Exploration of Pyrazolo[1,5-a]pyrimidines as Membrane-Bound Pyrophosphatase Inhibitors

Inhibition of membrane-bound pyrophosphatase (mPPase) with small molecules offer a new approach in the fight against pathogenic protozoan parasites. mPPases are absent in humans, but essential for many protists as they couple pyrophosphate hydrolysis to the active transport of protons or sodium ions across acidocalcisomal membranes. So far, only few nonphosphorus inhibitors have been reported. Here, we explore the chemical space around previous hits using a combination of screening and synthetic medicinal chemistry, identifying compounds with low micromolar inhibitory activities in the Thermotoga maritima mPPase test system. We furthermore provide early structure-activity relationships around a new scaffold having a pyrazolo[1,5-a]pyrimidine core. The most promising pyrazolo[1,5-a]pyrimidine congener was further investigated and found to inhibit Plasmodium falciparum mPPase in membranes as well as the growth of P. falciparum in an ex vivo survival assay.     

Integrating Bayesian Inference with Scanning Probe Experiments for Robust Identification of Surface Adsorbate Configurations

Controlling the properties of organic/inorganic materials requires detailed knowledge of their molecular adsorption geometries. This is often unattainable, even with current state-of-the-art tools. Visualizing the structure of complex non-planar adsorbates with atomic force microscopy (AFM) is challenging, and identifying it computationally is intractable with conventional structure search. In this fresh approach, cross-disciplinary tools are integrated for a robust and automated identification of 3D adsorbate configurations. Bayesian optimization is employed with first-principles simulations for accurate and unbiased structure inference of multiple adsorbates. The corresponding AFM simulations then allow fingerprinting adsorbate structures that appear in AFM experimental images. In the instance of bulky (1S)-camphor adsorbed on the Cu(111) surface, three matching AFM image contrasts are found, which allow correlating experimental image features to distinct cases of molecular adsorption.     

Effect of heat‐treatment on the performance of gas barrier layers applied by atomic layer deposition onto polymer‐coated paperboard

The effect of heat treatment on the gas barrier of the polymer‐coated board further coated with an Al₂O₃ layer by atomic layer deposition (ALD) was studied. Heat treatment below the melting point of the polymer followed by quenching at room temperature was used for the polylactide‐coated board [B(PLA)], while over‐the‐melting‐point treatment was utilized for the low‐density polyethylene‐coated board [B(PE)] followed by quenching at room temperature or in liquid nitrogen. Heat treatment of B(PLA) and B(PE) followed by quenching at room temperature improved the water vapor barrier. However, because of the changes in the polymer morphology, quenching of B(PE) with liquid nitrogen impaired the same barrier. No improvement in oxygen barrier was observed explained by, e.g., the spherulitic structure of PLA and the discontinuities and possible short‐chain amorphous material around the spherulites forming passages for oxygen molecules. This work emphasizes the importance of a homogeneous surface prior to the ALD growth Al₂O₃ barrier layer. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Modification of buffered peptone water for improved recovery of heat-injured Salmonella Typhimurium

Abstract: Rapid detection of Salmonella in foods is often limited by the high demand for the sensitivity of detection, poor physiological conditions of the target cells, and high concentration of background flora. In this study, the conditions of nonselective enrichment cultivation were modified in order to improve the quantitative detection of heat‐injured Salmonella in minced meat. The effect of the modifications on the recovery was observed by means of RNA‐based sandwich hybridization, which was adjusted for the quantification of Salmonella enterica 23S rRNA in crude cell extracts. The supplementation of buffered peptone water with the enzyme‐controlled substrate delivery system EnBase‐Flo^® and ferrioxamine E was shown to improve the recovery of cells in both single strain cultures and in the presence of minced meat. The presented results can be used for the development of more efficient enrichment cultivation media for faster detection of food borne Salmonella.     

Influence of powder composition and manufacturing method on electrical and chromium barrier properties of atmospheric plasma sprayed spinel coatings prepared from MnCo2O4 and Mn2CoO4 + Co powders on Crofer 22 APU interconnectors

Protective coatings based on manganese cobalt oxide spinels are required in solid oxide fuel cells (SOFCs) to prevent the evaporation of volatile Cr(VI)-compounds from the metallic interconnectors and to minimize high temperature corrosion. Atmospheric plasma spraying (APS) was used to manufacture dense manganese cobalt oxide protective coatings on Crofer 22 APU substrates by employing two different spinel powders. The spray powders were MnCo₂O₄ and Mn₂CoO₄ + Co (equivalence for Mn_1.5Co_1.5O₄). The Mn₂CoO₄ + Co powder was prepared by agglomerating the oxide powder with fine metallic cobalt powder. The coated substrates were oxidized at 700 °C in air for 1000 h. During the high temperature oxidation, a four-point on-line measurement technique with a current density of 640 mA/cm² was simultaneously used for area specific resistance (ASR) studies. The coatings were characterized by X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), an energy dispersive spectrometer (EDS) and Raman spectroscopy.     

Evaluation of a gas chromatographic method for detection of irradiation of chicken and a chicken meat product

A method was developed for the detection of irradiation of chicken and chicken meat products. The method consists of the extraction of fat from chicken skin or a chicken meat product, separation of hydrocarbons with an alumina column and gas chromatography (GC) and GC-mass spectrometry analyses of the hydrocarbons 16:2, 16:3, 17:1 and 17:2 formed from oleic, linoleic and stearic acids during irradiation. These hydrocarbons were only detected in irradiated samples at doses of 5 and 10 kGy. The mean concentrations of the hydrocarbons were linearly related to the dose levels of irradiation in the case of chicken fat. The concentrations of two of the hydrocarbons (16:2 and 17:1) gave the best correlation with dose. When a dose of 10 kGy was used, the concentrations of major degradation products were 1.5-5.0 mg/kg fat. The same relationship was not found in the case of chicken meat products because the amounts of hydrocarbons detected after irradiation with the same doses were similar. On the basis of this study it was clearly demonstrated that it is possible to judge analytically whether or not a chicken sample or a chicken meat product has been irradiated at doses of 5 or 10 kGy. It should also be possible to recognise samples irradiated with doses below 5 kGy.     

Manufacturing of prestressed piezoelectric unimorphs using a postfired biasing layer

A novel manufacturing method for prestressed piezoelectric unimorphs is introduced and the actuator properties are examined. Prestressed PZT 5A and PZT 5H unimorphs with piezo material thickness of 250 microm and 375 microm were manufactured by using sintering and thermal shrinkage of the prestressing material. The process was carried out by screen printing a layer of AgPd paste on one side of the sintered bulk ceramic. As an alternative method, dielectric low temperature co-fired ceramic (LTCC) tape was used as the prestressing material. Different configurations were tested to obtain high displacements and to make a comparison between materials. After firing, the samples were poled, and the displacement versus load characteristics of the resulting actuators were investigated. A maximum displacement of 118 microm was obtained from a 250 microm thick, prestressed PZT 5H actuator with a diameter of 25 mm, in which LTCC tape was used as the prestressing layer. Similarly, the PZT 5H material provided a maximum displacement of 63 microm with a screen-printed AgPd prestressing layer. The manufacturing method described offers a novel approach for the production of a wide range of integrated active structures on, for instance, an LTCC circuit board. This is especially important because piezoelectric bulk materials with high piezoelectric coefficients can be used to produce high displacements.     

Feasibility of pulse combustion in micro gas turbines

In gas turbines, a fast decrease of efficiency appears when the output decreases; the efficiency of a large gas turbine (20…30 MW) is in the order of 40 %, the efficiency of a 30 kW gas turbine with a recuperator is in the order of 25 %, but the efficiency of a very small gas turbine (2…6 kW) in the order of 4…6 % (or 8…12 % with an optimal recuperator). This is mainly a result of the efficiency decrease in kinetic compressors, due to the Reynolds number effect. Losses in decelerating flow in a flow passage are sensitive to the Reynolds number effects. In contrary to the compression, the efficiency of expansion in turbines is not so sensitive to the Reynolds number; very small turbines are made with rather good efficiency because the flow acceleration stabilizes the boundary layer. This study presents a system where the kinetic compressor of a gas turbine is replaced with a pulse combustor. The combustor is filled with a combustible gas mixture, ignited, and the generated high pressure gas is expanded in the turbine. The process is repeated frequently, thus producing a pulsating flow to the turbine; or almost a uniform flow, if several parallel combustors are used and triggered alternately in a proper way. Almost all the compression work is made by the temperature increase from the combustion. This gas turbine type is investigated theoretically and its combustor also experimentally with the conclusion that in a 2 kW power size, the pulse flow gas turbine is not as attractive as expected due to the big size and weight of parallel combustors and due to the efficiency being in the order of 8 % to 10 %. However, in special applications having a very low power demand, below 1000 W, this solution has better properties when compared to the conventional gas turbine and it could be worth of a more detailed investigation.