Past literature has supported the supplementation of 25-OHD3 into poultry diets to reduce leg issues and improve muscle accretion. In addition, exogenous feed enzymes are included into poultry diets to increase nutrient utilization. The first objective of this thesis was to determine the effects of different sources and levels 25-OHD3 supplementation on D0-53 Ross x Ross 708 male broiler performance, processing yield, tibia ash, serum Ca and 25-OHD3 status. Data demonstrated that 25-OHD3 supplementation into diets with Low VitD3 (165 IU/kg) can improve broiler performance compared to High VitD3 (2756 IU/kg). The second objective was to investigate the effects of varying phytase inclusion with different xylanase levels on D0-56 Ross x Ross 708 male broiler performance, processing yield and tibia ash. Data exhibited some performance benefit (D46 and D56) when utilizing phytase (1000 and 1500 FTU/kg) with 1500 EPU/kg xylanase and phytase (250 and 1500 FTU/kg) with 3000 EPU/kg xylanase.

The dopamine D2 receptor exists in vitro in two states of agonist affinity: a high-affinity state mediating dopamine’s physiological effects, and a physiologically-inert low-affinity state. Our primary goal was to determine the in vivo relevance of this two-affinity-state model for the agonist PET radiotracer [11C]-(+)-PHNO, developed for measurement of the D2 high-affinity state. Our second goal was to characterize the regional D2 versus D3 pharmacology of [3H]-(+)-PHNO binding and assess its utility for measuring drug occupancy at both receptor subtypes. Using ex vivo dual-radiotracer experiments in conscious rats, we showed that, contrary to the two-affinity-state model, the binding of [11C]-(+)-PHNO and the antagonist [3H]-raclopride were indistinguishably inhibited by D2 partial agonist (aripiprazole), indirect agonist (amphetamine) and full agonist ((-)-NPA) pretreatment. Furthermore, ex vivo [11C]-(+)-PHNO binding was unaffected by treatments that increase in vitro high-affinity state density (chronic amphetamine, ethanol-withdrawal), whereas unilateral 6-OHDA lesion, which increases total D2 receptor expression, similarly increased the ex vivo binding of [11C]-(+)-PHNO and [3H]-raclopride. These results do not support the in vivo validity of the two-affinity-state model, suggesting instead a single receptor state for [11C]-(+)-PHNO and [3H]-raclopride in conscious rat. Importantly, we also demonstrated that the increased amphetamine-sensitivity of the agonist radiotracers [11C]-(+)-PHNO and [11C]-(-)-NPA, commonly seen in isoflurane-anaesthetized animals and cited as evidence for the two-affinity-state model, is due to the confounding effects of anaesthesia. Using in vitro and ex vivo autoradiography in rat and the D3 receptor-selective drug SB277011, we found that [3H]-(+)-PHNO binding in striatum and cerebellum lobes 9 and 10 was due exclusively to D2 and D3 receptor binding, respectively, but in other extra-striatal regions to a mix of the two receptor subtypes. Surprisingly, the D3 contribution to [3H]-(+)-PHNO binding was greater ex vivo than in vitro. Also surprising, several antipsychotic drugs, at doses producing 80% D2 occupancy, produced insignificant (olanzapine, risperidone, haloperidol) or small (clozapine, ~35%) D3 occupancy, despite similarly occupying both receptor subtypes in vitro. These data reveal a significant discrepancy between in vitro and ex vivo measures of dopamine receptor binding and suggest that the D3 occupancy is not necessary for the therapeutic effect of antispychotic drugs.

The dopamine D2 receptor exists in vitro in two states of agonist affinity: a high-affinity state mediating dopamine’s physiological effects, and a physiologically-inert low-affinity state. Our primary goal was to determine the in vivo relevance of this two-affinity-state model for the agonist PET radiotracer [11C]-(+)-PHNO, developed for measurement of the D2 high-affinity state. Our second goal was to characterize the regional D2 versus D3 pharmacology of [3H]-(+)-PHNO binding and assess its utility for measuring drug occupancy at both receptor subtypes. Using ex vivo dual-radiotracer experiments in conscious rats, we showed that, contrary to the two-affinity-state model, the binding of [11C]-(+)-PHNO and the antagonist [3H]-raclopride were indistinguishably inhibited by D2 partial agonist (aripiprazole), indirect agonist (amphetamine) and full agonist ((-)-NPA) pretreatment. Furthermore, ex vivo [11C]-(+)-PHNO binding was unaffected by treatments that increase in vitro high-affinity state density (chronic amphetamine, ethanol-withdrawal), whereas unilateral 6-OHDA lesion, which increases total D2 receptor expression, similarly increased the ex vivo binding of [11C]-(+)-PHNO and [3H]-raclopride. These results do not support the in vivo validity of the two-affinity-state model, suggesting instead a single receptor state for [11C]-(+)-PHNO and [3H]-raclopride in conscious rat. Importantly, we also demonstrated that the increased amphetamine-sensitivity of the agonist radiotracers [11C]-(+)-PHNO and [11C]-(-)-NPA, commonly seen in isoflurane-anaesthetized animals and cited as evidence for the two-affinity-state model, is due to the confounding effects of anaesthesia. Using in vitro and ex vivo autoradiography in rat and the D3 receptor-selective drug SB277011, we found that [3H]-(+)-PHNO binding in striatum and cerebellum lobes 9 and 10 was due exclusively to D2 and D3 receptor binding, respectively, but in other extra-striatal regions to a mix of the two receptor subtypes. Surprisingly, the D3 contribution to [3H]-(+)-PHNO binding was greater ex vivo than in vitro. Also surprising, several antipsychotic drugs, at doses producing 80% D2 occupancy, produced insignificant (olanzapine, risperidone, haloperidol) or small (clozapine, ~35%) D3 occupancy, despite similarly occupying both receptor subtypes in vitro. These data reveal a significant discrepancy between in vitro and ex vivo measures of dopamine receptor binding and suggest that the D3 occupancy is not necessary for the therapeutic effect of antispychotic drugs.

Neuroblastoma as a pediatric tumor develops in the sympathetic nervous system. DLG2 is a gene that encodes a member of the membrane-associated guanylate kinase (MAGUK) family and it resides in the chromosome region 11q. SK-N-AS is a neuroblastoma cell line with 11q deletion and consequently only one copy of the potential tumor suppressor gene DLG2. This study investigated synergistic effect by a combination treatment with 1,25(OH)2D3 and the vitamin A metabolite, retinoic acid.  Separately, SK-N-AS cells was transfected with expression vector pcDNA3.1+‐DYK that contained the DLG2-gene, followed by monitoring cell proliferation and qPCR, investigating the expression of the genes DLG2, DLG3, DLG4, VDR and PDIA3. Simultaneously, effects of knocked-down of DLG2, by siRNA transfection was monitored.  Transfection of expression plasmid with the DLG2 gene increased significantly gene expression in SK-N-AS cells with significant inhibition of the proliferation rate. Furthermore, silencing of DLG2 gene had no effect on the cell growth as well. Slower cell growth showed in combination treatment with 1,25(OH)2D3 (1nM) and 9-cis RA after 48 hours of treatment. Down-regulated VDR and possible missing RARRES3 could be the reason why SK-N-AS cell line showed resistance to the combination treatment with vitamin metabolites. All these results raised the question if another vitamin D synthetic analog could be a better choice for the future study of SK-N-AS cells. Moreover, overexpression of NAIP, large amounts of IGF-II, or not responsive RXR-VDR heterodimer to 1,25(OH)2D3 could be a potential explanation for the SK-N-AS cell unresponsiveness to the treatment.

1 Abstract Vitamin D3 is important for keeping the right concetration of Ca2+ in plasma. Therefore it is essential for proper bone growth and development. Nevertheless, vitamin D3 has also a number of immunomodulating effects. Our thesis has been targeted on evaluation and comparison of vitamin D3 influence on expression of chosen surface markers (CD14, CD54, HLA-DR, CD16, CD36 and CD163) with THP-1 cells and monocytes gained from human peripheral blood. Other aims have been analysing the vitamin D3 influence on longevity of THP-1 cells and measuring the soluble CD14 and IL-8 production with THP-1 cells under the vitamin D3 influence. The cells have been stimulated with five different concentrations of vitamin D3 for the time 24, 48 and 72 hours. Higher used concetrations of vitamin D3, i.e. 100 nM and 1000 nM have increased the expression of CD14 with THP-1 cells in the time 48 and 72 hours of the stimulation time. With the monocytes from peripheral human blood the increase of the CD14 expression hasn't been remarkable from the physiological point of view. Together with the vitamin D3 concentration increase the sCD14 production with THP­1 cells was considerably higher. The sCD14 was the highest in the time 72 hours after the stimulation with the highest used vitamin D3 concetration. The IL-8 quantity with...

Loggning är en viktig del i utvecklingen av en hemsida för att kunna förstå sina användare och hur de använder applikationen. Med hjälp av visualisering går det att visa data på ett tydligare sätt och det blir enklare att dra slutsatser om vad datan faktiskt säger. Lagring är ett av de problem som finns med loggar eftersom de tenderar att växa snabbt. I denna studien utförst ett experiment för att svara på frågan  ”Är MongoDB mer effektiv än MySQL vid inläsning av sparad loggdata med avseende på prestanda”. Detta svaras på genom ett mäta svarstider för respektive databas. Hypotesen för arbetet är att MongoDB är mer effektiv än MySQL, men resultatet visar att MongoDB är långsammare i samtliga testfall som genomfördes i studien. I framtiden skulle det vara intressant att utöka arbetet med fler databaser samt att bygga om drivrutien för hur MongoDB och PHP kommunicerar med varandra.

Database outsourcing is an emerging paradigm for data management in which data are stored in third-party servers. With the advance of cloud computing, database outsourcing has become popular and highly adopted. However, as a result, many technology challenges have arisen. / In this thesis, we study two problems with respect to the challenges, and propose solutions for each problem with the consideration of access patterns. The first problem is raised from theviewpoint of service providers. We study the problem of data allocation in scalable distributed database systems for achieving the high availability feature of cloud services. We propose a data allocation algorithm, which makes use of time series models from previous access patterns to perform load forecasting and reallocate data fragments to balance the workload within the system. Simulation results show that, with accurate forecasting, the proposed algorithm gives a better performance than general threshold-based algorithms. / The second problem addresses the clients' concern that service providers may not be trustworthy. We first illustrate how service providers can infer sensitive information through query access patterns even when data are encrypted. Then, we propose techniques that break down large queries and randomize query access patterns such that service providers cannot infer sensitive information with a high degree of certainty. Experiments on benchmark data show that a high level of access privacy can be achieved by the proposed techniques with a reasonable overhead. / 數據庫外包是近年新興的一種數據管理服務，其特點是數據儲存於第三方的伺服器內。隨著雲端科技的發展，數據庫外包服務日趨普及，同時亦產生不少技術問題。 / 本文著重探討兩個問題。首先，從服務供應商的角度研究可擴展的分布式數據庫系統如何分配數據來提供高可用性的雲端服務。鑑於用戶訪問模式會隨著時間轉變，我們提出以時間序列模型預測負荷的算法重新分配數據，以平衡系統的工作量。通過模擬實驗可知在準確的負荷預測下，我們提出的算法比基於闆值的算法有更好的表現。 / 第二個探討的問題是如何保障用戶私隱，避免洩露給服務供應商。文中列舉了數據加密的情況下，服務供應商如何通過分析用戶訪問模式獲取資料，進而提出相應的保障技術。透過用戶訪問模式的隨機化，能使服務供應商無法準確比對用戶的資料。基準數據實驗指出此項技術可有效保護私隱，而且不會對訪問速度造成太大影響。 / Li, Shun Pun. / Thesis M.Phil. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 86-93). / Abstracts also in Chinese. / Title from PDF title page (viewed on 11, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

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Dopamine D3 receptors (DRD3) are implicated in relapse to drugs. The current study investigated the role of DRD3 in cue-induced reinstatement of nicotine-seeking in rats. Rats were trained to lever-press for intravenous infusions of nicotine, associated with the illumination of a cue-light, under a fixed-ratio schedule of reinforcement. Following extinction of the behaviour, where lever pressing had no consequences, reinstatement testing was performed by reintroduction of the cues after systemic or local administration (into discrete brain areas) of the DRD3 selective antagonist SB277011-A. Systemic antagonism of DRD3 significantly attenuated cue-induced reinstatement of nicotine-seeking. The same effect was observed upon infusions of SB277011-A into the basolateral amygdala or the lateral habenula, but not the nucleus accumbens. The current findings implicate DRD3 in cue-induced reinstatement of nicotine, delineate some of the neural substrates underlying this role and support a potential for using selective DRD3 antagonists for the prevention of relapse to smoking.

Dopamine D3 receptors (DRD3) are implicated in relapse to drugs. The current study investigated the role of DRD3 in cue-induced reinstatement of nicotine-seeking in rats. Rats were trained to lever-press for intravenous infusions of nicotine, associated with the illumination of a cue-light, under a fixed-ratio schedule of reinforcement. Following extinction of the behaviour, where lever pressing had no consequences, reinstatement testing was performed by reintroduction of the cues after systemic or local administration (into discrete brain areas) of the DRD3 selective antagonist SB277011-A. Systemic antagonism of DRD3 significantly attenuated cue-induced reinstatement of nicotine-seeking. The same effect was observed upon infusions of SB277011-A into the basolateral amygdala or the lateral habenula, but not the nucleus accumbens. The current findings implicate DRD3 in cue-induced reinstatement of nicotine, delineate some of the neural substrates underlying this role and support a potential for using selective DRD3 antagonists for the prevention of relapse to smoking.