510 research outputs found

    Toll-Managed Lanes: Benefit-Cost Analyses of Seven Projects. Year 25 Final Report

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    Toll managed lanes are expressway lanes where tolls are used--often in combination with preferred access for high occupancy vehicles and other special traffic management techniques-- to improve the highway’s capacity, speed or reliability. Such lanes, and particularly a variant called High Occupancy Toll (HOT) lanes, have become popular with transportation policymakers as a way of maintaining free-flowing traffic on existing lanes while also, in some cases, financing the construction of new lanes in congested urban areas. This study examines whether toll-managed lanes are as beneficial as they are popular. The heart of the analysis is the application of a simplified social benefit-cost analysis to seven projects. In brief, the results suggest that toll-managed lanes, while promising, are not a surefire strategy for managing congestion. Only two of the seven projects have benefit-cost ratios above 1.0 using our base case assumptions about the value of travel time saved and the discount rate, although three others approach or exceed 1.0 with more optimistic but plausible assumptions. The most successful generate not only a significant savings of around 4 to 5 minutes per trip for motorists who switch to the managed lane but also smaller per-trip savings for the large majority of motorists who continue to use the general-purpose lanes. It is important to acknowledge, however, that these calculations depend upon some uncertain assumptions about the value of travel time savings and improved reliability

    Boundaries of Semantic Distraction: Dominance and Lexicality Act at Retrieval

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    Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category-exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1) and occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech is discussed

    HLA Immunogenotype Determines Persistent Human Papillomavirus Virus Infection in HIV-Infected Patients Receiving Antiretroviral Treatment

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    A proportion of human immunodeficiency virus (HIV)–infected patients develop persistent, stigmatizing human papillomavirus (HPV)–related cutaneous and genital warts and anogenital (pre)cancer. This is the first study to investigate immunogenetic variations that might account for HPV susceptibility and the largest to date to categorize the HPV types associated with cutaneous warts in HIV-positive patients. The HLA class I and II allele distribution was analyzed in 49 antiretroviral (ART)–treated HIV-positive patients with persistent warts, 42 noninfected controls, and 46 HIV-positive controls. The allele HLA-B*44 was more frequently identified in HIV-positive patients with warts (P = .004); a susceptible haplotype (HLA-B*44, HLA-C*05; P = .001) and protective genes (HLA-DQB1*06; P = .03) may also contribute. Cutaneous wart biopsy specimens from HIV-positive patients harbored common wart types HPV27/57, the unusual wart type HPV7, and an excess of Betapapillomavirus types (P = .002), compared with wart specimens from noninfected controls. These findings suggest that HLA testing might assist in stratifying those patients in whom vaccination should be recommended

    Different types of FC γ -receptors are involved in anti-Lewis Y antibody induced effector functions in vitro

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    Stimulation of monocytes by interaction of monoclonal antibodies (mAbs) with Fc gamma receptors (FcγRs) results in the activation of various monocyte effector functions. In the present investigation we show that the anti-Lewis Y (LeY) anti-tumour mAb ABL 364 and its mouse/human IgG1 chimaera induce both antibody-dependent cellular cytotoxicity (ADCC) and the release of tumour necrosis factor α (TNF-α) during mixed culture of monocytes with LeY+SKBR5 breast cancer cells in vitro. Although anti-LeY mAb-mediated TNF-α release paralleled ADCC activity, cytokine release required a higher concentration of sensitizing mAb than the induction of cytolysis. The determination of the FcγR classes involved in the induction of the distinct effector functions showed that anti-LeY mAb-induced cytolysis was triggered by interaction between anti-LeY mAbs and FcγRI. In contrast, mAb-induced TNF-α release mainly depended on the activation of monocyte FcγRII. Neutralization of TNF-α showed no influence on monocyte ADCC activity towards SKBR5 target cells. Our data indicate an independent regulation of anti-LeY mAb induced effector functions of ADCC and TNF-α release which seemed to be triggered by activation of different types of FcγR. © 2000 Cancer Research Campaig

    Ocean stratification and low melt rates at the Ross Ice Shelf grounding zone

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    Ocean‐driven melting of ice shelves is a primary mechanism for ice loss from Antarctica. However, due to the difficulty in accessing the sub‐ice shelf ocean cavity, the relationship between ice shelf melting and ocean conditions is poorly understood, particularly near the grounding zone, where the ice transitions from grounded to floating. We present the first borehole oceanographic observations from the grounding zone of the Ross Ice Shelf, Antarctica's largest ice shelf by area. Contrary to predictions that tidal currents near grounding zones mix the water column, we found that Ross Ice Shelf waters were vertically stratified. Current velocities at middepth in the ocean cavity did not change significantly over measurement periods at two different parts of the tidal cycle. The observed stratification resulted in low melt rates near this portion of the grounding zone, inferred from phase‐sensitive radar observations. These melt rates were generally <10 cm/year, which is lower than average for the Ross Ice Shelf (∼20 cm/year). Melt rates may be higher at portions of the grounding zone that experience higher subglacial discharge or stronger tidal mixing. Stratification in the cavity at the borehole site was prone to diffusive convection as a result of ice shelf melting. Since diffusive convection influences vertical heat and salt fluxes differently than shear‐driven turbulence, this process may affect ice shelf melting and merits further consideration in ocean models of sub‐ice shelf circulation

    Human Papillomavirus Type 16 Entry: Retrograde Cell Surface Transport along Actin-Rich Protrusions

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    The lateral mobility of individual, incoming human papillomavirus type 16 pseudoviruses (PsV) bound to live HeLa cells was studied by single particle tracking using fluorescence video microscopy. The trajectories were computationally analyzed in terms of diffusion rate and mode of motion as described by the moment scaling spectrum. Four distinct modes of mobility were seen: confined movement in small zones (30–60 nm in diameter), confined movement with a slow drift, fast random motion with transient confinement, and linear, directed movement for long distances. The directed movement was most prominent on actin-rich cell protrusions such as filopodia or retraction fibres, where the rate was similar to that measured for actin retrograde flow. It was, moreover, sensitive to perturbants of actin retrograde flow such as cytochalasin D, jasplakinolide, and blebbistatin. We found that transport along actin protrusions significantly enhanced HPV-16 infection in sparse tissue culture, cells suggesting a role for in vivo infection of basal keratinocytes during wound healing

    Entry of Human Papillomavirus Type 16 by Actin-Dependent, Clathrin- and Lipid Raft-Independent Endocytosis

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    Infectious endocytosis of incoming human papillomavirus type 16 (HPV-16), the main etiological agent of cervical cancer, is poorly characterized in terms of cellular requirements and pathways. Conflicting reports attribute HPV-16 entry to clathrin-dependent and -independent mechanisms. To comprehensively describe the cell biological features of HPV-16 entry into human epithelial cells, we compared HPV-16 pseudovirion (PsV) infection in the context of cell perturbations (drug inhibition, siRNA silencing, overexpression of dominant mutants) to five other viruses (influenza A virus, Semliki Forest virus, simian virus 40, vesicular stomatitis virus, and vaccinia virus) with defined endocytic requirements. Our analysis included infection data, i.e. GFP expression after plasmid delivery by HPV-16 PsV, and endocytosis assays in combination with electron, immunofluorescence, and video microscopy. The results indicated that HPV-16 entry into HeLa and HaCaT cells was clathrin-, caveolin-, cholesterol- and dynamin-independent. The virus made use of a potentially novel ligand-induced endocytic pathway related to macropinocytosis. This pathway was distinct from classical macropinocytosis in regards to vesicle size, cholesterol-sensitivity, and GTPase requirements, but similar in respect to the need for tyrosine kinase signaling, actin dynamics, Na+/H+ exchangers, PAK-1 and PKC. After internalization the virus was transported to late endosomes and/or endolysosomes, and activated through exposure to low pH

    Bactericidal Action of Photogenerated Singlet Oxygen from Photosensitizers Used in Plaque Disclosing Agents

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    Photodynamic therapy (PDT) has been suggested as an efficient clinical approach for the treatment of dental plaque in the field of dental care. In PDT, once the photosensitizer is irradiated with light of a specific wavelength, it transfers the excitation energy to molecular oxygen, which gives rise to singlet oxygen., a major causative pathogen of caries, followed by erythrosine and phloxine, both of which showed activity similar to each other. One of the reasons for the discrepancy between the singlet oxygen generating ability and bactericidal activity was the incorporation efficiency of the photosensitizers into the bacterial cells. The incorporation rate of rose bengal was the highest among the three photosensitizers examined in the present study, likely leading to the highest bactericidal activity. Meanwhile, the addition of L-histidine, a singlet oxygen quencher, cancelled the bactericidal activity of any of the three photoactivated photosensitizers, proving that singlet oxygen was responsible for the bactericidal action.It is strongly suggested that rose bengal is a suitable photosensitizer for the plaque disclosing agents as compared to the other two photosensitizers, phloxine and erythrosine, when used for PDT
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