CDNF and MANF are members of a recently discovered and evolutionarily conserved neurotrophic factor family implicated in supporting the survival and protection of midbrain dopaminergic neurons in the nigrostriatal pathway, which degenerate in Parkinson’s Disease (PD). Increasing evidence demonstrated that MANF overexpression resulted in significant protection and repair of TH+ cells and DA neurons in the substantia nigra (SN). In addition, continuous infusion of CDNF demonstrated greater protection of TH-positive neurons in the SNc and fibers in striatum than GDNF in the 6-OHDA neurotoxin model. Current literature suggests that CDNF and MANF are involved in regulating ER stress and are upregulated in vitro and in vivo during the unfolded protein response (UPR). Thus, this study sought to investigate whether selective knockdown (K/D) of MANF and CDNF causes pathophysiological conditions that lead to the behavioural manifestation of PD in preclinical models. Male Sprague-Dawley rats underwent stereotaxic surgery, whereby 2 μL at 0.5 μL/minute of MANF, CDNF, MANF and CDNF combined, or a scrambled negative control (N=44) of rat lentiviral-mediated shRNA formulations were infused into the SN in reference to bregma: Anterior/Posterior=-5.3 mm, Medial/Lateral=±2.3 mm, Dorsal/Ventral=-7.8 mm. Rats were tested on a battery of behavioural tests for the assessment of PD phenotypes, such as impairments in balance, gait and motor coordination. MANF K/D rats demonstrated PD phenotypes in the rearing duration, beam traversal, rotarod and cylinder test (P <0.05). These results were largely mirrored in the combined MANF and CDNF K/D group, however, CDNF K/D rats failed to demonstrate consistent motor deficits (P >0.05). Additionally, CDNF mRNA expression from the platelets of PD patients revealed no significant differences compared to healthy controls (P >0.05). In conclusion, the etiology of PD remains to be elucidated, and this is the first study to demonstrate that MANF K/D rats recapitulate key motor features of parkinsonism. / Thesis / Master of Science (MSc) / CDNF and MANF are members of a recently discovered and evolutionarily conserved neurotrophic factor family implicated in supporting the survival and protection of midbrain dopaminergic neurons in the nigrostriatal pathway, which degenerate in Parkinson’s Disease (PD). Increasing evidence demonstrated that MANF overexpression resulted in significant protection and repair of DA neurons in the substantia nigra (SN). Current literature suggests that CDNF and MANF are involved in regulating ER stress and are upregulated in cells and in rodents during the unfolded protein response (UPR). Thus, this study sought to investigate whether selective knockdown (K/D) of MANF and CDNF causes the underlying changes in the brain that lead to the behavioural manifestation of PD in preclinical models. 2 μL at 0.5 μL/minute of MANF, CDNF, MANF and CDNF combined, or a scrambled negative control (N=44) of rat lentiviral-mediated shRNA formulations were infused into the SN. Rats were tested on a battery of behavioural tests for the assessment of PD phenotypes, such as impairments in balance, gait and motor coordination. MANF K/D rats demonstrated PD phenotypes in the rearing duration, beam traversal, rotarod and cylinder test (P <0.05). These results were largely mirrored in the combined MANF and CDNF K/D group, however, CDNF K/D rats failed to demonstrate consistent motor deficits (P >0.05). Additionally, CDNF mRNA expression from the platelets of PD patients revealed no significant differences compared to healthy controls (P >0.05). In conclusion, the etiology of PD remains to be elucidated, and this is the first study to demonstrate that MANF K/D rats recapitulate key motor features of parkinsonism.

Noise shaping is one of the distinguishing characteristics of the sigma-delta modulation technique that separates it from other types of pulse-width modulation schemes. In sigma-delta modulation, unwanted noise and harmonics caused by quantization are intentionally pushed toward the high-frequency band in order to achieve high resolution data conversion within the signal bandwidth. Due to its robust, high in-band linearity, the sigma-delta modulation technique finds numerous applications in industry. Generally speaking, as the order of a sigma-delta modulator increases, the modulator performance becomes better, which unfortunately comes along with a decrease in the modulator¡¦s stable input range. This thesis presents a novel adaptive law which is capable of on-line tuning the loop filter of a sigma-delta modulator and reducing the out of band gain of the resulting noise transfer function when the modulator input is large, thereby widening the stable input range of the modulator without significant sacrifice of the performance. The simulation and experimental results prove the effectiveness of the proposed adaptive sigma-delta modulator.

Táto práca popisuje niekoľko vybraných algoritmov, ktoré boli primárne vyvinuté pre CPU procesory, avšak vzhľadom k vysokému dopytu po ich vylepšeniach sme sa rozhodli ich využiť v prospech GPGPU (procesorov grafického adaptéra). Modifikácia týchto algoritmov bola zároveň cieľom nášho výskumu, ktorý  bol prevedený pomocou CUDA rozhrania. Práca je členená podľa troch skupín algoritmov, ktorým sme sa venovali: detekcia objektov v reálnom čase, spektrálna analýza obrazu a detekcia čiar v reálnom čase. Pre výskum detekcie objektov v reálnom čase sme zvolili použitie LRD a LRP funkcií.  Výskum spektrálnej analýzy obrazu bol prevedný pomocou PCA a NTF algoritmov. Pre potreby skúmania detekcie čiar v reálnom čase sme používali dva rôzne spôsoby modifikovanej akumulačnej schémy Houghovej transformácie. Pred samotnou časťou práce venujúcej sa konkrétnym algoritmom a predmetu skúmania, je v úvodných kapitolách, hneď po kapitole ozrejmujúcej dôvody skúmania vybranej problematiky, stručný prehľad architektúry GPU a GPGPU. Záverečné kapitoly sú zamerané na konkretizovanie vlastného prínosu autora, jeho zameranie, dosiahnuté výsledky a zvolený prístup k ich dosiahnutiu. Súčasťou výsledkov je niekoľko vyvinutých produktov.