Оligoarginines were recently discovered (Lebedev et al., 2019 Nov) as a novel class of nicotinic acetylcholine receptors (nAChRs) inhibitors, octaoligoarginine R8 showing a relatively high affinity ...(44 nM) for the α9/α10 nAChR. Since the inhibition of α9/α10 nAChR by α-conotoxin RgIA and its analogs is a possible way to drugs against neuropathic pain, here in a mice model we compared R8 with α-conotoxin RgIA in the effects on the chemotherapy-induced peripheral neuropathy (CIPN), namely on the long-term oxaliplatin induced neuropathy. Tests of cold allodynia, hot plate, Von Frey and grip strength analysis revealed for R8 and α-conotoxin RgIA similar positive effects, expressed most prominently after two weeks of administration. Histological analysis of the dorsal root ganglia sections showed for R8 and RgIA a similar partial correction of changes in the nuclear morphology of neurons. Since α9/α10 nAChR might be not the only drug target for R8, we analyzed the R8 action on rat TRPV1 and TRPA1, well-known nociceptive receptors. Against rTRPV1 at 25 μM there was no inhibition, while for rTRPA1 IC50 was about 20 μM. Thus, involvement of rTRPA1 cannot be excluded, but in view of the R8 much higher affinity for α9/α10 nAChR the latter seems to be the main target and the easily synthesized R8 can be considered as a potential candidate for a drug design.
•Oligoarginine R8 and α-conotoxin RgIA exert therapeutic effects on CIPN after oxaliplatin cessation.•R8 and RgIA demonstrated similar anti-pain activity.•R8 corrected some changes in the nuclear morphology of DRG neurons.•R8 and R16, known to inhibit α 9/α 10 nAChRs in nM range, block rTRPA1 in the micromolar range.
The research represents an overview of the use of non-conventional raw materials in the food industry, as a means used for cost-cutting the final product and ensuring food's functional properties. ...The use of dietary fibers in functional food products has been considered. Relevance of using wheat fibers in functional food products has been substantiated. The article contains data on the chemical composition of bran, on the study of adsorption properties of wheat bran, namely the absorption of water and vegetable oil. Conclusions have been made about the wheat bran's ability to absorb water-soluble toxins and fat-containing substances from traditional raw materials and about the efficiency of using wheat bran for ensuring functional properties of cupcakes. The article presents the research on non-conventional use of spring wheat bran. Consumer quality of traditional cupcakes made with the use of bran have been investigated.
The scattering of dark matter (DM) particles with sub-GeV masses off nuclei is difficult to detect using liquid xenon-based DM search instruments because the energy transfer during nuclear recoils is ...smaller than the typical detector threshold. However, the tree-level DM-nucleus scattering diagram can be accompanied by simultaneous emission of a bremsstrahlung photon or a so-called "Migdal" electron. These provide an electron recoil component to the experimental signature at higher energies than the corresponding nuclear recoil. The presence of this signature allows liquid xenon detectors to use both the scintillation and the ionization signals in the analysis where the nuclear recoil signal would not be otherwise visible. We report constraints on spin-independent DM-nucleon scattering for DM particles with masses of 0.4-5 GeV/c^{2} using 1.4×10^{4} kg day of search exposure from the 2013 data from the Large Underground Xenon (LUX) experiment for four different classes of mediators. This analysis extends the reach of liquid xenon-based DM search instruments to lower DM masses than has been achieved previously.
The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective
action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 ...shares the common molecular scaffold with other short scorpion
toxins. The toxin spatial structure resolved by NMR consists of a short α-helix and a triple-stranded antiparallel β-sheet.
By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K + (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located in the α-helix and following loop
whereas the âtraditionalâ functional site of other short scorpion toxins is formed by residues from the β-sheet. Thus the
unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.
Dual-phase xenon detectors, as currently used in direct detection dark matter experiments, have observed elevated rates of background electron events in the low energy region. While this background ...negatively impacts detector performance in various ways, its origins have only been partially studied. In this paper we report a systematic investigation of the electron pathologies observed in the LUX dark matter experiment. We characterize different electron populations based on their emission intensities and their correlations with preceding energy depositions in the detector. By studying the background under different experimental conditions, we identified the leading emission mechanisms, including photoionization and the photoelectric effect induced by the xenon luminescence, delayed emission of electrons trapped under the liquid surface, capture and release of drifting electrons by impurities, and grid electron emission. We discuss how these backgrounds can be mitigated in LUX and future xenon-based dark matter experiments.
We present a comprehensive analysis of electronic recoil vs nuclear recoil discrimination in liquid/gas xenon time projection chambers, using calibration data from the 2013 and 2014–2016 runs of the ...Large Underground Xenon experiment. We observe strong charge-to-light discrimination enhancement with increased event energy. For events with S1 = 120 detected photons, i.e., equivalent to a nuclear recoil energy of ∼100 keV, we observe an electronic recoil background acceptance of < 10−5 at a nuclear recoil signal acceptance of 50%. We also observe modest electric field dependence of the discrimination power, which peaks at a field of around 300 V/cm over the range of fields explored in this study (50 – 500 V/cm). In the weakly interacting massive particle search region of S1 = 1−80 phd , the minimum electronic recoil leakage we observe is (7.3 ± 0.6) × 10−4, which is obtained for a drift field of 240 – 290V/cm. Pulse shape discrimination is utilized to improve our results, and we find that, at low energies and low fields, there is an additional reduction in background leakage by a factor of up to 3. We develop an empirical model for recombination fluctuations which, when used alongside the Noble Element Scintillation Technique simulation package, correctly reproduces the skewness of the electronic recoil data. We use this updated simulation to study the width of the electronic recoil band, finding that its dominant contribution comes from electron-ion recombination fluctuations, followed in magnitude of contribution by fluctuations in the S1 signal, fluctuations in the S2 signal, and fluctuations in the total number of quanta produced for a given energy deposition.
We present a novel analysis technique for liquid xenon time projection chambers that allows for a lower threshold by relying on events with a prompt scintillation signal consisting of single detected ...photons. The energy threshold of the LUX dark matter experiment is primarily determined by the smallest scintillation response detectable, which previously required a twofold coincidence signal in its photomultiplier arrays, enforced in data analysis. The technique presented here exploits the double photoelectron emission effect observed in some photomultiplier models at vacuum ultraviolet wavelengths. We demonstrate this analysis using an electron recoil calibration dataset and place new constraints on the spin-independent scattering cross section of weakly interacting massive particles (WIMPs) down to 2.5 GeV/c2 WIMP mass using the 2013 LUX dataset. This new technique is promising to enhance light WIMP and astrophysical neutrino searches in next-generation liquid xenon experiments.
Various dark matter models predict annual and diurnal modulations of dark matter interaction rates in Earth-based experiments as a result of the Earth’s motion in the halo. Observation of such ...features can provide generic evidence for detection of dark matter interactions. This paper reports a search for both annual and diurnal rate modulations in the LUX dark matter experiment using over 20 calendar months of data acquired between 2013 and 2016. This search focuses on electron recoil events at low energies, where leptophilic dark matter interactions are expected to occur and where the DAMA experiment has observed a strong rate modulation for over two decades. By using the innermost volume of the LUX detector and developing robust cuts and corrections, we obtained a stable event rate of 2.3±0.2 cpd/keVee/tonne, which is among the lowest in all dark matter experiments. No statistically significant annual modulation was observed in energy windows up to 26 keVee. Between 2 and 6 keVee, this analysis demonstrates the most sensitive annual modulation search up to date, with 9.2σ tension with the DAMA/LIBRA result. We also report no observation of diurnal modulations above 0.2 cpd/keVee/tonne amplitude between 2 and 6 keVee.
We present a new three-dimensional Monte-Carlo code MUSIC (MUon SImulation Code) for muon propagation through the rock. All processes of muon interaction with matter with high energy loss (including ...the knock-on electron production) are treated as stochastic processes. The angular deviation and lateral displacement of muons due to multiple scattering, as well as bremsstrahlung, pair production and inelastic scattering are taken into account. The code has been applied to obtain the energy distribution and angular and lateral deviations of single muons at different depths underground. The muon multiplicity distributions obtained with MUSIC and CORSIKA (Extensive Air Shower simulation code) are also presented. We discuss the systematic uncertainties of the results due to different muon bremsstrahlung cross-sections.
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