106 research outputs found

    Designing Efficient Taxi Pickup Operations at Airports

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    This paper provides a practical procedure for designing efficient taxi pickup operations at airports. How to do this effectively is an open question. Solutions are not available, and practices vary. They reflect different approaches to and lack of research on the subject. The solutions are often unsatisfactory. At many airports, passengers routinely suffer long waits outdoors, exposed to the elements, after a tiring journey. Such disagreeable experiences are avoidable. Designing efficient taxi pickup operations at airports is problematic. The peculiarities of the process preclude easy solutions. First, the process involves queuing, so system performance is a nonlinear function of the loads. Second, it features unstable transient situations, since travelers typically arrive in bulk over short periods. Third, traffic is significantly differentiated and consists of a wide variety of groups implying different service characteristics. Standard results from queuing theory thus do not have a useful application to this problem. The design process uses simulation that is based on detailed observation of local practices. It involves four steps: (a) detailed local measurements of the arrival of both travelers and taxis, and the service rates provided by taxis in different queuing positions; (b) creation and validation of a simulation model sufficiently detailed to account for these realities; (c) exploration of design alternatives to estimate the characteristics of the service they would provide; and (d) selection of a preferred design that properly balances efforts to minimize average and extreme wait times. The paper demonstrates the procedure through application to Lisbon International Airport, Portugal.SIMUL8 Corporatio

    Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy

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    Tropomyosin (Tm) is a key component of the actin cytoskeleton and >40 isoforms have been described in mammals. In addition to the isoforms in the sarcomere, we now report the existence of two nonsarcomeric (NS) isoforms in skeletal muscle. These isoforms are excluded from the thin filament of the sarcomere and are localized to a novel Z-line adjacent structure. Immunostained cross sections indicate that one Tm defines a Z-line adjacent structure common to all myofibers, whereas the second Tm defines a spatially distinct structure unique to muscles that undergo chronic or repetitive contractions. When a Tm (Tm3) that is normally absent from muscle was expressed in mice it became associated with the Z-line adjacent structure. These mice display a muscular dystrophy and ragged-red fiber phenotype, suggestive of disruption of the membrane-associated cytoskeletal network. Our findings raise the possibility that mutations in these tropomyosin and these structures may underpin these types of myopathies

    Prevention and early detection of prostate cancer

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    This Review was sponsored and funded by the International Society of Cancer Prevention (ISCaP), the European Association of Urology (EAU), the National Cancer Institute, USA (NCI) (grant number 1R13CA171707-01), Prostate Cancer UK, Cancer Research UK (CRUK) (grant number C569/A16477), and the Association for International Cancer Research (AICR

    A State of the Art on Railway Simulation Modelling Software Packages and Their Application to Designing Baggage Transfer Services

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    There is a new baggage transfer service suggested in Newcastle Central Station. In order to prove that this service is feasible, a simulation model can be developed to test the concept and operating pattern behind. For the purposes of this paper, we intend to organize a literature review on simulation modelling software packages employed to study service design. Specifically, this paper has compared five different simulation software packages used by the railway industry to study service-related challenges. As a result, it is suggested that SIMUL8, a macroscopic discrete event-based software package, should be used among the five compared ones because of its simplicity and the ability to give practical results for the design and performance of such a baggage transfer system

    Actin Nemaline Myopathy Mouse Reproduces Disease, Suggests Other Actin Disease Phenotypes and Provides Cautionary Note on Muscle Transgene Expression

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    Mutations in the skeletal muscle α-actin gene (ACTA1) cause congenital myopathies including nemaline myopathy, actin aggregate myopathy and rod-core disease. The majority of patients with ACTA1 mutations have severe hypotonia and do not survive beyond the age of one. A transgenic mouse model was generated expressing an autosomal dominant mutant (D286G) of ACTA1 (identified in a severe nemaline myopathy patient) fused with EGFP. Nemaline bodies were observed in multiple skeletal muscles, with serial sections showing these correlated to aggregates of the mutant skeletal muscle α-actin-EGFP. Isolated extensor digitorum longus and soleus muscles were significantly weaker than wild-type (WT) muscle at 4 weeks of age, coinciding with the peak in structural lesions. These 4 week-old mice were ∼30% less active on voluntary running wheels than WT mice. The α-actin-EGFP protein clearly demonstrated that the transgene was expressed equally in all myosin heavy chain (MHC) fibre types during the early postnatal period, but subsequently became largely confined to MHCIIB fibres. Ringbinden fibres, internal nuclei and myofibrillar myopathy pathologies, not typical features in nemaline myopathy or patients with ACTA1 mutations, were frequently observed. Ringbinden were found in fast fibre predominant muscles of adult mice and were exclusively MHCIIB-positive fibres. Thus, this mouse model presents a reliable model for the investigation of the pathobiology of nemaline body formation and muscle weakness and for evaluation of potential therapeutic interventions. The occurrence of core-like regions, internal nuclei and ringbinden will allow analysis of the mechanisms underlying these lesions. The occurrence of ringbinden and features of myofibrillar myopathy in this mouse model of ACTA1 disease suggests that patients with these pathologies and no genetic explanation should be screened for ACTA1 mutations

    Concepts and practice of multidimensional high-performance liquid chromatography

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    High-performance liquid chromatography (HPLC) is a long established method used for the separation, identification, and determination of chemical components in complex mixtures [1]. This analytical tool is employed for the qualitative identification and quantitative determination of separated species [1, 2] and finds widespread application in almost all areas of science. Many different modes of liquid chromatography exist that depend on the type of liquid and the type of stationary phase. For example, the technique referred to as normal phase liquid chromatography (NPLC) employs a polar stationary phase and a nonpolar mobile phase. The reverse of this process, referred to as reversed-phase liquid chromatography (RPLC), utilizes a nonpolar stationary phase and a polar mobile phase. In both these techniques, the stationary phase is usually a chemically modified solid support with either a polar or nonpolar ligand, depending on the desired mode of separation. Ion exchange liquid chromatography is a technique for separating ionic species where the solid support is chemically modified using an ionic ligand. Separation of charged species depends on the pH and electrolytic strength of the mobile phase. Ion exclusion and ion-paired chromatographies are two other techniques employed for the separation of ionic substances. Size-exclusion chromatography (SEC) separates species according to their molecular size. Molecules traverse a porous stationary phase in a mobile-phase environment that is unfavorable for enthalpic interactions. The molecules are consequently separated according to their entropic exclusion from within the porous network. This technique is also referred to as gel permeation chromatography (GPC). Affinity chromatography is a technique with widespread use in the biosciences. In this technique, the stationary phase is modified with a solute receptor targeted for the retention and hence isolation of a specific solute. Chiral chromatography is employed for the separation of enantiomers. The stationary phase is modified with chiral ligands that preferentially retain one enantiomer; the technique is spatially selective. Chiral mobile phases can also be employed to exploit the "handedness" of the target molecules. These illustrations of the different modes of separation are by no means comprehensive but they do show the vast number of liquid chromatographic processes at the disposal of the chromatographer. In fact, too many different stationary phases exist to list here but a scan through any supplies catalogue will Concepts and Practice of High-Performance Liquid Chromatography 179 illustrate the vast choices available to the chromatographer. Even then, there are many specialty stationary phases that are not commercially available. As a consequence, by appropriate selection of the most suitable techniques, there is virtually no sample - regardless of the complexity - that cannot be reduced to a simpler form, allowing for analysis of the sample constituents. In this chapter, we are not concerned with mechanisms of retntion; rather, our interest lies in selectivity. The aim of this chapter is therefore to investigate processes in which selectivity can be exploited in order to gain separation. One way to increase selectivity and also increase the peak capacity of a liquid chromatographic system is to incorporate more than one separation dimension - that is, utilize the process referred to as multidimensional liquid chromatography. Here, multiple separating columns are coupled together in an automated system in such a manner as to improve the separation potential, allowing complex samples to be resolved into simpler systems. Before we begin our discussion on multidimensional chromatography, we must first discuss single-dimensional systems and understand factors that control selectivity

    HPLC-hyphenated techniques

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    Chromatography, detailed in previous chapters, is one of the most widely employed analytical methods. Chromatography serves to separate species into ideally individual constituents. However, as the technique has evolved and separation performance has increased, scientists are discovering that what they once thought may have been individually resolved isolated components from within mixtures, may now be combinations of coeluting species. ID chromatography cannot be used to identify species as retention times are not unique. This fact, together with the need to evaluate complex sample matrices, has driven the demand for techniques to be developed that are complementary. As we seek to gain more information regarding the constitution of sample matrices and subsequent quantitation, methods of analysis necessarily become more sophisticated. The increase in separation performance and analysis has followed two paths. There is currently growth in the development of multidimensional methods of analysis namely, coupled chromatographic systems. In particular, multidimensional gas chromatographic methods of analysis have been heavily investigated, but more recently there has ben growing interest in multidimensional separations in liquid chromatography. The second path has been in the development of coupled and complementary methods of analysis; that is, chromatography, which is employed for its ability to bring about separation, and other analytical methods of analysis for detection and identification of species. This has developed into what is now referred to as hyphenated methods of analysis

    Segmented flow and curtain flow chromatography : overcoming the wall effect and heterogeneous bed structures

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    The variation in mobile phase velocity as a function of the column radius has been shown to be a major limitation in the efficiency of HPLC columns. One contributing factor to the variability in the flow velocity stems from the heterogeneity in the radial packing density, leading to what has been described as the 'wall-effect'. The wall-effect generates parabolic-type elution profiles, which dilutes the sample and creates tailing bands. In this communication a new column technology is discussed that has been designed to overcome the wall effect, minimising the limitations associated with packing heterogeneity. This technology has been referred to as active flow technology and consists of two types of column designs, parallel segmented flow and curtain flow. In both these column designs sample that elutes through the column in the radial central region of the bed is separated from the flow that elutes along the wall region. Hence, the sample that elutes through the most efficiently packed region of the bed is collected to the detector. As a consequence more theoretical plates are obtained, and sensitivity is increased since the sample is not diluted by the diffuse tail. Sensitivity is enhanced further in the curtain flow design. The benefits of these new columns are discussed
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