Understanding the role of domain-domain linkers in the spatial orientation of domains in multi-domain proteins

Inter-domain linkers (IDLs)' bridge flanking domains and support inter-domain communication in multi-domain proteins. Their sequence and conformational preferences enable them to carry out varied functions. They also provide sufficient flexibility to facilitate domain motions and, in conjunction with the interacting interfaces, they also regulate the inter-domain geometry (IDG). In spite of the basic intuitive understanding of the inter-domain orientations with respect to linker conformations and interfaces, we still do not entirely understand the precise relationship among the three. We show that IDG is evolutionarily well conserved and is constrained by the domain-domain interface interactions. The IDLs modulate the interactions by varying their lengths, conformations and local structure, thereby affecting the overall IDG. Results of our analysis provide guidelines in modelling of multi-domain proteins from the tertiary structures of constituent domain components.

Anthropogenic aerosol fraction over the Indian region: model simulations versus multi-satellite data analysis

Anthropogenic aerosols play a crucial role in our environment, climate, and health. Assessment of spatial and temporal variation in anthropogenic aerosols is essential to determine their impact. Aerosols are of natural and anthropogenic origin and together constitute a composite aerosol system. Information about either component needs elimination of the other from the composite aerosol system. In the present work we estimated the anthropogenic aerosol fraction (AF) over the Indian region following two different approaches and inter-compared the estimates. We espouse multi-satellite data analysis and model simulations (using the CHIMERE Chemical transport model) to derive natural aerosol distribution, which was subsequently used to estimate AF over the Indian subcontinent. These two approaches are significantly different from each other. Natural aerosol satellite-derived information was extracted in terms of optical depth while model simulations yielded mass concentration. Anthropogenic aerosol fraction distribution was studied over two periods in 2008: premonsoon (March-May) and winter (November-February) in regard to the known distinct seasonality in aerosol loading and type over the Indian region. Although both techniques have derived the same property, considerable differences were noted in temporal and spatial distribution. Satellite retrieval of AF showed maximum values during the pre-monsoon and summer months while lowest values were observed in winter. On the other hand, model simulations showed the highest concentration of AF in winter and the lowest during pre-monsoon and summer months. Both techniques provided an annual average AF of comparable magnitude (similar to 0.43 +/- 0.06 from the satellite and similar to 0.48 +/- 0.19 from the model). For winter months the model-estimated AF was similar to 0.62 +/- 0.09, significantly higher than that (0.39 +/- 0.05) estimated from the satellite, while during pre-monsoon months satellite-estimated AF was similar to 0.46 +/- 0.06 and the model simulation estimation similar to 0.53 +/- 0.14. Preliminary results from this work indicate that model-simulated results are nearer to the actual variation as compared to satellite estimation in view of general seasonal variation in aerosol concentrations.

Shallow Water Model On Cubed-Sphere By Multi-Moment Finite Volume Method

A global numerical model for shallow water flows on the cubed-sphere grid is proposed in this paper. The model is constructed by using the constrained interpolation profile/multi-moment finite volume method (CIP/MM FVM). Two kinds of moments, i.e. the point value (PV) and the volume-integrated average (VIA) are defined and independently updated in the present model by different numerical formulations. The Lax-Friedrichs upwind splitting is used to update the PV moment in terms of a derivative Riemann problem, and a finite volume formulation derived by integrating the governing equations over each mesh element is used to predict the VIA moment. The cubed-sphere grid is applied to get around the polar singularity and to obtain uniform grid spacing for a spherical geometry. Highly localized reconstruction in CIP/MM FVM is well suited for the cubed-sphere grid, especially in dealing with the discontinuity in the coordinates between different patches. The mass conservation is completely achieved over the whole globe. The numerical model has been verified by Williamson's standard test set for shallow water equation model on sphere. The results reveal that the present model is competitive to most existing ones. (C) 2008 Elsevier Inc. All rights reserved.

Multi-species and multi-interest management: An ecosystem approach to market squid (Loligo opalescens) harvest in California

Market squid (Loligo opalescens) plays a vital role in the California ecosystem and serves as a major link in the food chain as both a predator and prey species. For over a century, market squid has also been harvested off the California coast from Monterey to San Pedro. Expanding global markets, coupled with a decline in squid product from other parts of the world, in recent years has fueled rapid expansion of the virtually unregulated California fishery. Lack of regulatory management, in combination with dramatic increases in fishing effort and landings, has raised numerous concerns from the scientific, fishing, and regulatory communities. In an effort to address these concerns, the National Oceanic and Atmospheric Administration’s (NOAA) Channel Islands National Marine Sanctuary (CINMS) hosted a panel discussion at the October 1997 California Cooperative Oceanic and Fisheries Investigations (CalCOFI) Conference; it focused on ecosystem management implications for the burgeoning market squid fishery. Both panel and audience members addressed issues such as: the direct and indirect effects of commercial harvesting upon squid biomass; the effects of harvest and the role of squid in the broader marine community; the effects of environmental variation on squid population dynamics; the sustainability of the fishery from the point of view of both scientists and the fishers themselves; and the conservation management options for what is currently an open access and unregulated fishery. Herein are the key points of the ecosystem management panel discussion in the form of a preface, an executive summary, and transcript. (PDF contains 33 pages.)

Multi-drug resistance profiles and the genetic features of Acinetobacter baumannii isolates from Bolivia

Introduction: Acinetobacter baumannii is opportunistic in debilitated hospitalised patients. Because information from some South American countries was previously lacking, this study examined the emergence of multi-resistant A. baumannii in three hospitals in Cochabamba, Bolivia, from 2008 to 2009. Methodology: Multiplex PCR was used to identify the main resistance genes in 15 multi-resistant A. baumannii isolates. RT-PCR was used to measure gene expression. The genetic environment of these genes was also analysed by PCR amplification and sequencing. Minimum inhibitory concentrations were determined for key antibiotics and some were determined in the presence of an efflux pump inhibitor, 1-(1-napthylmethyl) piperazine. Results: Fourteen strains were found to be multi-resistant. Each strain was found to have the bla(OXA-58) gene with the ISAba3-like element upstream, responsible for over-expression of the latter and subsequent carbapenem resistance. Similarly, ISAba1, upstream of the bla(ADC) gene caused over-expression of the latter and cephalosporin resistance; mutations in the gyrA(Ser83 to Leu) and parC (Ser-80 to Phe) genes were commensurate with fluoroquinolone resistance. In addition, the adeA, adeB efflux genes were over-expressed. All 15 isolates were positive for at least two aminoglycoside resistance genes. Conclusion: This is one of the first reports analyzing the multi-drug resistance profile of A. baumannii strains isolated in Bolivia and shows that the over-expression of thebla(OXA-58), bla(ADC) and efflux genes together with aminoglycoside modifying enzymes and mutations in DNA topoisomerases are responsible for the multi-resistance of the bacteria and the subsequent difficulty in treating infections caused by them.

Coupled effects of mechanics, geometry, and chemistry on bio-membrane behavior

Lipid bilayer membranes are models for cell membranes--the structure that helps regulate cell function. Cell membranes are heterogeneous, and the coupling between composition and shape gives rise to complex behaviors that are important to regulation. This thesis seeks to systematically build and analyze complete models to understand the behavior of multi-component membranes.

We propose a model and use it to derive the equilibrium and stability conditions for a general class of closed multi-component biological membranes. Our analysis shows that the critical modes of these membranes have high frequencies, unlike single-component vesicles, and their stability depends on system size, unlike in systems undergoing spinodal decomposition in flat space. An important implication is that small perturbations may nucleate localized but very large deformations. We compare these results with experimental observations.

We also study open membranes to gain insight into long tubular membranes that arise for example in nerve cells. We derive a complete system of equations for open membranes by using the principle of virtual work. Our linear stability analysis predicts that the tubular membranes tend to have coiling shapes if the tension is small, cylindrical shapes if the tension is moderate, and beading shapes if the tension is large. This is consistent with experimental observations reported in the literature in nerve fibers. Further, we provide numerical solutions to the fully nonlinear equilibrium equations in some problems, and show that the observed mode shapes are consistent with those suggested by linear stability. Our work also proves that beadings of nerve fibers can appear purely as a mechanical response of the membrane.

A multi-scale approach to shaping carbon nanotube structures for hollow microneedles

The concept of a carbon nanotube microneedle array is explored in this thesis from multiple perspectives including microneedle fabrication, physical aspects of transdermal delivery, and in vivo transdermal drug delivery experiments. Starting with standard techniques in carbon nanotube (CNT) fabrication, including catalyst patterning and chemical vapor deposition, vertically-aligned carbon nanotubes are utilized as a scaffold to define the shape of the hollow microneedle. Passive, scalable techniques based on capillary action and unique photolithographic methods are utilized to produce a CNT-polymer composite microneedle. Specific examples of CNT-polyimide and CNT-epoxy microneedles are investigated. Further analysis of the transport properties of polymer resins reveals general requirements for applying arbitrary polymers to the fabrication process.

The bottom-up fabrication approach embodied by vertically-aligned carbon nanotubes allows for more direct construction of complex high-aspect ratio features than standard top-down fabrication approaches, making microneedles an ideal application for CNTs. However, current vertically-aligned CNT fabrication techniques only allow for the production of extruded geometries with a constant cross-sectional area, such as cylinders. To rectify this limitation, isotropic oxygen etching is introduced as a novel fabrication technique to create true 3D CNT geometry. Oxygen etching is utilized to create a conical geometry from a cylindrical CNT structure as well as create complex shape transformations in other CNT geometries.

CNT-polymer composite microneedles are anchored onto a common polymer base less than 50 µm thick, which allows for the microneedles to be incorporated into multiple drug delivery platforms, including modified hypodermic syringes and silicone skin patches. Cylindrical microneedles are fabricated with 100 µm outer diameter and height of 200-250 µm with a central cavity, or lumen, diameter of 30 µm to facilitate liquid drug flow. In vitro delivery experiments in swine skin demonstrate the ability of the microneedles to successfully penetrate the skin and deliver aqueous solutions.

An in vivo study was performed to assess the ability of the CNT-polymer microneedles to deliver drugs transdermally. CNT-polymer microneedles are attached to a hand actuated silicone skin patch that holds a liquid reservoir of drugs. Fentanyl, a potent analgesic, was administered to New Zealand White Rabbits through 3 routes of delivery: topical patch, CNT-polymer microneedles, and subcutaneous hypodermic injection. Results demonstrate that the CNT-polymer microneedles have a similar onset of action as the topical patch. CNT-polymer microneedles were also vetted as a painless delivery approach compared to hypodermic injection. Comparative analysis with contemporary microneedle designs demonstrates that the delivery achieved through CNT-polymer microneedles is akin to current hollow microneedle architectures. The inherent advantage of applying a bottom-up fabrication approach alongside similar delivery performance to contemporary microneedle designs demonstrates that the CNT-polymer composite microneedle is a viable architecture in the emerging field of painless transdermal delivery.

Multi-channel 2-D pattern transfer model based on imaging optics for submarine laser uplink communication

An optical communication scheme of 2-D pattern transfer based on imaging optics for submarine laser uplink communication (SLUC) is suggested. Unlike the methods aiming at avoiding neighboring crosstalk used in traditional multi-channel optical beam transferring, we make full use of the overlapping of each spreading beam other than controlling divergence effect of each beam to avoid interference noise. The apparent parameters have been introduced to simplify theoretical analysis of optical pattern transfer problem involving underwater condition, with the help of which the complex beam propagation inside two kinds of mediums can be easily reduced to brief beam transfer only inside air medium. In this paper, optical transmission path and receiver terminal optics geometry have been described in detail. The link range equation and system uplink performance analysis have also been given. At last, results of a proof-of-concept experiment indicate good feasibility of the proposed SLUC model. © 2007 Elsevier GmbH. All rights reserved.

Otimização multi-objetivo de projetos de redes de transporte dutoviário de gás natural

Dutos de transmissão são tubulações especialmente desenvolvidas para transportar produtos diversos a longas distâncias e representam a forma mais segura e econômica de transporte para grandes quantidades de fluidos. Os dutos de gás natural, denominados gasodutos, são usados para transportar o gás desde os campos de produção até os centros consumidores, onde o gás é inserido em redes de distribuição para entrega aos consumidores finais. Os gasodutos de transporte apresentam diversas características de monopólio natural, que são o principal argumento econômico para sua regulação. A regulação visa garantir que esta atividade seja explorada de maneira eficiente, refletindo em tarifas de transporte justas para os consumidores e que proporcionem o retorno adequado aos investidores, levando-se em consideração a quantidade de gás transportado. Neste contexto, o presente trabalho tem como objetivo propor metodologias de otimização multi-objetivo de projetos de redes de gasodutos de transporte, envolvendo métodos a posteriori. O problema de otimização formulado contempla restrições associadas ao escoamento do gás e o comportamento das estações de compressão. A solução do problema fornece um conjunto de projetos ótimos de redes de transporte em função da maximização da quantidade de gás natural transportado e da minimização da tarifa associada a esse serviço. A ferramenta foi aplicada a diversos estudos de caso com configurações típicas da indústria de transporte de gás natural. Os resultados mostraram que as metodologias propostas são capazes de fornecer subsídios que permitem ao tomador de decisão do ponto de vista regulatório realizar uma análise de trade-off entre a quantidade de gás transportado e a tarifa, buscando assim atender ao interesse da sociedade em relação à exploração do serviço de transporte

Generation of conjugate meshes for complex geometries for coupled multi-physics simulations

Over recent years we have developed and published research aimed at producing a meshing, geometry editing and simulation system capable of handling large scale, real world applications and implemented in an end-to-end parallel, scalable manner. The particular focus of this paper is the extension of this meshing system to include conjugate meshes for multi-physics simulations. Two contrasting applications are presented: export of a body-conformal mesh to drive a commercial, third-party simulation system; and direct use of the cut-Cartesian octree mesh with a single, integrated, close-coupled multi-physics simulation system. Copyright © 2010 by W.N.Dawes.

Supply network integration in multi-organisational network systems

This paper explores supply network integration in complex product service systems involving close collaboration between primes. Four case study networks are studied (aerospace, naval, power and telecoms), each involving equipment manufacture and service provision. Factors that support network integration, identified from the literature and refined in the in-depth pilot case, were used to explore which processes support integration of the extended enterprise. Results suggests that a select set of processes support integration of the extended enterprise and that the absence of a shared view on these critical enabling processes results from contextual complexity of the network rather than from competing commercial interests. Copyright © 2011 Inderscience Enterprises Ltd.

Multi-objective aerodynamic design optimisation for axial compressors

This paper considers the aerodynamic design optimisation of turbomachinery blades from a multi-objective perspective. The aim is to improve the performance of a specific stage and eventually of the whole engine. The integrated system developed for this purpose is described. It combines an existing geometry parameterisation scheme, a well-established CFD package and a novel multi-objective variant of the Tabu Search optimisation algorithm. Its performance is illustrated through a case study in which the flow characteristics most important to the overall performance of turbomachinery blades are optimised.

An advanced multi-configuration stator well cooling test facility

Optimisation of cooling systems within gas turbine engines is of great interest to engine manufacturers seeking gains in performance, efficiency and component life. The effectiveness of coolant delivery is governed by complex flows within the stator wells and the interaction of main annulus and cooling air in the vicinity of the rim seals. This paper reports the development of a test facility which allows the interaction of cooling air and main gas paths to be measured at conditions representative of those found in modern gas turbine engines. The test facility features a two stage turbine with an overall pressure ratio of approximately 2.6:1. Hot air is supplied to the main annulus using a Rolls-Royce Dart compressor driven by an aero-derivative engine plant. Cooling air can be delivered to the stator wells at multiple locations and at a range of flow rates which cover bulk ingestion through to bulk egress. The facility has been designed with adaptable geometry to enable rapid changes of cooling air path configuration. The coolant delivery system allows swift and accurate changes to the flow settings such that thermal transients may be performed. Particular attention has been focused on obtaining high accuracy data, using a radio telemetry system, as well as thorough through-calibration practices. Temperature measurements can now be made on both rotating and stationary discs with a long term uncertainty in the region of 0.3 K. A gas concentration measurement system has also been developed to obtain direct measurement of re-ingestion and rim seal exchange flows. High resolution displacement sensors have been installed in order to measure hot running geometry. This paper documents the commissioning of a test facility which is unique in terms of rapid configuration changes, non-dimensional engine matching and the instrumentation density and resolution. Example data for each of the measurement systems is presented. This includes the effect of coolant flow rate on the metal temperatures within the upstream cavity of the turbine stator well, the axial displacement of the rotor assembly during a commissioning test, and the effect of coolant flow rate on mixing in the downstream cavity of the stator well. Copyright © 2010 by ASME.

Multi-objective optimization for multiphase orbital rendezvous missions

A multi-objective optimization approach was proposed for multiphase orbital rendezvous missions and validated by application to a representative numerical problem. By comparing the Pareto fronts obtained using the proposed method, the relationships between the three objectives considered are revealed, and the influences of other mission parameters, such as the sensors' field of view, can also be analyzed effectively. For multiphase orbital rendezvous missions, the tradeoff relationships between the total velocity increment and the trajectory robustness index as well as between the total velocity increment and the time of flight are obvious and clear. However, the tradeoff relationship between the time of flight and the trajectory robustness index is weak, especially for the four- and five-phase missions examined. The proposed approach could be used to reorganize a stable rendezvous profile for an engineering rendezvous mission, when there is a failure that prevents the completion of the nominal mission.

Differential geometry and design coupling in MDO

The notion of coupling within a design, particularly within the context of Multidisciplinary Design Optimization (MDO), is much used but ill-defined. There are many different ways of measuring design coupling, but these measures vary in both their conceptions of what design coupling is and how such coupling may be calculated. Within the differential geometry framework which we have previously developed for MDO systems, we put forth our own design coupling metric for consideration. Our metric is not commensurate with similar types of coupling metrics, but we show that it both provides a helpful geo- metric interpretation of coupling (and uncoupledness in particular) and exhibits greater generality and potential for analysis than those similar metrics. Furthermore, we discuss how the metric might be profitably extended to time-varying problems and show how the metric's measure of coupling can be applied to multi-objective optimization problems (in unconstrained optimization and in MDO). © 2013 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.