Renalase is a ~38 kDa flavin-adenine dinucleotide (FAD) domain-containing protein that can function as a cytokine and an anomerase. It is emerging as a novel regulator of cardiometabolic diseases. ...Expressed mainly in the kidneys, renalase has been reported to have a hypotensive effect and may control blood pressure through regulation of sympathetic tone. Furthermore, genetic variations in the renalase gene, such as a functional missense polymorphism (Glu37Asp), have implications in the cardiovascular and renal systems and can potentially increase the risk of cardiometabolic disorders. Research on the physiological functions and biochemical actions of renalase over the years has indicated a role for renalase as one of the key proteins involved in various disease states, such as diabetes, impaired lipid metabolism, and cancer. Recent studies have identified three transcription factors (viz., Sp1, STAT3, and ZBP89) as key positive regulators in modulating the expression of the human renalase gene. Moreover, renalase is under the post-transcriptional regulation of two microRNAs (viz., miR-29b, and miR-146a), which downregulate renalase expression. While renalase supplementation may be useful for treating hypertension, inhibition of renalase signaling may be beneficial to patients with cancerous tumors. However, more incisive investigations are required to unravel the potential therapeutic applications of renalase. Based on the literature pertaining to the function and physiology of renalase, this review attempts to consolidate and comprehend the role of renalase in regulating cardiometabolic and renal disorders.
Uniform transfection of biomolecules into live cells with high delivery efficiency and cell viability is an immensely important area of biological research and has many biomedical applications. In ...the present study, we report highly efficient, uniform parallel intracellular delivery of small to very large biomolecules into diverse cell types using a titanium micro-ring (TMR) device activated by infrared (IR) light pulse. A TMR array device (2 cm × 2 cm) consists of a 10 μm outer diameter and 3 μm inner diameter for each micro-ring, and 10 μm interspacing between two micro-rings. Upon IR (1050 nm) pulse laser irradiation on the TMR device, photothermal cavitation bubbles are generated, disrupting the cell plasma membrane, and biomolecules are gently delivered into the cells by a simple diffusion process. This TMR device successfully delivered diverse types of small to very large biomolecules such as propidium iodide (PI; 668.4 Da) dye, dextran (3 kDa), small interfering RNA (13.3 kDa), enhanced green fluorescent protein expression plasmid DNA (6.2 kb), and β-galactosidase enzyme (465 kDa) into human cervical (SiHa), mouse fibroblast (L929), and mouse neural crest-derived (N2a) cancer cells. For smaller molecules (PI dye), delivery efficiency and cell viability were achieved at ∼96% and ∼97%, respectively, with a laser fluence of 21 mJ cm
−2
for 250 pulses. In contrast, ∼85% transfection efficiency and ∼90% cell viability were achieved for plasmid DNA with 45 mJ cm
−2
laser fluence for 250 pulses in SiHa cells. Moreover, the intracellular delivery of β-galactosidase enzyme was confirmed with confocal microscopy and flow cytometry analysis resulting in ∼83% co-staining of β-galactosidase enzyme and calcein AM. Based on these efficient deliveries of diverse types of biomolecules in different cell types, the device has the potential for cellular diagnostic and therapeutic applications.
Highly efficient large cargo delivery using an infrared light-activated titanium micro-ring device.
We present the first limits on inelastic electron-scattering dark matter and dark photon absorption using a prototype SuperCDMS detector having a charge resolution of 0.1 electron-hole pairs (CDMS ...HVeV, a 0.93 g CDMS high-voltage device). These electron-recoil limits significantly improve experimental constraints on dark matter particles with masses as low as 1 MeV/c^{2}. We demonstrate a sensitivity to dark photons competitive with other leading approaches but using substantially less exposure (0.49 g d). These results demonstrate the scientific potential of phonon-mediated semiconductor detectors that are sensitive to single electronic excitations.
The CDMS low ionization threshold experiment (CDMSlite) uses cryogenic germanium detectors operated at a relatively high bias voltage to amplify the phonon signal in the search for weakly interacting ...massive particles (WIMPs). Results are presented from the second CDMSlite run with an exposure of 70 kg day, which reached an energy threshold for electron recoils as low as 56 eV. A fiducialization cut reduces backgrounds below those previously reported by CDMSlite. New parameter space for the WIMP-nucleon spin-independent cross section is excluded for WIMP masses between 1.6 and 5.5 GeV/c^{2}.
Molecular docking is a widely-employed method in structure-based drug design. An essential component of molecular docking programs is a scoring function (SF) that can be used to identify the most ...stable binding pose of a ligand, when bound to a receptor protein, from among a large set of candidate poses. Despite intense efforts in developing conventional SFs, which are either force-field based, knowledge-based, or empirical, their limited docking power (or ability to successfully identify the correct pose) has been a major impediment to cost-effective drug discovery. Therefore, in this work, we explore a range of novel SFs employing different machine-learning (ML) approaches in conjunction with physicochemical and geometrical features characterizing protein-ligand complexes to predict the native or near-native pose of a ligand docked to a receptor protein's binding site. We assess the docking accuracies of these new ML SFs as well as those of conventional SFs in the context of the 2007 PDBbind benchmark dataset on both diverse and homogeneous (protein-family-specific) test sets. Further, we perform a systematic analysis of the performance of the proposed SFs in identifying native poses of ligands that are docked to novel protein targets.
We find that the best performing ML SF has a success rate of 80% in identifying poses that are within 1 Å root-mean-square deviation from the native poses of 65 different protein families. This is in comparison to a success rate of only 70% achieved by the best conventional SF, ASP, employed in the commercial docking software GOLD. In addition, the proposed ML SFs perform better on novel proteins that they were never trained on before. We also observed steady gains in the performance of these scoring functions as the training set size and number of features were increased by considering more protein-ligand complexes and/or more computationally-generated poses for each complex.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σE = 3.86 ± 0.04 ( stat ) +0.19 −0.00 ( syst ) ...eV . This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV / c2 , with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.
In the present work, zinc oxide (ZnO) microrods with the average diameter of 350 nm have been synthesized on fluorine doped tin oxide (FTO) substrate using a hydrothermal reaction process at a low ...temperature of 90°C. The methanol gas sensing behaviour of as-synthesized ZnO microrods have been studied at different operating temperatures (100–300°C). The gas sensing results show that the ZnO microrods exhibit excellent sensitivity, selectivity, and stability toward methanol gas at 300°C. The as-grown ZnO microrods sensor also shows the good sensitivity for methanol even at a low operating temperature of 100°C. The ultra-high sensitivity of 4.41 × 10
4
% gas sensitivity,
S
g
= (
I
g
−
I
a
)/
I
a
× 100% and 5.11 × 10
2
% to 100 ppm methanol gas at a temperature of 300°C and 100°C, respectively, has been observed. A fast response time of 200 ms and 270 ms as well as a recovery time of 120 ms and 1330 ms to methanol gas have also been found at an operating temperature of 300°C and 100°C, respectively. The response and recovery time decreases with increasing operation temperature of the sensor.
We report a first search for weakly interacting massive particles (WIMPs) using the background rejection capabilities of SuperCDMS. An exposure of 577 kg days was analyzed for WIMPs with mass <30 ...GeV/c(2), with the signal region blinded. Eleven events were observed after unblinding. We set an upper limit on the spin-independent WIMP-nucleon cross section of 1.2×10(-42) cm(2) at 8 GeV/c(2). This result is in tension with WIMP interpretations of recent experiments and probes new parameter space for WIMP-nucleon scattering for WIMP masses <6 GeV/c(2).
We report the result of a blinded search for weakly interacting massive particles (WIMPs) using the majority of the SuperCDMS Soudan data set. With an exposure of 1690 kg d, a single candidate event ...is observed, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP-nucleon cross section of 1.4×10^{-44} (1.0×10^{-44}) cm^{2} at 46 GeV/c^{2}. These results set the strongest limits for WIMP-germanium-nucleus interactions for masses >12 GeV/c^{2}.
For the first time, time-dependent internal charge amplification through impact ionization has been observed in a planar germanium (Ge) detector operated at cryogenic temperature. In a time period of ...30 and 45 min after applying a bias voltage, the charge energy corresponding to a baseline of the 59.54 keV
γ
rays from a
241
Am source is amplified for a short period of time and then decreases back to the baseline. The amplification of charge energy depends strongly on the applied positive bias voltage with drifting holes across the detector. No such phenomenon is visible with drifting electrons across the detector. We find that the observed charge amplification is dictated by the impact ionization of charged states, which has a strong correlation with impurity level and applied electric field. We analyze the dominant physics mechanisms that are responsible for the creation and the impact ionization of charged states. Our analysis suggests that the appropriate level of impurity in a Ge detector can enhance charge yield through the impact ionization of charged states to achieve extremely low-energy detection threshold (< 10 meV) for MeV-scale dark matter searches if the charge amplification can be stabilized.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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