L-Selectin and P-Selectin Are Novel Biomarkers of Cervicovaginal Inflammation for Preclinical Mucosal Safety Assessment of Anti-HIV-1 Microbicide
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Authors: Zhong, Maohua; He, Benxia; Yang, Jingyi; Bao, Rong; Zhang, Yan; Zhou, Dihan; Chen, Yaoqing; Li, Liangzhu; Han, Chen; Yang, Yi; Sun, Ying; Cao, Yuan; Li, Yaoming; Shi, Wei; Jiang, Shibo; Zhang, Xiaoyan; Yan, Huimin
Abstract
A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a refined murine model of agent-induced cervicovaginal inflammation. We found that patterns of detection of L-selectin and P-selectin were obviously different from those of the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of these two soluble selectins correlated better than those of MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of infection with HIV and other sexually transmitted pathogens.
A Modular Approach to Arithmetic and Logic Unit Design on a Reconfigurable Hardware Platform for Educational Purpose
INTELLIGENT COMPUTING AND INFORMATION SCIENCE, PT II
Authors: Oztekin, Halit; Temurtas, Feyzullab; Gulbag, Ali
Abstract
The Arithmetic and Logic Unit (ALU) design is one of the important topics in Computer Architecture and Organization course in Computer and Electrical Engineering departments. There are ALU designs that have non-modular nature to be used as an educational tool. As the programmable logic technology has developed rapidly, it is feasible that ALU design based on Field Programmable Gate Array (FPGA) is implemented in this course. In this paper, we have adopted the modular approach to ALU design based on FPGA. All the modules in the ALU design are realized using schematic structure on Altera's Cyclone II Development board. Under this model, the ALU content is divided into four distinct modules. These are arithmetic unit except for multiplication and division operations, logic unit, multiplication unit and division unit. User can easily design any size of ALU unit since this approach has the modular nature. Then, this approach was applied to microcomputer architecture design named BZK.SAU.FPGA10.0 instead of the current ALU unit.