964 resultados para Induced Exposure.


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Prevention and safety promotion programmes. Traditionally, in-depth investigations of crash risks are conducted using exposure controlled study or case-control methodology. However, these studies need either observational data for control cases or exogenous exposure data like vehicle-kilometres travel, entry flow or product of conflicting flow for a particular traffic location, or a traffic site. These data are not readily available and often require extensive data collection effort on a system-wide basis. Aim: The objective of this research is to propose an alternative methodology to investigate crash risks of a road user group in different circumstances using readily available traffic police crash data. Methods: This study employs a combination of a log-linear model and the quasi-induced exposure technique to estimate crash risks of a road user group. While the log-linear model reveals the significant interactions and thus the prevalence of crashes of a road user group under various sets of traffic, environmental and roadway factors, the quasi-induced exposure technique estimates relative exposure of that road user in the same set of explanatory variables. Therefore, the combination of these two techniques provides relative measures of crash risks under various influences of roadway, environmental and traffic conditions. The proposed methodology has been illustrated using Brisbane motorcycle crash data of five years. Results: Interpretations of results on different combination of interactive factors show that the poor conspicuity of motorcycles is a predominant cause of motorcycle crashes. Inability of other drivers to correctly judge the speed and distance of an oncoming motorcyclist is also evident in right-of-way violation motorcycle crashes at intersections. Discussion and Conclusions: The combination of a log-linear model and the induced exposure technique is a promising methodology and can be applied to better estimate crash risks of other road users. This study also highlights the importance of considering interaction effects to better understand hazardous situations. A further study on the comparison between the proposed methodology and case-control method would be useful.

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The CD3ε cytoplasmic tail contains a conserved proline-rich sequence (PRS) that influences TCR-CD3 expression and signaling. Although the PRS can bind the SH3.1 domain of the cytosolic adapter Nck, whether the PRS is constitutively available for Nck binding or instead represents a cryptic motif that is exposed via conformational change upon TCR-CD3 engagement (CD3Δc) is currently unresolved. Furthermore, the extent to which a cis-acting CD3ε basic amino acid-rich stretch (BRS), with its unique phosphoinositide-binding capability, might impact PRS accessibility is not clear. In this study, we found that freshly harvested primary thymocytes expressed low to moderate basal levels of Nck-accessible PRS ("open-CD3"), although most TCR-CD3 complexes were inaccessible to Nck ("closed-CD3"). Ag presentation in vivo induced open-CD3, accounting for half of the basal level found in thymocytes from MHC(+) mice. Additional stimulation with either anti-CD3 Abs or peptide-MHC ligands further elevated open-CD3 above basal levels, consistent with a model wherein antigenic engagement induces maximum PRS exposure. We also found that the open-CD3 conformation induced by APCs outlasted the time of ligand occupancy, marking receptors that had been engaged. Finally, CD3ε BRS-phosphoinositide interactions played no role in either adoption of the initial closed-CD3 conformation or induction of open-CD3 by Ab stimulation. Thus, a basal level of open-CD3 is succeeded by a higher, induced level upon TCR-CD3 engagement, involving CD3Δc and prolonged accessibility of the CD3ε PRS to Nck.

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A key step in signal transduction in the visual cell is the light-induced conformational change of rhodopsin that triggers the binding and activation of the guanine nucleotide-binding protein. Site-directed mAbs against bovine rhodopsin were produced and used to detect and characterize these conformational changes upon light activation. Among several antibodies that bound exclusively to the light-activated state, an antibody (IgG subclass) with the highest affinity (Ka ≈ 6 × 10−9 M) was further purified and characterized. The epitope of this antibody was mapped to the amino acid sequence 304–311. This epitope extends from the central region to the cytoplasmic end of the seventh transmembrane helix and incorporates a part of a highly conserved NPXXY motif, a critical region for signaling and agonist-induced internalization of several biogenic amine and peptide receptors. In the dark state, no binding of the antibody to rhodopsin was detected. Accessibility of the epitope to the antibody correlated with formation of the metarhodopsin II photointermediate and was reduced significantly at the metarhodopsin III intermediate. Further, incubation of the antigen–antibody complex with 11-cis-retinal failed to regenerate the native rhodopsin chromophore. These results suggest significant and reversible conformational changes in close proximity to the cytoplasmic end of the seventh transmembrane helix of rhodopsin that might be important for folding and signaling.

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Crash statistics in Singapore from 2001 to 2005 have shown that motorcycles are involved in about 54% of intersection crashes. The overall involvement of motorcycles in crashes as the not-at-fault party is about 43% but at intersections, the corresponding percentage is increased to 57%. Quasi-induced exposure estimates show that the motorcycle exposure rate at signalized intersections is 41.7% even though motorcycles account for only 19% of the vehicle population. This study seeks to examine in greater details, the problem of motorcycle exposure at signalized intersections. In particular, the exposure arising from potential crashes with red light running vehicles from the conflicting stream at four signalized intersections is investigated. The results show that motorcycles are more exposed because they tend to accumulate near the stop-line during the red phase to facilitate an earlier discharge during the initial period of the green which is the more vulnerable period. At sites where there are more weaving opportunities because the lanes are wider or where there are exclusive right-turn lanes, the accumulation is higher and hence an increased exposure is observed. The analysis also shows that the presence of heavy vehicles tends to decrease motorcycle exposure as their weaving opportunities become restricted as well as there is a greater reluctance for them to weave past or queue alongside the heavy vehicles and their effects intensify for narrower lane width.

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Exposure control or case-control methodologies are common techniques for estimating crash risks, however they require either observational data on control cases or exogenous exposure data, such as vehicle-kilometres travelled. This study proposes an alternative methodology for estimating crash risk of road user groups, whilst controlling for exposure under a variety of roadway, traffic and environmental factors by using readily available police-reported crash data. In particular, the proposed method employs a combination of a log-linear model and quasi-induced exposure technique to identify significant interactions among a range of roadway, environmental and traffic conditions to estimate associated crash risks. The proposed methodology is illustrated using a set of police-reported crash data from January 2004 to June 2009 on roadways in Queensland, Australia. Exposure-controlled crash risks of motorcyclists—involved in multi-vehicle crashes at intersections—were estimated under various combinations of variables like posted speed limit, intersection control type, intersection configuration, and lighting condition. Results show that the crash risk of motorcycles at three-legged intersections is high if the posted speed limits along the approaches are greater than 60 km/h. The crash risk at three-legged intersections is also high when they are unsignalized. Dark lighting conditions appear to increase the crash risk of motorcycles at signalized intersections, but the problem of night time conspicuity of motorcyclists at intersections is lessened on approaches with lower speed limits. This study demonstrates that this combined methodology is a promising tool for gaining new insights into the crash risks of road user groups, and is transferrable to other road users.

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Mode of access: Internet.

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Federal Highway Administration, Office of Research and Development, McLean, Va.

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Federal Highway Administration, Office of Research and Development, McLean, Va.

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Motorcyclists are the most crash-prone road-user group in many Asian countries including Singapore; however, factors influencing motorcycle crashes are still not well understood. This study examines the effects of various roadway characteristics, traffic control measures and environmental factors on motorcycle crashes at different location types including expressways and intersections. Using techniques of categorical data analysis, this study has developed a set of log-linear models to investigate multi-vehicle motorcycle crashes in Singapore. Motorcycle crash risks in different circumstances have been calculated after controlling for the exposure estimated by the induced exposure technique. Results show that night-time influence increases crash risks of motorcycles particularly during merging and diverging manoeuvres on expressways, and turning manoeuvres at intersections. Riders appear to exercise more care while riding on wet road surfaces particularly during night. Many hazardous interactions at intersections tend to be related to the failure of drivers to notice a motorcycle as well as to judge correctly the speed/distance of an oncoming motorcycle. Road side conflicts due to stopping/waiting vehicles and interactions with opposing traffic on undivided roads have been found to be as detrimental factors on motorcycle safety along arterial, main and local roads away from intersections. Based on the findings of this study, several targeted countermeasures in the form of legislations, rider training, and safety awareness programmes have been recommended.

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Unlicensed driving is a serious problem in many countries, despite ongoing improvements in traffic law enforcement practices and technology. Unlike alcohol impairment and speeding, unlicensed driving does not play a direct causative role in road crashes. However it represents a major problem for road safety in two respects. Firstly, it undermines the effectiveness of driver licensing systems by preventing the allocation of demerit points and reducing the impact of licence loss (Watson, 2004b). Secondly, there is a growing body of evidence linking unlicensed driving to a cluster of high-risk behaviours including drink driving, speeding, failure to wear seat belts and motorcycle use (Griffin & DeLaZerda, 2000; Harrison, 1997; Watson, 1997, 2004b). Consistent with this, utilising the quasi-induced exposure method, Watson (2004a) estimated that in Queensland, unlicensed drivers were almost three times more likely to be involved in a reported crash than licensed drivers.

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Inspired by molecular mechanisms that cells exploit to sense mechanical forces and convert them into biochemical signals, chemists dream of designing mechanochemical switches integrated into materials. Using the adhesion protein fibronectin, whose multiple repeats essentially display distinct molecular recognition motifs, we derived a computational model to explain how minimalistic designs of repeats translate into the mechanical characteristics of their fibrillar assemblies. The hierarchy of repeat-unfolding within fibrils is controlled not only by their relative mechanical stabilities, as found for single molecules, but also by the strength of cryptic interactions between adjacent molecules that become activated by stretching. The force-induced exposure of cryptic sites furthermore regulates the nonlinearity of stress-strain curves, the strain at which such fibers break, and the refolding kinetics and fraction of misfolded repeats. Gaining such computational insights at the mesoscale is important because translating protein-based concepts into novel polymer designs has proven difficult.

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We used integrin αLβ2 heterodimers containing I domains locked open (active) or closed (inactive) with disulfide bonds to investigate regulatory interactions among domains in integrins. mAbs to the αL I domain and β2 I-like domain inhibit adhesion of wild-type αLβ2 to intercellular adhesion molecule-1. However, with αLβ2 containing a locked open I domain, mAbs to the I domain were subdivided into subsets (i) that did not inhibit, and thus appear to inhibit by favoring the closed conformation, and (ii) that did inhibit, and thus appear to bind to the ligand binding site. Furthermore, αLβ2 containing a locked open I domain was completely resistant to inhibition by mAbs to the β2 I-like domain, but became fully susceptible to inhibition after disulfide reduction with DTT. This finding suggests that the I-like domain indirectly contributes to ligand binding by regulating opening of the I domain in wild-type αLβ2. Conversely, locking the I domain closed partially restrained conformational change of the I-like domain by Mn2+, as measured with mAb m24, which we map here to the β2 I-like domain. By contrast, locking the I domain closed or open did not affect constitutive or Mn2+-induced exposure of the KIM127 epitope in the β2 stalk region. Furthermore, locked open I domains, in αLβ2 complexes or expressed in isolation on the cell surface, bound to intercellular adhesion molecule-1 equivalently in Mg2+ and Mn2+. These results suggest that Mn2+ activates αLβ2 by binding to a site other than the I domain, most likely the I-like domain of β2.

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The structural changes accompanying stretch-induced early unfolding events were investigated for the four type III fibronectin (FN-III) modules, FN-III7, FN-III8, FN-III9, and FN-III10 by using steered molecular dynamics. Simulations revealed that two main energy barriers, I and II, have to be overcome to initiate unraveling of FN-III's tertiary structure. In crossing the first barrier, the two opposing β-sheets of FN-III are rotated against each other such that the β-strands of both β-sheets align parallel to the force vector (aligned state). All further events in the unfolding pathway proceed from this intermediate state. A second energy barrier has to be overcome to break the first major cluster of hydrogen bonds between adjacent β-strands. Simulations revealed that the height of barrier I varied significantly among the four modules studied, being largest for FN-III7 and lowest for FN-III10, whereas the height of barrier II showed little variation. Key residues affecting the mechanical stability of FN-III modules were identified. These results suggest that FN-III modules can be prestretched into an intermediate state with only minor changes to their tertiary structures. FN-III10, for example, extends 12 Å from the native “twisted” to the intermediate aligned state, and an additional 10 Å from the aligned state to further unfolding where the first β-strand is peeled away. The implications of the existence of intermediate states regarding the elasticity of fibrillar fibers and the stretch-induced exposure of cryptic sites are discussed.

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Mode of access: Internet.

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Wind- induced exposure is one of the major forces shaping the geomorphology and biota in coastal areas. The effect of wave exposure on littoral biota is well known in marine environments (Ekebon et al., 2003; Burrows et al., 2008). In the Cabrera Archipelago National Park wave exposure has demostrated to have an effect on the spatial distribution of different stages of E.marginatus (Alvarez et al., 2010). Standarized average wave exposures during 2008 along the Cabrera Archipelago National park coast line were calculated to be applied in studies of littoral species distribution within the archipelago. Average wave exposure (or apparent wave power) was calculated for points located 50 m equidistant on the coastline following the EXA methodology (EXposure estimates for fragmented Archipelagos) (Ekebon et al., 2003). The average wave exposures were standardized from 1 to 100 (minimum and maximum in the area), showing coastal areas with different levels of mea wave exposure during the year. Input wind data (direction and intensity) from 2008 was registered at the Cabrera mooring located north of Cabrera Archipelago. Data were provided by IMEDEA (CSIC-UIB, TMMOS http://www.imedea.uib-csic.es/tmoos/boyas/). This cartography has been developed under the framework of the project EPIMHAR, funded by the National Park's Network (Spanish Ministry of Environment, Maritime and Rural Affairs, reference: 012/2007 ). Part of this work has been developed under the research programs funded by "Fons de Garantia Agrària i Pesquera de les Illes Balears (FOGAIBA)".