993 resultados para Complex questions


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Thesis (Ph.D.)--University of Washington, 2016-06

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Direct continuity between the membranes of cisternae in the Golgi complex in mammalian cells rarely has been observed; when seen, its documentation has been equivocal. Here we have used dual-axis electron microscope tomography to examine the architecture of the Golgi in three dimensions at approximate to6-nm resolution in rapidly frozen, freeze-substituted murine cells that make and secrete insulin in response to glucose challenge. Our data show three types of direct connections between Golgi cisternae that are normally distinct from one another. These connections all bypass interceding cisternae. We propose that when pancreatic beta cells are stimulated to synthesize and secrete insulin rapidly in vivo, such connections provide a continuous lumen that facilitates the rapid transit of large amounts of newly made protein for secretion. The heterotypic fusion of cisternae, even transiently, raises important questions about the molecular mechanisms that (i) facilitate the fusion/fission of cisternal membranes and control the directionality and specificity of such events, and (it) retain Golgi processing enzymes at specific places within individual cisternae when two cisternae at different levels in the Golgi have fused, maintaining the sequential processing hierarchy that is a hallmark of Golgi organization.

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The law of landlord and tenant has become an increasingly complex area for both professionals and students. Apart from the double hurdle of mastering both common law principles and statutory codes, various aspects of the subject have become increasingly specialised and challenging. This new edition of Question and Answer Landlord and Tenant demonstrates that even complex problems can be explained in straightforward and inspiring terms. The authors, both experienced academics and barristers, provide detailed answers to typical questions in this difficult field. The third edition of this book has been updated in the new Question and Answer style of questions followed by commentary, bullet points and diagrams and flowcharts. It offers new questions based on the latest recommendations of the Law Commission on renting homes and the abolition of the law of forfeiture. There are new questions on the human rights dimension, the recent changes to Part II of the Landlord and Tenant Act 1954 and the substantial amendments made to leasehold enfranchisement under the Commonhold and Leasehold Reform Act 2002.

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Research and development of mathematical model of optimum distribution of resources (basically financial) for maintenance of the new (raised) quality (reliability) of complex system concerning, which the decision on its re-structuring is accepted, is stated. The final model gives answers (algorithm of calculation) to questions: how many elements of system to allocate on modernization, which elements, up to what level of depth modernization of each of allocated is necessary, and optimum answers are by criterion of minimization of financial charges.

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Thee rise of computing and the internet have brought about an ethical eld of studies that some term information ethics, computer ethics, digital media ethics, or internet ethics e aim of this contribution is to discuss information ethics’ foundations in the context of the internet’s political economy e chapter rst looks to ground the analysis in a comparison of two information ethics approaches, namely those outlined by Rafael Capurro and Luciano Floridi It then develops, based on these foundations, analyses of the information ethical dimensions of two important areas of social media: one concerns the framing of social media by a surveillance-industrial complex in the context of Edward Snowden’s revelations and the other deals with issues of digital labour processes and issues of class that arises in this context e contribution asks ethical questions about these two phenomena that bring up issues of power, exploitation, and control in the information age It asks if, and if so, how, the approaches of Capurro and Floridi can help us to understand ethico-political aspects of the surveillance-industrial complex and digital labour

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This thesis explores how to design a peer support system to facilitate self-organized knowledge sharing in non-formal learning environments, in particular when learners work on complex tasks. The peer support system aims to replace two teacher-led didactic arrangements: selecting a tutor at the initial stage, and guidance during the interaction process (Dillenbourg, 1999; Topping, 1996). Such a system has previously been developed by Van Rosmalen (2008) and De Bakker (2010) and has been tentatively used to facilitate knowledge sharing on content-related questions. In this thesis, we would like to find out how to further improve the design of this peer support system, especially to facilitate knowledge sharing on complex tasks. Since little pedagogical theory is available to inform the design of our peer support system, this thesis attempts to apply cognitive load theory (Sweller, Van Merriënboer, & Paas, 1998; Van Merriënboer & Sweller, 2005) that informs instructional designs in classroom settings to the design of our peer support system in Learning Networks.

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Our society is currently facing complex challenges, such us climate change, loss of biodiversity, ageing population, unemployment, to name but a few. This has created growing expectations on designers and engineers to explore, experiment and implement innovative solutions to such issues. At this critical time, if we want design to be part of the solution, we need to wonder whether we are asking designers suitable and sustainable questions. Both in post-graduate design education and in business, the brief still overwhelmingly requires designers to follow a linear problem-solving approach that focuses on product rather than strategies, services and systems. Traditional design briefs result no longer appropriate to face the challenges of our unsustainable world, as they relate to market, growth economy and human needs rather than society, business models and the needs of nature. Instead, we need to be asking questions about, for example, how we create sustainable business opportunities, how we overcome the barriers for change, or how we facilitate the process of innovation through design methodology. If the role of design is to create new visions and outline strategic directions towards a sustainable future world - for policy makers, businesses, communities and individual citizens – we need those stakeholders to create briefs for designers that allow them to do that. This paper will explain how the reframing of questions has been embedded into SustainRCA’s teaching practice in post-graduate design, art and engineering, leading to the development of new tools and methods, as well as some innovative outcomes

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This thesis is a research about the recent complex spatial changes in Namibia and Tanzania and local communities’ capacity to cope with, adapt to and transform the unpredictability engaged to these processes. I scrutinise the concept of resilience and its potential application to explaining the development of local communities in Southern Africa when facing various social, economic and environmental changes. My research is based on three distinct but overlapping research questions: what are the main spatial changes and their impact on the study areas in Namibia and Tanzania? What are the adaptation, transformation and resilience processes of the studied local communities in Namibia and Tanzania? How are innovation systems developed, and what is their impact on the resilience of the studied local communities in Namibia and Tanzania? I use four ethnographic case studies concerning environmental change, global tourism and innovation system development in Namibia and Tanzania, as well as mixed-methodological approaches, to study these issues. The results of my empirical investigation demonstrate that the spatial changes in the localities within Namibia and Tanzania are unique, loose assemblages, a result of the complex, multisided, relational and evolutional development of human and non-human elements that do not necessarily have linear causalities. Several changes co-exist and are interconnected though uncertain and unstructured and, together with the multiple stressors related to poverty, have made communities more vulnerable to different changes. The communities’ adaptation and transformation measures have been mostly reactive, based on contingency and post hoc learning. Despite various anticipation techniques, coping measures, adaptive learning and self-organisation processes occurring in the localities, the local communities are constrained by their uneven power relationships within the larger assemblages. Thus, communities’ own opportunities to increase their resilience are limited without changing the relations in these multiform entities. Therefore, larger cooperation models are needed, like an innovation system, based on the interactions of different actors to foster cooperation, which require collaboration among and input from a diverse set of stakeholders to combine different sources of knowledge, innovation and learning. Accordingly, both Namibia and Tanzania are developing an innovation system as their key policy to foster transformation towards knowledge-based societies. Finally, the development of an innovation system needs novel bottom-up approaches to increase the resilience of local communities and embed it into local communities. Therefore, innovation policies in Namibia have emphasised the role of indigenous knowledge, and Tanzania has established the Living Lab network.

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Molecular simulation provides a powerful tool for connecting molecular-level processes to physical observables. However, the facility to make those connections relies upon the application and development of theoretical methods that permit appropriate descriptions of the systems or processes to be studied. In this thesis, we utilize molecular simulation to study and predict two phenomena with very different theoretical challenges, beginning with (1) lithium-ion transport behavior in polymers and following with (2) equilibrium isotope effects with relevance to position-specific and clumped isotope studies. In the case of ion transport in polymers, there is motivation to use molecular simulation to provide guidance in polymer electrolyte design, but the length and timescales relevant for ion diffusion in polymers preclude the use of direct molecular dynamics simulation to compute ion diffusivities in more than a handful of candidate systems. In the case of equilibrium isotope effects, the thermodynamic driving forces for isotopic fractionation are often fundamentally quantum mechanical in nature, and the high precision of experimental instruments demands correspondingly accurate theoretical approaches. Herein, we describe respectively coarse-graining and path-integral strategies to address outstanding questions in these two subject areas.

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The presence of Lusitanian amphorae in the region of Carthago Nova (Cartagena, Spain) has been known for a few years, and yet it has never been the subject of a monographic study. Integrated in the commercial networks of the western Mediterranean, these products circulated within the harbour system of this city between the 1st and the 5th century AD. This paper aims to present a synthesised review of the main Lusitanian imports that were detected: Dressel 14 and Almagro 50, Almagro 51a-b and Almagro 51c. The difficulty in identifying the ceramic fabrics and the scarce documentation regarding some finds pose complex problems. This study extends to the hinterland of the colony and to other nearby settlements, such as Portmán and Puerto de Mazarrón.

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Introduzimos o leitor ao estudo de um sistema diferencial exterior fundamental, descoberto anteriormente pelo autor, que se pode sempre associar a qualquer dada variedade riemanniana M de dimensão n+1. Depois de recordarmos a geometria do fibrado de esferas tangente SM--->M com a métrica de Sasaki, apresentamos o sistema de formas diferencias de grau n que complementa a conhecida estrutura de contacto de SM. A partir daí vemos como o sistema diferencial se aplica ao estudo de problemas métricos em hipersuperfícies de M, bem como a outros que são próprios de SM, e as diversas questões que se podem colocar neste novo contexto.

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The epididymis has an important role in the maturation of sperm for fertilization, but little is known about the epididymal molecules involved in sperm modifications during this process. We have previously described the expression pattern for an antigen in epididymal epithelial cells that reacts with the monoclonal antibody (mAb) TRA 54. Immunohistochemical and immunoblotting analyses suggest that the epitope of the epididymal antigen probably involves a sugar moiety that is released into the epididymal lumen in an androgen-dependent manner and subsequently binds to luminal sperm. Using column chromatography, SDS-PAGE with in situ digestion and mass spectrometry, we have identified the protein recognized by mAb TRA 54 in mouse epididymal epithelial cells. The ∼65 kDa protein is part of a high molecular mass complex (∼260 kDa) that is also present in the sperm acrosomal vesicle and is completely released after the acrosomal reaction. The amino acid sequence of the protein corresponded to that of albumin. Immunoprecipitates with anti-albumin antibody contained the antigen recognized by mAb TRA 54, indicating that the epididymal molecule recognized by mAb TRA 54 is albumin. RT-PCR detected albumin mRNA in the epididymis and fertilization assays in vitro showed that the glycoprotein complex containing albumin was involved in the ability of sperm to recognize and penetrate the egg zona pellucida. Together, these results indicate that epididymal-derived albumin participates in the formation of a high molecular mass glycoprotein complex that has an important role in egg fertilization.

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The aim of this work was to characterize the effects of partial inhibition of respiratory complex I by rotenone on H2O2 production by isolated rat brain mitochondria in different respiratory states. Flow cytometric analysis of membrane potential in isolated mitochondria indicated that rotenone leads to uniform respiratory inhibition when added to a suspension of mitochondria. When mitochondria were incubated in the presence of a low concentration of rotenone (10 nm) and NADH-linked substrates, oxygen consumption was reduced from 45.9 ± 1.0 to 26.4 ± 2.6 nmol O2 mg(-1) min(-1) and from 7.8 ± 0.3 to 6.3 ± 0.3 nmol O2 mg(-1) min(-1) in respiratory states 3 (ADP-stimulated respiration) and 4 (resting respiration), respectively. Under these conditions, mitochondrial H2O2 production was stimulated from 12.2 ± 1.1 to 21.0 ± 1.2 pmol H2O2 mg(-1) min(-1) and 56.5 ± 4.7 to 95.0 ± 11.1 pmol H2O2 mg(-1) min(-1) in respiratory states 3 and 4, respectively. Similar results were observed when comparing mitochondrial preparations enriched with synaptic or nonsynaptic mitochondria or when 1-methyl-4-phenylpyridinium ion (MPP(+)) was used as a respiratory complex I inhibitor. Rotenone-stimulated H2O2 production in respiratory states 3 and 4 was associated with a high reduction state of endogenous nicotinamide nucleotides. In succinate-supported mitochondrial respiration, where most of the mitochondrial H2O2 production relies on electron backflow from complex II to complex I, low rotenone concentrations inhibited H2O2 production. Rotenone had no effect on mitochondrial elimination of micromolar concentrations of H2O2. The present results support the conclusion that partial complex I inhibition may result in mitochondrial energy crisis and oxidative stress, the former being predominant under oxidative phosphorylation and the latter under resting respiration conditions.

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A new platinum(II) complex with the amino acid L-tryptophan (trp), named Pt-trp, was synthesized and characterized. Elemental, thermogravimetric and ESI-QTOF mass spectrometric analyses led to the composition [Pt(C11H11N2O2)2]⋅6H2O. Infrared spectroscopic data indicate the coordination of trp to Pt(II) through the oxygen of the carboxylate group and also through the nitrogen atom of the amino group. The (13)C CP/MAS NMR spectroscopic data confirm coordination through the oxygen atom of the carboxylate group, while the (15)N CP/MAS NMR data confirm coordination of the nitrogen of the NH2 group to the metal. Density functional theory (DFT) studies were applied to evaluate the cis and trans coordination modes of trp to platinum(II). The trans isomer was shown to be energetically more stable than the cis one. The Pt-trp complex was evaluated as a cytotoxic agent against SK-Mel 103 (human melanoma) and Panc-1 (human pancreatic carcinoma) cell lines. The complex was shown to be cytotoxic over the considered cells.