Structure-activity relationships of fluorene compounds inhibiting HCV variants

Approximately 71 million people suffer from hepatitis C virus (HCV) infection worldwide. Persistent HCV infection causes liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, resulting in approximately 400,000 deaths annually. Effective direct-acting antiviral agents (DAAs) have been developed and are currently used for HCV treatment targeting the following three proteins: NS3/4A proteinase that cleaves the HCV polyprotein into various functional proteins, RNA-dependent RNA polymerase (designated as NS5B), and NS5A, which is required for the formation of double membrane vesicles serving as RNA replication organelles. At least one compound inhibiting NS5A is included in current HCV treatment regimens due to the high efficacy and low toxicity of drugs targeting NS5A. Here we report fluorene compounds showing strong inhibitory effects on GT 1b and 3a of HCV. Moreover, some compounds were effective against resistance-associated variants to DAAs. The structure-activity relationships of the compounds were analyzed. Furthermore, we investigated the molecular bases of the inhibitory activities of some compounds by the molecular docking method.11Ysciescopu

Droplet Velocity in an Electrowetting on Dielectric Digital Microfluidic Device

In many electrowetting on dielectric (EWOD) based microfluidics devices, droplet actuation speed is a crucial performance-controlling parameter. Our present study aims to characterize and study droplet speed in a typical EWOD device. First, a practical droplet speed measurement method has been methodically demonstrated and some related velocity terms have been introduced. Next, influence of electrode shape on droplet speed has been studied and a new design to enhance droplet speed has been proposed and experimentally demonstrated. Instead of using square shaped electrodes, rectangular electrodes with smaller widths are used to actuate droplets. Additionally, different schemes of activating electrodes are studied and compared for the same applied voltage. The experiments show that a particular scheme of activating the array of rectangular electrodes enhances the droplet speed up to 100% in comparison to the droplet speed in a conventional device with square shaped electrodes

Thermal performance of copper micro-pillar structure fabricated by powder injection molding

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Fabrication of Micro-Patterned Surface for Pool-boiling Enhancement by Using Powder Injection Molding Process

In this study, two kinds of copper micro-patterned surfaces with different heights were fabricated by using a powder injection molding (PIM) process. The micro-pattern’s size was 100 μm, and the gap size was 50 μm. The short micro-pattern’s height was 100 μm, and the height of the tall one was 380 μm. A copper powder and wax-polymer-based binder system was used to fabricate the micro-patterned surfaces. The critical heat flux (CHF) and heat transfer coefficient (HTC) during pool-boiling tests were measured with the micro-patterned surfaces and a reference plain copper surface. The CHF of short and tall micro-patterned surfaces were 1434 and 1444 kW/m2, respectively, and the plain copper surface’s CHF was 1191 kW/m2. The HTC of the plain copper surface and the PIM surface with short and tall micro-patterned surfaces were similar in value up to a heat flux 1000 kW/m2. Beyond that value, the plain surface quickly reached its CHF, while the HTC of the short micro-patterned surface achieved higher values than that of the tall micro-patterned surface. At CHF, the maximum values of HTC for the short micro-pattern, tall micro-pattern, and the plain copper surface were 68, 58, and 57 kW/m2 K

Frosting characteristics on hydrophilic and superhydrophobic copper surfaces

The main objective of this study is to examine the frosting characteristics affected by the surface wettability. Two different copper surfaces – bare and nano structured - were prepared for the experiments. Their static contact angles are 74° (bare: without surface treatment) and 154° (nano-structured), respectively. The temperature of the copper substrate was measured by using resistance temperature detector (RTD) sensors embedded inside small holes drilled at 1 mm underneath the surface. During the phase change, the temperature of the copper substrates remained -7.8±0.6°C and the ambient temperature was set as 24±0.5°C with the relative humidity of 45%. Images were captured by using the CMOS camera with the 5 second time interval. Film condensation occurred because of higher wettability of the bare copper surface. Film condensates were frozen at the early stage and frost crystal grew in the vertical direction. On the other hand, dropwise condensates formed on the nano-structured copper surface remained as the supercooled liquid phase for 44 minutes owing to its low wettability. After 4 minutes, frosting on the bare copper substrate was triggered and propagated until it covered the whole surface. The frosting was significantly delayed on the superhydrophobic copper surface due to the lower surface free energy. The different porous media composed of frost which directly influence the heat transfer characteristics was formed on each surfaces. Therefore, additional investigation for heat transfer phenomenon on superhydrophobic surface should be conducted.</jats:p

Development of a Novel Diagnostic Biomarker Set for Rheumatoid Arthritis Using a Proteomics Approach

Background. Rheumatoid arthritis (RA) is an autoimmune disease that starts with inflammation of the synovial membrane. Studies have been conducted to develop methods for efficient diagnosis of RA and to identify the mechanisms underlying RA development. Blood samples can be useful for detecting disturbance of homeostasis in patients with RA. Nanoliquid chromatography-tandem mass spectrometry (LC-MS/MS) is an efficient proteomics approach to analyze blood sample and quantify serum proteins. Methods. Serum samples of 18 healthy controls and 18 patients with RA were analyzed by LC-MS/MS. Selected candidate biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) using sera from 43 healthy controls and 44 patients with RA. Results. Thirty-eight proteins were significantly differentially expressed by more than 2-fold in healthy controls and patients with RA. Based on a literature survey, we selected six candidate RA biomarkers. ELISA was used to evaluate whether these proteins effectively allow distinguishing patients with RA from healthy controls and monitoring drug efficacy. SAA4, gelsolin, and vitamin D-binding protein were validated as potential biomarkers of RA for screening and drug efficacy monitoring of RA. Conclusions. We identified a panel of three biomarkers for RA which has potential for application in RA diagnosis and drug efficacy monitoring. Further, our findings will aid in understanding the pathogenesis of RA