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In Brazil, the buffalo milk market has been growing. However, identity and quality standards have not been established for this raw material, nor have proper distinctions between buffalo milk and bovine milk been defined. Currently, the State of Rio Grande do Sul (RS) has only three producers that supply raw material for officially marketed derivatives. The aim of this study was to determine the identity and quality standards of raw buffalo milk in this region. Samples were obtained biweekly from three farm cooling tanks between June 2017 and August 2018, to reach a total of 69 samples. The averages for the results of the physicochemical parameters fat, protein, lactose, total solids, SNF (solids-not-fat), calcium, density, FP, acidity and SCC were 5.5 g/100 g, 4.06 g/100 g, 5.07 g/100 g, 15.5 g/100 g, 9.96 g/100 g, 0.161 g/100 g, 1.034 g/ml, −0.527°C, 16°D and 95 × 103 cells/ml, respectively. With reference to the microbiological parameters, the mean of the Standard Plate Count (SPC) and thermotolerant coliforms were 9,0 × 104 CFU/ml and 1.6 × 102 MPN/ml, respectively. Regarding coagulase-positive staphylococci, 36 samples tested positive (52% of total). Neither Salmonella spp. nor Listeria monocytogenes, nor antibiotic or antiparasitic residues were detected in any sample. In conclusion, the buffalo milk used as raw material for dairy products in southern Brazil demonstrated satisfactory physicochemical and microbiological characteristics, in accordance with recent scientific literature.

Xenon oscillations in pressurized water reactors were analyzed, using linear stability analysis and weak nonlinear analysis based on the multiple time-scales method. The dynamics are described by a spatio-temporal nonlinear model, which includes feedback processes of xenon absorption, as well as fuel and coolant temperature changes. It is shown that the homogeneous steady-state solution that describes nominal operation of a large reactor can go through uniform Hopf bifurcations at several values of the neutron flux, and the long-wavelength modes that can grow beyond the instability thresholds are identified. In order to study the dynamics beyond the Hopf bifurcation, a nonlinear equation for the amplitude of the growing oscillatory mode is derived. The amplitude equation is used to identify parameter ranges of bounded periodic oscillations and of oscillations with diverging amplitudes. The approach described may be used to broaden the operational limits required to suppress xenon oscillations for safe operation.

Several studies have addressed the poor stability of meropenem in aqueous solutions, though not considering the main degradation product, the open-ring metabolite (ORM) form. In the present work, we elucidate the metabolic fate of meropenem and ORM from continuous infusion to the human bloodstream. We performed in vitro infusate stability tests at ambient temperature with 2% meropenem reconstituted in 0.9% normal saline, and body temperature warmed buffered human serum with 2, 10, and 50 mg/L meropenem, covering the therapeutic range. We also examined meropenem and ORM levels over several days in six critically ill patients receiving continuous infusions. Meropenem exhibited a constant degradation rate of 0.006/h and 0.025/h in normal saline at 22 °C and serum at 37 °C, respectively. Given that 2% meropenem remains stable for 17.5 h in normal saline (≥90% of the initial concentration), we recommend replacement of the infusate every 12 h. Our patients showed inter-individually highly variable, but intra-individually constant molar ORM/(meropenem + ORM) ratios of 0.21–0.52. Applying a population pharmacokinetic approach using the degradation rate in serum, spontaneous degradation accounted for only 6% of the total clearance.

Significance Chronic HEV infections pose a significant clinical problem in immunocompromised individuals. The lack of an efficient cell culture system has severely limited investigation of the HEV life cycle and the development of effective antivirals. Here we report the establishment of a robust HEV cell culture system in human hepatocytes with viral titers up to 106 FFU/mL. These produced intracellular-derived HEVcc particles demonstrated replication to high viral loads in human liver chimeric mice and were able to efficiently infect primary human as well as porcine hepatocytes. This unique infectious cell culture model provides a powerful tool for the analysis of host–virus interactions that should facilitate the discovery of antiviral drugs for this important zoonotic pathogen., Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and the leading cause for acute viral hepatitis worldwide. The virus is classified as a member of the genus Orthohepevirus A within the Hepeviridae family. Due to the absence of a robust cell culture model for HEV infection, the analysis of the viral life cycle, the development of effective antivirals and a vaccine is severely limited. In this study, we established a protocol based on the HEV genotype 3 p6 (Kernow C-1) and the human hepatoma cell lines HepG2 and HepG2/C3A with different media conditions to produce intracellular HEV cell culture-derived particles (HEVcc) with viral titers between 105 and 106 FFU/mL. Viral titers could be further enhanced by an HEV variant harboring a mutation in the RNA-dependent RNA polymerase. These HEVcc particles were characterized in density gradients and allowed the trans-complementation of subgenomic reporter HEV replicons. In addition, in vitro produced intracellular-derived particles were infectious in liver-humanized mice with high RNA copy numbers detectable in serum and feces. Efficient infection of primary human and swine hepatocytes using the developed protocol could be observed and was inhibited by ribavirin. Finally, RNA sequencing studies of HEV-infected primary human hepatocytes demonstrated a temporally structured transcriptional defense response. In conclusion, this robust cell culture model of HEV infection provides a powerful tool for studying viral–host interactions that should facilitate the discovery of antiviral drugs for this important zoonotic pathogen.

Hepatitis E virus (HEV) is an increasingly recognised pathogen, affecting several hundred thousand individuals in western countries each year. Importantly, the majority of immunocompromised individuals are not able to clear HEV but develop a chronic course of infection. In the case of lymphoma, which is an inherent immunosuppressive disease per se, chemotherapy can even further exacerbate the immunosuppressive status. As the mechanism of HEV chronification is barely understood, it is important to gain knowledge about the influence of chemotherapeutic drugs on the HEV replication cycle to guide rational clinical management of HEV infection in such patients. In this case report, a 70 year old man was diagnosed with lymphoplasmacytic lymphoma. As we observed the occurrence of chronic HEV after treatment with the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib \(\textit {in vivo}\), we investigated the influence of BTK signaling and ibrutinib treatment in the HEV replication cycle \(\textit {in vitro}\). First, we detected an HEV-induced mobilisation of BTK in human liver cells during HEV replication. A moderate antiviral effect against HEV replicating isolates including genotypes 1 and 3 was observed, suggesting that ibrutinib did not support HEV replication in a direct manner. Combinatory treatments of ibrutinib with ribavirin indicated that ibrutinib did not influence the antiviral effect of ribavirin. Taken together, chemotherapy targeting cellular factors for the treatment of lymphomas may be a neglected risk factor for the chronification of HEV. For ibrutinib, despite the upregulation of its target BTK during HEV replication, we observed neither a proviral effect on HEV replication nor an influence on the antiviral effect of ribavirin, suggesting that the chronification of HEV may be favoured by its immunosuppressive effect.

Silicon particle reinforced aluminum containing 42 wt.% silicon (Al-42Si) offers higher specific stiffness, higher resistance to thermal gradients, and an athermal behavior combined with electroless nickel, in comparison to state-of-the-art aluminum alloys (e.g. Al6061). Nevertheless, typical surface modifications (e.g. black anodization) lead to a nonsufficient optical stray light suppression due to the high amount of silicon particles on the surface. Therefore, a coating technique is required that fulfils the optical and the mechanical (e.g. adhesive strength) specifications for stray light reduction on Al-42Si. Different components like housings and barrels made of Al-42Si were coated with amorphous NiP and with Fractal Black™ by Acktar Ltd. The optical performance is analyzed by angle-resolved light scattering (ARS) at two different wavelengths (532 nm and 1064 nm). Fractal Black™ offers a total scattering level of lower than 2 % at 532 nm and 1064 nm. Fractal Black™ has been proven as a suitable coating for components made of Al-42Si.

Hepatitis E virus (HEV) is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. The current therapy options are limited to the unspecific antivirals Ribavirin (RBV) and pegylated Interferon-α (pegIFN-α). RBV leads to viral clearance in only 80% of patients treated, and is, similar to pegIFN-α, contraindicated in the major risk group of pregnant women, emphasizing the importance of new therapy options. In this review, we focus on the urgent need and current efforts in HEV drug development. We provide an overview of the current status of HEV antiviral research. Furthermore, we discuss strategies for drug development and the limitations of the approaches with respect to HEV.

For ground- and spaced based applications, Ag coated reflectors are indispensable because of their high reflectivity. The transport, assembling and storage of these reflectors takes a long time, before they are finally commissioned for the actual applications. To endure this period without a decrease of reflectivity, protective coatings with a final layer, which offers a high resistance to aqueous solutions and a low mechanical stress should be used. These criteria were taken into account for the selection of a final layer for a protected Ag-coating, which was applied for reflectors utilized in the CRIRES+- instrument (an IR spectrograph used at the VLT). Reactively sputtered Al2O3, SiO2 and Si3N4 layers were investigated with regard to these criteria. In aqueous (basic) solutions, the investigated Si3N4 layers are more stable than the SiO2 layers, and the SiO2 layers are more stable than the Al2O3 layers. This shows the influence of the intrinsic material properties. The mechanical stress of the sputtered layers depends on the deposition conditions and thus on the selected parameters. A Si3N4 layer with a high resistance to aqueous solutions also offers a low and stable mechanical stress. Therefore, the deposition-parameters which have been used for this layer were applied for sputtering the final layer of the protected Ag-coating for the reflectors.

Weakly nonlinear stability analysis is applied to study xenon oscillations in nuclear reactors using the approach of multiple time-scales method. This approach allows to characterize the dynamics of the system beyond the Hopf instability point. It provides important insight on the characteristics of the oscillations, namely if they diverge with time, or converge into a bounded limit cycle. Detailed derivation of the amplitude equation is presented. This equation is used to identify parameter ranges of bounded periodic oscillations, which may be allowed for safe operation. The influence of neutron generation time and the power feedback coefficients on the amplitude of limit cycles, as well as on convergence times, is discussed. The described method may be used to extend the safety margins required to prevent xenon unstable oscillations in reactor cores.

In the current direct dark matter search landscape, the leading experiments in the sub-GeV mass region mostly rely on cryogenic techniques which employ crystalline targets. One attractive type of crystals for these experiments is those containing lithium, due to the fact that $$^7\hbox {Li}$$7Li is an ideal candidate to study spin-dependent dark matter interactions in the low mass region. Furthermore, $$^6\hbox {Li}$$6Li can absorb neutrons, a challenging background for dark matter experiments, through a distinctive signature which allows the monitoring of the neutron flux directly on site. In this work, we show the results obtained with three different detectors based on $$\hbox {LiAlO}_2$$LiAlO2, a target crystal never used before in cryogenic experiments.

Infection of healthy individuals with human cytomegalovirus (HCMV) is usually unnoticed and results in life-long latency, whereas HCMV reactivation as well as infection of newborns or immunocompromised patients can cause life-threatening disease. To better understand HCMV pathogenesis we studied mechanisms that restrict HCMV spread. We discovered that HCMV-infected cells can directly trigger plasmacytoid dendritic cells (pDC) to mount antiviral type I interferon (IFN-I) responses, even in the absence of cell-free virus. In contrast, monocyte-derived cells only expressed IFN-I when stimulated by cell-free HCMV, or upon encounter of HCMV-infected cells that already produced cell-free virus. Nevertheless, also in the absence of cell-free virus, i.e., upon co-culture of infected epithelial/endothelial cells and monocyte-derived macrophages (moMΦ) or dendritic cells (moDC), antiviral responses were induced that limited HCMV spread. The induction of this antiviral effect was dependent on cell-cell contact, whereas cell-free supernatants from co-culture experiments also inhibited virus spread, implying that soluble factors were critically needed. Interestingly, the antiviral effect was independent of IFN-γ, TNF-α, and IFN-I as indicated by cytokine inhibition experiments using neutralizing antibodies or the vaccinia virus-derived soluble IFN-I binding protein B18R, which traps human IFN-α and IFN-β. In conclusion, our results indicate that human macrophages and dendritic cells can limit HCMV spread by IFN-I dependent as well as independent mechanisms, whereas the latter ones might be particularly relevant for the restriction of HCMV transmission via cell-to-cell spread., German Research Foundation (DFG) [SFB900 (TP B2)]; and the Helmholtz Virtual Institute “Viral Strategies of Immune Evasion (VISTRIE)” [VH-VI-424]

Several mirrors for the upgrade of the CRyogenic high-resulution InfraRed Echelle Sprectrograph (CRIRES) at the Very Large Telescope, were manufactured by diamond turning and polishing. These mirrors will be used in the crossdispersion unit (CDU) and the fore optics of the instrument. For background level reasons, the operational temperature of the CDU is set to 65 K. Therefore, the flat and spherical mirrors used in the CDU, which are made of melt-spun aluminum alloy Al6061, had to be artificially aged, to improve the dimensional stability at cryogenic temperatures. After diamond turning, magnetorheological finishing (MRF) was used for a deterministic shape correction and to remove the turning marks of the RSA6061 mirrors. To reduce the micro-roughness, a further smoothing step was necessary. A micro-roughness between 1 nm RMS and 5 nm RMS as well as shape deviations below 35 nm RMS were achieved. The mirrors were coated by inline magnetron sputtering with a high-reflective gold layer or protected silver, respectively.

Herein, we have synthesized Ti–Ta based mixed oxide vertically oriented and highly ordered freestanding nanotubes having an average length of 60 μm by anodic oxidation of a homemade Ti–Ta (50–50 at%) alloy. The effect of heat treatment on the morphology, phase transformation to TiTa2O7 nanostructures, crystalline structures, optical and surface properties has been investigated by a variety of characterization techniques. The samples remained mainly amorphous at temperatures up to 700 °C, and according to the Rietveld refinement analyses the bulk formation of crystalline Ta2O5 and TiO2-anatase phases occurred only at 800 °C in the tubular matrix followed by a slight solid to solid transformation of TiTa2O7 and TiO2-rutile phases starting from 850 °C. At 1000 °C, the content of TiTa2O7 increased followed by a decrease in TiO2 and Ta2O5 content; however, the nanotubes appeared to be interconnected particles imitating the verticality of the nanotubes. Compared to the literature (∼1350 °C), in this work the transformation of TiTa2O7 occurred at a lower temperature which is related to the amorphous nature of the starting nanotubular samples. The HAADF-STEM images and localized EDS mapping showed the distribution of Ti and Ta elements along the tubular matrix demonstrating that the as-anodized nanotubes consist of a uniform mixture of TiO2 and Ta2O5 whereas for the calcined samples random distribution of Ti was observed indicating the migration of Ti inside the tubular matrix for the formation of mixed oxide and TiTa2O7 phases. X-ray photoelectron spectroscopy (XPS) analysis identified the dislocation in the binding energies of Ti 2p and Ta 4f regions for the heat treated samples as compared to the as-anodized nanotubes; related to the formation of TiTa2O7. The optical band gap of TiTa2O7 was found to be 3.08 eV. These oxide mixtures were applied in photocatalytic H2 generation under solar irradiation; where the sample heat treated at 1000 °C has resulted in a production rate of 41.58 μmol h−1 g−1 which was higher than all the other samples synthesized in this work. For continuous 48 h irradiation the photocatalytic activity of the sample remained highly stable. This result is related to the higher content and lower bandgap energy of TiTa2O7 in the mixed oxide matrix indicating that TiTa2O7 is a promising photocatalyst.

Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. HEV infections are the common cause of acute hepatitis but can also take chronic courses. Ribavirin is the treatment of choice for most patients and type I interferon (IFN) has been evaluated in a few infected transplantation patients in vivo. However, no effective and specific treatments against HEV infections are currently available. In this study, we evaluated the natural compound silvestrol, isolated from the plant Aglaia foveolata, and known for its specific inhibition of the DEAD-box RNA helicase eIF4A in state-of-the-art HEV experimental model systems. Silvestrol blocked HEV replication of different subgenomic replicons in a dose-dependent manner at low nanomolar concentrations and acted additive to ribavirin (RBV). In addition, HEV p6-based full length replication and production of infectious particles was reduced in the presence of silvestrol. A pangenotypic effect of the compound was further demonstrated with primary isolates from four different human genotypes in HEV infection experiments of hepatocyte-like cells derived from human embryonic and induced pluripotent stem cells. In vivo, HEV RNA levels rapidly declined in the feces of treated mice while no effect was observed in the vehicle treated control animals. In conclusion, silvestrol could be identified as pangenotypic HEV replication inhibitor in vitro with additive effect to RBV and further demonstrated high potency in vivo. The compound therefore may be considered in future treatment strategies of chronic hepatitis E in immunocompromised patients., Highlights • The natural compound silvestrol is a potent inhibitor of HEV replication. • HEV infection of laboratory and primary isolates could be inhibited by silvestrol. • Silvestrol demonstrated high potency in human liver chimeric mice. • Targeting translation initiation could be a novel antiviral strategy for the treatment of chronic hepatitis E.

Metal optics is an inherent part of space instrumentation for years. Diamond turned aluminum (Al6061) mirrors are widely used for application in the mid- and near-infrared (mid-IR and NIR, respectively) spectral range. Aluminum mirrors plated with electroless nickel (NiP) expand the field of application towards multispectral operating instruments down to the ultraviolet wavelengths. Due to the significant mismatch in the coefficient of thermal expansion (CTE) between aluminum and NiP, however, this advantage occurs at the cost of bimetallic bending. Challenging requirements can be met by using bare beryllium or aluminum beryllium composites (AlBeMet) as a CTE tailored substrate material and amorphous NiP as polishable layer. For health reasons, the use of beryllium causes complications in the process chain. Thus, the beryllium approach is subjected to specific applications only. Metal optics has proven to be advantageous in respect of using conventional CNC and ultra-precision fabrication methods to realize complex and light-weighted instrument structures. Moreover, the mirror designs can be effectively optimized for a deterministic system assembly and optimization. Limitations in terms of dimensional stability over temperature and time are mainly given by the inherent material properties (figures of merit) of the substrate material in interaction with the polishing layer. To find an optimal compromise, a thermal matched aluminum-silicon alloy (silicon contents ≈ 40 wt%) plated with NiP (AlSi40/NiP ) was investigated in a joined project of the Max Planck Institute for Astronomy MPIA and the Fraunhofer Institute for Applied Optics and Precision Engineering IOF. The main tasks of the project were the minimization of the bimetallic bending, the development of reliable stabilizing and aging procedures, and the establishment of a proven fabrication method. This paper describes fundamental results regarding the optimization of the athermal material combination. Furthermore, the developed production chain for high quality freeform mirrors made of AlSi40/NiP is pointed out.

Ultra precise mirrors are particularly useful for space applications and scientific instrumentations for large telescopes, covering a highly variable temperature range.

Hypoxanthine phosphoribosyl transferase (HPRT) deficiency results in Lesch-Nyhan disease (LND). The link between the HPRT defect and the self-injurious behavior in LND is still unknown. HPRT-deficient rat B103 neuroblastoma cells serve as a model system for LND. In B103 cell membranes, HPRT deficiency is associated with a decrease of basal and guanosine triphosphate-stimulated adenylyl cyclase (AC) activity (Pinto and Seifert, J Neurochem 96:454-459, 2006). Since recombinant AC2 possesses a high basal activity, we tested the hypothesis that AC2 function and expression is impaired in HPRT deficiency. We examined AC regulation in B103 cell membranes, cAMP accumulation in intact B103 cells, AC isoform expression, and performed morphological studies. As most important pharmacological tool, we used 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene forskolin (BODIPY-FS) that inhibits recombinant AC2 but activates ACs 1 and 5 (Erdorf et al., Biochem Pharmacol 82:1673-1681, 2011). In B103 control membranes, BODIPY-FS reduced catalysis, but in HPRT(-) membranes, BODIPY-FS was rather stimulatory. 2'(3')-O-(N-methylanthraniloyl) (MANT)-nucleoside 5'-[γ-thio]triphosphates inhibit recombinant ACs 1 and 5 more potently than AC2. In B103 control membranes, MANT-guanosine 5'-[γ-thio]triphosphate inhibited catalysis in control membranes less potently than in HPRT(-) membranes. Quantitative real-time PCR revealed that in HPRT deficiency, AC2 was virtually absent. In contrast, AC5 was up-regulated. Forskolin (FS) and BODIPY-FS induced cell clustering and rounding and neurite extension in B103 cells. The effects of FS and BODIPY-FS were much more prominent in control than in HPRT(-) cells, indicative for a differentiation defect in HPRT deficiency. Neither FS nor BODIPY-FS significantly changed cAMP concentrations in intact B103 cells. Collectively, our data show that HPRT deficiency in B103 cells is associated with impaired AC2 function and expression and reduced sensitivity to differentiation induced by FS and BODIPY-FS. We discuss the pathophysiological implications of our data for LND.

The fibrillization of α-synuclein (α-syn) is a key event in the pathogenesis of α-synucleinopathies. Mutant α-syn (A53T, A30P, or E46K), each linked to familial Parkinson's disease, has altered aggregation properties, fibril morphologies, and fibrillization kinetics. Besides α-syn, Lewy bodies also contain several associated proteins including small heat shock proteins (sHsps). Since α-syn accumulates intracellularly, molecular chaperones like sHsps may regulate α-syn folding and aggregation. Therefore, we investigated if the sHsps αB-crystallin, Hsp27, Hsp20, HspB8, and HspB2B3 bind to α-syn and affect α-syn aggregation. We demonstrate that all sHsps bind to the various α-syns, although the binding kinetics suggests a weak and transient interaction only. Despite this transient interaction, the various sHsps inhibited mature α-syn fibril formation as shown by a Thioflavin T assay and atomic force microscopy. Interestingly, HspB8 was the most potent sHsp in inhibiting mature fibril formation of both wild-type and mutant α-syn. In conclusion, sHsps may regulate α-syn aggregation and, therefore, optimization of the interaction between sHsps and α-syn may be an interesting target for therapeutic intervention in the pathogenesis of α-synucleinopathies

[reaction: see text] The fully functionalized core structure 23 of abyssomicin C (6) containing an oxabicyclooctane ring and a tetronate was prepared via a Diels-Alder approach. After hydroxylation of lactone 10 to the alpha-hydroxylactone 12, lactone opening led to the hydroxy ester 16. A directed epoxidation furnished the desired syn-epoxide 20. Acetylation of the tertiary hydroxyl group, followed by intramolecular Claisen condensation, gave directly the core structure 23.

The isotatic polypropylene (i-PP) plastically deformed by uniaxial plane strain compression was investigated using X-ray diffraction and transmission electron microscopy. The apparent crystallinity was evaluated by means of X-ray diffraction with a profile matching using a FULLPROF code. Two crystalline phases, α and β, were identified in the non-deformed polymer as well as with an amorphous halo. The deformation with 3, 10 and 100 MPa, induces an increase of the amorphous halo. The microstructural orientation of the i-PP, before and after deformation was evaluated using the “Quantikov” image analysis of transmission electron microscopy (TEM) data. The non-deformed material presents spherulitic structure, without any preferential orientation. The high resolution, in the nanometer scale, shows two preferential orientation axes. The deformation at 3, 10 and 100 MPa, affects the spherulitic, as well as, the lamellae structure, introducing fiber orientation, a break up of the lamellae in to small blocks and consequently amorphization of the system.

The core structure of abyssomicin C (1) containing an oxabicyclooctanone ring and a tetronate was prepared from the addition product of lithium ethyl propiolate and 4-tert-butyldimethylsilyloxycyclohexanone. Tetronate formation via addition of sodium methanolate followed by hydrolysis gave the hydroxy tetronic acid 27. The spiro compound 27 could be cyclized to the tricyclic ­tetronate 23 by a transannular Mitsunobu lactonization. Alterna­tively, 27 could be prepared from the cyanohydrin cis-19.

Near-surface composition and tribological behaviour of plasma nitrided commercially pure (CP) Ti have been investigated using x-ray diffraction, nuclear reaction analysis, scanning electron microscopy, wear assays with stainless steel Gracey scaler and sonic apparatus, and friction coefficient measurements. The total wear behaviour can be divided into two steps. The first step is the growth of an oxynitride layer. The second step is the breakdown of the oxynitride layer during which debris is produced, increasing the friction coefficient. Each sample exhibits features that correlate with the near-surface composition. For instance, the presence of thin layers of e-Ti2N and δ-TiN precipitating on the near-surface region control the transition from the first to the second step.

A systematic investigation was undertaken on commercially pure titanium submitted to plasma nitriding. Thirteen different sets of operational parameters (nitriding time, sample temperature and plasma atmosphere) were used. Surface analyses were performed using X-ray diffraction, nuclear reaction and scanning electron microscopy. Wear tests were done with stainless steel Gracey scaler, sonic apparatus and pin-on-disc machine. The obtained results indicate that the tribological performance can be improved for samples treated with the following conditions: nitriding time of 3 h; plasma atmosphere consisting of 80%N2+20%H2 or 20%N2+80%H2; sample temperature during nitriding of 600 or 800 degreesC.

Purpose: To evaluate the impact of ascorbic acid of different doses as additional support during luteal phase in infertility treatment by means of a prospective, randomized, placebo-controlled, group comparative, double-blind study. Methods: Voluntary daily oral intake of either ascorbic acid (1, 5, or 10 g/day) or Placebo for 14 days after follicle aspiration for IVF-ET procedure. Data was obtained on 620 cases of women, age

We report X-ray powder diffraction (XRD), electron probe microanalysis (EPMA), and Mossbauer spectroscopy (MS) measurements performed on a natural tapiolite with composition Fe0.57Mn0.37Ti0.10Ta1.27Nb0.67O6. XRD and MS suggest that besides being partially ordered the as-collected sample is a mixture of trirutile (P42/mnm, a=4.7532(9) A, c=9.228(7) A) and Nb-rich rutile (P42/mnm, a=4.856(2) A, c=3.098(1) A) structures. The Mossbauer spectra of the rutile (Fe, Mn, Ta, Nb)O2 were fitted to Δ=1.72±0.05 mm/s and δ=1.10±0.03 mm/s at 300 K and to Δ=2.10±0.06 mm/s and δ=1.18±0.03 mm/s at 80 K. The present results suggest that cation ordering in compounds of the tapiolite series can be easily assessed by Mossbauer spectroscopy in a way similar to that as previously demonstrated for the columbite series.

Ultra-precise metal optics are key components of sophisticated scientific instruments in astronomy and space applications. Especially for cryogenic applications, a detailed knowledge and the control of the coefficient of thermal expansion (CTE) of the used materials are essential. Reflective optical components in IR- and NIR-instruments primarily consist of the aluminum alloy Al6061. The achievable micro-roughness of diamond machined and directly polished Al6061 does not fulfill the requirements for applications in the visible spectral range. Electroless nickel enables the reduction of the mirror surface roughness to the sub-nm range by polishing. To minimize the associated disadvantageous bimetallic effect, a novel material combination for cryogenic mirrors based on electroless nickel and hypereutectic aluminum-silicon is investigated. An increasing silicon content of the aluminum material decreases the CTE in the temperature range to be considered. This paper shows the CTE for aluminum materials containing about 42 wt% silicon (AlSi42) and for electroless nickel with a phosphorous content ranging from 10.5 to 13 %. The CTE differ to about 0.5 × 10-6 K-1 in a temperature range from -185 °C (LN2) to 100 °C. Besides, the correlations between the chemical compositions of aluminum-silicon materials and electroless nickel are shown. A metrology setup for cryo-interferometry was developed to analyze the remaining and reversible shape deviation at cryogenic temperatures. Changes could be caused by different CTE, mounting forces and residual stress conditions. In the electroless nickel layer, the resulting shape deviation can be preshaped by deterministic correction processes such as magnetorheological finishing (MRF) at room temperature.

We report X-ray powder diffraction measurements performed on synthetic samples of the tapiolite-like Fe x Co 1− x Ta 2 O 6 solid solution. The crystal structure has been refined by the Rietveld method, by using the program fullprof . All the samples are tetragonal and were indexed to the space group P 4 2 / mnm . The end-members (FeTa 2 O 6 and CoTa 2 O 6 ) have unit-cell parameters quite similar to those previously published. The unit-cell parameters a and c for the mixed samples vary linearly with the cation substitution (Co→Fe) according to the Vegard's law in all the range of substitution.

Heat treatments in air and in vacuum have been performed on crystal and powder of the natural tantalite (Mn2+0.88Fe2+0.09)(Ta5+0.86Nb5+0.14)2O2-6, as well as on powder of synthetic Fe2+(Nb5+0.6Ta5+0.4)2O6. Crystal parameters and hyperfine interactions were obtained by use of x-ray diffraction and Mossbauer spectroscopy. It is shown that the partially ordered natural sample is completely ordered after heat treatment in vacuum. Conversely, heat treatment in air induced the tantalite [(Mn2+0.88Fe2+0.09)(Ta5+0.86Nb5+0.14)2O2-6]wodginite [(Mn2+,Fe2+)Fe3+(Ta,Nb)2O8] transformation on the powdered sample. When applied to the crystal sample, the heat treatment in air produced a mixture of two phases: the one in large amount is the ordered (Mn2+0.88Fe2+0.09)(Ta5+0.86Nb0.145+)2O62-, the other, in minor amount, is (Mn2+0.88,Fe2+0.09)Fe3+(Ta,Nb)2O8. The former arrives from cation ordering in the bulk portion of the sample, while the latter results from the near-surface oxidation. The Mn content as well as the oxidant atmosphere appears to play an important role in the transition mechanism. The same heat treatment applied to the synthetic columbite induces a different reaction: ferrocolumbite is transformed into the ixiolite Fe3+(Nb0.6Ta0.4)O4 with a minor amount of (Nb,Ta)2O5.

Children with the opsoclonus-myoclonus syndrome (OMS) usually respond to corticotropin (adrenocorticotrophic hormone, ACTH) treatment but the mechanism of benefit is unknown. We previously showed that both cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) concentrations are low in pediatric OMS. In this study, we measured levels of CSF Dopa, catecholamines, deaminated metabolites of catecholamines, as well as HVA and 5-HIAA in eight patients before and during treatment with ACTH. All the children were ACTH-responsive with 50-70% improvement in multiple clinical features of OMS. ACTH treatment reduced the HVA concentration in every child by a mean of 21% (p < 0.001). Treatment with ACTH was associated with significant correlations between dopaminergic markers such as HVA, dihydroxyphenylacetic acid (DOPAC), and Dopa. There were no significant changes in the CSF concentrations of the noradrenergic markers norepinephrine (NE) and dihydroxyphenylglycol (DHPG), or the serotonergic marker 5-HIAA. The only child with a marked inflammatory pattern in CSF, which was reversed by ACTH, was atypical for a large increase in NE and decrease in 5-HIAA during ACTH treatment. Beneficial effects of ACTH in OMS are not associated with normalization of HVA or 5-HIAA levels. The pattern of decreased HVA and unchanged DOPAC levels could reflect decreased extraneuronal uptake of catecholamines (which steroids inhibit) or decreased 0-methylation of catecholamines in nonneuronal cells.

Since 2003 bread and fine bakery products must not contain more than 350 μg Deoxynivalenol (DON). As a prerequisite for the label “Geprufte Qualitat”—Thuringen [proved quality Thuringia] and since coming into force of the respective evaluation prescription a total of 25 breads and 41 fine bakery products was investigated by ELISA with regard of this compound. In the 66 samples of the year 2003 no DON concentrations above the limit were detected and in the preparation period 2001/2002 only one sample exceeded the maximum. In several samples, most narrow to the maximum limit, an additional determination by HPLC was performed which resulted in lower DON-concentrations as compared to the values analyzed by ELISA.

Contains fulltext : 125482.pdf (Publisher’s version ) (Open Access) Serotonin, in its function as neurotransmitter, is well-known for its role in depression, autism and other neuropsychiatric disorders, however, less known as a neurodevelopmental factor. The serotonergic system is one of the earliest to develop during embryogenesis and early changes in serotonin levels can have large consequences for the correct development of specific brain areas. The regulation and functioning of serotonin is influenced by genetic risk factors, such as the serotonin transporter polymorphism in humans. This polymorphism is associated with anxiety-related symptoms, changes in social behavior, and cortical gray and white matter changes also seen in patients suffering from autism spectrum disorders (ASD). The human polymorphism can be mimicked by the knockout of the serotonin transporter in rodents, which are as a model system therefore vital to explore the precise neurobiological mechanisms. Moreover, there are pharmacological challenges influencing serotonin in early life, like prenatal/neonatal exposure to selective serotonin reuptake inhibitors (SSRI) in depressed pregnant women. There is accumulating evidence that this dysregulation of serotonin during critical phases of brain development can lead to ASD-related symptoms in children, and reduced social behavior and increased anxiety in rodents. Furthermore, prenatal valproic acid (VPA) exposure, a mood stabilizing drug which is also thought to interfere with serotonin levels, has the potency to induce ASD-like symptoms and to affect the development of the serotonergic system. Here, we review and compare the neurodevelopmental and behavioral consequences of serotonin transporter gene variation, and prenatal SSRI and VPA exposure in the context of ASD.

A new approach is proposed to determine unambiguously the location of four cations within the crystal structure of a naturalAB2O6columbite-type compound and derivatives, when submitted to order–disorder transitions caused by heat treatments. This method is based on the successive use of electron microprobe analysis to determine the cation concentration, Mössbauer spectroscopy to identify the Fe occupation, and a crystal structure determination of the samples combining Rietveld refinements of both neutron and X-ray diffraction. This approach is tested successfully to investigate (Fe, Mn, Nb, Ta) natural minerals as well as oxides obtained by heat treatment of the initialAB2O6columbite-type compound.

Novel nontoxic (S)-2-aminoalkylbenzimidazole derivatives were found to be effective against Candida spp. at low micromolar concentrations using high-throughput screening with infected HeLa cells. A collection of analogues defined the chemical groups relevant for activity. The most active compound was characterized by transcriptional analysis of the response of C. albicans Sc5314. (S)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole had a strong impact on membrane biosynthesis. Testing different clinically relevant pathogenic fungi showed the selectivity of the antimycotic activity against Candida species.

International audience; The structural and magnetic properties of the CoNb2O6 compound have been investigated with a particular interest in their low-dimensional magnetic behavior which is characterized by the presence of weakly interacting ferromagnetic chains. We investigate this cobalt niobate by combining magnetic measurements; x-ray and neutron diffraction (ND). The ND was carried out on powder samples at different temperatures above (20 K) and below the ordering temperature (2.4, 1.8, and 1.4 K). The compound exhibits an orthorhombic crystal structure of Pbcn symmetry, typical of a columbite structure. Magnetic ordering at 2.5 K is found with the propagation vector (0, 0.4, 0), in agreement with earlier studies. However, at lower temperatures the present investigation shows the coexistence of two different magnetic phases: the propagation vector (0.5, 0.5, 0) is found to be necessary to refine the ND measurements at both 1.8 and 1.4 K, in addition to (0, 0.5, 0) which was the only one reported in earlier works.

International audience; We report new results on the magnetic properties of the FexCo1 - xTa2O6 series of compounds. Essentially using neutron-diffraction and magnetic measurements we study, in more detail, the low-x limit of the temperature versus x phase diagram, where a new bicritical point is observed. The complete phase diagram shows three different magnetic phases at low temperature, for a high, intermediate and very low iron content. These phases consist of distinct antiferromagnetic orderings, characterized by different pairs of propagation vectors. We obtain information about the intraplane exchange interactions by fitting a high-temperature series of the magnetic susceptibility. Here we improve on a previously employed model, showing that two non-equivalent next-nearest-neighbor interactions must be taken into account in order to allow for in-plane magnetic orderings that are consistent with the neutron-diffraction results.

This paper describes a new athermal approach for high performance metal optics, particularly with regard to extreme environmental conditions as they usually may occur in terrestrial as well as in space applications. Whereas for mid infrared applications diamond turned aluminium is the preferred mirror substrate, it is insufficient for the visual range. For applications at near infrared wavelengths (0.8 μm - 2.4 μm) as well as at on cryogenic temperatures (-200°C) requirements exist, which are only partially met for diamond turned substrates. In this context athermal concepts such as optical surfaces with high shape accuracy and small surface micro-roughness without diffraction effect and marginal loss of stray light, are of enormous interest. The novel, patented material combination matches the Coefficient of Thermal Expansion (CTE) of an aluminium alloy with high silicon content (AlSi, Si ≥ 40 %) as mirror substrate with the CTE of the electroless nickel plating (NiP). Besides the harmonization of the CTE (~ 13 * 10-6 K-1), considerable advantages are achieved due to the high specific stiffness of these materials. Hence, this alloy also fulfils an additional requirement: it is ideal for the manufacturing of very stable light weight metal mirrors. To achieve minimal form deviations occurring due to the bimetallic effect, a detailed knowledge of the thermal expansion behavior of both, the substrate and the NiP layer is essential. The paper describes the reduction of the bimetallic bending by the use of expansion controlled aluminium-silicon alloys and NiP as a polishing layer. The acquisition of CTE-measurement data, the finite elements simulations of light weight mirrors as well as planned interferometrical experiments under cryogenic conditions are pointed out. The use of the new athermal approach is described exemplary.

We report on a detailed investigation of magnetic properties of CoTa2O6 using several techniques: neutron and X-ray diffraction, specific-heat, magnetic susceptibility, and magnetization measurements. The compound shows quasi-two-dimensional behavior due to its layered structure of alternating Co–O and Ta–O planes. We find that all magnetic moments lie entirely in the Co–O planes, along easy axes determined by the orientations of oxygen octahedra that surround the Co ions. The easy axes in successive magnetic planes have relative orientations that differ by 90°. Antiferromagnetic ordering is observed below 6.6 K, with propagation vectors ( ± 1/4,1/4,1/4) associated to the two non-equivalent sets of Co2+ ions, whose magnetic moments are perpendicularly oriented.

International audience; We report on a detailed investigation of magnetic properties of CoTa2O6 using several techniques: neutron and X-ray diffraction, specific-heat, magnetic susceptibility, and magnetization measurements. The compound shows quasi-two-dimensional behavior due to its layered structure of alternating Co-O and Ta-O planes. We find that all magnetic moments lie entirely in the Co-O planes, along easy axes determined by the orientations of oxygen octahedra that surround the Co ions. The easy axes in successive magnetic planes have relative orientations that differ by 90°. Antiferromagnetic ordering is observed below 6.6 K, with propagation vectors (±1/4,1/4,1/4) associated to the two non-equivalent sets of Co2+ ions, whose magnetic moments are perpendicularly oriented.

The trirutile family of the tapiolite-like compound FexNi1−xTa2O6 was investigated by means of x-ray powder diffraction (XRD) and magnetic susceptibility measurements. From Rietveld refinement it is demonstrated that the family is a homogeneous solid solution obeying Vegard's law. Magnetic susceptibility curves exhibit typical signatures of low-dimensional systems, with broadened maxima due to short range correlations immediately above the antiferromagnetic transition temperature TN. The T versus x phase diagram presents a minimum that suggests bicritical behaviour.

Die Aminomethylierung der acyclischen Ketone 1/2 fuhrt zu den Aminoketonen 3/4, die nach Reduktion, Quaternierung und Ionenaustausch oder vorhergehender Reaktion mit einem Grignard-Reagenz die Hydroxyammonium-Verbindungen 9/10 bzw. 14 ergeben. Kurzzeit-Thermolyse von 9/10 liefert die Aldehyde 7 und von 14 das Keton 15, in dem die eine Seitenkette des Edukts 2b durch den Alkylrest des Grignard-Reagenzes ersetzt ist. Transformation of Acyclic Ketones into Aldehydes and Ketones with Substituted Side Chains Aminomethylation of the acyclic ketones 1/2 leads to the aminoketones 3/4 which give, after reduction, quaternisation and ion exchange or previous reaction with a Grignard reagent, the hydroxyammonium compounds 9/10 and 14, respectively. Flash thermolysis of 9/10 yields the aldehydes 7 and of 14 the ketone 15 in which one side-chain of the educt 2b is substituted by the alkyl group of the Grignard reagent.

Die enzymatische Spaltung der glycosidischen Bindung in Secologanin (1) fuhrte unter Isomerisierung und Bildung einer α,β-ungesattigten Aldehydgruppe mit (E)-Konfiguration zu dem Epimeren-Gemisch 10a, das mit Acetanhydrid/Pyridin die Acetate 10b lieferte. Das bei der Umsetzung erwartete Primarprodukt 8 wurde nicht gefunden. Iridoids, VIEnzymatic Cleavage of SecologaninA Model for the Biosynthesis of the Indole Alkaloids The enzymatic cleavage of the glycosidic linkage in secologanin (1) afforded by isomerisation and formation of an α,β-unsaturated aldehyde group with (E)-configuration the epimeric mixture 10a, which was converted by acetic anhydride/pyridine into the acetates 10b. The primarily expected product 8 could not be discovered in the cleavage reaction.

6-α-Hydroxy-6-β-acylureidobenzylpenicillins and 7-α-Hydroxy-7-β-acylureidobenzylcephalosporins are prepared by direct hydroxylation of the unsubstituted parent compounds.

Die Reaktion der Oxim-O-tosylate 1 mit den Amidinoessigestern 2 fuhrt nicht zu den erwarteten Pyrazinen 4, sondern unter Umlagerung uber 7 zu den neuartigen 4,5-Dihydro-1 H-pyrrol-3-carbonsaureestern 8 (= 2-Pyrrolin-3-carbonsaureester). Die Hydrolyse der Pyrrole 8 sowie deren Umsetzung mit Aminen wird untersucht. Condensations with Oxime O-Sulfonates, I. — Synthesis of 2-Amino-4,5-dihydro-4,5-diimino-1 H-pyrrole-3-carboxylates The reaction of the oxime O-tosylates 1 with the amidinoacetic acid esters 2 does not lead to the expected pyrazines 4, but rather to the novel 4,5-dihydro-1 H-pyrrole-3-carboxylates 8 (= 2-pyrroline-3-carboxylates) by rearrangement via7. The hydrolysis of the pyrroles 8 and their reactions with amines have been studied.

Administration of high doses of 131I-6 beta-iodocholesterol to rabbits is followed by marked size reduction of the adrenal glands with concomitant changes of the histological structure and with a decrease of serum cortisol. Stimulation of 131I-6 beta-iodocholesterol uptake into the adrenals by additional administration of ACTH had only a minor additional effect on adrenal weight. However, with further accumulation of labeled cholesterol in the adrenals the radioactivity was reduced in blood urine, and the ovaries.

Umsetzung des “trans”-p-Toluolsulfonates 9b mit Natrium-methylsulfinylmethid in Dimethylsulfoxid fuhrte neben Kondensationsprodukten zum δ,ϵ-ungesattigten Aldehyd 12a. Die baseninduzierte Reaktion des “cis”-p-Toluolsulfonates 10b ergab dagegen durch intramolekulare Susbtitution ausschlieslich das Oxetan 13. In analoger Weise reagierte das Hydroxyloganin-Derivate 16c zum Oxetan 18, wahrend das 6-Epihydroxyloganin-Derivat 15c mit 67% Ausbeute zum Secologanin-aglyconmethylather (1b) gespalten werden konnte. In Abhangigkeit von den Reaktionsbedingungen wurde hierbei als zweites Produkt das Secologaninsaure-Derivat 20a gebildet, das sich mit Natriumborhydrid zur Hydroxycarbonsaure 24 reduzieren und durch anschliesende Destillation in den Swerosid-aglyconmethylather 2b uberfuhren lies. Die Reduktion von 1b fuhre direkt zu 2b. Iridoide, V Biogenetic Type Synthesis of Secologanin- and Sweroside Aglycone O-Methyl Ether Reaction of the “trans”-p-toluenesulfonate 9b with sodium methylsulfinylmethide in dimethyl sulfoxide gave the δ,ϵ-unsaturated aldehyde 12a besides polymeric products. On the other hand treatement of the “cis”-p--toluenesulfonate 10b with base yielded by intramolecular nucleophilic substitution only an oxetane 13. According to this the hydroxyloganin derivative 16c led to the oxetane 18, whereas the 6-epihydroxyloganin derivative 15c could be cleaved to secologanin-aglycone O-methyl ether 1b. Depending on the reaction-conditions the secologanic acid compound 20a was formed as a byproduct. 20a could be reduced to the hydroxy acid 24, which was converted to sweroside aglycone O-methyl ether 2b by distillation. Reduction of 1b led directly to 2b.

PHA-activated lymphocytes release colony-stimulating activity (CSA) for macrophage-granulocyte precursor cells (colony forming units, CFUc) in the culture medium. Somatostatin, known to interfer with ribosomal protein synthesis, was demonstrated to reduce the release of CSA from PHA-treated mouse spleen lymphocytes.