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1.
The 2011 AASHTO Roadside Design Guide (RDG) contains perhaps the most widely used procedure for choosing an appropriate length of need (LON) for roadside barriers. However, this procedure has several limitations. The procedure uses a highly simplified model of vehicle departure, and the procedure does not allow designers to specify an explicit level of protection. A new procedure for choosing LON that addresses these limitations is presented in this paper. This new procedure is based on recent, real-world road departure trajectories and uses this departure data in a more realistic way. The new procedure also allows LON to be specified for a precisely known level of protection – a level which can be based on number of crashes, injury outcomes or even estimated crash cost – while still remaining straightforward and quick to use like the 2011 RDG procedure.  相似文献   
2.
Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.  相似文献   
3.
Lateral scattering of retrograde well implants is shown to have an effect on the threshold voltage of nearby devices. The threshold voltage of both NMOSFETs and PMOSFETs increases in magnitude for conventional retrograde wells, but for triple-well isolated NMOSFETs the threshold voltage decreases for narrow devices near the edge of the well. Electrical data, SIMS, and SUPREM4 simulations are shown that elucidate the phenomenon.  相似文献   
4.
Students may choose to play drinking games not only for reasons related to alcohol consumption but also because of incentives related to other aspects of play (competition, fun, interpersonal dominance, etc.). College students (120 men and 167 women) completed measures of motives for playing (based on T. J. Johnson, S. Hamilton, & V. L. Sheets, 1999) and consequences of playing drinking games. Exploratory principal-components analysis identified 8 reasons for playing. Men and women differed in their endorsement of the factors. Motives for play directly predicted consequences of play independently of alcohol consumption. Specific motives predicted specific types of consequences. In multiple regression analyses, Conformity motives were negatively related to consequences and may represent a form of protective motive. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
5.
Pressurized fabric tubes, pressure-stabilized beams (known as air beams) and air-inflated structures are considered to be valuable technologies for lightweight, rapidly deployable structures. Design optimization of an inflated structure depends on a thorough understanding of woven fabric mechanics. In this paper the bending response of woven pressure-stabilized beams have been experimentally tested and analytically investigated. Additionally, the micromechanical effects of interacting tows have been studied through finite element models containing contact surfaces and nonlinear slip/stick conditions. Local unit cell models consisting of pairs of woven tows were created to characterize the effective constitutive relations. The material properties from the unit cell models were then used for the global continuum model subjected to 4-point flexure. An experimental set-up was designed and manufactured for testing of Vectran and PEN air beams. The air beam mid-span deflections were measured as functions of inflation pressure and bending load. Plots of the elastic and shear moduli with respect to the pressure and coefficient of friction have been generated. It was determined that the effective elastic and shear moduli were functions of inflation pressure, the material used and the geometry of the weave. It was shown that pneumatic or pressurized tube structures differ fundamentally from conventional metal structures.  相似文献   
6.
Examination of the wreckage of a light aircraft revealed that approximately 20 cm was missing from one tip of the aluminum alloy propeller. Fractographic and metallographic examination of the remaining portion of the propeller revealed extensive grain-boundary separation in the vicinity of the fracture, and grain edges and corners rounded by corrosion on the fracture surface. Energy dispersive X-ray analysis (EDXA) revealed fluorine on, and in the vicinity of, the fracture surface. In the ensuing litigation, it was asserted that the crash occurred because the propeller fractured in flight as the result of intergranular attack caused by the use of a fluorine-bearing cleaner.  相似文献   
7.
The transjugular intrahepatic portosystemic shunt procedure is an accepted treatment for adults with complications of portal hypertension. We performed a retrospective review of all pediatric TIPS placements performed at the University of California, San Francisco between 1990 and 1996. Twelve procedures were attempted in nine children, with a mean age (+/- SD) of 9.4 +/- 3.9 years (range, 5 to 15 years) and a mean weight of 31 +/- 18 kg (range, 16 to 70 kg). The indications for TIPS placement were portal hypertension complicated by chronic variceal hemorrhage not controlled with sclerotherapy (n = 7) and hypersplenism with thrombocytopenia (n = 2). TIPS placement was successfully completed initially in seven of nine (78%) patients. Unfavorable vascular anatomy was the cause of failure in two cases. The seven patients who underwent successful TIPS placement were followed up for an average of 136 days (range, 1 to 800 days); two still have patent shunts, three underwent liver transplantation, one had a splenorenal shunt after stenosis, and one died of underlying liver disease. Variceal bleeding was controlled in four of five patients who successfully underwent TIPS placement. Shunt occlusion occurred in four patients; patency was restored by transjugular shunt revision in three, and a splenorenal shunt was performed in one.  相似文献   
8.
Reducing the food intake of rodents to well below that of ad libitum fed animals increases the life span. This action, which gerontologists often refer to as the antiaging action of dietary restriction (DR), is due to the slowing of the aging processes. DR also maintains most physiological processes in a youthful state and delays the occurrence and/or slows the progression of age-associated disease processes. This antiaging action of DR results from the reduced intake of calories. Reduction of the body fat content does not play a causal role in the antiaging action of DR, nor does reduction in the metabolic rate. Alterations in the characteristics of carbohydrate metabolism and of oxidative metabolism in response to DR have been found that are of such a nature that they could, at least in part, underlie the antiaging action. Several theories have recently been proposed in regard to the mechanisms responsible for the antiaging action of DR, but none has been tested by rigorously designed studies. Of these theories, the one that seems most promising is based on the fact that DR protects rats and mice of all ages against the damaging actions of acute stressors. This protective action against stressors may play a major role in the antiaging action of DR.  相似文献   
9.
Recurrent erosion of the corneal epithelium has been treated successfully by phototherapeutic keratectomy when convention therapy has failed. We present a case of recurrent corneal erosion occurring 1 year after photorefractive keratectomy in a 55-year-old myopic woman. No corneal abnormalities were previously identified in either the affected or the fellow eye. This case demonstrates the potential for ineffective healing of the corneal epithelial basement membrane complex after excimer laser photorefractive keratectomy.  相似文献   
10.
Some specific characteristics of the aging of the Brazilian population in different areas, states and communities all over the country, have shown significant variations. Historical series of demographic and health indicators for the population in their sixties and over in Brazil, state of S. Paulo and in the municipal district of Araraquara are listed as follows: level of education and urban population growth rate, income distribution, mortality rates and main causes of death. In 1991 the aged constituted were 7.8% of the Brazilian population and 9.7% in Araraquara community. The elderly population (of 70 years of aged and above) as a proportion of the whole, has increased and already stands for 40%. The same trend holds good for both the proportion of aged within the urban population and their level of education which increased to 90% in 1991. The main causes of death are chronic degenerative diseases which have replaced the infectious illness: first, the diseases of the circulatory system (which account for more than 40% of all deaths) and the neoplasms (which let to 15% of the deaths). On the basis of these health and demographic data relating to people of 60 years of age and over, this study suggests some procedures for the improvement of the quality of the assistance given to the target population: a) the assistance give to the aged should be improved by providing gerontological training for general physicians and nurses, both of public and private clinics; b) the already existing educational activities for the aged, for health workers and for teachers of secondary education should be further developed; c) the number of day-hospitals should be increased for the purpose of avoiding unnecessary confinement so as maintain the low rate of institutionalization in homes for the elderly (0.7% in Araraquara). It is reported that at least 35% of the aged population in this area is entitled to private health assistance, which brings out the importance of including such services in the local health programs for this group.  相似文献   
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