903 resultados para Cable and membrane structures


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This study investigates the use of reported loan loss provisions (LLP) by investors in their valuations of banks within the Middle East and North Africa region between the years 2006 and 2011. We decompose LLP into discretionary and non-discretionary components to test for differential valuations in the two banking sectors. We use alternative criteria to define the components of LLP in banks: loan quality/size and earnings management/ manipulation incentives. We employ a price-level valuation model estimated using two-stage analyses. We find that LLP has positive value relevance to investors in both banking sectors. Investors in Islamic banks price the discretionary component relatively lower than their conventional counterparts. We attribute this result to differences in product and governance structures as well as to the religious perception of Islamic banking. In both banking sectors, investors construe an increase in the non-discretionary component as irrelevant valuation information. Our results are relevant to bank regulators in showing the signalling effect of LLP to bank value and stability.

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Over the last twenty years, we have been continuously seeing R&D efforts and activities in developing optical fibre grating devices and technologies and exploring their applications for telecommunications, optical signal processing and smart sensing, and recently for medical care and biophotonics. In addition, we have also witnessed successful commercialisation of these R&Ds, especially in the area of fibre Bragg grating (FBG) based distributed sensor network systems and technologies for engineering structure monitoring in industrial sectors such as oil, energy and civil engineering. Despite countless published reports and papers and commercial realisation, we are still seeing significant and novel research activities in this area. This invited paper will give an overview on recent advances in fibre grating devices and their sensing applications with a focus on novel fibre gratings and their functions and grating structures in speciality fibres. The most recent developments in (i) femtosecond inscription for microfluidic/grating devices, (2) tilted grating based novel polarisation devices and (3) dual-peak long-period grating based DNA hybridisation sensors will be discussed.

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This study investigates the use of reported loan loss provisions (LLP) by investors in their valuations of banks within the Middle East and North Africa region between the years 2006 and 2011. We decompose LLP into discretionary and non-discretionary components to test for differential valuations in the two banking sectors. We use alternative criteria to define the components of LLP in banks: loan quality/size and earnings management/manipulation incentives. We employ a price-level valuation model estimated using two-stage analyses. We find that LLP has positive value relevance to investors in both banking sectors. Investors in Islamic banks price the discretionary component relatively lower than their conventional counterparts. We attribute this result to differences in product and governance structures as well as to the religious perception of Islamic banking. In both banking sectors, investors construe an increase in the non-discretionary component as irrelevant valuation information. Our results are relevant to bank regulators in showing the signalling effect of LLP to bank value and stability. © 2013 Elsevier B.V.

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The eye is the major organ of vision and highly specialized for photoreception. It focusses light from an object onto the light-sensitive retina. Changes in specialized neurons in the retina result in nerve action potentials which are relayed to the brain via the optic nerve. Visual processing by the brain results in ‘visual perception’, the construction of a sensory image which is consciously appreciated as vision. All other structures of the eye are subsidiary to this function, either by facilitating focusing of light rays or by supporting the tissues of the eye. This chapter is an introduction to the various parts of the eye including the eyelids and associated structures, conjunctiva, cornea, sclera, iris, lens, vitreous body, retina, optic disc and nerve, and orbit. This chapter describes the functions of these various structures and their importance in achieving a visual image.

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The molecular dynamics (MD) simulations play a very important role in science today. They have been used successfully in binding free-energy calculations and rational design of drugs and vaccines. MD simulations can help visualize and understand structures and dynamics at an atomistic level when combined with molecular graphics programs. The molecular and atomistic properties can be displayed on a computer in a time-dependent way, which opens a road toward a better understanding of the relationship of structure, dynamics, and function. In this chapter, the basics of MD are explained, together with a step-by-step description of setup and running an MD simulation.

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Objective: There is evidence to suggest a beneficial role for growth factors, including vascular endothelial growth factor (VEGF), in tissue repair and proliferation after injury within the lung. Whether this effect is mediated predominantly by actions on endothelial cells or epithelial cells is unknown. This study tested the hypothesis that VEGF acts as an autocrine trophic factor for human adult alveolar epithelial cells and that under situations of pro-apoptotic stress, VEGF reduces cell death. Design: In vitro cell culture study looking at the effects of 0.03% H2O2 on both A549 and primary distal lung epithelial cells.Measurement and Main Results: Primary adult human distal lung epithelial cells express both the soluble and membrane-associated VEGF isoforms and VEGF receptors 1 and 2. At physiologically relevant doses, soluble VEGF isoforms stimulate wound repair and have a proliferative action. Specific receptor ligands confirmed that this effect was mediated by VEGF receptor 1. In addition to proliferation, we demonstrate that VEGF reduces A549 and distal lung epithelial cell apoptosis when administered after 0.03% H2O2 injury. This effect occurs due to reduced caspase-3 activation and is phosphatidylinositol 3′–kinase dependent. Conclusion: In addition to its known effects on endothelial cells, VEGF acts as a growth and anti-apoptotic factor on alveolar epithelial cells. VEGF treatment may have potential as a rescue therapy for diseases associated with alveolar epithelial damage such as acute respiratory distress syndrome.

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Endothelial tip cells guide angiogenic sprouts by exploring the local environment for guidance cues such as vascular endothelial growth factor (VegfA). Here we present Flt1 (Vegf receptor 1) loss- and gain-of-function data in zebrafish showing that Flt1 regulates tip cell formation and arterial branching morphogenesis. Zebrafish embryos expressed soluble Flt1 (sFlt1) and membrane-bound Flt1 (mFlt1). In Tg(flt1(BAC):yfp) × Tg(kdrl:ras-cherry)(s916) embryos, flt1:yfp was expressed in tip, stalk and base cells of segmental artery sprouts and overlapped with kdrl:cherry expression in these domains. flt1 morphants showed increased tip cell numbers, enhanced angiogenic behavior and hyperbranching of segmental artery sprouts. The additional arterial branches developed into functional vessels carrying blood flow. In support of a functional role for the extracellular VEGF-binding domain of Flt1, overexpression of sflt1 or mflt1 rescued aberrant branching in flt1 morphants, and overexpression of sflt1 or mflt1 in controls resulted in short arterial sprouts with reduced numbers of filopodia. flt1 morphants showed reduced expression of Notch receptors and of the Notch downstream target efnb2a, and ectopic expression of flt4 in arteries, consistent with loss of Notch signaling. Conditional overexpression of the notch1a intracellular cleaved domain in flt1 morphants restored segmental artery patterning. The developing nervous system of the trunk contributed to the distribution of Flt1, and the loss of flt1 affected neurons. Thus, Flt1 acts in a Notch-dependent manner as a negative regulator of tip cell differentiation and branching. Flt1 distribution may be fine-tuned, involving interactions with the developing nervous system.

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This article investigates the relationship between zoning by-laws, as put forward in governmental land-use plans and the viability of urban residential neighbourhood economies. The Dutch planning tradition has long been characterized by strict separation of functions and top-down planning. We argue that profound changes in social and economic structures make land-use planning practices less suitable for the current policy formula of "mixed urban milieus". Although the residential neighbourhood might not be the location of large firms, it definitely attracts small ones, and facilitates starting businesses whose presence (and potential growth) can be beneficial to the city as a whole. We present a typology of spatial patterns of neighbourhood economies based on land-use plans and describe whether these are related to the distinctive economic development of the neighbourhood over the period 1999-2007. © 2013 Taylor & Francis.

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Full text: The idea of producing proteins from recombinant DNA hatched almost half a century ago. In his PhD thesis, Peter Lobban foresaw the prospect of inserting foreign DNA (from any source, including mammalian cells) into the genome of a λ phage in order to detect and recover protein products from Escherichia coli [ 1 and 2]. Only a few years later, in 1977, Herbert Boyer and his colleagues succeeded in the first ever expression of a peptide-coding gene in E. coli — they produced recombinant somatostatin [ 3] followed shortly after by human insulin. The field has advanced enormously since those early days and today recombinant proteins have become indispensable in advancing research and development in all fields of the life sciences. Structural biology, in particular, has benefitted tremendously from recombinant protein biotechnology, and an overwhelming proportion of the entries in the Protein Data Bank (PDB) are based on heterologously expressed proteins. Nonetheless, synthesizing, purifying and stabilizing recombinant proteins can still be thoroughly challenging. For example, the soluble proteome is organized to a large part into multicomponent complexes (in humans often comprising ten or more subunits), posing critical challenges for recombinant production. A third of all proteins in cells are located in the membrane, and pose special challenges that require a more bespoke approach. Recent advances may now mean that even these most recalcitrant of proteins could become tenable structural biology targets on a more routine basis. In this special issue, we examine progress in key areas that suggests this is indeed the case. Our first contribution examines the importance of understanding quality control in the host cell during recombinant protein production, and pays particular attention to the synthesis of recombinant membrane proteins. A major challenge faced by any host cell factory is the balance it must strike between its own requirements for growth and the fact that its cellular machinery has essentially been hijacked by an expression construct. In this context, Bill and von der Haar examine emerging insights into the role of the dependent pathways of translation and protein folding in defining high-yielding recombinant membrane protein production experiments for the common prokaryotic and eukaryotic expression hosts. Rather than acting as isolated entities, many membrane proteins form complexes to carry out their functions. To understand their biological mechanisms, it is essential to study the molecular structure of the intact membrane protein assemblies. Recombinant production of membrane protein complexes is still a formidable, at times insurmountable, challenge. In these cases, extraction from natural sources is the only option to prepare samples for structural and functional studies. Zorman and co-workers, in our second contribution, provide an overview of recent advances in the production of multi-subunit membrane protein complexes and highlight recent achievements in membrane protein structural research brought about by state-of-the-art near-atomic resolution cryo-electron microscopy techniques. E. coli has been the dominant host cell for recombinant protein production. Nonetheless, eukaryotic expression systems, including yeasts, insect cells and mammalian cells, are increasingly gaining prominence in the field. The yeast species Pichia pastoris, is a well-established recombinant expression system for a number of applications, including the production of a range of different membrane proteins. Byrne reviews high-resolution structures that have been determined using this methylotroph as an expression host. Although it is not yet clear why P. pastoris is suited to producing such a wide range of membrane proteins, its ease of use and the availability of diverse tools that can be readily implemented in standard bioscience laboratories mean that it is likely to become an increasingly popular option in structural biology pipelines. The contribution by Columbus concludes the membrane protein section of this volume. In her overview of post-expression strategies, Columbus surveys the four most common biochemical approaches for the structural investigation of membrane proteins. Limited proteolysis has successfully aided structure determination of membrane proteins in many cases. Deglycosylation of membrane proteins following production and purification analysis has also facilitated membrane protein structure analysis. Moreover, chemical modifications, such as lysine methylation and cysteine alkylation, have proven their worth to facilitate crystallization of membrane proteins, as well as NMR investigations of membrane protein conformational sampling. Together these approaches have greatly facilitated the structure determination of more than 40 membrane proteins to date. It may be an advantage to produce a target protein in mammalian cells, especially if authentic post-translational modifications such as glycosylation are required for proper activity. Chinese Hamster Ovary (CHO) cells and Human Embryonic Kidney (HEK) 293 cell lines have emerged as excellent hosts for heterologous production. The generation of stable cell-lines is often an aspiration for synthesizing proteins expressed in mammalian cells, in particular if high volumetric yields are to be achieved. In his report, Buessow surveys recent structures of proteins produced using stable mammalian cells and summarizes both well-established and novel approaches to facilitate stable cell-line generation for structural biology applications. The ambition of many biologists is to observe a protein's structure in the native environment of the cell itself. Until recently, this seemed to be more of a dream than a reality. Advances in nuclear magnetic resonance (NMR) spectroscopy techniques, however, have now made possible the observation of mechanistic events at the molecular level of protein structure. Smith and colleagues, in an exciting contribution, review emerging ‘in-cell NMR’ techniques that demonstrate the potential to monitor biological activities by NMR in real time in native physiological environments. A current drawback of NMR as a structure determination tool derives from size limitations of the molecule under investigation and the structures of large proteins and their complexes are therefore typically intractable by NMR. A solution to this challenge is the use of selective isotope labeling of the target protein, which results in a marked reduction of the complexity of NMR spectra and allows dynamic processes even in very large proteins and even ribosomes to be investigated. Kerfah and co-workers introduce methyl-specific isotopic labeling as a molecular tool-box, and review its applications to the solution NMR analysis of large proteins. Tyagi and Lemke next examine single-molecule FRET and crosslinking following the co-translational incorporation of non-canonical amino acids (ncAAs); the goal here is to move beyond static snap-shots of proteins and their complexes and to observe them as dynamic entities. The encoding of ncAAs through codon-suppression technology allows biomolecules to be investigated with diverse structural biology methods. In their article, Tyagi and Lemke discuss these approaches and speculate on the design of improved host organisms for ‘integrative structural biology research’. Our volume concludes with two contributions that resolve particular bottlenecks in the protein structure determination pipeline. The contribution by Crepin and co-workers introduces the concept of polyproteins in contemporary structural biology. Polyproteins are widespread in nature. They represent long polypeptide chains in which individual smaller proteins with different biological function are covalently linked together. Highly specific proteases then tailor the polyprotein into its constituent proteins. Many viruses use polyproteins as a means of organizing their proteome. The concept of polyproteins has now been exploited successfully to produce hitherto inaccessible recombinant protein complexes. For instance, by means of a self-processing synthetic polyprotein, the influenza polymerase, a high-value drug target that had remained elusive for decades, has been produced, and its high-resolution structure determined. In the contribution by Desmyter and co-workers, a further, often imposing, bottleneck in high-resolution protein structure determination is addressed: The requirement to form stable three-dimensional crystal lattices that diffract incident X-ray radiation to high resolution. Nanobodies have proven to be uniquely useful as crystallization chaperones, to coax challenging targets into suitable crystal lattices. Desmyter and co-workers review the generation of nanobodies by immunization, and highlight the application of this powerful technology to the crystallography of important protein specimens including G protein-coupled receptors (GPCRs). Recombinant protein production has come a long way since Peter Lobban's hypothesis in the late 1960s, with recombinant proteins now a dominant force in structural biology. The contributions in this volume showcase an impressive array of inventive approaches that are being developed and implemented, ever increasing the scope of recombinant technology to facilitate the determination of elusive protein structures. Powerful new methods from synthetic biology are further accelerating progress. Structure determination is now reaching into the living cell with the ultimate goal of observing functional molecular architectures in action in their native physiological environment. We anticipate that even the most challenging protein assemblies will be tackled by recombinant technology in the near future.

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Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton and membrane organization, cell division and host/pathogen interactions. The precise function of many family members remains elusive. We show that SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3 membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP interactions also influence the membrane interaction of ESCRT (endosomal-sorting complex required for transport)-I, which selects ubiquitinated cargos for degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7 function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane domains, they uncover an unsuspected coordination of these sorting machineries during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3 interactor regulating ESCRT-I sorting activity and whose mutations are linked with Charcot-Marie-Tooth neuropathies.

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Gram-positive bacteria possess a permeable cell wall that usually does not restrict the penetration of antimicrobials. However, resistance due to restricted penetration can occur, as illustrated by vancomycin-intermediate resistant Staphylococcus aureus strains (VISA) which produce a markedly thickened cell wall. Alterations in these strains include increased amounts of nonamidated glutamine residues in the peptidoglycan and it is suggested that the resistance mechanism involves 'affinity trapping' of vancomycin in the thickened cell wall. VISA strains have reduced doubling times, lower sensitivity to lysostaphin and reduced autolytic activity, which may reflect changes in the D-alanyl ester content of the wall and membrane teichoic acids. Mycobacterial cell walls have a high lipid content, which is assumed to act as a major barrier to the penetration of antimicrobial agents. Relatively hydrophobic antibiotics such as rifampicin and fluoroquinolones may be able to cross the cell wall by diffusion through the hydrophobic bilayer composed of long chain length mycolic acids and glycolipids. Hydrophilic antibiotics and nutrients cannot diffuse across this layer and are thought to use porin channels which have been reported in many species of mycobacteria. The occurrence of porins in a lipid bilayer supports the view that the mycobacterial wall has an outer membrane analogous to that of gram-negative bacteria. However, mycobacterial porins are much less abundant than in the gram-negative outer membrane and allow only low rates of uptake for small hydrophilic nutrients and antibiotics.

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Agriculture accounts for ~70% of freshwater usage worldwide. Seawater desalination alone cannot meet the growing needs for irrigation and food production, particularly in hot, desert environments. Greenhouse cultivation of high-value crops uses just a fraction of freshwater per unit of food produced when compared with open field cultivation. However, desert greenhouse producers face three main challenges: freshwater supply, plant nutrient supply, and cooling of the greenhouse. The common practice of evaporative cooling for greenhouses consumes large amounts of fresh water. In Saudi Arabia, the most common greenhouse cooling schemes are fresh water-based evaporative cooling, often using fossil groundwater or energy-intensive desalinated water, and traditional refrigeration-based direct expansion cooling, largely powered by the burning of fossil fuels. The coastal deserts have ambient conditions that are seasonally too humid to support adequate evaporative cooling, necessitating additional energy consumption in the dehumidification process of refrigeration-based cooling. This project evaluates the use of a combined-system liquid desiccant dehumidifier and membrane distillation unit that can meet the dual needs of cooling and freshwater supply for a greenhouse in a hot and humid environment.

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Political corruption in the Caribbean Basin retards state economic growth and development, undermines government legitimacy, and threatens state security. In spite of recent anti-corruption efforts of intergovernmental and nongovernmental organizations (IGO/NGOs), Caribbean political corruption problems appear to be worsening in the post-Cold War period. This dissertation discovers why IGO/NGO efforts to arrest corruption are failing by investigating the domestic and international causes of political corruption in the Caribbean. The dissertation's theoretical framework centers on an interdisciplinary model of the causes of political corruption built within the rule-oriented constructivist approach to social science. The model first employs a rational choice analysis that broadly explains the varying levels of political corruption found across the region. The constructivist theory of social rules is then used to develop the structural mechanisms that further explain the region's levels of political corruption. The dissertation advances its theory of the causes of political corruption through qualitative disciplined-configurative case studies of political corruption in Jamaica and Costa Rica. The dissertation finds that IGO/NGO sponsored anti-corruption programs are failing because they employ only technical measures (issuing anti-corruption laws and regulations, providing transparency in accounting procedures, improving freedom of the press, establishing electoral reforms, etc.). While these IGO/NGO technical measures are necessary, they are not sufficient to arrest the Caribbean's political corruption problems. This dissertation concludes that to be successful, IGO/NGO anti-corruption programs must also include social measures, e.g., building civil societies and modernizing political cultures, for there to be any hope of lowering political corruption levels and improving Caribbean social conditions. The dissertation also highlights the key role of Caribbean governing elite in constructing the political and economic structures that cause their states' political corruption problems. ^

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Federal transportation legislation in effect since 1991 was examined to determine outcomes in two areas: (1) The effect of organizational and fiscal structures on the implementation of multimodal transportation infrastructure, and (2) The effect of multimodal transportation infrastructure on sustainability. Triangulation of methods was employed through qualitative analysis (including key informant interviews, focus groups and case studies), as well as quantitative analysis (including one-sample t-tests, regression analysis and factor analysis). ^ Four hypotheses were directly tested: (1) Regions with consolidated government structures will build more multimodal transportation miles: The results of the qualitative analysis do not lend support while the results of the quantitative findings support this hypothesis, possibly due to differences in the definitions of agencies/jurisdictions between the two methods. (2) Regions in which more locally dedicated or flexed funding is applied to the transportation system will build a greater number of multimodal transportation miles: Both quantitative and qualitative research clearly support this hypothesis. (3) Cooperation and coordination, or, conversely, competition will determine the number of multimodal transportation miles: Participants tended to agree that cooperation, coordination and leadership are imperative to achieving transportation goals and objectives, including targeted multimodal miles, but also stressed the importance of political and financial elements in determining what ultimately will be funded and implemented. (4) The modal outcomes of transportation systems will affect the overall health of a region in terms of sustainability/quality of life indicators: Both the qualitative and the quantitative analyses provide evidence that they do. ^ This study finds that federal legislation has had an effect on the modal outcomes of transportation infrastructure and that there are links between these modal outcomes and the sustainability of a region. It is recommended that agencies further consider consolidation and strengthen cooperation efforts and that fiscal regulations are modified to reflect the problems cited in qualitative analysis. Limitations of this legislation especially include the inability to measure sustainability; several measures are recommended. ^