Kingfisher’s Philosophy of Eating

Now, Kingfisher was tired of eating fish every day. One day, he decided to try something new and went on a hunt for frogs. After a few attempts, Kingfisher finally caught a frog and was excited to try it

Mobile AME: A Handheld Application to Support Decision Making for Ammunition Personnel

Wireless technology and the emergence of handheld devices provide new ways to deliver and present information. In the military setting, availability of needed information can be crucial during the decision-making process, especially in a war zone. This paper describes the extension of a Web-based ammunition encyclopedia system developed for the U.S. Army Defense Ammunition Center (DAC) called the ammunition multimedia encyclopedia system (AME). The extension, known as Mobile AME, exploits handheld technology to provide Quality Assurance Specialist Ammunition Surveillance (QASAS) personnel with access to needed ammunition information via a personal digital assistant (PDA). The focus was on developing a highly usable system that supports QASAS decision making and training in choosing the best practices to properly handle an ammunition item including Discarded Military Munitions (DMM). This paper discusses the motivation behind Mobile AME, design and development of the system, and future directions

pre-clinical assessment of pharmacological and molecular properties

SARS-CoV-2, the cause of the COVID-19 pandemic, exploits host cell proteins for viral entry into human lung cells. One of them, the protease TMPRSS2, is required to activate the viral spike protein (S). Even though two inhibitors, camostat and nafamostat, are known to inhibit TMPRSS2 and block cell entry of SARS-CoV-2, finding further potent therapeutic options is still an important task. In this study, we report that a late-stage drug candidate, otamixaban, inhibits SARS-CoV-2 cell entry. We show that otamixaban suppresses TMPRSS2 activity and SARS-CoV-2 infection of a human lung cell line, although with lower potency than camostat or nafamostat. In contrast, otamixaban inhibits SARS-CoV-2 infection of precision cut lung slices with the same potency as camostat. Furthermore, we report that otamixaban's potency can be significantly enhanced by (sub-) nanomolar nafamostat or camostat supplementation. Dominant molecular TMPRSS2-otamixaban interactions are assessed by extensive 109 μs of atomistic molecular dynamics simulations. Our findings suggest that combinations of otamixaban with supplemental camostat or nafamostat are a promising option for the treatment of COVID-19

東南アジアの持続的発展を考える (3) : タイ王国における自動車，半導体，エピ養殖

1. はじめに　2. 調査日程のあらまし　3. タイ王国投資委員会(BOI)　4. 工業団地と日系企業　5. ジェトロ・海外ビジネス・サポートセンター　6. 塩田とエピ養殖　7. おわりに

Molecular mechanism of inhibiting the SARS-CoV-2 cell entry facilitator TMPRSS2 with camostat and nafamostat

The entry of the coronavirus SARS-CoV-2 into human lung cells can be inhibited by the approved drugs camostat and nafamostat. Here we elucidate the molecular mechanism of these drugs by combining experiments and simulations. In vitro assays confirm that both drugs inhibit the human protein TMPRSS2, a SARS-Cov-2 spike protein activator. As no experimental structure is available, we provide a model of the TMPRSS2 equilibrium structure and its fluctuations by relaxing an initial homology structure with extensive 330 microseconds of all-atom molecular dynamics (MD) and Markov modeling. Through Markov modeling, we describe the binding process of both drugs and a metabolic product of camostat (GBPA) to TMPRSS2, reaching a Michaelis complex (MC) state, which precedes the formation of a long-lived covalent inhibitory state. We find that nafamostat has a higher MC population than camostat and GBPA, suggesting that nafamostat is more readily available to form the stable covalent enzyme-substrate intermediate, effectively explaining its high potency. This model is backed by our in vitro experiments and consistent with previous virus cell entry assays. Our TMPRSS2-drug structures are made public to guide the design of more potent and specific inhibitors

Choosing best practices for managing impacts of trawl fishing on seabed habitats and biota

Bottom trawling accounts for almost one quarter of global fish landings but may also have significant and unwanted impacts on seabed habitats and biota. Management measures and voluntary industry actions can reduce these impacts, helping to meet sustainability objectives for fisheries, conservation and environmental management. These include changes in gear design and operation of trawls, spatial controls, impact quotas and effort controls. We review nine different measures and actions and use published studies anda simple conceptual model to evaluate and compare their performance. The risks and benefits of these management measures depend on the extent to which the fishery is already achieving management objectives for target stocks and the characteristics of the management system that is already in place. We offer guidance on identifying best practices for trawl-fisheries management and show that best practices and their likelihood of reducing trawling impacts depend on local, national and regional management objectives and priorities, societal values and resources for implementation. There is no universalbest practice, and multiple management measures and industry actions are required to meet sustainability objectives and improve trade-offs between food production and environmental protection