Details about molecular membrane dynamics in living cells, such as lipid-protein interactions, are often hidden from the observer because of the limited spatial resolution of conventional far-field ...optical microscopy. The superior spatial resolution of stimulated emission depletion (STED) nanoscopy can provide new insights into this process. The application of fluorescence correlation spectroscopy (FCS) in focal spots continuously tuned down to 30 nm in diameter distinguishes between free and anomalous molecular diffusion due to, for example, transient binding of lipids to other membrane constituents, such as lipids and proteins. We compared STED-FCS data recorded on various fluorescent lipid analogs in the plasma membrane of living mammalian cells. Our results demonstrate details about the observed transient formation of molecular complexes. The diffusion characteristics of phosphoglycerolipids without hydroxyl-containing headgroups revealed weak interactions. The strongest interactions were observed with sphingolipid analogs, which showed cholesterol-assisted and cytoskeleton-dependent binding. The hydroxyl-containing headgroup of gangliosides, galactosylceramide, and phosphoinositol assisted binding, but in a much less cholesterol- and cytoskeleton-dependent manner. The observed anomalous diffusion indicates lipid-specific transient hydrogen bonding to other membrane molecules, such as proteins, and points to a distinct connectivity of the various lipids to other membrane constituents. This strong interaction is different from that responsible for forming cholesterol-dependent, liquid-ordered domains in model membranes.
DANSS is a highly segmented 1 m3 plastic scintillator detector. Its 2500 one meter long scintillator strips have a Gd-loaded reflective cover. The DANSS detector is placed under an industrial 3.1 ...GWth reactor of the Kalinin Nuclear Power Plant 350 km NW from Moscow. The distance to the core is varied on-line from 10.7 m to 12.7 m. The reactor building provides about 50 m water-equivalent shielding against the cosmic background. DANSS detects almost 5000 ν˜e per day at the closest position with the cosmic background less than 3%. The inverse beta decay process is used to detect ν˜e. Sterile neutrinos are searched for assuming the 4ν model (3 active and 1 sterile ν). The exclusion area in the Δm142,sin22θ14 plane is obtained using a ratio of positron energy spectra collected at different distances. Therefore results do not depend on the shape and normalization of the reactor ν˜e spectrum, as well as on the detector efficiency. Results are based on 966 thousand antineutrino events collected at three different distances from the reactor core. The excluded area covers a wide range of the sterile neutrino parameters up to sin22θ14<0.01 in the most sensitive region.
•1,3-dichorobenzene is an occupationally relevant noxious agent in silicone rubber industry.•First method to quantify urinary mercapturates of 1,3-dichlorobenzene using online-SPE LC-MS/MS.•Authentic ...mercapturate standards and labelled analogues were self-synthesized.•The method is fully automated, precise, sensitive and accurate.•Post-shift urine of exposed workers shows that mercapturates are suitable biomarkers.
1,3-dichlorobenzene (1,3-DCB) is an aromatic solvent that might be formed during thermal decomposition of bis(2,4-dichlorobenzoyl)peroxide used as initiator in silicone rubber production with many workers exposed worldwide. During metabolism of 1,3-DCB, two isomeric mercapturic acids can be formed from ring oxidation of 1,3-DCB in the liver, namely 2,4-dichlorophenylmercapturic acid (24CPhMA) and 3,5-dichlorophenylmercapturic acid (35CPhMA). These urinary mercapturic acids might serve as biomarkers of the toxicologically relevant absorbed dose of 1,3-DCB and have not been determined so far. Thus, we were aimed to develop an analytical method for quantification of these biomarkers.
Authentic standards of both mercapturic acids as well as deuterium-labelled analogues were self-synthesized. A method for the quantification of both CPhMAs in human urine using online-SPE LC/MS/MS was developed and validated with an LOQ of 0.1 ng mL−1 for both CPhMAs. The analytes were extracted from urine by online-SPE on a restricted access material phase, transferred to the analytical column and quantified by tandem mass spectrometry. Interday (n = 6) and Intraday (n = 10) precision for both CPhMAs ranged from 1.7 to 4.3 % with accuracies between 99.4 and 109.9 % at concentrations of 0.6 and 3 ng mL−1. We applied the method on post-shift urine samples of 16 workers of the silicone rubber industry with occupational exposure to 1,3-DCB. Both CPhMAs were above LOQ in 15 of 16 urine samples with median levels (range) for 24CPhMA and 35CPhMA of 1.64 ng mL−1 (<0.1 – 8.2 ng mL−1) and 3.98 ng mL−1 (0.36 – 24.1 ng mL−1), respectively.
This is the first report on specific urinary mercapturic acids of 1,3-DCB in humans. Our results show that ring oxidation of 1,3-DCB is considered to be a toxicologically relevant metabolic pathway in humans. This might improve risk assessment of 1,3-DCB-emissions in silicone rubber industry.
STARE2: Detecting Fast Radio Bursts in the Milky Way Bochenek, Christopher D.; McKenna, Daniel L.; Belov, Konstantin V. ...
Publications of the Astronomical Society of the Pacific,
03/2020, Volume:
132, Issue:
1009
Journal Article
Peer reviewed
Open access
There are several unexplored regions of the short-duration radio transient phase space. One such unexplored region is the luminosity gap between giant pulses (from pulsars) and cosmologically located ...fast radio bursts (FRBs). The Survey for Transient Astronomical Radio Emission 2 (STARE2) is a search for such transients out to 7 Mpc. STARE2 has a field of view of 3.6 steradians and is sensitive to 1 millisecond transients above ∼300 kJy. With a two-station system we have detected and localized a solar burst, demonstrating that the pilot system is capable of detecting short duration radio transients. We found no convincing non-solar transients with duration between 65 s and 34 ms in 200 days of observing, limiting with 95% confidence the all-sky rate of transients above ∼300 kJy to <40 sky−1 yr−1. If the luminosity function of FRBs could be extrapolated down to 300 kJy for a distance of 10 kpc, then one would expect the rate to be ∼2 sky−1 yr−1.
Germany’s transition to a climate-neutral economy, the main parameters of which were determined by the European Green Exchange Rate (December 2019) and clarified in the updated Law on Climate ...Protection of Germany (June 2021) and the EU Fit-for-55 program (July 2021), leads to the abandonment of the use of primary energy sources, including their importation from Russia. The energy transformation of the German market economy presumed a gradual restructuring of the existing model of German–Russian cooperation in the energy sector, including its transfer to priority cooperation in the field of energy efficiency and renewable energy sources. Brussels and Berlin responded to the special military operation of the Russian Federation on the territory of Ukraine with large-scale economic and political sanctions, which included significant restrictions on the import of Russian coal and oil. At the same time, the German federal authorities outlined the necessity to abandon Russian pipeline gas and petroleum products, as well as the deprivation of ownership of the two main players from the Russian Federation in the German oil and gas market—Gazprom and Rosneft. Their German partners have frozen participation in Russian projects. At the end of February, the certification of the Nord Stream-2 offshore gas pipeline was stopped. Interdepartmental state interaction and scientific and technical cooperation in the energy sector have been terminated. These events indicated the readiness of the government coalition in the short term to replace the previous model of energy cooperation, which has performed well for half a century, and to move to independence from Russian fossil resources and their derivatives. The author analyzes the reasons and content of the current measures taken by Berlin, as well as their medium- and long-term consequences for German–Russian cooperation.
The search for new forms of already known drug compounds is an urgent problem of high relevance as more potent drugs with fewer side effects are needed. The trifluoromethyl group in flufenamic acid ...renders its chemical structure differently from other fenamates. This modification is responsible for a large number of conformational polymorphs. Therefore, flufenamic acid is a promising structural modification of well-known drug molecules. An effective approach in this field is micronization, employing "green" supercritical fluid technologies. This research raises some key questions to be answered on how to control polymorphic forms during the micronization of drug compounds. The results presented in this work demonstrate the ability of two-dimensional nuclear Overhauser effect spectroscopy to determine conformational preferences of small molecular weight drug compounds in solutions and fluids, which can be used to predict the polymorphic form during the micronization. Quantitative analysis was carried out to identify the conformational preferences of flufenamic acid molecules in dimethyl sulfoxide-d6 medium at 25 °C and 0.1 MPa, and in mixed solvent medium containing supercritical carbon dioxide at 45 °C and 9 MPa. The data presented allows predictions of the flufenamic acid conformational preferences of poorly soluble drug compounds to obtain new micronized forms.
An atmospheric correction algorithm is proposed for the reconstruction of the ground surface reflectance from the data of satellite measurements. A distinctive feature of the algorithm is that it ...takes into account the influence of the ground surface inhomogeneity on the adjacency effect and additional illumination of the ground surface by reflected radiation. These factors are important for the reconstruction of the reflectance of ground surface fragments with sharp reflectance changes and high atmospheric turbidity. The algorithm is based on Monte Carlo programs developed by the authors. To reduce the computing time, we have proposed some original criteria and approaches. To estimate the capabilities of the developed algorithm, its results have been validated by comparing with the results of the MOD09 algorithm for four MODIS bands and measurements for the Portugal surface fragment with coordinates 38.829 N, 8.791 W. Good agreement of the results obtained by the proposed algorithm with the surface measurements and the data obtained by the MOD09 algorithm demonstrates the efficiency of the proposed algorithm in the reconstruction of the ground surface reflectance.
Several industrial wastes including biomass, fly ashes, red mud, mill scales, water treatment residues, have significant concentrations of metal oxides: Fe2O3, Al2O3, TiO2, SiO2 etc. Several efforts ...have been made towards recovering metals within these wastes. Rather than recovering one metal at a time, we report a novel approach for simultaneously extracting multiple metals from mixed oxides in a single process step. Using three distinct furnaces/heating regimes, the carbothermic reduction of Fe2O3/Al2O3/SiO2 system was investigated at 1450–1700 °C for up to 2 h over a wide composition range. Complete reduction was achieved for both Fe2O3 and SiO2 in all cases leading to the formation of Fe and Fe–Si alloys. The reduction of alumina at moderate temperatures was the key challenge. No alumina reduction was observed during reductions at 1450 °C. A partial reduction of alumina and the formation of Fe–Al alloys was detected in the Al2O3/Fe2O3/C system at 1550 °C. The formation of Fe–Si–Al alloys was also observed in the Fe2O3/SiO2/Al2O3/C system at 1550 °C. Complete reduction of alumina was observed at 1600–1700 °C, even for up to 50 wt% alumina in the system. Optimal operating conditions and reference standards were established for the simultaneous recovery of multiple metals from waste oxides. While conserving natural resources, this novel route will lower the burden on waste storage facilities with significant contributions to the economic and environmental sustainability of industrial waste management.
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•Carbothermic reduction of mixed oxides at 1450–1700 °C under argon atmosphere.•Simultaneous extraction of multiple metals from waste oxides in a single process.•Novel route applicable to biomass, fly ashes, red mud, mill scales and other wastes.•Benefits include resource conservation and associated reductions in waste storage.
Presently, there are no effective treatments for several diseases involving the CNS, which is protected by the blood–brain, blood–CSF, and blood–arachnoid barriers. Traversing any of these barriers ...is difficult, especially for macromolecular drugs and particulates. However, there is significant experimental evidence that large molecules can be delivered to the CNS through the cerebrospinal fluid (CSF). The flux of the interstitial fluid in the CNS parenchyma, as well as the macro flux of CSF in the leptomeningeal space, are believed to be generally opposite to the desirable direction of CNS-targeted drug delivery. On the other hand, the available data suggest that the layer of pia mater lining the CNS surface is not continuous, and the continuity of the leptomeningeal space (LMS) with the perivascular spaces penetrating into the parenchyma provides an unexplored avenue for drug transport deep into the brain via CSF. The published data generally do not support the view that macromolecule transport from the LMS to CNS is hindered by the interstitial and CSF fluxes. The data strongly suggest that leptomeningeal transport depends on the location and volume of the administered bolus and consists of four processes: (i) pulsation-assisted convectional transport of the solutes with CSF, (ii) active “pumping” of CSF into the periarterial spaces, (iii) solute transport from the latter to and within the parenchyma, and (iv) neuronal uptake and axonal transport. The final outcome will depend on the drug molecule behavior in each of these processes, which have not been studied systematically. The data available to date suggest that many macromolecules and nanoparticles can be delivered to CNS in biologically significant amounts (>1% of the administered dose); mechanistic investigation of macromolecule and particle behavior in CSF may result in a significantly more efficient leptomeningeal drug delivery than previously thought.
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