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ecto-5'-Nucleotidase (eN, CD73) plays a major role in controlling extracellular adenosine levels. eN inhibitors have potential as novel drugs, for example, for the treatment of cancer. In the present study, we synthesized and investigated a series of 55 anthraquinone derivatives as potential inhibitors of eN, 11 of which are novel compounds and another 11 of which had previously been described but have now been synthesized by an improved method. We identified several potent inhibitors of rat eN. The most potent compounds were 1-amino-4-[4-fluoro-2-carboxyphenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (45, PSB-0952, K(i) = 260 nM) and 1-amino-4-[2-anthracenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (52, PSB-0963, 150 nM), with 52 being the most potent eN inhibitor described to date. Selected compounds were further characterized and found to exhibit a competitive mechanism of inhibition. Investigations of ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) and the P2Y receptor subtypes P2Y(2), P2Y(4), P2Y(6), and P2Y(12) showed that compound 45 exhibited the highest degree of selectivity (>150-fold).

2-(Acyl)amino-4H-3,1-benzothiazin-4-ones and related thienothiazinones were identified as structurally novel antagonists at adenosine receptors (ARs). 6-Methyl-2-benzoylamino-4H-3,1-benzothiazin-4-one (10d) was found to be a balanced AR antagonist with affinity for all human (h) subtypes (K(i) hA(1) 65.6 nM; hA(2A) 120 nM; hA(2B) 360 nM; hA(3) 30.4 nM), while in rat (r), 10d was a highly potent A(1)-selective antagonist (rA(1) 7.7 nM; rA(2A) 546 nM; rA(2B) 679 nM, rA(3) >10000 nM). 2-(4-Methylbenzoylamino)-4H-3,1-benzothiazin-4-one (10g) was found to be a potent antagonist at human A(2A) (68.8 nM) and A(3) ARs (23.0 nM) with high selectivity versus the other human AR subtypes. In contrast to A(1) and A(3) ARs, A(2A) and A(2B) ARs tolerated bulky 2-acyl substituents. tert-Butyl (4-oxo-4H-3,1-benzothiazin-2-ylcarbamoyl)benzylcarbamate (15g, K(i) hA(2B) 186 nM; hA(2A) 603 nM) and 4-(4-benzylpiperazine-1-carbonyl)-N-(4-oxo-4H-3,1-benzothiazin-2-yl)benzamide (15k, hA(2A) 69.5 nM; hA(2B) 178 nM) were highly selective versus the other AR subtypes. 2-Acylamino-3,1-benzothiazin-4-ones represent novel scaffolds suitable for the development of potent and selective AR antagonists for each of the four receptor subtypes.

A capillary electrophoresis (CE) method for the characterization of recombinant NTPDase1, 2, and 3, and for assaying NTPDase inhibitors has been developed performing the enzymatic reaction within the capillary. After hydrodynamic injection of plugs of substrate solution with or without inhibitor in reaction buffer, followed by a suspension of an enzyme-containing membrane preparation, and subsequent injection of another plug of substrate solution with or without inhibitor, the reaction took place close to the capillary inlet. After 5 min, the electrophoretic separation of the reaction products was initiated by applying a constant current of j 60 mA. The method employing a polyacrylamide-coated capillary and reverse polarity mode provided baseline resolution of substrates and products within a short separation time of less than 7 min. A 50 mM phosphate buffer (pH 6.5) was used for the separations and the products were detected by their UV absorbance at 210 nm. The MichaelisYMenten constants (K m ) for the recombinant rat NTPDases 1, 2, and 3 obtained with this method were consistent with previously reported data. The inhibition studies revealed pronounced differences in the potency of reactive blue 2, pyridoxalphosphate-6-azophenyl-2 0 ,4 0 -disulfonic acid (PPADS), suramin, and N 6 -diethyl-b,g-dibromomethylene-ATP (ARL67156) towards the NTPDase isoforms. Notably, ARL67156 does not inhibit all NTPDases, having only a minor inhibitory effect on NTPDase2. Dipyridamole is not an inhibitor of the NTPDase isoforms investigated. The new method is fast and accurate, it requires only tiny amounts of material (nanoliter scale), no sample pretreatment and can be fully automated; thus it is clearly superior to the current standard methods.Abbreviations: ARL67156 -N 6 -diethyl-b,g-dibromomethylene-ATP; CE -capillary electrophoresis; CHO -Chinese hamster ovary; EMMA -electrophoretically mediated microanalysis; (E)-NTPDase -(ecto)-nucleoside triphosphate diphosphohydrolase; I.S. -internal standard; PPADS -pyridoxalphosphate-6-azophenyl-2 0 ,4 0 -disulfonic acid; RB2 -reactive blue 2

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Technological advancements in various domains have broadened the application horizon of robotics to an incredible extent. Highlighting a very recent application area, this paper presents a comprehensive review of robotics application in food industry. Robots essentially have the potential to transform the processes in food processing and handling, palletizing and packing and food serving. Therefore, recent years witnessed tremendously increased trend of robots deployment in food sector. Consequently, the aspects related with robot kinematics, dynamics, hygiene, economic efficiency, human-robot interaction, safety and protection and operation and maintenance are of critical importance and are discussed in the present review. A comparison of actual robots being used in the industry is also presented. The review reveals that the food serving sector is the new potential area in which ample research opportunities exist by integrating advancements from various technology domains. It is anticipated that wider dissemination of research developments in 'robo-food' will stimulate more collaborations among the research community and contribute to further developments.Keywords: robotics in food industry; cyber physical systems; mechatronics in food handling and processing; food serving robots.Practical Application: Automation in food processing industry.

Miniaturized bioanalytical systems are increasingly being used in the field of biochemical research. Immobilized enzyme microbioreactors in capillary electrophoresis (CE) have been constructed and used to fulfill the increasing demands for miniaturized bioanalytical systems. This manipulation permits low sample consumption, reduced costs, short analysis times and efficient analyses. This review provides an overview of the distinct characteristics of immobilized microbioreactors in CE. After an introduction on miniaturized microreactors, the various methods of enzyme immobilization will be discussed. The emphasis will be on two common constructions of microreactors in CE, i.e. CE-coupled microreactors, and microreactors directly integrated into the CE capillary. Such microbioreactors offer straightforward automation of reaction steps followed by separation in the same capillary.

Last five decades witnessed remarkable developments in linear control systems and thus problems in this subject has been largely resolved. The scope of the present paper is beyond linear solutions. Modern technology demands sophisticated control laws to meet stringent design specifications thus highlighting the increasingly conspicuous position of nonlinear control systems, which is the topic of this paper. Historical role of analytical concepts in analysis and design of nonlinear control systems is briefly outlined. Recent advancements in these systems from applications perspective are examined with critical comments on associated challenges. It is anticipated that wider dissemination of this comprehensive review will stimulate more collaborations among the research community and contribute to further developments.