775 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

    Fine structure in the off-resonance conductance of small Coulomb blockade systems

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    We show how a fine, multiple-peak structure can arise in the off-resonance, zero-bias conductance of Coulomb blockade systems. In order to understand how this effect comes about one must abandon the orthodox, mean-field understanding of the Coulomb blockade phenomenon and consider quantum fluctuations in the occupation of the single-particle electronic levels. We illustrate such an effect with a spinless Anderson-like model for multi-level systems and an equation-of-motion method for calculating Green's functions that combines two simple decoupling schemes.Comment: 5 pages, 3 figures, postscript file also available at http://www.pa.uky.edu/~palacios/papers/eom.ps One figure added. Discussion of results extende

    G-Quadruplex Dynamics Contribute To Regulation Of Mitochondrial Gene Expression

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    Single-stranded DNA or RNA sequences rich in guanine (G) can adopt non-canonical structures known as G-quadruplexes (G4). Mitochondrial DNA (mtDNA) sequences that are predicted to form G4 are enriched on the heavy-strand and have been associated with formation of deletion breakpoints. Increasing evidence supports the ability of mtDNA to form G4 in cancer cells; however, the functional roles of G4 structures in regulating mitochondrial nucleic acid homeostasis in non-cancerous cells remain unclear. Here, we demonstrate by live cell imaging that the G4-ligand RHPS4 localizes primarily to mitochondria at low doses. We find that low doses of RHPS4 do not induce a nuclear DNA damage response but do cause an acute inhibition of mitochondrial transcript elongation, leading to respiratory complex depletion. We also observe that RHPS4 interferes with mtDNA levels or synthesis both in cells and isolated mitochondria. Importantly, a mtDNA variant that increases G4 stability and anti-parallel G4-forming character shows a stronger respiratory defect in response to RHPS4, supporting the conclusion that mitochondrial sensitivity to RHPS4 is G4-mediated. Taken together, our results indicate a direct role for G4 perturbation in mitochondrial genome replication, transcription processivity, and respiratory function in normal cells

    In vivo measurements of muscle specific tension in adults and children

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    This article is available open access through the publisher’s website at the link below. Copyright @ 2009 The Authors.To better understand the effects of pubertal maturation on the contractile properties of skeletal muscle in vivo, the present study investigated whether there are any differences in the specific tension of the quadriceps muscle in 20 adults and 20 prepubertal children of both sexes. Specific tension was calculated as the ratio between the quadriceps tendon force and the sum of the physiological cross-sectional area (PCSA) multiplied by the cosine of the angle of pennation of each head within the quadriceps muscle. The maximal quadriceps tendon force was calculated from the knee extension maximal voluntary contraction (MVC) by accounting for EMG-based estimates of antagonist co-activation, incomplete quadriceps activation using the interpolation twitch technique and magnetic resonance imaging (MRI)-based measurements of the patellar tendon moment arm. The PCSA was calculated as the muscle volume, measured from MRI scans, divided by optimal fascicle length, measured from ultrasound images during MVC at the estimated angle of peak quadriceps muscle force. It was found that the quadriceps tendon force and PCSA of men (11.4 kN, 214 cm2) were significantly greater than those of the women (8.7 kN, 152 cm2; P 0.05) between groups: men, 55 ± 11 N cm−2; women, 57.3 ± 13 N cm−2; boys, 54 ± 14 N cm−2; and girls, 59.8 ± 15 N cm−2. These findings indicate that the increased muscle strength with maturation is not due to an increase in the specific tension of muscle; instead, it can be attributed to increases in muscle size, moment arm length and voluntary activation level

    The scientific foundations and associated injury risks of early soccer specialisation

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    Early specialisation is characterised by formal participation in a single sport at the exclusion of others. Limited data are available to support this approach in the development of soccer players who attain elite status later in life. Of growing concern is the associated increased risk of injury and suggestions that single sport specialisation is a risk factor independent of age, growth, biological maturation and training volumes In the United Kingdom, elite soccer organisations have recently adopted an early sport specialisation approach following the introduction of the Elite Player Performance Plan. A key tenet of this programme is increased opportunities for training through a marked rise in the specified on-pitch hours per week. The accumulation of high training hours may be less of a relevant marker for success, and the impact of such a significant increase in training volume for young athletes who are experiencing a range of growth and maturational processes is currently unknown. This critical commentary includes an evidence based discussion of the effectiveness of early sport specialisation and the potential injury risks associated with such programmes placing a specific focus on elite male youth soccer players. Available data indicate that modifications to the existing EPPP framework could enhance player development and reduce injury risk. Proposed alterations include reduced volume of soccer specific training at key stages of growth and maturation and guidelines for the provision of a greater variety of physical activities that are integrated within other programme components

    Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1

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    Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β–induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment

    Intracellular survival of Streptococcus pneumoniae in human alveolar macrophages is augmented with HIV infection

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    People Living with HIV (PLHIV) are at an increased risk of pneumococcal pneumonia than HIV-uninfected adults, but the reasons for this are still not well understood. We investigated whether alveolar macrophages (AM) mediated control of pneumococcal infection is impaired in PLHIV compared to HIV-uninfected adults. We assessed anti-bactericidal activity against Streptococcus pneumoniae of primary human AM obtained from PLHIV and HIV-uninfected adults. We found that pneumococcus survived intracellularly in AMs at least 24 hours post ex vivo infection, and this was more frequent in PLHIV than HIV-uninfected adults. Corroborating these findings, in vivo evidence showed that PLHIV had a higher propensity for harboring S. pneumoniae within their AMs than HIV-uninfected adults. Moreover, bacterial intracellular survival in AMs was associated with extracellular propagation of pneumococcal infection. Our data suggest that failure of AMs to eliminate S. pneumoniae intracellularly could contribute to the increased risk of pneumococcal pneumonia in PLHIV
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