952 resultados para Frederick III, Elector of Saxony, 1463-1525.
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ACM Computing Classification System (1998): I.2.8 , I.2.10, I.5.1, J.2.
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Ribonucleotide reductases (RNR) are essential enzymes that catalyze the reduction of ribonucleotides to 2'-deoxyribonucleotides, which is a critical step that produces precursors for DNA replication and repair. The inactivation of RNR, logically, would discontinue producing the precursors of the DNA of viral or cancer cells, which then would consequently end the cycle of DNA replication. Among different compounds that were found to be inhibitors of RNR, 2'-azido-2'-deoxynucleotide diphosphates (N3NDPs) have been investigated in depth as potent inhibitors of RNR. Decades of investigation has suggested that the inactivation of RNR by N3NDPs is a result of the formation of a nitrogen-centered radical (N·) that is covalently attached to the nucleotide at C3' and cysteine molecule C225 [3'-C(R-S-N·-C-OH)]. Biomimetic simulation reactions for the generation of the nitrogen-centered radicals similar to the one observed during the inactivation of the RNR by azionuclotides was investigated. The study included several modes: (i) theoretical calculation that showed the feasibility of the ring closure reaction between thiyl radicals and azido group; (ii) synthesis of the model azido nucleosides with a linker attached to C3' or C5' having a thiol or vicinal dithiol functionality; (iii) generation of the thiyl radical under both physiological and radiolysis conditions whose role is important in the initiation on RNR cascades; and (iv) analysis of the nitrogen-centered radical species formed during interaction between the thiyl radical and azido group by electron paramagnetic resonance spectroscopy (EPR). Characterization of the aminyl radical species formed during one electron attachment to the azido group of 2'-azido-2'-deoxyuridine and its stereospecifically labelled 1'-, 2'-, 3'-, 4'- or 5,6-[2H 2]-analogues was also examined. This dissertation gave insight toward understanding the mechanism of the formation of the nitrogen-centered radical during the inactivation of RNRs by azidonucleotides as well as the mechanism of action of RNRs that might provide key information necessary for the development of the next generation of antiviral and anticancer drugs.
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Bacteria are known to release a large variety of small molecules known as autoinducers (AI) which effect quorum sensing (QS) initiation. The interruption of QS effects bacterial communication, growth and virulence. ^ Three novel classes of S-ribosylhomocysteine (SRH) analogues as potential inhibitors of S-ribosylhomocysteinase (LuxS enzyme) and AI-2 modulators of QS were developed. The synthesis of 2-deoxy-2-bromo-SRH analogues was attempted by coupling of the corresponding 2-bromo-2-deoxypentafuranosyl precursors with the homocysteinate anion. The displacement of the bromide from C2 rather than the expected substitution of the mesylate from C5 was observed. The synthesis of 4-C-alkyl/aryl-S-ribosylhomocysteine analogues involved the following steps: (i) conversion of the D-ribose to the ribitol-4-ulose; (ii) diastereoselective addition of various alkyl or aryl or vinyl Grignard reagents to 4-ketone intermediate; (iii) oxidation of the primary hydroxyl group at C1 followed by the intramolecular ring closure to the corresponding 4-C-alkyl/aryl-substituted ribono-1,4-lactones; (iv) displacement of the activated 5-hydroxyl group with the protected homocysteinate. Treatment of the 4-C-alkyl/aryl-substituted SRH analogues with lithium triethylborohydride effected reduction of the ribonolactone to the ribose (hemiacetal) and subsequent global deprotection with trifluoroacetic acid provided 4-C-alkyl/aryl-SRHs. ^ The 4-[thia]-SRH were prepared from the 1-deoxy-4-thioribose through the coupling of the &agr;-fluoro thioethers (thioribosyl fluorides) with homocysteinate anion. The 4-[thia]-SRH analogues showed concentration dependent effect on the growth on las (50% inhibitory effect at 200 µg/mL). The most active was 1-deoxy-4-[thia]-SRH analogue with sufur atom in the ring oxidized to sulfoxide decreasing las gene activity to approximately 35% without affecting rhl gene. Neither of the tested compounds had effect on bioluminescence nor on total growth of V. harveyi, but had however slight inhibition of the QS.^
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The objective of this study was to verify the association between some mobility items of the International Classification Functionality (ICF), with the evaluations Gross Motor Function Measure (GMFM-88), 1-minute walk test (1MWT) and if the motor impairment influences the quality of life in children with Cerebral Palsy (PC), by using the Paediatric Quality of Life Inventory (PedsQL 4.0 versions for children and parents). The study included 22 children with cerebral palsy spastic, classified in levels I, II, and III on the Gross Motor Function Classification System (GMFCS), with age group of 9.9 years old. Among those who have participated, seven of them were level I, eight of them were level II and seven of them were level III. All of the children and teenagers were rated by using check list ICF (mobility item), GMFM-88, 1-minute walk test and PedsQL 4.0 questionnaires for children and parents. It was observed a strong correlation between GMFM-88 with check list ICF (mobility item), but moderate correlation between GMFM-88 and 1-minute walk test (1MWT). It was also moderate the correlation between the walking test and the check list ICF (mobility item). The correlation between PedsQl 4.0 questionnaires for children and parents was weak, as well as the correlation of both with GMFM, ICF (mobility item) and the walking test. The lack of interrelation between physical function tests and quality of life, indicates that, regardless of the severity of the motor impairment and the difficulty with mobility, children and teenagers suffering of PC spastic, functional level I, II and III GMFCS and their parents have a varied opinion regarding the perception of well being and life satisfaction.
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Membrane lipids of marine planktonic archaea have provided unique insights into archaeal ecology and paleoceanography. However, past studies of archaeal lipids in suspended particulate matter (SPM) and sediments mainly focused on a small class of fully saturated glycerol dibiphytanyl glycerol tetraether (GDGT) homologues identified decades ago. The apparent low structural diversity of GDGTs is in strong contrast to the high diversity of metabolism and taxonomy among planktonic archaea. Furthermore, adaptation of archaeal lipids in the deep ocean remains poorly constrained. We report the archaeal lipidome in SPM from diverse oceanic regimes. We extend the known inventory of planktonic archaeal lipids to include numerous unsaturated archaeal ether lipids (uns-AELs). We further reveal i) different thermal regulations and polar headgroup compositions of membrane lipids between the epipelagic (<= 100 m) and deep (> 100 m) populations of archaea; ii) stratification of unsaturated GDGTs with varying redox conditions; and iii) enrichment of tetra-unsaturated archaeol and fully saturated GDGTs in epipelagic and deep oxygenated waters, respectively. Such stratified lipid patterns are consistent with the typical distribution of archaeal phylotypes in marine environments. We thus provide an ecological context for GDGT-based paleoclimatology and bring about the potential use of uns-AELs as biomarkers for planktonic Euryarchaeota. This article is protected by copyright. All rights reserved.
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At present, when the influence of human economic activity is progressively increasing, significant attention is devoted to the state of water ecosystems. All researchers engaged in these problems agree that the state of the water system (pollution and eutrophication) can only be estimated on the basis of long-term researches. Systemic monitoring (at least once per month) of ionic components (Ca2+, Mg2+, Na+, K+, bicarbonates, sulfates, and chlorides) in unfiltered water of Lake Baikal and its tributaries had been carried out under the supervision of Votintsev since 1947. Based on the analysis of systematic data on trophic components obtained during 1965-2005, we tried to estimate the present-day trophic status of the pelagic zone in the lake, define the trend of long-term changes of trophic components and understand the reasons of the distortion of cyclicity in the development of spring diatom algae, which create a favorable environment in any water basin. It should be noted that the station near Cape Polovinnyi is located 20 km away from the town of Baikal'sk. Wastewaters of the Baikal'sk pulp and paper mill is the main source of dioxins and furans in Baikal. Based on the significant difference between sulfate contents in wastewaters of the plant (>300 mg/l), tributaries of Baikal (7.5 mg/l), and waters in the southern part of the lake (3.9 mg/l), we defined the following periods: (i) period of natural seasonal patterns until 1967-1968 (prior to putting the Baikal'sk Mill into operation; (ii) period of weak anthropogenic pollution (1969-1985); and (iii) period of strong anthropogenic pollution since 1986.
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Defining goals and objectives is a critical component of adaptive management of natural resources because they provide the basis on which management strategies can be designed and evaluated. The aims of this study are: (i) to apply and test a collaborative method to elicit goals and objectives for inshore fisheries and biodiversity in the coastal zone of a regional city in Australia; (ii) to understand the relative importance of management objectives for different community members and stakeholders; and (iii) to understand how diverse perceptions about the importance of management objectives can be used to support multiple-use management in Australia’s iconic Great Barrier Reef. Management goals and objectives were elicited and weighted using the following steps: (i) literature review of management objectives, (ii) development of a hierarchy tree of objectives, and (iii) ranking of management objectives using survey methods. The overarching goals identified by the community group were to: (1) protect and restore inshore environmental assets; (2) improve governance systems; and (3) improve regional (socio-economic) well-being. Interestingly, these goals differ slightly from the usual triple-bottom line objectives (environmental, social and economic) often found in the literature. The objectives were ranked using the Analytical Hierarchical Process, where a total of 141 respondents from industry, government agencies, and community from across Queensland State undertook the survey. The environment goal received the highest scores, followed by governance and lastly well-being. The approach to elicit and rank goals and objectives developed in this study can be used to effectively support coastal resource management by providing opportunities for local communities to participate in the setting of regional objectives.
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Defining goals and objectives is a critical component of adaptive management of natural resources because they provide the basis on which management strategies can be designed and evaluated. The aims of this study are: (i) to apply and test a collaborative method to elicit goals and objectives for inshore fisheries and biodiversity in the coastal zone of a regional city in Australia; (ii) to understand the relative importance of management objectives for different community members and stakeholders; and (iii) to understand how diverse perceptions about the importance of management objectives can be used to support multiple-use management in Australia’s iconic Great Barrier Reef. Management goals and objectives were elicited and weighted using the following steps: (i) literature review of management objectives, (ii) development of a hierarchy tree of objectives, and (iii) ranking of management objectives using survey methods. The overarching goals identified by the community group were to: (1) protect and restore inshore environmental assets; (2) improve governance systems; and (3) improve regional (socio-economic) well-being. Interestingly, these goals differ slightly from the usual triple-bottom line objectives (environmental, social and economic) often found in the literature. The objectives were ranked using the Analytical Hierarchical Process, where a total of 141 respondents from industry, government agencies, and community from across Queensland State undertook the survey. The environment goal received the highest scores, followed by governance and lastly well-being. The approach to elicit and rank goals and objectives developed in this study can be used to effectively support coastal resource management by providing opportunities for local communities to participate in the setting of regional objectives.
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Title of Thesis: Thesis directed by: ABSTRACT EXAMINING THE IMPLEMENTATION CHALLENGES OF PROJECT-BASED LEARNING: A CASE STUDY Stefan Frederick Brooks, Master of Education, 2016 Professor and Chair Francine Hultgren Teaching and Learning, Policy and Leadership Department Project-based learning (PjBL) is a common instructional strategy to consider for educators, scholars, and advocates who focus on education reform. Previous research on PjBL has focused on its effectiveness, but a limited amount of research exists on the implementation challenges. This exploratory case study examines an attempted project- based learning implementation in one chemistry classroom at a private school that fully supports PjBL for most subjects with limited use in mathematics. During the course of the study, the teacher used a modified version of PjBL. Specifically, he implemented some of the elements of PjBL, such as a driving theme and a public presentation of projects, with the support of traditional instructional methods due to the context of the classroom. The findings of this study emphasize the teacher’s experience with implementing some of the PjBL components and how the inherent implementation challenges affected his practice.
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Normal grain growth of calcite was investigated by combining grain size analysis of calcite across the contact aureole of the Adamello pluton, and grain growth modeling based on a thermal model of the surroundings of the pluton. In an unbiased model system, i.e., location dependent variations in temperature-time path, 2/3 and 1/3 of grain growth occurs during pro- and retrograde metamorphism at all locations, respectively. In contrast to this idealized situation, in the field example three groups can be distinguished, which are characterized by variations in their grain size versus temperature relationships: Group I occurs at low temperatures and the grain size remains constant because nano-scale second phase particles of organic origin inhibit grain growth in the calcite aggregates under these conditions. In the presence of an aqueous fluid, these second phases decay at a temperature of about 350 °C enabling the onset of grain growth in calcite. In the following growth period, fluid-enhanced group II and slower group III growth occurs. For group II a continuous and intense grain size increase with T is typical while the grain growth decreases with T for group III. None of the observed trends correlate with experimentally based grain growth kinetics, probably due to differences between nature and experiment which have not yet been investigated (e.g., porosity, second phases). Therefore, grain growth modeling was used to iteratively improve the correlation between measured and modeled grain sizes by optimizing activation energy (Q), pre-exponential factor (k0) and grain size exponent (n). For n=2, Q of 350 kJ/mol, k0 of 1.7×1021 μmns−1 and Q of 35 kJ/mol, k0 of 2.5×10-5 μmns−1 were obtained for group II and III, respectively. With respect to future work, field-data based grain growth modeling might be a promising tool for investigating the influences of secondary effects like porosity and second phases on grain growth in nature, and to unravel differences between nature and experiment.
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In this article we propose a new symmetric version of the interior penalty discontinuous Galerkin finite element method for the numerical approximation of the compressible Navier-Stokes equations. Here, particular emphasis is devoted to the construction of an optimal numerical method for the evaluation of certain target functionals of practical interest, such as the lift and drag coefficients of a body immersed in a viscous fluid. With this in mind, the key ingredients in the construction of the method include: (i) An adjoint consistent imposition of the boundary conditions; (ii) An adjoint consistent reformulation of the underlying target functional of practical interest; (iii) Design of appropriate interior-penalty stabilization terms. Numerical experiments presented within this article clearly indicate the optimality of the proposed method when the error is measured in terms of both the L_2-norm, as well as for certain target functionals. Computational comparisons with other discontinuous Galerkin schemes proposed in the literature, including the second scheme of Bassi & Rebay, cf. [11], the standard SIPG method outlined in [25], and an NIPG variant of the new scheme will be undertaken.
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Tese de Doutoramento em Ciências Veterinárias, especialidade de Produção Animal
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Background: It is important that the residual bowel adapts after massive resection. The necessary intestinal adaptation is a progressive recovery from intestinal failure through increase in absorptive surface area and functional capacity and includes both morphological and functional adaptations. Objectives: The aim of this study was to investigate intestinal morphological and functional adaptations of small bowel syndrome (SBS) model rats (SBS1W) 7 days after bowel resection. Materials and Methods: Male sprague–dawley rats (n = 20/group) underwent either a 75% proximal small bowel resection (SBS1W group) or a control operation (control group). Markers of morphological adaptation were revealed by TEM analysis of H&E-stained tissue samples. The intestinal barrier condition was assessed by BT, and sIgA concentration in intestinal mucus was measured by ELISA. Contractility and the slow wave rhythm of the entire intestinal remnant were measured and recorded. Results: The SBS1W group experienced more weight loss than control group and had a clearly different intestinal morphology as revealed in TEM images. Compared with control rats, the SBS1W group had a lower sIgA concentration in intestinal mucus and higher BT to lymph nodes (70% vs 40%; level I), portal blood (40% vs 10%; level II), and peripheral blood (60% vs 30%; level III). Disorder of spontaneous rhythmic contraction, irregular amplitude, and slow frequency were detected in the SBS1W group by a muscle strips test. Similarly, the slow wave of the entire intestinal remnant in the SBS1W group was irregular and uncoordinated. Conclusions: The finding of intestinal adaptation following massive SBR in SBS1W rats provides more understanding of the mechanisms of progressive recovery from the intestinal failure that underlies SBS. The mechanical, chemical, immunological, and biological barriers were all impaired at 7 days following bowel resection, indicating that the SBS model rats were still in the intestinal adaptation phase.
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Purpose: To investigate the effect of β3-adrenoceptors (β3-AR) up-regulation on fibrosis in cardiac fibroblast cells in rats and its potential mechanism. Methods: Cardiac fibroblast cells (CFB) were isolated and identified from rats’ hearts. The β3-ARupregulated cardiac fibroblast cells were constructed by lentiviral transfection technology. Thereafter, Ang II was used to induce fibrosis in cardiac fibroblast cells, and subsequently, Western blot assay was performed to investigate fibrosis related marker proteins (TGF-β, Smad-2, p-Smad-2, Col-I and Col-III) in cardiac fibroblast cells. Results: β3-AR up-regulated cardiac fibroblast cells were successfully constructed. Furthermore, the results show that up-regulation of β3-AR increased the expressions of TGF-β, p-Smad-2, Col-I and Col- III proteins in Ang II treated cardiac fibroblast cells. Conclusion: The results suggest that up-regulation of β3-AR aggravates fibrosis of cardiac fibroblast cells. In other words, inhibition of β3-AR expressions in cardiac tissues would be beneficial for treating cardiac fibrosis and its related cardiac diseases.