather conditions and wind power potential for large offshore wind farm sites. / Dissertation (MEng (Electrical Engineering))--University of Pretoria, 2020. / Electrical, Electronic and Computer Engineering / MEng (Electrical Engineering) / Unrestricted

The aim of the dissertation is to investigate the role of Industrial architecture in facilitating emergent functions through adaptive re-use of discarded spaces that will demonstrate low energy architecture, energy production and social integration. The function of the production place in the city is to define production so that it will:<ul><li> Emphasize the community over the individual</li><li> Stimulate production to steer away from the concept of being a linear process that is focused on the product, to that of a cyclical process that imitate the concept of an ecosystem</li><li> Work with existing energy</li><li> Establish emerging opportunities through connectivity between production process and the local urban fabric</li></ul> The industrial intervention of the production place takes the form of a Bio-diesel plant that will be situated on the Pretoria West Power Station, in the Pretoria West Industrial area, west of the City of Tshwane Central Business District. / Dissertation (MArch(Prof))--University of Pretoria, 2010. / Architecture / unrestricted

Energy production in power plants comes with both high costs and turnover whereas variations in the production strategy—that is, which boilers, coolers, or generators that should be running—have big impact on the economic result. This is especially true for a combined heat and power (CHP) plant where the production of district heating and electricity is linked, thus allowing for a higher flexibility in the production strategy and potential of increasing the revenue. Previous research states that thermo-economic optimization can have a great impact on economic result of power plants, but every power plant is operating under a unique set of conditions depending on its location, operating market, load demand, construction, surrounding, and the like, and comparable studies on CHP plants in Sweden are very few. This study aims to fill this research gap by evaluating savings potential of a CHP plant in Lidköping, Sweden by utilizing thermo-economic optimization with the approach of combining actual historical data from the power plant with mass-flow equations and constraints to construct a mathematical MODEST model that is optimized by linear programming. The result demonstrates a clear theoretical potential to improve earnings and the conclusion that the studied CHP would benefit by implementing optimization procedures or software to schedule production. The result was also comparable to previous research but varied over time, which highlights how unique conditions may impact the result.

Energieeffizienz gewinnt als Wettbewerbs- und Kostenfaktor für die industrielle Produktion seit einigen Jahren immer mehr an Bedeutung und sollte bereits in der Produkt- und Prozessentwicklung bzw. -verbesserung berücksichtigt werden. Entsprechend zeigt der Beitrag, wie mittels Maschinensimulation auf der Basis empirischer Messdaten die Energieverbräuche für zukünftige Fertigungsprozesse durch eine integrierte Visualisierung abgeschätzt werden können.

The nuclear fuel cycle is modelled as a cyclic, multi-stage production-to-inventory system. The objective is to meet a known deterministic demand for energy while minimizing acquisition, production, and inventory holding costs for all stages of the fuel cycle. The model allows for cyclic flow (feedback) of materials, material flow conversion factors at each stage, production lag times at each stage, and for escalating costs of uranium ore. It does not allow shortages to occur in inventories. The model is optimized by the application of the calculus of variations and specifically through recently developed theorems on the solution of functionals constrained by inequalities. The solution is a set of optimal cumulative production trajectories which define the stagewise production rates. Analysis of these production rates reveals the optimal nuclear fuel cycle costs and that inventories (stockpiles) occur in uranium fields, enriched uranium hexafluoride, and fabricated fuel assemblies. An analysis of the sensitivity of the model to variation in three important parameters is performed. / Ph. D.

Hydropower generates renewable energy, but also local environmental damage. In Sweden, hydropower facilities are undergoing a process of environmental adaptation which aims at protecting water environments while also ensuring electricity production. Regional stakeholder collaboration has been introduced as part of the decision-making process. To explore opportunities and challenges with this governance strategy, this study analyses hydropower collaborations using the Integrative Framework for Collaborative Governance (Emerson &amp; Nabatchi, 2015). Several types of documentation from all 27 finished collaborations have been collected and subjected to a qualitative thematic analysis. The results show that the main challenges are related to organising collaboration, balancing interests and managing needs for knowledge. While these appear closely interrelated, knowledge emerged as especially important. Knowledge contestation was a major driver for disagreements over interest balance, and accepted knowledge can overall be seen as a crucial capacity for joint action. The analysis also identified a discrepancy between stakeholders’ expectations for interest negotiation and reality. More research is however required to establish the connection between collaborative procedural arrangements and agreement among stakeholders.

Thesis (PhD)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: In the developed and developing world, the use of lipids for the production of alkyl esters, also known as biodiesel, showed phenomenal growth during the ten year period up to the end of 2007. The main sources for these lipids are the oils extracted from oil seeds such as soya-, palm-, and rape seed, but other products in the food chain such as waste cooking oil (yellow grease) and animal fats are also used. In Africa and Asia vast tracks of land not previously tilled, are now being cultivated to yield oils which are not edible and in a number of countries intensive research is focused on lipid producing species such as algae. Meanwhile more evidence is coming to the fore pronouncing biodiesel and other first generation biofuels not to be the panacea for the predicament the world is facing on unbridled population growth, energy security concerns and environmental issues such as indirect land use changes, global warming and climate changes. The acceptance of the National Biofuels Industrial Strategy at Cabinet level has not yet resulted in significant commensurate activity in South Africa. The availability, other uses and volumes of selected feed stocks for biodiesel production invite debate on the choice between food- and energy security and the appropriateness of some identified socio-economical and socio-political drivers for a viable industry. Somehow the unique characteristics of South Africa and its resources seem not to feature in debate and constraints on the production of biodiesel, as described in this dissertation. The conventional process routes for commercial biodiesel production are based on a mature technology which has inherent pollution and economical limitations. This called for a detailed critical evaluation on process routes more environmentally friendly or involving fewer unit processes generating more desirable products, albeit with more severe process conditions. By comparison, the homogeneous alkali catalyst alcoholysis (HACA), the enzymatic catalyst alcoholysis (ECA) and the super critical alcoholysis (SCA) process routes as developed in this study, are found to be competitive on total manucturing costs as assessed, if results emanating from selected sensitivity analyses and optimisation studies, are accepted. The total manufacturing and operating costs in the selected process routes as estimated, assuming the same capacities for commercial biodiesel production, are dominated by feed stock costs. Incentives on depreciation and fuel levies are deemed not effective, if costs are compared to the price of fossil diesel at the retail level – October 2011. It is concluded that using the feed stocks indicated in the Strategy, commercial biodiesel production is not economically feasible in South Africa at present. In this study process routes and feed stocks were identified that can change this position. Note should be taken of the intensive research activities being conducted on second generation technologies and biorefineries in the developed world, as discussed in this dissertation. / AFRIKAANSE OPSOMMING: In die ontwikkelde en ontwikkelende wêreld het die gebruik van vette vir die produksie van alkielesters, ook bekend as biodiesel, in die tienjaarperiode tot die einde van 2007 fenomenale groei getoon. Die hoofbronne vir hierdie lipiede is die olies onttrek van oliesade soos soja-, palm-, en raapsaad, maar ander produkte in die voedselketting soos gebruikte kookolie en dierevette word ook gebruik. In Afrika en Asië word uitgestrekte stukke grond voorheen onbewerk, nou bewerk om olies wat nie eetbaar is nie, op te lewer, en in verskeie lande word intensiewe navorsing op vetproduserende spesies soos alge gedoen. Intussen kom meer bewyse na vore wat verklaar dat biodiesel en ander eerste-generasie biobrandstowwe nie die wondermiddel is vir die moeilike posisie wat die wêreld in die gesig staar oor onbeteuelde bevolkingsaanwas, kwellings oor energiesekuriteit en omgewingskwessies soos indirekte grondverbruike, aardverwarming en klimaatsveranderings nie . Die aanvaarding van die Nasionale Biobrandstowwe Industriële Strategie op kabinetsvlak het nog nie verhoogde soortgelyke aktiwiteite in Suid-Afrika tot gevolg gehad nie. Die beskikbaarheid, gebruike en volumes van gekose grondstowwe, lok debatte uit oor die keuse tussen voedsel- en energiesekuriteit en die toepaslikheid van sekere geïndentifiseerde sosio-ekonomiese en sosio-politieke stimulante vir ‘n lewensvatbare nywerheid. Op een of ander manier is die unieke kenmerke van Suid- Afrika en sy bronne nog nie in die debat op die knelpunte van biodiesel nie, soos beskryf in hierdie proefskrif. Die gewone prosesroetes vir kommersiële produksie van biodiesel is gebaseer op ‘n beproefde tegnologie met inherente besoedelings- en ekonomiese beperkings. Dit het gevra vir ‘n uitvoerige kritiese evaluasie van meer omgewingsvriendelike- en minder eenheidsprosesse wat meer gewensde produkte genereer, al is dit met erger prosesbepalings. By vergelyking, is dit bevind dat die homogene alkali-katalisator- alkoholisis (HAKA), ensiem-katalisator-alkoholisis (EKA) en die superkritiese-alkoholisis (SKA) prosesroetes soos in hierdie studie ontwikkel, mededingend is op ‘n totale vervaardigingskoste-vlak, as die resultate wat spruit uit geselekteerde sensiwiteitsanalises en optimiseringsstudies, aanvaar word. Die totale vervaardigings- en bedryfskostes soos beraam vir die gekose prosesroetes vir kommersiële biodieselvervaardiging vir dieselfde deursette, word oorheers deur grondstofkostes. Aansporings op afskrywings en brandstofheffings word gesien as nie effektief nie, as kostes vergelyk word met die prys van fossieldiesel op kleinhandelsvlak – Oktober 2011. Die gevolgtrekking word gemaak dat met die grondstowwe aangedui in die Strategie, kommersiële biodieselvervaardiging tans nie ekonomies gangbaar is vir Suid-Afrika nie. In hierdie studie is prosesroetes en grondstowwe geïdentifiseer wat die posisie kan verander. Kennis moet geneem word van die intensiewe navorsingsaktiwiteite op tweede-geslag tegnologieë en bioraffinaderye in die ontwikkelde wereld, soos in hierdie proefskrif bespreek.