Las enfermedades neurodegenerativas cursan con la degeneración y muerte de las neuronas las cuales son incapaces de suplir su propia muerte. Debido a esta característica enfermedades como el Alzheimer, el Parkinson o el Glaucoma no tienen cura en la actualidad. La retina es una proyección del sistema nervioso central (SNC) encapsulada en el globo ocular y aislada del resto del SNC, lo que la hace fácilmente accesible a la manipulación experimental. En este trabajo estudiamos las alteraciones funcionales de la retina con el electrorretinograma de campo completo (ERG), técnica basada en el registro de la respuesta eléctrica retiniana tras la presentación de un estímulo de luz homogéneo. Así hemos estudiado los efectos de la sección del nervio, del aumento de presión intraocular y de la fototoxicidad, dichas lesiones afectan selectivamente a determinadas poblaciones neuronales retinianas e imitan enfermedades neurodegenerativas como el Glaucoma o la Degeneración Macular Asociada a la Edad. / Neurodegenerative diseases are characterized by degeneration and death of neurons which are unable to recover after a given insult, thus impairing functional recuperation. Because of this, there is no cure for diseases such as Alzheimer, Parkinson or Glaucoma. The retina is a projection of the central nervous system (CNS) located in the eye and therefore, isolated from the rest of the CNS. This makes the retina a very good model for experimental manipulation. In this work we have studied the functional changes in the retina by full field electroretinograme (ERG). This technique records the electric response of the retina after presentation of homogeneous light stimuli. We have studied the effects that optic nerve sections, increase of the intraocular pressure and phototoxicity have on ERG recordings. These lesions impair selectively certain retinal neuronal populations and imitate neurodegenerative diseases as Glaucoma or Age-related Macular Degeneration.

A new technology for biotechnological treatment of mine waters with both high concentrations of heavy metals and sulphate was developed. The technology is based on the technical coupling of microbially mediated hydrolysis, fermentation and microbial sulphate reduction in a self-stabilising process. Electron donor for sulphate reduction is supplied by degradation of a solid substrate (silage). Elimination of metals is primarily achieved by sulphide precipitation within the sulphate reduction zone. The organic compounds are either supplied by elution or by hydrolysis of polymeric compounds which was named active elution. The concept was realised as a two-phase process with (active) elution in the first phase (R1) and sulphate reduction and metal elimination in the second phase (R2). With this process setup the supply of sufficient amounts of electron donor in R1, a stable and effective sulphate reduction yield as the basis of metal elimination in R2 and a stable separation of microbial processes in R1 and R2 was achieved at hydraulic retention times of 69 h in R1 and 40 h in R2. Almost complete elimination of heavy metals was achieved from wastewaters with 0.2 mM Ni2+, Cu2+, Zn2+, Fe2+ and Mn2. A structurised mathematical model describing the two-phase process was developed on the basis of literature values and tested with data from continuous experiments. Microbial processes were significantly influenced in the presence of precipitated heavy metal sulfides. The effect was dependent on both the bound metal (Ni2+ or Fe2+) and the relative distance between sediment and biomass. / Es wurde eine neuartige Technologie zur biotechnologischen Reinigung von schwermetallbelasteten, sulfathaltigen Bergbauwässern entwickelt. Die Technologie basiert auf der technischen Kopplung von mikrobiell vermittelter Hydrolyse, Fermentation und mikrobieller Sulfatreduktion in einem selbststabilisierenden Prozess, wobei aus Abbau eines festen Substanzgemisches (Silage) Elektronendonor zur Sulfatreduktion bereitgestellt wird. Die Schwermetallelimination erfolgt vorrangig durch sulfidische Fällung, die technisch einstufig mit der mikrobiellen Sulfatreduktion realisiert wurde. Die organischen Verbindungen wurden durch Elution bereitgestellt bzw. durch hydrolytischen Abbau von polymeren Verbindungen. Hierfür wurde der Begriff der ?Aktiven Elution? geprägt. Die Konzeption wurde technisch zweistufig umgesetzt. In der ersten Stufe (R1) erfolgt die (Aktive) Elution, in der zweiten Stufe (R2) erfolgen Sulfatreduktion und Schwermetallelimination. Mit der verfahrenstechnischen Umsetzung wurde die Bereitstellung einer ausreichenden Menge an Elektronendonor in R1, eine effektive und stabile Sulfatreduktionsausbeute als Bedingung der Schwermetallelimination in R2 und eine weitgehende Trennung der mikrobiellen Prozesse in R1 und R2 bei Verweilzeiten von 69 h in R1 und 40 h in R2 erreicht. Bei Behandlung von wässrigen Lösungen mit 0,2 mM Ni2+, Cu2+, Zn2+, Fe2+ und Mn2+ konnte eine nahezu vollständige Elimination der Schwermetalle aus der Lösung erreicht werden. Es wurde ein strukturiertes mathematisches Modell für den zweistufigen Prozess auf der Basis von Literaturangaben entwickelt und anhand der kontinuierlichen Laborversuche überprüft. Es wurde ein erheblicher Einfluss schwermetallsulfidischer Präzipitate auf die mikrobiellen Prozesse festgestellt. Dabei wurde dieser Einfluss in Abhängigkeit von der Art der gebundenen Metallionen (Ni2+ oder/und Fe2+) und in Abhängigkeit der relativen räumlichen Anordnung von Sediment und Biomasse festgestellt.

MENVSC / Department of Ecology and Resource Management / Mine tailings (MT) have been a global problem due to the environmental impacts the waste generates such as air, soil and water pollution. The detrimental impacts include a global problem such as acid mine drainage (AMD) which has been difficult to cleanup. Several studies have been conducted to find alternative measures in reducing or mitigating impacts such as AMD and air pollution. Several studies have revealed how alumino-silicate mineral waste can be used as raw material to produce construction materials. This study aimed at evaluating the potential of synthesizing a geopolymer material from Musina copper mine tailings. Tailings were characterized for their physicochemical and mineralogical compositions using standard laboratory techniques in order to evaluate suitability in geopolymerization. First section of the results presented physicochemical and mineralogical characterization of the Musina copper tailings together with the bioavailability of the chemical species. It was observed that the tailings are mainly composed of SiO2 and Al2O3 as the major oxides indicating that they are aluminosilicate material. Mineralogical analysis revealed dominance of quartz, epidote and chlorite as the major minerals. The bioavailability assessment showed that largely Cu and Ca are bioavailable and highly soluble in an aqueous solution while Al, Mg, Ni, Co, Cr and Fe have a high proportion in non-labile phase. Second section presented the preliminary results wherein the potential application of Musina copper tailings in geopolymerization was evaluated. The results showed that Musina copper tailings can be used to synthesize a geopolymer material. However, it was recommended that several parameters influencing geopolymerization need to be evaluated. The third section presented the evaluation of optimum parameters that influence the geopolymerization process, which include type of alkali activators, alkali activator concentration, curing temperature, liquid-solid (L/S) ratio and curing regime. It was observed that a mixture of NaOH:Na2SiO3.5H20 at a ratio of 70:30 yields a better geopolymer material. The concentration of 10 M NaOH:Na2SiO3.5H20 at a ratio of 70:30 was observed to be the best that yielded the UCS that is acceptable according to SANS1215 standards. When evaluating curing regime, it was found that the material cured using greenhouse has lower UCS as compared to the material cured using oven. The v effect of temperature showed that the UCS decreases with increasing curing temperature. An admixture of river sand and cement was introduced which resulted in a high UCS of 21.16 MPa when using an admixture of cement. The mineralogical composition of the geopolymer bricks showed formation of secondary minerals such as phlogopite, fluorapatite, diopside and actinolite. Batch leaching conducted on the geopolymer bricks detected high leaching of Na from the bricks. Based on the findings of the study of the raw MT potential to produce geopolymer bricks, it was concluded that the material can be used to produce bricks that are within the SANS 1215 requirements. The study further recommended that the study a focus on using cylindrical moulds, other alkali activators and a mechanical mixer. It was also recommended that the greenhouse be restructured to contain heat within the greenhouse during the evening so as to allow constant temperature within / NRF

A new technology for biotechnological treatment of mine waters with both high concentrations of heavy metals and sulphate was developed. The technology is based on the technical coupling of microbially mediated hydrolysis, fermentation and microbial sulphate reduction in a self-stabilising process. Electron donor for sulphate reduction is supplied by degradation of a solid substrate (silage). Elimination of metals is primarily achieved by sulphide precipitation within the sulphate reduction zone. The organic compounds are either supplied by elution or by hydrolysis of polymeric compounds which was named active elution. The concept was realised as a two-phase process with (active) elution in the first phase (R1) and sulphate reduction and metal elimination in the second phase (R2). With this process setup the supply of sufficient amounts of electron donor in R1, a stable and effective sulphate reduction yield as the basis of metal elimination in R2 and a stable separation of microbial processes in R1 and R2 was achieved at hydraulic retention times of 69 h in R1 and 40 h in R2. Almost complete elimination of heavy metals was achieved from wastewaters with 0.2 mM Ni2+, Cu2+, Zn2+, Fe2+ and Mn2. A structurised mathematical model describing the two-phase process was developed on the basis of literature values and tested with data from continuous experiments. Microbial processes were significantly influenced in the presence of precipitated heavy metal sulfides. The effect was dependent on both the bound metal (Ni2+ or Fe2+) and the relative distance between sediment and biomass. / Es wurde eine neuartige Technologie zur biotechnologischen Reinigung von schwermetallbelasteten, sulfathaltigen Bergbauwässern entwickelt. Die Technologie basiert auf der technischen Kopplung von mikrobiell vermittelter Hydrolyse, Fermentation und mikrobieller Sulfatreduktion in einem selbststabilisierenden Prozess, wobei aus Abbau eines festen Substanzgemisches (Silage) Elektronendonor zur Sulfatreduktion bereitgestellt wird. Die Schwermetallelimination erfolgt vorrangig durch sulfidische Fällung, die technisch einstufig mit der mikrobiellen Sulfatreduktion realisiert wurde. Die organischen Verbindungen wurden durch Elution bereitgestellt bzw. durch hydrolytischen Abbau von polymeren Verbindungen. Hierfür wurde der Begriff der ?Aktiven Elution? geprägt. Die Konzeption wurde technisch zweistufig umgesetzt. In der ersten Stufe (R1) erfolgt die (Aktive) Elution, in der zweiten Stufe (R2) erfolgen Sulfatreduktion und Schwermetallelimination. Mit der verfahrenstechnischen Umsetzung wurde die Bereitstellung einer ausreichenden Menge an Elektronendonor in R1, eine effektive und stabile Sulfatreduktionsausbeute als Bedingung der Schwermetallelimination in R2 und eine weitgehende Trennung der mikrobiellen Prozesse in R1 und R2 bei Verweilzeiten von 69 h in R1 und 40 h in R2 erreicht. Bei Behandlung von wässrigen Lösungen mit 0,2 mM Ni2+, Cu2+, Zn2+, Fe2+ und Mn2+ konnte eine nahezu vollständige Elimination der Schwermetalle aus der Lösung erreicht werden. Es wurde ein strukturiertes mathematisches Modell für den zweistufigen Prozess auf der Basis von Literaturangaben entwickelt und anhand der kontinuierlichen Laborversuche überprüft. Es wurde ein erheblicher Einfluss schwermetallsulfidischer Präzipitate auf die mikrobiellen Prozesse festgestellt. Dabei wurde dieser Einfluss in Abhängigkeit von der Art der gebundenen Metallionen (Ni2+ oder/und Fe2+) und in Abhängigkeit der relativen räumlichen Anordnung von Sediment und Biomasse festgestellt.

Acid maltase deficiency (AMD) is a rare autosomal recessive genetic disorder that results in an accumulation of glycogen in the lysosomal storage vacuoles. It is classified as a glycogen storage disease (type II) and is also known as Pompe's disease. The prognosis of the patient with AMD is poor and the main cause of death is respiratory failure. We report a female patient whose respiratory insufficiency was documented to occur most severely during rapid eye movement sleep and who benefited clinically from the institution of nocturnal noninvasive bilevel positive airway pressure.

Android is the second most targeted operating system for malware authors and to counter the development of Android malware, more knowledge about their behavior is needed. There are mainly two approaches to analyze Android malware, namely static and dynamic analysis. Recently in 2017, a study and well labeled dataset, named AMD (Android Malware Dataset), consisting of over 24,000 malware samples was released. It is divided into 135 varieties based on similar malicious behavior, retrieved through static analysis of the file classes.dex in the APK of each malware, whereas the labeled features were determined by manual inspection of three samples in each variety. However, static analysis is known to be weak against obfuscation techniques, such as repackaging or dynamic loading, which can be exploited to avoid the analysis. In this study the second approach is utilized and all malware in the dataset are analyzed at run-time in order to monitor their dynamic behavior. However, analyzing malware at run-time has known weaknesses as well, as it can be avoided through, for instance, anti-emulator techniques. Therefore, the study aimed to explore the available sandbox environments for dynamic analysis, study the effectiveness of fingerprinting Android malware using one of the tools and investigate whether static features from AMD and the dynamic analysis correlate. For instance, by an attempt to classify the samples based on similar dynamic features and calculating the Pearson Correlation Coefficient (r) for all combinations of features from AMD and the dynamic analysis. The comparison of tools for dynamic analysis, showed a need of development, as most popular tools has been released for a long time and the common factor is a lack of continuous maintenance. As a result, the choice of sandbox environment for this study ended up as Droidbox, because of aspects like ease of use/install and easily adaptable for large scale analysis. Based on the dynamic features extracted with Droidbox, it could be shown that Android malware are more similar to the varieties which they belong to. The best metric for classifying samples to varieties, out of four investigated metrics, turned out to be Cosine Similarity, which received an accuracy of 83.6% for the entire dataset. The high accuracy indicated a correlation between the dynamic features and static features which the varieties are based on. Furthermore, the Pearson Correlation Coefficient confirmed that the manually extracted features, used to describe the varieties, and the dynamic features are correlated to some extent, which could be partially confirmed by a manual inspection in the end of the study.

No description available.

L’obésité est en croissance rapide à l’échelle mondiale et représente un facteur de risque important pour plusieurs pathologies, dont la dégénérescence maculaire liée à l’âge (DMLA). Dans l’obésité, le tissu adipeux blanc (WAT) subi un remodelage pathologique caractérisé par le recrutement de macrophages pro-inflammatoires facilitant l’établissement de l’inflammation stérile systémique. Contrairement au WAT, les tissus adipeux brun (BAT) et beige (BgAT) participent à la thermogénèse, un processus qui libère de la chaleur en métabolisant les lipides. En raison de leurs potentiels effets physiologiques bénéfiques, le recrutement d’adipocytes et l’activation de ces types spécifiques de tissu adipeux (AT) ont fait l’objet de multiples recherches et débats. Malgré les avancées considérables dans le domaine, les mécanismes impliqués dans l’activation du BAT et du BgAT ainsi que les mécanismes impliqués dans le développement de l’obésité et leur contribution à des maladies comme la DMLA, restent mal définis. Dans un premier temps, nous avons développé le protocole RELi pour permettre une extraction et une quantification fiable des protéines du AT murin saturé en lipides. Notre protocole élimine les lipides contaminants en excès, réduit la variabilité du chargement de protéines pour le western blot et l’usage de gènes de ménage standards (Article #1). Ensuite, nous avons étudié l’inflammation au niveau du BAT dans un modèle d’obésité induite par l’alimentation. La délétion de la Neuropiline 1 (NRP1) chez les macrophages résidents du tissu adipeux (ATMs) a provoqué une diminution des densités de la vasculature et de l’innervation. De plus ces souris sont devenues plus sensibles à l’exposition au froid suggérant un rôle des ATMs-Nrp1+ dans la régulation de l’homéostasie du BAT et de la température corporelle (Article #2). Finalement, nous avons exploré l’axe BgAT-DMLA; plus spécifiquement son impact potentiel sur la néovascularization choroïdienne (CNV) en utilisant des approches in vivo et in vitro. Nous avons démontré que la délétion génétique de PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), un gène impliqué dans la thermogénèse, conduit à une réduction de la CNV, et que la réintroduction d’AT-PRDM16+ exacerbe la formation de CNV pathologique. Le traitement d’explants de choroïde avec du milieu conditionné par des adipocytes-PRDM16+ augmente la croissance des vaisseaux sanguins. Ensemble, les données suggèrent un rôle sécrétoire potentiel pour le BgAT-PRDM16+ capable d’influencer la formation distale de CNV qui pourrait être pertinente pour la DMLA (Article #3). Les travaux présentés dans cette thèse établissent les bases d’un protocole permettant l’obtention de résultats reproductibles dans l’étude du AT, soulignent l’importance des ATMs- Nrp1+ dans la régulation de l’homéostasie du BAT et explorent pour la première fois l’implication du BgAT-PRDM16+ chez la DMLA neovasculaire. Ce travail établit les bases de la compréhension des mécanismes moléculaires reliant la régulation du AT thermogénique et les pathologies caractérisées par un excès de gras. Ce travail souligne également l’importance d’évaluer l’activation du BgAT chez les patients atteints de la DMLA. / Obesity is rapidly growing worldwide and represents a significant risk factor to several pathologies, including age-related macular degeneration (AMD). In obesity, the white adipose tissue (WAT) undergoes a strong remodeling characterized by the recruitment of pro- inflammatory macrophages, facilitating low-grade chronic inflammation. Unlike WAT, brown (BAT) and beige (BgAT) adipose tissues participate in thermogenesis, a process that releases heat by metabolizing lipids. Due to the likely beneficial physiological effects of BAT and BgAT, the recruitment of adipocytes and activation of these specific types of adipose tissue (AT) has been the subject of much research and debate. Despite considerable advances in the field, the mechanisms involved in BAT- and BgAT-activation as well as mechanisms involved in the development of obesity and their contribution to diseases such as AMD, remain ill-defined. First, we developed the RELi protocol to allow a reliable extraction and quantification of proteins from murine AT saturated with lipids. Our protocol eliminates excess contaminating lipids, reduces the variability of protein loading in Western blot and stabilizes expression of housekeeping genes (Article #1). Next, we investigated the inflammatory component of BAT in a diet-induced obesity model. The deletion of NRP1 in resident adipose tissue macrophages (ATMs) led to the expansion of the BAT and affected the densities of the vasculature and the innervation. Moreover, these mice became more sensitive to cold exposure, suggesting a role of ATMs-Nrp1+ in the regulation of BAT homeostasis and body temperature (Article #2). Lastly, we explored the axis of BgAT and AMD; more specifically, its potential impact on choroidal neovascularization (CNV) using in vivo and in vitro approaches. We demonstrated that the genetic deletion in BgAT of PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), a gene involved in thermogenesis, leads to a reduction of CNV, and that the reintroduction of BgAT-PRDM16+ via AT transplantation exacerbates the formation of pathological CNV. Treatment of choroid explants with PRDM16+-adipocyte-conditioned medium augmented blood vessel growth. Altogether, the data suggest a potential secretory role for BgAT-PRDM16+ to influence distal CNV formation that could be relevant to AMD (Article #3). The work presented in this thesis establishes the basis of a protocol allowing reproducible results in the study of AT, underlines the importance of ATMs-Nrp1+ in the regulation of BAT homeostasis and explores, for the first time, the involvement of BgAT-PRDM16+ in neovascular AMD. This work sets the basis for the understanding of the molecular mechanisms linking the regulation of thermogenic AT and pathologies characterized by an excess of fat. This work also highlights the importance of assessing the activation of BgAT in patients with AMD.

No description available.

No description available.