Selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) have considerable potential as treatments for type 2 diabetes. Presented herein are the syntheses, structure-activity ...relationships, and efficacy evaluation of 4-(phenylsulfonamidomethyl)benzamides as 11beta-HSD1 inhibitors. Through modification of our initial lead 5, we have identified potent and selective 11beta-HSD1 inhibitors, such as 11n, which demonstrated improved glycemic control, decreased serum lipids, and enhanced insulin sensitivity when dosed ip in diabetic ob/ob mice.
With Empirical Orthogonal Function （EOF） and trend analysis method adopted, the spatio-temporal variation of total cloud amount is analyzed for 75 stations on the Qinghai-Tibet Plateau during the ...period 1971-2004. Analysis indicates that the total cloud amount decreases from the southeast to the northwest of the plateau, and that the annual and seasonal variations in total cloud amount both show an apparent declining tendency over the past decades. Correlation analysis demonstrates that the total cloud amount is negative with sunshine duration and diurnal temperature range （DTR）, and is positive with precipitation and the relative humidity, respectively. The negative correlation is consistent with the radiative effect of cloud, while the positive correlation between total cloud amount and precipitation is obscured because of the influence of topographic factors. Discussion implies that the decrease of total cloud amount is possibly due to the variation of atmospheric aerosol content and ozone concentration over the plateau, although it is difficult to quantify the driving force mechanism up to now.
The existence and uniqueness of two dimensional steady compressible Euler flows past a wall or a symmetric body are established. More precisely, given positive convex horizontal veloicty in the ...upstream, there exists a critical value \(\rho_{cr}\) such that if the incoming density in the upstream is larger than \(\rho_{cr}\), then there exists a subsonic flow past a wall. Furthermore, \(\rho_{cr}\) is critical in the sense that there is no such subsonic flow if the density of the incoming flow is less than \(\rho_{cr}\). The subsonic flows possess large vorticity and positive horizontal velocity above the wall except at the corner points on the boundary. Moreover, the existence and uniqueness of a two dimensional subsonic Euler flow past a symmetric body are also obtained when the incoming velocity field is a general small perturbation of a constant velocity field and the density of the incoming flow is larger than a critical value. The asymptotic behavior of the flows is obtained with the aid of some integral estimates for the velocity field and its far field states.
Vehicular Ad Hoc Networks (VANET), which are composed of vehicles equipped with advanced wireless communication devices, is a paradigm of the decentralized Advanced Traveler Information Systems ...(ATIS). With inter-vehicle communication being enabled, VANET present high potential to overcome the disadvantages of current centralized ATIS. Therefore, they attracted significant interest of researchers from several academic disciplines such as transportation science, computer science, and electrical engineering. However, very few previous efforts have integrated traffic flow features into vehicular ad hoc networks research. As an effort to make up this deficiency, this research investigates several properties of VANET taking account of the traffic flow characteristics. In particular, we address the geometric connectivity, reachability, interference, broadcast capacity, and online routing problems respectively. The first part of this research explores the geometric connectivity which represents the probability that the network is connected at any time instant over a given time period. This study considers a VANET as a nominal system with uncertain disturbance. The nominal system is represented by a free flow, in which space headway is assumed to obey an exponential distribution. The unexpected driver behavior such as acceleration, deceleration, and lane changing are modeled as uncertain disturbance which is further characterized by a robustness factor in our analytical model. Our regression results show that the robustness factor is a function of the traffic flow parameters including average traffic speed, average space headway and its variance. Analytical expressions are developed to characterize the connectivity of VANET on freeway segments incorporating traffic flow features and driver behavior. The simulation validation demonstrates that our analytical expression can evaluate the geometric connectivity of VANET more accurately than previous efforts in literature. We study the influence of vehicular mobility on information propagation in VANET in the second part of the dissertation. In our study, we first define an "information flow network" and then introduce "reachability" to characterize information propagation performance. An information flow network is a time expanded graph composed of asynchronous communication link (based on geometric distance) and nodes (vehicles). The reachability is the probability that every two vehicles in the information flow network are connected in a given time interval. To capture various driver behavior, we separate the drivers into three clusters which are aggressive, defensive, and slow drivers respectively. Correspondingly, we approximate the relative movement between individual vehicles by the relative movement between different driver clusters. Based on this approximation, we develop analytical expressions to evaluate the reachability during a short time period. Our results show that the relative movement between vehicles enables individual vehicles to communicate with more neighbors and therefore improves the opportunity that the traffic information is transmitted in a forward direction. Simulation results validate our assumptions and analytical expressions. Based on the analytical results in the previous topics, the third part of this research further explores the interference in VANET under various traffic flow conditions. Both our analytical expressions and the simulation results show that the vehicular mobility impacts the interference that individual vehicles experiences significantly. The capacity of VANET, which is another important aspect to evaluate the performance of VANET, is explored in the fourth part of this research. In our study, the capacity of VANET is defined as the number of vehicles that can successfully transmit information simultaneously. This number is constrained by the interference in the physical layer. Under the constraints of the interference, the capacity of VANET is first explored using an integer programming formulation. And then, based on the integer programming model, we further develop statistical model to characterize the capacity of VANET by the parameters of the traffic flow network as well as the communication network. To improve the prediction accuracy of the statistical model, central composite experiment design method is applied. The last issue of this dissertation focuses on developing an online routing algorithm for vehicles accessing to real-time traffic information through VANET. The presented routing policy attempts to take into account the dynamic traffic features so that we model the system as a network with stochastic time-varying link cost information, and at each intersection instead of specifying an optimal path, our routing policy only identifies the optimal immediate arc to take. In addition, we consider uncertain VANET performance. The proposed routing policy involves time-dependent information reliability and time delay in the optimal arc decision procedure. Our routing policy is formulated as a set of recurrent equations which is solved by the proposed modified label-correcting algorithm. In summary, this research contributes to understanding the performance of VANET by integrating transportation science and wireless networking concepts. (Abstract shortened by UMI.)
R131; In order to investigate the mortality of a cohort of chrysotile asbestos miners in China and evaluate its association with exposure to chrysotile,a fixed cohort of 1932 workers in chrysotile ...asbestos mine was established in 1981 and followed till June 1,2010.Information on vital status,cause of death and smoking habits was collected.The workers were divided into two groups according to their exposure status.The exposed group was composed of frontline workers who worked directly on mining or processing asbestos products.The control group consisted of those who were not directly exposed to asbestos in their work.Standardized mortality ratio (SMR) was calculated according to Chinese national death rates.Cox proportional hazards model was applied to estimate the adjusted relative risks of deaths from major causes in exposed and control groups:The results of this study showed that main causes of mortality were malignant neoplasm,cardiovascular disease,cerebrovascular disease and respiratory disease for chrysotile miners.The mortality rate was 939.20 per 100 000 person-years for workers.The SMR for all causes of death was 1.46 in the cohort.Statistically significant mortality excesses were found for lung cancer (SMR=1.51),pulmonary heart disease (SMR=2.70),respiratory disease (SMR=1.93),asbestosis (SMR=9.62),and accident (SMR=l.59).The mortalities from malignant neoplasm,lungcancer,cerebrovascular disease and digestive disease in the exposed group were significantly higher than those in the control group.The findings indicate that chrysotile exposure is a risk factor for lung cancer,respiratory disease,cerebrovascular disease and digestive disease.
In order to investigate the mortality of a cohort of chrysotile asbestos miners in China and evaluate its association with exposure to chrysotile,a fixed cohort of 1932 workers in chrysotile ...asbes-tos mine was established in 1981 and followed till June 1,2010.Information on vital status,cause of death and smoking habits was collected.The workers were divided into two groups according to their exposure status.The exposed group was composed of frontline workers who worked directly on mining or processing asbestos products.The control group consisted of those who were not directly exposed to asbestos in their work.Standardized mortality ratio (SMR) was calculated according to Chinese national death rates.Cox proportional hazards model was applied to estimate the adjusted relative risks of deaths from major causes in exposed and control groups.The results of this study showed that main causes of mortality were malignant neoplasm,cardiovascular disease,cerebrovascular disease and respiratory disease for chrysotile miners.The mortality rate was 939.20 per 100 000 person-years for workers.The SMR for all causes of death was 1.46 in the cohort.Statistically significant mortality excesses were found for lung cancer (SMR=1.51),pulmonary heart disease (SMR=2.70),respiratory disease (SMR=1.93),asbestosis (SMR=9.62),and accident (SMR=1.59).The mortalities from malignant neo-plasm,lung cancer,cerebrovascular disease and digestive disease in the exposed group were signifi-cantly higher than those in the control group.The findings indicate that chrysotile exposure is a risk factor for lung cancer,respiratory disease,cerebrovascular disease and digestive disease.
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