Development of an SPS/DPS hydrogen shrouded cryogenic helium storage system Summary report

Storag of helium gas at higher temperature and pressure using liquid hydrogen refrigerant to surround primary fluid within inner vesse

Development of an SPS/DPS Hydrogen Shrouded Cryogenic Helium Storage System Final Report, Jul. 1967 - Sep. 1968

Development of SPS/DPS hydrogen shrouded cryogenic helium storage syste

The value-added of primary schools: what is it really measuring?

This paper compares the official value-added scores in 2005 for all primary schools in three adjacent LEAs in England with the raw-score Key Stage 2 results for the same schools. The correlation coefficient for the raw- and value-added scores of these 457 schools is around +0.75. Scatterplots show that there are no low attaining schools with average or higher value-added, and no high attaining schools with below average value-added. At least some of the remaining scatter is explained by the small size of some schools. Although some relationship between these measures is to be expected – so that schools adding considerable value would tend to have high examination outcome scores – the relationship shown is too strong for this explanation to be considered sufficient. Value-added analysis is intended to remove the link between a schools’ intake scores and their raw-score outcomes at KS2. It should lead to an estimate of the differential progress made by pupils, assessed between schools. In fact, however, the relationship between value-added and raw scores is of the same size as the original relationship between intake scores and raw-scores that the value-added is intended to overcome. Therefore, however appealing the calculation of value-added figures is, their development is still at the stage where they are not ready to move from being a research tool to an instrument of judgement on schools. Such figures may mislead parents, governors and teachers and, even more importantly, they are being used in England by OFSTED to pre-determine the results of school inspections

On the Maximum Crossing Number

Research about crossings is typically about minimization. In this paper, we consider \emph{maximizing} the number of crossings over all possible ways to draw a given graph in the plane. Alpert et al. [Electron. J. Combin., 2009] conjectured that any graph has a \emph{convex} straight-line drawing, e.g., a drawing with vertices in convex position, that maximizes the number of edge crossings. We disprove this conjecture by constructing a planar graph on twelve vertices that allows a non-convex drawing with more crossings than any convex one. Bald et al. [Proc. COCOON, 2016] showed that it is NP-hard to compute the maximum number of crossings of a geometric graph and that the weighted geometric case is NP-hard to approximate. We strengthen these results by showing hardness of approximation even for the unweighted geometric case and prove that the unweighted topological case is NP-hard.Comment: 16 pages, 5 figure

Probing the Interaction of the Diarylquinoline TMC207 with Its Target Mycobacterial ATP Synthase

Infections with Mycobacterium tuberculosis are substantially increasing on a worldwide scale and new antibiotics are urgently needed to combat concomitantly emerging drug-resistant mycobacterial strains. The diarylquinoline TMC207 is a highly promising drug candidate for treatment of tuberculosis. This compound kills M. tuberculosis by binding to a new target, mycobacterial ATP synthase. In this study we used biochemical assays and binding studies to characterize the interaction between TMC207 and ATP synthase. We show that TMC207 acts independent of the proton motive force and does not compete with protons for a common binding site. The drug is active on mycobacterial ATP synthesis at neutral and acidic pH with no significant change in affinity between pH 5.25 and pH 7.5, indicating that the protonated form of TMC207 is the active drug entity. The interaction of TMC207 with ATP synthase can be explained by a one-site binding mechanism, the drug molecule thus binds to a defined binding site on ATP synthase. TMC207 affinity for its target decreases with increasing ionic strength, suggesting that electrostatic forces play a significant role in drug binding. Our results are consistent with previous docking studies and provide experimental support for a predicted function of TMC207 in mimicking key residues in the proton transfer chain and blocking rotary movement of subunit c during catalysis. Furthermore, the high affinity of TMC207 at low proton motive force and low pH values may in part explain the exceptional ability of this compound to efficiently kill mycobacteria in different microenvironments

The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis.

An estimated one-third of the world population is latently infected with Mycobacterium tuberculosis. These nonreplicating, dormant bacilli are tolerant to conventional anti-tuberculosis drugs, such as isoniazid. We recently identified diarylquinoline R207910 (also called TMC207) as an inhibitor of ATP synthase with a remarkable activity against replicating mycobacteria. In the present study, we show that R207910 kills dormant bacilli as effectively as aerobically grown bacilli with the same target specificity. Despite a transcriptional down-regulation of the ATP synthase operon and significantly lower cellular ATP levels, we show that dormant mycobacteria do possess residual ATP synthase enzymatic activity. This activity is blocked by nanomolar concentrations of R207910, thereby further reducing ATP levels and causing a pronounced bactericidal effect. We conclude that this residual ATP synthase activity is indispensable for the survival of dormant mycobacteria, making it a promising drug target to tackle dormant infections. The unique dual bactericidal activity of diarylquinolines on dormant as well as replicating bacterial subpopulations distinguishes them entirely from the current anti-tuberculosis drugs and underlines the potential of R207910 to shorten tuberculosis treatment. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

The Role of Structural Flexibility in Plasmon Driven Coupling Reactions Kinetic Limitations in the Dimerization of Nitro Benzenes

Abstract The plasmon-driven dimerization of 4-nitrothiophenol (4NTP) to 4-4′-dimercaptoazobenzene (DMAB) is a testbed for understanding bimolecular photoreactions enhanced by nanoscale metals, in particular, regarding the relevance of electron transfer and heat transfer from the metal to the molecule. By adding a methylene group between the thiol bond and the nitrophenyl, structural flexibility is added to the reactant molecule. Time-resolved surface-enhanced Raman-spectroscopy proves that this (4-nitrobenzyl)mercaptan (4NBM) molecule has a larger dimerization rate and dimerization yield than 4NTP and higher selectivity toward dimerization. X-ray photoelectron spectroscopy and density functional theory calculations show that the electron transfer prefers activation of 4NTP over 4NBM. It is concluded that the rate limiting step of this plasmonic reaction is the dimerization step, which is dramatically enhanced by the additional flexibility of the reactant. This study may serve as an example for using nanoscale metals to simultaneously provide charge carriers for bond activation and localized heat for driving bimolecular reaction steps. The molecular structure of reactants can be tuned to control the reaction kinetics