Toward the Development of Dual‐Targeted Glyceraldehyde‐3‐phosphate Dehydrogenase/Trypanothione Reductase Inhibitors against Trypanosoma brucei and Trypanosoma cruzi

A significant improvement in the treatment of trypanosomiases has been achieved with the recent development of nifurtimox–eflornithine combination therapy (NECT). As an alternative to drug combinations and as a means to overcome most of the antitrypanosomatid drug discovery challenges, a multitarget drug design strategy has been envisaged. To begin testing this hypothesis, we designed and developed a series of quinone–coumarin hybrids against glyceraldehyde‐3‐phosphate dehydrogenase/trypanothione reductase (GAPDH/TR). These enzymes belong to metabolic pathways that are vital to Trypanosoma brucei and Trypanosoma cruzi, and have thus been considered promising drug targets. The synthesized molecules were characterized for their dual‐target antitrypanosomal profile, both in enzyme assays and in in vitro parasite cultures. The merged derivative 2‐{[3‐(3‐dimethylaminopropoxy)‐2‐oxo‐2H‐chromen‐7‐yl]oxy}anthracene‐1,4‐dione ( 10 ) showed an IC₅₀ value of 5.4 μM against TbGAPDH and a concomitant K_i value of 2.32 μM against TcTR. Notably, 2‐{4‐[6‐(2‐dimethylaminoethoxy)‐2‐oxo‐2H‐chromen‐3‐yl]phenoxy}anthracene‐1,4‐dione (compound 6 ) displayed a remarkable EC₅₀ value for T. brucei parasites (0.026 μM ) combined with a very low cytotoxicity toward mammalian L6 cells (7.95 μM ). This promising low toxicity of compound 6 might be at least partially due to the fact that it does not interfere with human glutathione reductase.     

Efficiently Detecting Metallodrug–Protein Adducts: Ion Trap versus Time‐of‐Flight Mass Analyzers

Modern mass spectrometry techniques have increasingly found use in studies on the binding of anticancer metallodrugs to potential cellular targets. In this context, investigations on the detection efficiency of adduct formation between antiproliferative Ru(arene) complexes and proteins in dependence of the mass analyzer used in the electrospray ionization (ESI) mass spectrometer are presented. The potential in detecting adducts between the metal center and the protein was found to be dependent on the mass analyzer and the denticity of the metal–protein interaction. This might be related to the design of the mass analyzers with different conditions in the ion travelling pathways, which affects adducts when the protein acts as a monodentate ligand more highly than in cases when the protein is a multidentate ligand. This could also impact the biological activity and indicate different pathways of metabolism of biomolecule adducts.     

Comparative performance of healthcare and transport PFI projects: Empirical study on the influence of key factors

Private Finance Initiative (PFI) has been used on many projects in the UK in the delivery of public services. Cost, time and risk performance in public projects was anticipated to be improved by the superior skills of the private sector. So far, there are limited empirical studies on the life cycle performance of PFI projects, especially performance comparison between different sectors. This study investigated and compared variations in costs, time, and client requirements tracking it through the strategic business case stage to the operational phase in healthcare and transport sectors. It explored the influence of sector-specific factors, project size and maturity of the PFI on these variations. It used documentary analysis of full business cases of five PFI projects and a questionnaire survey of 44 PFI projects in the UK. The findings reveal that there are still considerable cost and time overruns and requirement changes in PFI projects in both sectors over the development of the project and its early use. The health sector was better than the transport sector for time overruns but was worse on costs. Smaller-value projects outperformed larger projects on cost variations but underperformed on time.     

Transfer of Ultrafine Particles and Air in Multi-storey Buildings

An emerging issue in Denmark is passive smoking in residential buildings where non-smokers are exposed to smoke from their neighbours. There are various ways that smoke is transferred from one flat to another. The air transfer rate between two flats in a multi-storey building depends on its construction, tightness and age. This paper presents results of a study on the transfer of ultrafine particles and tracer gas in an older multi-storey building in Copenhagen. The aim of the study was to quantify the transfer ofultrafine particles and gases from one flat to another fiat before and after sealing the floor. A new floor-sealing method was applied to seal the floor between the two flats. The sealing method was developed by a firm specialising in sealing. Indoor ultrafine particle concentrations and tracer gas were measured continuously in the two fiats during the measuring periods. In the unoccupied fiat, the gas source was N20 and the particle source was burning cigarettes. Reduction of the concentration of ultrafine particles and tracer gas by sealing the floor with polyethylene and joint filler made of bitumen was studied. It was evaluated how the sealing performed with regard to decreasing the amount of ultrafine particles and a tracer gas transferred between two fiats separated by a floor. When the floor between the flats was not sealed, the results showed that about 4% of the ultraflne particles and 14% of the tracer gas were transferred. After sealing, the amount transferred was reduced to 1.6% and 5%, respectively.     

Nanoscale FeS2 (Pyrite) as a Sustainable Thermoelectric Material

We have synthesized undoped, Co-doped (up to 5%), and Se-doped (up to 4%) FeS₂ materials by mechanical alloying in a planetary ball mill and investigated their thermoelectric properties from room temperature (RT) to 600 K. With decreasing particle size, the undoped FeS₂ samples showed higher electrical conductivity, from 0.02 S cm^?1 for particles with 70 nm grain size up to 3.1 S cm^?1 for the sample with grain size of 16 nm. The Seebeck coefficient of the undoped samples showed a decrease with further grinding, from 128 μV K^?1 at RT for the sample with 70-nm grains down to 101 μV K^?1 for the sample with grain size of 16 nm. The thermal conductivity of the 16-nm undoped sample lay within the range from 1.3 W m^?1 K^?1 at RT to a minimal value of 1.2 W m^?1 K^?1 at 600 K. All doped samples showed improved thermoelectric behavior at 600 K compared with the undoped sample with 16 nm particle size. Cobalt doping modified the p-type semiconducting behavior to n-type and increased the thermal conductivity (2.1 W m^?1 K^?1) but improved the electrical conductivity (41 S cm^?1) and Seebeck coefficient (-129 μV K^?1). Isovalent selenium doping led to a slightly higher thermal conductivity (1.7 W m^?1 K^?1) as well as to an improved electrical conductivity (26 S cm^?1) and Seebeck coefficient (110 μV K^?1). The ZT value of FeS₂ was increased by a factor of five by Co doping and by a factor of three by Se doping.     

Sicherheit und rechtliche Herausforderungen in Bezug auf Cloud Computing und Kritische Infrastruktur-IT

The prevalence of machine-to-machine (M2M) will continue to increase because of the connection and interlinking of services in the domain of critical infrastructures (e.g. “smart grids”, traffic management or surveillance systems). This is leading to a constant rise of required computational and storage resources. As field systems typically offer only limited computing and storage capabilities and as many applications require a global view to integrated data from various devices, a natural location to store data and perform analysis tasks is in the Cloud, where an abundance of flexible resources can be used. However, this results in a number of security and privacy challenges in combination with some legal and technical considerations that need to be addressed. In this paper, we will investigate and categorize the above challenges associated with using the Cloud in a critical infrastructure and M2M context.     

Effect of Bismuth Nanotubes on the Thermoelectric Properties of BiSb Alloy Nanocomposites

Bismuth nanotubes have been synthesized and successfully included in Bi_1?x Sb _x nanoalloys to form composite structures. The nanotubes were synthesized by transformation of a β-BiI precursor with n-BuLi solution leading to tubular bismuth structures. The Bi_1?x Sb _x nanoalloys were produced by ball milling. Three series of composite structures were synthesized by including different fractions (0 wt.%, 3 wt.%, 5 wt.%) of nanotubes in nanoalloys of different composition x. Investigation of thermoelectric and structural properties revealed a decrease of the thermal conductivity of up to 40% for the composites in comparison with alloys without nanotube inclusions. This effect can be attributed to enhanced phonon scattering. Seebeck coefficients and electrical conductivities were both slightly enhanced in the composite series with 3 wt.% nanotube inclusions, leading to enhancement of $$ ZT \ \left(ZT=\frac {(S^2 \sigma)}{\kappa}\,{ {T}}\right) $$ throughout the series compared with the nanoalloy series without nanotube inclusions.     

Detection and Identification of Oestrogen‐Active Substances in Plastic Food Packaging Migrates

Migrates from plastic food packaging were tested for oestrogen activity by yeast oestrogen screen and subsequently analysed by gas chromatography—mass spectrometry and high‐performance liquid chromatography—mass spectrometry to identify oestrogen‐active chemicals. Plastic samples were migrated according to EC 10/2011 with worst case scenarios being used. Food simulants consisted of either 10–95% ethanol or ultrapure water. Migrates were concentrated afterwards by solid phase extraction. Food contact material tested included polyethylene terephthalate, polypropylene, polyethylene, polystyrene and composite films. Oestrogenic activity ranging from 0.7 to 59 ng/l 17ß‐estradiol equivalents was detected in seven out of 42 samples tested. The highest activity was found in a composite film sample. All 11 polyethylene terephthalate samples tested negative for oestrogen activity. A number of chemicals with known or supposed oestrogen activity were identified in migrates of oestrogen‐active samples. These include butylated hydroxytoluene, 1,3‐diphenylpropane, 1,2‐diphenylcyclobutane and dibutyl phthalate. Copyright © 2013 John Wiley & Sons, Ltd.     

The Effect of High Pressure Processing on the Integrity of Polymeric Packaging – Analysis and Categorization of Occurring Defects

As high‐pressure processing is used increasingly for the treatment of packed products, different packaging has been investigated with respect to their structural behaviour and stability under high‐pressure processing. Often, failures and changes of the polymeric structure occur. Common damage symptoms of high‐pressure‐treated packaging materials are defined and classified in this review. These damage symptoms are allocated to the physico‐chemical effects that created them. The effects may be separated into direct effects induced by the action of the high‐pressure alone and indirect effects that are mediated via compressed contents of the package, i.e. filled product and gaseous headspace. The direct effects split up again in reversible and irreversible structural changes. The indirect effects are generated by compressed headspace gases, other compressed substances and the consequences of increased amounts of gases dissolved in the polymers. If applicable, current theoretical approaches have been allocated to the different categories of damage. Copyright © 2013 John Wiley & Sons, Ltd.