984 resultados para Machinery.


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We compared student performance on large-scale take-home assignments and small-scale invigilated tests that require competency with exactly the same programming concepts. The purpose of the tests, which were carried out soon after the take home assignments were submitted, was to validate the students' assignments as individual work. We found widespread discrepancies between the marks achieved by students between the two types of tasks. Many students were able to achieve a much higher grade on the take-home assignments than the invigilated tests. We conclude that these paired assessments are an effective way to quickly identify students who are still struggling with programming concepts that we might otherwise assume they understand, given their ability to complete similar, yet more complicated, tasks in their own time. We classify these students as not yet being at the neo-Piagetian stage of concrete operational reasoning.

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This one-day workshop brings together researchers and practitioners to share knowledge and practices on how people can connect and interact with the Internet of Things in a playful way. Open to participants with a diverse range of interests and expertise, and by exploring novel ways to playfully connect people through their everyday objects and activities, the workshop will facilitate discussion across a range of HCI discipline areas. The outcomes from the workshop will include an archive of participants' initial position papers along with the materials created during the workshop. The result will be a road map to support the development of a Model of Playful Connectedness, focusing on how best to design and make playful networks of things, identifying the challenges that need to be addressed in order to do so.

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As Asia experiences the demographic imbalance between working and ageing populations, the need for attention in this area is highlighted. The shift of a country's age structure that results from people having small families and living long lives, where previously they had large families and lived short lives, results in more workers and fewer dependents creating economic growth, known as the demographic dividend. However for a generation after this bulge and dividend, a disproportionate number of older people must be supported by a smaller working population, a current concern in Asia with its rapidly growing number of older adults. This extended abstract draws practical and unique insights from three of the oldest and richest nations in Asia - Japan, South Korea and China, on the perspective of interactive technology design for older adults. ICT has powerful potential to ameliorate the imbalance in the population demographic through its potential to leverage various kinds of support. As HCI researchers, this is a challenge we embrace; a challenge for the ageing society of unique individuals to exploit the technologies that they have helped to create. The paper draws lessons from key sample studies, one from each country, which aimed to understand their ageing population. The insights for interaction designers are presented in the form of a practical set of reflections to guide the authors, who are in the early stages of research on technology design for older adults.

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Currently, we live in an era characterized by the completion and first runs of the LHC accelerator at CERN, which is hoped to provide the first experimental hints of what lies beyond the Standard Model of particle physics. In addition, the last decade has witnessed a new dawn of cosmology, where it has truly emerged as a precision science. Largely due to the WMAP measurements of the cosmic microwave background, we now believe to have quantitative control of much of the history of our universe. These two experimental windows offer us not only an unprecedented view of the smallest and largest structures of the universe, but also a glimpse at the very first moments in its history. At the same time, they require the theorists to focus on the fundamental challenges awaiting at the boundary of high energy particle physics and cosmology. What were the contents and properties of matter in the early universe? How is one to describe its interactions? What kind of implications do the various models of physics beyond the Standard Model have on the subsequent evolution of the universe? In this thesis, we explore the connection between in particular supersymmetric theories and the evolution of the early universe. First, we provide the reader with a general introduction to modern day particle cosmology from two angles: on one hand by reviewing our current knowledge of the history of the early universe, and on the other hand by introducing the basics of supersymmetry and its derivatives. Subsequently, with the help of the developed tools, we direct the attention to the specific questions addressed in the three original articles that form the main scientific contents of the thesis. Each of these papers concerns a distinct cosmological problem, ranging from the generation of the matter-antimatter asymmetry to inflation, and finally to the origin or very early stage of the universe. They nevertheless share a common factor in their use of the machinery of supersymmetric theories to address open questions in the corresponding cosmological models.

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Although prevention and early detection of the disease greatly improved over the past few years, lung cancer remains the leading cause of cancer deaths. In order to be able to treat a larger population, we are in urgent need for novel treatments. While it is known that DNA repair genes play a major role in the oncogenic transformation, they also represent a weakness of cancers that constitute a therapeutic opportunity. To identify novel DNA repair genes implicated in Lung cancers, we conducted an in silico investigation to identify genes co-regulated with two DNA repair factors, BRCA2 and hSSB1. This approach allowed for the identification of EXOSC4, a component of the RNA Exosome machinery, as a potential factor involved in the maintenance of genome stability and that is deregulated in lung cancer.

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This study investigates how offshore information technology (IT) service providers (vendors) coordinate work with their clients (employers) in order to succeed in the global IT offshore outsourcing industry. We reviewed literature on coordination studies, interviewed offshore service providers in the Philippines, and used thematic analysis to analyse coordination practices from the point of view of these individual vendors in a newly industrialized country. We used Olson and Olson's framework on 'collaboration at a distance' as a lens to structure the results. The study provides an understanding of vendors' individual attitudes towards the coordination of distributed work and draws attention to how differences in power affect the work situation of vendors, and by implication all stakeholders. We offer this insight as a way to enhance existing CSCW frameworks, by imbuing them with the perspective of non-equal relationships. The study found that vendors were generally able to produce outputs that satisfy their clients, however these results were only achieved because individuals were willing to take risks and make sacrifices in their personal lives. The relationship was further characterised by a complex interplay between the client's control of the overall work arrangements and the vendors' ability to establish a level of autonomy in their work practices and their flexible use of coordination tools.

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Rotavirus is a major cause of acute infantile diarrhoea worldwide. The virus genome consists of 11 segments of double-stranded RNA that codesfor six structural proteins (VP1-6) and six non-structural proteins(NSP1-6). NSPs are proteins expressed from the virus genome in the infected cell, but are not incorporated into the mature virus article. NSPs play an essential role in virus replication, morphogenesis and pathogenesis, and most of them exhibit multifunctional properties. Structure-function analysis of the NSPs is essential for understanding the molecular mechanisms by which the virus circumvents host innate immune responses, inhibits cellular protein synthesis, hijacks the protein synthetic machinery for its own propagation and manifests the disease process. Because of their essential roles in virus biology, NSPs represent potential targets for the development of antiviral agents. Determination of the three-dimensional structure of NSPs has been hindered due to low-level expression and aggregation. To date, the complete three-dimensional structure of only NSP2 has been determined. The structures of the N- and C-terminal domains of NSP3 and the diarrhoea-inducing domain of NSP4 have also been determined. This review primarily covers the structural and biological functions of the NSPs whose three-dimensional structural aspects have been fully or partially understood, but provides a brief account of other NSPs and the structural features of the mature virion as determined by electron cryomicroscopy.

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Recommender systems aggregate individual user ratings into predictions of products or services that might interest visitors. The quality of this aggregation process crucially affects the user experience and hence the effectiveness of recommenders in e-commerce. We present a characterization of nearest-neighbor collaborative filtering that allows us to disaggregate global recommender performance measures into contributions made by each individual rating. In particular, we formulate three roles-scouts, promoters, and connectors-that capture how users receive recommendations, how items get recommended, and how ratings of these two types are themselves connected, respectively. These roles find direct uses in improving recommendations for users, in better targeting of items and, most importantly, in helping monitor the health of the system as a whole. For instance, they can be used to track the evolution of neighborhoods, to identify rating subspaces that do not contribute ( or contribute negatively) to system performance, to enumerate users who are in danger of leaving, and to assess the susceptibility of the system to attacks such as shilling. We argue that the three rating roles presented here provide broad primitives to manage a recommender system and its community.

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Acyl carrier protein (ACP) plays a central role in fatty acid biosynthesis. However, the molecular machinery that mediates its function is not yet fully understood. Therefore, structural studies were carried out on the acyl-ACP intermediates of Plasmodium falciparum using NMR as a spectroscopic probe. Chemical shift perturbation studies put forth a new picture of the interaction of ACP molecule with the acyl chain, namely, the hydrophobic core can protect up to 12 carbon units, and additional carbons protrude out from the top of the hydrophobic cavity. The latter hypothesis stems from chemical shift changes observed in C-alpha and C-beta of Ser-37 in tetradecanoyl-ACP. C-13, N-15-Double-filtered nuclear Overhauser effect (NOE) spectroscopy experiments further substantiate the concept; in octanoyl (C-8)- and dodecanoyl (C-12)-ACP, a long range NOE is observed within the phosphopantetheine arm, suggesting an arch-like conformation. This NOE is nearly invisible in tetradecanoyl (C-14)-ACP, indicating a change in conformation of the prosthetic group. Furthermore, the present study provides insights into the molecular mechanism of ACP expansion, as revealed from a unique side chain-to-backbone hydrogen bond between two fairly conserved residues, Ile-55 HN and Glu-48 O. The backbone amide of Ile-55 HN reports a pK(a) value for the carboxylate, similar to 1.9 pH units higher than model compound value, suggesting strong electrostatic repulsion between helix II and helix III. Charge-charge repulsion between the helices in combination with thrust from inside due to acyl chain would energetically favor the separation of the two helices. Helix III has fewer structural restraints and, hence, undergoes major conformational change without altering the overall-fold of P. falciparum ACP.

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The emergence of strains of Plasmodium falciparum resistant to the commonly used antimalarials warrants the development of new antimalarial agents. The discovery of type II fatty acid synthase (FAS) in Plasmodium distinct from the FAS in its human host (type I FAS) opened up new avenues for the development of novel antimalarials. The process of fatty acid synthesis takes place by iterative elongation of butyryl-acyl carrier protein (butyryl-ACP) by two carbon units, with the successive action of four enzymes constituting the elongation module of FAS until the desired acyl length is obtained. The study of the fatty acid synthesis machinery of the parasite inside the red blood cell culture has always been a challenging task. Here, we report the in vitro reconstitution of the elongation module of the FAS of malaria parasite involving all four enzymes, FabB/F (β-ketoacyl-ACP synthase), FabG (β-ketoacyl-ACP reductase), FabZ (β-ketoacyl-ACP dehydratase), and FabI (enoyl-ACP reductase), and its analysis by matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF MS). That this in vitro systems approach completely mimics the in vivo machinery is confirmed by the distribution of acyl products. Using known inhibitors of the enzymes of the elongation module, cerulenin, triclosan, NAS-21/91, and (–)-catechin gallate, we demonstrate that accumulation of intermediates resulting from the inhibition of any of the enzymes can be unambiguously followed by MALDI-TOF MS. Thus, this work not only offers a powerful tool for easier and faster throughput screening of inhibitors but also allows for the study of the biochemical properties of the FAS pathway of the malaria parasite.

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The emergence of strains of Plasmodium falciparum resistant to the commonly used antimalarials warrants the development of new antimalarial agents. The discovery of type II fatty acid synthase (FAS) in Plasmodium distinct from the FAS in its human host (type I FAS) opened up new avenues for the development of novel antimalarials. The process of fatty acid synthesis takes place by iterative elongation of butyryl-acyl carrier protein (butyryl-ACP) by two carbon units, with the successive action of four enzymes constituting the elongation module of FAS until the desired acyl length is obtained. The study of the fatty acid synthesis machinery of the parasite inside the red blood cell culture has always been a challenging task. Here, we report the in vitro reconstitution of the elongation module of the FAS of malaria parasite involving all four enzymes, FabB/F (β-ketoacyl-ACP synthase), FabG (β-ketoacyl-ACP reductase), FabZ (β-ketoacyl-ACP dehydratase), and FabI (enoyl-ACP reductase), and its analysis by matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF MS). That this in vitro systems approach completely mimics the in vivo machinery is confirmed by the distribution of acyl products. Using known inhibitors of the enzymes of the elongation module, cerulenin, triclosan, NAS-21/91, and (–)-catechin gallate, we demonstrate that accumulation of intermediates resulting from the inhibition of any of the enzymes can be unambiguously followed by MALDI-TOF MS. Thus, this work not only offers a powerful tool for easier and faster throughput screening of inhibitors but also allows for the study of the biochemical properties of the FAS pathway of the malaria parasite.

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Direct contact mechanism in bioleaching implies prior mineral adhesion of Acidithiobacillus ferrooxidans and subsequent enzymatic attack.Prior bacterial adaptation to sulfide mineral substrates influences bacterial ferrous ion oxidation rates. It is highly beneficial to understand major biooxidation mechanisms with reference to solution- and mineral-grown cells in order to optimize bioleaching reactions. For A. ferrooxidans grown in the presence of solid substrates such as sulfur, pyrite and chalcopyrite, bacterial adhesion is required for its enzymatic machinery to come into close contact for mineral dissolution.But when grown in solution substrate such as ferrous ions and thiosulfate, such an adhesion machinery is not required for substrate utilization. Proteinaceous compounds were observed on the surface of sulfur-grown cells. Such an induction of relatively hydrophobic proteins and down regulation of exposed polysaccharides leads to changes in cell surface chemistry. Sulfur-grown and pyrite- and chalcopyrite-grown bacterial cells were found to be more efficient in the bioleaching of chalcopyrite than those grown in the presence of ferrous ions and thiosulfate. (C) 2010 Elsevier B.V. All rights reserved.

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Adherent cells undergo remarkable changes in shape during cell division. However, the functional interplay between cell adhesion turnover and the mitotic machinery is poorly understood. The endo/exocytic trafficking of integrins is regulated by the small GTPase Rab21, which associates with several integrin alpha subunits. Here, we show that targeted trafficking of integrins to and from the cleavage furrow is required for successful cytokinesis, and that this is regulated by Rab21. Rab21 activity, integrin-Rab21 association, and integrin endocytosis are all necessary for normal cytokinesis, which becomes impaired when integrin-mediated adhesion at the cleavage furrow fails. We also describe a chromosomal deletion and loss of Rab21 gene expression in human cancer, which leads to the accumulation of multinucleate cells. Importantly, reintroduction of Rab21 rescued this phenotype. In conclusion, Rab21-regulated integrin trafficking is essential for normal cell division, and its defects may contribute to multinucleation and genomic instability, which are hallmarks of cancer.

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Sjögren s syndrome (SS) is a strongly female dominant autoimmune disease. SS targets mainly salivary and lacrimal glands and leads to loss of the secreting acinar cells of these glands. Accordingly, secretion of the affected glands is diminished and the main symptoms of SS, dryness of mouth and eyes, follow. In addition to these sicca symptoms, SS patients suffer from severe fatigue and can have various extraglandular symptoms. To date, the etiology of SS still remains unknown. Female dominance and the late onset of the disease simultaneously with remarkable hormonal changes in the body (menopause, adrenopause) encouraged us to hypothesize that sex steroids, especially androgens, are involved in the onset and progression of SS. We confirmed our hypothesis and showed that patients with SS suffer from androgen depletion both systemically and locally in the target tissue of SS, salivary glands. We especially focused on the local androgen environment in salivary glands and demonstrated that healthy salivary glands contain a complete enzymatic machinery for local synthesis of androgens and estrogens from pro-hormone dehydroepiandrosterone (DHEA). However, in SS salivary glands the enzymes catalyzing the local androgen synthesis are defective and, in a subgroup of patients, practically non-functional. Probably due to this local defect in DHEA processing, therapy with DHEA was found unbeneficial for SS patients in the treatment of fatigue. We also studied the effect of the local androgen depletion on salivary glands. We found that in salivary gland cells and healthy labial salivary glands androgens upregulate integrin subunits α1 and α2, which are important for the communication, differentiation and function of the acinar cells. On the contrary, in SS salivary glands DHEA failed to upregulate these signaling molecules, again probably due to defective processing of DHEA into active androgens. Our finding highlights the importance of the local androgen environment and local DHEA processing for the function and welfare of salivary glands. In conclusion, this study showed that patients with SS are androgen depleted both systemically and locally in salivary glands. SS patients also have a defective local sex steroid synthesizing enzymatic machinery further impairing the local androgen depletion. We also showed that the local androgen defect leads to decreased expression of acinar cell specific integrin molecules, which impairs the signaling between the acinar cells and basement membrane and might thus explain the acinar cell loss seen in SS salivary glands. By showing the importance of the local sex steroid imbalance in SS we have clarified some etiopathogenetic mechanisms of SS, which have thus far remained unknown.

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We propose a novel second order cone programming formulation for designing robust classifiers which can handle uncertainty in observations. Similar formulations are also derived for designing regression functions which are robust to uncertainties in the regression setting. The proposed formulations are independent of the underlying distribution, requiring only the existence of second order moments. These formulations are then specialized to the case of missing values in observations for both classification and regression problems. Experiments show that the proposed formulations outperform imputation.