A suite of activity-based probes to dissect the KLK activome in drug-resistant prostate cancer

Kallikrein-related peptidases (KLKs) are a family of secreted serine proteases, which form a network – the KLK activome – with an important role in proteolysis and signaling. In prostate cancer (PCa), increased KLK activity promotes tumor growth and metastasis through multiple biochemical pathways, and specific quantification and tracking of changes in the KLK activome could contribute to validation of KLKs as potential drug targets. Herein we report a technology platform based on novel activity-based probes (ABPs) and inhibitors with unprecedented potency and selectivity enabling simultaneous orthogonal analysis of KLK2, KLK3 and KLK14 activity in hormone-responsive PCa cell lines and tumor homogenates. Using selective inhibitors and multiplexed fluorescent activity-based protein profiling (ABPP) we dissect the KLK activome in PCa cells and show that increased KLK14 activity leads to a migratory phenotype. Furthermore, using biotinylated ABPs we show that active KLK molecules are secreted into the bone microenvironment by PCa cells following stimulation by osteoblasts suggesting KLK-mediated signaling mechanisms could contribute to PCa metastasis to bone. Together our findings show that ABPP is a powerful approach to dissect dysregulation of the KLK activome as a promising and previously underappreciated therapeutic target in advanced PCa.

Increasing Efficiency of a Finned Heat Sink Using Orthogonal Analysis

As the heat flux of electronic components is increasing rapidly, the traditional air-cooling technique is gradually not meeting the requirements of thermal management. The immersion liquid-cooling technique shows great potential, and has attracted increasing attention due to its excellent performance in recent years. The finned heat sink is common and essential for cooling electric components. To analyze the influences of its structural parameters on heat dissipation and improve its efficiency while using a dielectric coolant, this study used the orthogonal analysis method to obtain the optimal structure via the numerical simulation method. The maximum temperature of the heat sink was selected as the evaluation criteria. The results showed that the parameters that affect the maximum temperature, in order of importance, are fin thickness, the number of fins, the height of the fins, and substrate thickness. Finally, taking the maximum temperature and mass as indexes obtained the optimal structure of the heat sink. The mass was reduced by 19%, while the temperature only increased by 4.5% when considering the mass index.

Study on the performance of a new type of bobbin silk reeling machine

This study mainly investigated the performance and process parameter optimization of a new type of bobbin silk reeling machine by using orthogonal analysis designs. This new type of bobbin silk reeling machine with advanced winding and tension control technology was built through the transformation of a traditional automatic reeling machine. Experimental results indicated that a reeling speed of 130 m/min, an overfeeding ratio of 1.15, and a drying temperature of 90°C were the optimal process parameters. The molecular group characteristics, crystal structures, breaking strengths, and breaking elongation rates of the raw silk from homemade silk slices on bobbins prepared by this machine were similar to those from silk slices on small reels prepared by automatic silk reeling machines and traditional silk slices on bobbins prepared by winders. The softness of the raw silk from homemade silk slices on bobbins was similar to that from traditional silk slices on bobbins, and the cohesion performance of the raw silk from homemade silk slices on bobbins was better than that from traditional silk slices on bobbins. The raw silk from homemade silk slices on bobbins prepared by this machine is directly suitable for postweaving processing. This study can provide a practical basis for the development of the raw silk reeling technique on bobbins.

The Performance Research and Orthogonal Analysis of Humidification-dehumidification Technology (HDH) System

HDH seawater desalination technology has characteristics of flexible scale, small investment, and suitable for decentralized fresh water demand. This paper designs a HDH seawater desalination system, and based on the principles of energy conservation and mass conservation, a theoretical calculation model is established, and the influence of spray liquid flow and temperature, airflow, cooling water temperature and flow on the system water production and Gained output ration (GOR) is studied. And the orthogonal analysis method is used to study the influence of different parameters on water production and GOR. The results show that: water production and GOR are positively related to temperature of the spray liquid, when spray liquid or air flow is large, fresh water output is negatively correlated with air flow, system water production and cooling water flow are positively correlated at first, then system fresh water production tends to be stable, GOR and cooling water flow are first negatively correlated, and then GOR become stable, water production is negatively correlated with cooling water temperature, GOR is positively correlated with cooling water temperature. The spray liquid flow rate has the greatest influence on water production, and spray liquid temperature has the greatest influence on GOR.