Shigella Outer Membrane Vesicles as Promising Targets for Vaccination

The clinical symptoms of shigellosis, a gastrointestinal infection caused by Shigella spp. range from watery diarrhea to fulminant dysentery. Endemic infections, particularly among children in developing countries, represent the majority of clinical cases. The situation is aggravated due to the high mortality rate of shigellosis, the rapid dissemination of multi-resistant Shigella strains and the induction of only serotype-specific immunity. Thus, infection prevention due to vaccination, encompassing as many of the circulating serotypes as possible, has become a topic of interest. However, vaccines have turned out to be ineffective so far. Outer membrane vesicles (OMVs) are promising novel targets for vaccination. OMVs are constitutively secreted by Gram-negative bacteria including Shigella during growth. They are composed of soluble luminal portions and an insoluble membrane and can contain toxins, bioactive periplasmic and cytoplasmic (lipo-) proteins, (phospho-) lipids, nucleic acids and/or lipopolysaccharides. Thus, OMVs play an important role in bacterial cell–cell communication, growth, survival and pathogenesis. Furthermore, they modulate the secretion and transport of biomolecules, the stress response, antibiotic resistance and immune responses of the host. Thus, OMVs serve as novel secretion machinery. Here, we discuss the current literature and highlight the properties of OMVs as potent vaccine candidates because of their immunomodulatory, antigenic and adjuvant properties.     

Electrorefining of aluminium scrap from chloride melts

The production of aluminium of primary quality from scrap by electrorefining may become an option of strategic importance. Two important requirements are: (i) substantial energy savings compared to electrowinning, and (ii) easy recycling of alloying elements and molten electrolyte without ecological hazards. The use of molten chloride instead of fluoride electrolytes is preferred as emissions are low, purification of contaminated salts in aqueous solution is easy and oxide ceramic materials for cells and diaphragms can be used. The measurement of formal potentials of most important alloying elements shows that only manganese should be expected to cause trouble in electrorefining of aluminium scrap from alkali chloride melts. Preparative batch refining experiments show that all these alloying metals can be easily separated; manganese is very likely because its activity in aluminium is decreased by alloying or compound formation in aluminium. Results with cells divided by alumina diaphragms show that energy consumptions can be kept below 5 kWh (kg Al)^–1.     

Stir bar sorptive extraction and trace analysis of selected endocrine disruptors in water, biosolids and sludge samples by thermal desorption with gas chromatography-mass spectrometry

Stir bar sorptive extraction (SBSE) in combination with thermal desorption coupled to gas chromatography-mass spectrometry (GC-MS) was successfully applied to analyze a range of endocrine disrupting compounds (EDCs) in wastewater, solids and sludge. The targeted EDCs include sex steroid hormones, phthalates, alkylphenols and tamoxifen. Recovery for the EDCs using this analytical technique ranged from 44% to 128%. Limit of detection (LOD) of the compounds was 2.0 ng/L for water samples and 0.02 ng/g for solid samples, whereas the limit of quantitation (LOQ) was 5.0 ng/L for water samples and 0.06 ng/g for solid samples. When this analytical technique was applied to measure EDC concentration in a biological nutrient removal (BNR) wastewater treatment plant located in South East Queensland, Australia, the results showed that there were high amounts of phthalates, alkylphenols and female hormones present in the raw influent wastewater and solids. These concentrations were dramatically reduced after passing through the various treatment zones of the bioreactor (anaerobic, aerobic and anoxic).     

Enzymes in organic synthesis. 2. Synthesis of enantiomerically pure prostaglandin intermediates by Enzymatic Hydrolysis of (1SR, 5RS, 6RS, 7RS)-7-acetoxy-6-acetoxymethyl-2-oxabicyclo[3.3.0]octan-3-one

Subtilisin DY as well as alkaline protease from Bacillus licheniformis 41 p catalyze the hydrolysis of (1SR, 5RS, 6RS, 7RS)-7-acetoxy-6-acetoxymethyl-2-oxabicyclo[3.3.0]octan-3-one ( rac-1 ) with practically useful enantio- and regioselectivity. Under the hitherto found optimal conditions (1S, 5R, 6R, 7R)-7-hydroxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one ( 4 ), an important intermediate in prostaglandin syntheses, could be prepared in a yield of 16% with an enantiomeric excess of 99%. The enantiomer ( ent-4 ) was obtained with the same enantiomeric excess in 20% yield. The chemical yields are related to the racemic starting material rac-1 .     

Planar multimode detector arrays for infrared and millimeter-wave applications

A new type of detector array is described. By means of a suitably designed metallic network, many detector elements (each individually small compared to wavelength) are assembled into an impedance-matched termination for radiation incident normally on the plane of the device. Residual reactance is tuned out by means of a movable backshort. An array of 400 bismuth-film microbolometers with a total area of 1 cm²has been tested at 215 GHz. A coupling efficiency of approximately 60 percent was observed. The detector has aD*of4 times 10^{8}cm . Hz^1/2/W at room temperature with response time on the order of2 times 10^{-7}s. Similar arrays of Schottky and SIS diodes can probably be constructed.     

Energy-aware resource sharing with mobile devices

Ad hoc sharing of resources by offering remote services through an appropriate infrastructure enables new applications for mobile devices. However, the willingness of device owners to contribute resources to such applications remains low as long as they cannot control the amount of energy spent in sharing. In this paper, we present a framework for energy-aware resource sharing among mobile devices of various kinds that comprises (1) energy-aware strategies for selecting remote service providers and (2) a generic energy estimator for forecasting and accounting the energy consumption of a remote service call. To illustrate the benefit of (1), we show by simulation that the battery lifetime of devices running the framework can be extended up to 40% by service selection strategies that take into account the energy cost of a requested service compared to energy-unaware (random) service selection. For providing the energy-related input for service selection, we present (2) a generic estimator that can be customized easily for different hardware-platforms by solving a linear equation system with coefficients derived from benchmark measurements. We present a prototype-based case study for three different platforms, the Nokia N810, the HTC Touch Cruise and the Samsung Galaxy S showing that for all of them the estimation error is below 10% for 90% of the service calls. Furthermore, measurements conducted with a prototype implementation of the resource sharing framework show that battery lifetime can in fact be extended by energy-aware service selection strategies.     

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated K_i ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification.