Understanding Lipase Action and Selectivity

In this article, a survey of recent lipase research, with special emphasis on molecular structure-function relationships, is presented. Determination of crystallographic structures of lipases from microbial and mammalian origin has shed light on the molecular mechanism of lipase catalyzed acyl ester hydrolysis. A catalytic triad similar to serine proteases is responsible for the cleavage of substrate ester bonds, involving the formation of an acyl-enzyme intermediate. Comparative structural studies revealed a common three dimensional fold and a superimposable topology of the catalytic machinery in lipases, esterases, and other hydrolytic enzymes. Availability of three dimensional structures is the basis for .understanding the mechanism of lipase catalysis and for elucidation of the molecular interactions that result in variant selectivities towards triacylglycerols and their analogs

Pharmacokinetic study of praziquantel enantiomers and its main metabolite R-trans-4-OH-PZQ in plasma, blood and dried blood spots in Opisthorchis viverrini-infected patients

Praziquantel (PZQ) is the treatment of choice for infections with the liver fluke Opisthorchis viverrini, a major health problem in Southeast Asia. However, pharmacokinetic (PK) studies investigating the disposition of PZQ enantiomers (R- and S-PZQ) and its main metabolite, R-trans-4-OH-PZQ, in diseased patients are lacking. The implementation of a dried blood spot (DBS) sampling technique would ease the performance of PK studies in remote areas without clinical facilities. The aim of the present study is to provide data on the disposition of PZQ enantiomers and R-trans-4-OH-PZQ in opisthorchiasis patients and to validate the use of DBS compared to plasma and blood sampling.; PZQ was administered to nine O. viverrini-infected patients at 3 oral doses of 25 mg/kg in 4 h intervals. Plasma, blood and DBS were simultaneously collected at selected time points from 0 to 24 h post-treatment. PK parameters were determined using non-compartmental analysis. Drug concentrations and areas under the curve (AUC0-24h) measured in the 3 matrices were compared using Bland-Altman analysis. We observed plasma AUC0-24hs of 1.1, 9.0 and 188.7 μg/ml*h and half-lives of 1.1, 3.3 and 6.4 h for R-PZQ, S-PZQ and R-trans-4-OH, respectively. Maximal plasma concentrations (Cmax) of 0.2, 0.9 and 13.9 μg/ml for R-PZQ, S-PQZ and R-trans-4-OH peaked at 7 h for PZQ enantiomers and at 8.7 h for the metabolite. Individual drug concentration measurements and patient AUC0-24hs displayed ratios of blood or DBS versus plasma between 79-94% for R- and S-PZQ, and between 108-122% for R-trans-4-OH.; Pharmacodynamic (PD) in vitro studies on PZQ enantiomers and R-trans-4-OH-PZQ are necessary to be able to correlate PK parameters with efficacy. DBS appears to be a valid alternative to conventional venous sampling for PK studies in PZQ-treated patients

Aynak : a world-class sediment-hosted copper deposit, Afghanistan

The Aynak copper deposit, located 30 km south of Kabul in Afghanistan, was discovered by Soviet geologists in the 1970s. Extensive exploration undertaken in the area between 1974-80 included several hundred boreholes, seventy trenches and nine exploratory adits. This delineated several large ore bodies and smaller lenses with a total “drill-indicated resource” of 240 Mt at 2.3% Cu (ESCAP, 1995). The mineralisation at Aynak consists of disseminated bornite and chalcopyrite, mainly concentrated in a stratabound orebody in a cyclic succession of metamorphosed dolomites, marls, siltstones and carbonaceous pelites. A model proposes Cu was leached from underlying volcanic rocks and flowed up faults to deposit Cu sulphides into overlying sediments

Feasibility Study on a Literary Translation Prize: Final Report

First paragraph: The aim of this study is to assess the feasibility of successfully creating a European award for literary translation and, in this perspective, to develop a set of models and variants for its possible implementation. The study presents as well potential benefits and constraints by defining the modalities to organise such a prize in accordance to the European Commission's call no. EAC/35/2009 and the steps as proposed in the respective tender and inceptive report presented to the European Commission by Rüdiger Wischenbart Content and Consulting

Experimental investigation of high speed milling of aluminium alloy

Sve veći zahtjevi kupaca za kvalitetnijim proizvodima prisilili su proizvodnu industriju da neprestano usavršava kontrolu kvalitete i tehnologije obrade. Jedan od osnovnih postupaka rezanja metala je glodanje. Cilj ovoga rada je istražiti optimalne parametre rezanja legure AlMgSi (EN-AW 6060), jedne od najčešće korištenih legura aluminija, primjenom čeonih glodala od neobloženog cementnog karbida. Analizirao se utjecaj geometrije alata (ugao zavojnice) i reznih uvjeta (brzina rezanja i veličina posmaka) na površinsku obradu tijekom brzog glodanja aluminijske legure. Djelovanje parametara na površinsku hrapavost ustanovljeno je analizom varijance (ANOVA). Analizirano je djelovanje parametara rezanja na indekse hrapavosti površine. Rezultati su prodiskutirani i procijenjeni.The customer´s growing demand for higher quality products has forced manufacturing industry to continuously progress in quality control and machining technologies. One of the fundamental metal cutting processes is milling. The aim of this study is to investigate optimum cutting parameters of AlMgSi alloy (EN-AW 6060), which is one of the most commonly used aluminium alloys, using uncoated cemented carbide end mills. The influence of tool geometry (helix angle) and cutting conditions (cutting velocity, and feed rate) on the surface finish produced during high speed milling of aluminium alloy have been investigated. The significance of the parameters on surface roughness has been established with analysis of variance (ANOVA). The cutting parameters regarding surface roughness performance indexes are analysed, and the findings are discussed and evaluated

Large scale structure around a z=2.1 cluster

The most prodigious starburst galaxies are absent in massive galaxy clusters today, but their connection with large scale environments is less clear at $z\gtrsim2$. We present a search of large scale structure around a galaxy cluster core at $z=2.095$ using a set of spectroscopically confirmed galaxies. We find that both color-selected star-forming galaxies (SFGs) and dusty star-forming galaxies (DSFGs) show significant overdensities around the $z=2.095$ cluster. A total of 8 DSFGs (including 3 X-ray luminous active galactic nuclei, AGNs) and 34 SFGs are found within a 10 arcmin radius (corresponds to $\sim$15 cMpc at $z\sim2.1$) from the cluster center and within a redshift range of $\Delta z=0.02$, which leads to galaxy overdensities of $\delta_{\rm DSFG}\sim12.3$ and $\delta_{\rm SFG}\sim2.8$. The cluster core and the extended DSFG- and SFG-rich structure together demonstrate an active cluster formation phase, in which the cluster is accreting a significant amount of material from large scale structure while the more mature core may begin to virialize. Our finding of this DSFG-rich structure, along with a number of other protoclusters with excess DSFGs and AGNs found to date, suggest that the overdensities of these rare sources indeed trace significant mass overdensities. However, it remains puzzling how these intense star formers are triggered concurrently. Although an increased probability of galaxy interactions and/or enhanced gas supply can trigger the excess of DSFGs, our stacking analysis based on 850 $\mu$m images and morphological analysis based on rest-frame optical imaging do not show such enhancements of merger fraction and gas content in this structure.Comment: 11 pages, 4 figures, ApJ accepte

CYBER-PHYSICAL SYSTEMS TECHNOLOGIES AS A KEY FACTOR IN THE PROCESS OF INDUSTRY 4.0 AND SMART MANUFACTURING DEVELOPMENT

The continuous development of production processes is currently observed in the fourth industrial revolution, where the key place is the digital transformation of production is known as Industry 4.0. The main technologies in the context of Industry 4.0 consist Cyber-Physical Systems (CPS) and Internet of Things (IoT), which create the capabilities needed for smart factories. Implementation of CPS solutions result in new possibilities creation – mainly in areas such as remote diagnosis, remote services, remote control, condition monitoring, etc. In this paper, authors indicated the importance of Cyber-Physical Systems in the process of the Industry 4.0 and the Smart Manufacturing development. Firstly, the basic information about Cyber-Physical Production Systems were outlined. Then, the alternative definitions and different authors view of the problem were discussed. Secondly, the conceptual model of Cybernetic Physical Production System was presented. Moreover, the case study of proposed solution implementation in the real manufacturing process was presented. The key stage of the verification concerned the obtained data analysis and results discussion