The aqueous electrolyte system of lithium bis(trifluoromethanesulfonyl)imide, LiTFSI–H2O, was systematically and accurately measured for a complete liquid–solid phase diagram and an extensive set ...of data on electrolytic conductivity and glass-transition temperature. The conductivity data set was fitted with a VFT-based function (VFT: Vogel–Fulcher–Tammann), of which the three parameters were set to Laurent polynomial functions of composition. The fitting results were correlated with other quantities, and comparisons were made between the results of this study and those of other aqueous and carbonate electrolyte systems. The results of these measurements, correlations, and comparisons strongly suggest a decoupling of cationic conduction from the movement of the bulk solution, in sharp contrast to what has been observed in any nonaqueous electrolytes so far.
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Practical implementation of next-generation Li-ion battery chemistries is to a large extent obstructed by the absence of an electrolyte that is capable of simultaneously supporting ...reversible electrochemical reactions at two extreme electrochemical potentials—above 4.5 V at the positive electrode and near 0 V vs. Li at the negative electrode. Electrolytes based on carbonate esters have been reliable in satisfying state-of-the-art Li-ion battery (LIB) chemistries below <4.2 V; however, it is the intrinsic thermodynamic tendency of these carbonates to decompose at potentials well below the thermodynamic threshold required for reversible reactions of high-voltage systems (>4.4 V), releasing CO2. In this work, we explore a carbonate-free electrolyte system based on a single sulfone solvent, in which a newly discovered synergy between solvent and salt simultaneously addresses the interfacial requirements of both graphitic anode and high-voltage cathode (LiNi0.5Mn1.5O4 (LNMO)). Experimental measurements, quantum chemistry (QC) calculations, and molecular dynamics simulations reveal the system’s fast ion conduction, stability over a wide temperature range, and non-flammability. At the anode, a LiF-rich interphase generated by early-onset reduction of the salt anion effectively suppresses solvent co-intercalation and subsequent graphite exfoliation, enabling unprecedented and highly reversible graphite cycling in a pure sulfone system. Under oxidative conditions, QC calculations predict that high salt concentration promotes complex/aggregate formation which slow the decomposition of sulfolane and leads to polymerizable rather than gaseous products—a fundamental improvement over carbonate solvents. These predictions are corroborated by X-ray photoelectron spectroscopy (XPS), cryogenic-transmission electron microscopy (TEM), and electron energy loss spectroscopy (EELS) experiments, which revealed the presence of a thin, conformal, sulfur-based cathode electrolyte interphase (CEI). Together, the functional interphases (SEI/CEI) generated by this electrolyte system supported long term operation of a high-voltage (4.85 V) LNMO/graphite full cell, which retained ∼70% of its original first-cycle discharge capacity after the 1000th cycle. Based on these results, this new carbonate-free electrolyte system, supported by the mechanistic understanding of its behavior, presents a promising new direction toward unlocking the potential of next generation Li-ion battery electrodes.
Antiviral RNA Interference in Mammalian Cells Maillard, P. V.; Ciaudo, C.; Marchais, A. ...
Science (American Association for the Advancement of Science),
10/2013, Letnik:
342, Številka:
6155
Journal Article
Recenzirano
Odprti dostop
In antiviral RNA interference (RNAi), the DICER enzyme processes virus-derived double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that guide ARGONAUTE proteins to silence complementary ...viral RNA. As a counterdefense, viruses deploy viral suppressors of RNAi (VSRs). Well-established in plants and invertebrates, the existence of antiviral RNAi remains unknown in mammals. Here, we show that undifferentiated mouse cells infected with encephalomyocarditis virus (EMCV) or Nodamura virus (NoV) accumulate ~22-nucleotide RNAs with all the signature features of siRNAs. These derive from viral dsRNA replication intermediates, incorporate into AGO2, are eliminated in Dicer knockout cells, and decrease in abundance upon cell differentiation. Furthermore, genetically ablating a NoV-encoded VSR that antagonizes DICER during authentic infections reduces NoV accumulation, which is rescued in RNAi-deficient mouse cells. We conclude that antiviral RNAi operates in mammalian cells.
To investigate the biological role and clinical significance of long non-coding RNAs (lncRNA) LINC01116 in breast cancer.
In the public database Gene Expression Omnibus (GEO), the breast cancer data ...set GSE54002 was screened for differentially expressed lncRNA LINC01116 in breast cancer tissues and paracancerous tissues. Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC01116 in 64 breast cancer tissues and 30 normal breast tissues. Level of LINC01116 and clinicopathological parameters of breast cancer were statistically analyzed. The effect of LINC01116 in breast cancer cells was investigated after knockdown of LINC01116. Luciferase reporter gene was further used to investigate the mechanism of endogenous RNA (ceRNA).
Results of GSE54002 showed that the expression of LINC01116 in breast cancer tissues was significantly increased. In clinical samples, the level of LINC01116 in patients with breast cancer was significantly increased, which was correlated with the overall survival, tumor size and tumor node metastasis (TNM) stage in patients, but not correlated with the age, sex and lymph node metastasis (p>0.05). LINC01116 can act as an endogenous sponge and bind directly to miR-145, resulting in the up-regulation of estrogen receptor 1 (ESR1), a target gene of miR-145.
LncRNA LINC01116 is highly expressed in breast cancer and is a new prognostic biomarker in breast cancer. Our study establishes a new link between LINC01116, miR-145 and ESR1.
We report on the first direct comparisons of microtearing turbulence simulations to experimental measurements in a representative high bootstrap current fraction (f_{BS}) plasma. Previous studies of ...high f_{BS} plasmas carried out in DIII-D with large radius internal transport barriers (ITBs) have found that, while the ion energy transport is accurately reproduced by neoclassical theory, the electron transport remains anomalous and not well described by existing quasilinear transport models. A key feature of these plasmas is the large value of the normalized pressure gradient, which is shown to completely stabilize conventional drift-wave and kinetic ballooning mode instabilities in the ITB, but destabilizes the microtearing mode. Nonlinear gyrokinetic simulations of the ITB region performed with the cgyro code demonstrate that the microtearing modes are robustly unstable and capable of driving electron energy transport levels comparable to experimental levels for input parameters consistent with the experimental measurements. These simulations uniformly predict that the microtearing mode fluctuation and flux spectra extend to significantly shorter wavelengths than the range of linear instability, representing significantly different nonlinear dynamics and saturation mechanisms than conventional drift-wave turbulence, which is also consistent with the fundamental tearing nature of the instability. The predicted transport levels are found to be most sensitive to the magnetic shear, rather than the temperature gradients more typically identified as driving turbulent plasma transport.
Abstract This study examined the hypothesis that apoptotic inhibition via mitochondrial pathway was involved in hyperbaric oxygen preconditioning (HBO-PC)–induced neuroprotection on ...ischemia–reperfusion injury in rat brain. Male Sprague–Dawley rats (250∼280 g, n =144) were divided into control, middle cerebral artery occlusion (MCAO) for 90 min, and HBO-PC plus MCAO groups. HBO-PC was conducted four times by giving 100% oxygen at 2.5 atm absolute (ATA), for 1 h at 12 h intervals for 2 days. At 24 h after the last HBO-PC, MCAO was performed and at 24 h after MCAO, neurological function, brain water content, infarct volume, and cell death were evaluated. Enzymatic activity of capase-3 and −9, and expression of cytochrome c , Bcl-2 and Bax proteins were performed in the samples from hippocampus, ischemic penumbra and core of the brain cortex, respectively. HBO-PC reduced brain edema, decreased infarction volume, and improved neurological recovery. HBO-PC reduced cytoplasm cytochrome c levels, decreased caspase enzyme activity, upregulated the ratio of Bcl-2 and Bax expression, and abated the apoptosis of ischemic tissue. HBO-PC protects brain tissues from ischemia–reperfusion injury by suppressing mitochondrial apoptotic pathways.
Aim
To comparatively examine the cell attachment, cytotoxicity, and antibacterial activity of radiopaque dicalcium silicate cement (RDSC) and ProRoot white‐coloured mineral trioxide aggregate (WMTA).
...Methodology
AlamarBlue was used for real‐time and repeated monitoring of MG63 cell attachment on freshly mixed and set cements. The pH changes in the growth medium at different time‐points were also measured. Cytotoxicity evaluation was performed according to ISO 10993–5 specifications. The antibacterial activity of the cement specimens was evaluated using Enterococcus faecalis.
Results
There were no significant differences (P > 0.05) between the two cements for cell attachment either in the fresh groups or in the set groups at all culture times. Neither freshly mixed group nor set groups had significant pH differences. In the case of cytotoxicity, RDSC was significantly (P < 0.05) superior to WMTA at 12 and 24 h of incubation. RDSC and WMTA possessed similar antimicrobial activity, substantiated by the formation of growth inhibition zones and bacteriostasis ratio in E. faecalis strains.
Conclusions
The cell attachment, cytotoxicity and antibacterial efficacy of RDSC were comparable to those reported for ProRoot WMTA. The results of the current study suggest that this RDSC could be used as a root‐end filling material and root sealer.
This paper studies the problem of designing a robust fault-detection system for uncertain Takagi-Sugeno fuzzy models. The worst case fault sensitivity measure is formulated in terms of linear matrix ...inequalities. The existence of a robust fault detection system that guarantees i) the L 2 -gain from a fault signal to a residual signal greater than a prescribed value and ii) the L 2 -gain from an exogenous input to a residual signal less than a prescribed value is given in terms of the solvability of linear matrix inequalities. Numerical examples are used to illustrate the effectiveness of the proposed design techniques.
Atomoxetine (ATX), a drug for treatment of depression and ADHD, has a high affinity for the norepinephrine transporter (NET); however, our previous study showed it had a blocking effect similar to ...fluoxetine on binding of 11CDASB, a selective serotonin transporter (SERT) ligand. Whether the therapeutic effects of ATX are due to inhibition of either or both transporters is not known. Here we report our comparative PET imaging studies with 11CMRB (a NET ligand) and 11CAFM (a SERT ligand) to evaluate in vivo IC50 values of ATX in monkeys.
Rhesus monkeys were scanned up to four times with each tracer with up to four doses of ATX. ATX or saline (placebo) infusion began 2h before each PET scan, lasting until the end of the 2-h scan. The final infusion rates were 0.01–0.12mg/kg/h and 0.045–1.054mg/kg/h for the NET and SERT studies, respectively. ATX plasma levels and metabolite-corrected arterial input functions were measured. Distribution volumes (VT) and IC50 values were estimated.
ATX displayed dose-dependent occupancy on both NET and SERT, with a higher occupancy on NET: IC50 of 31±10 and 99±21ng/mL plasma for NET and SERT, respectively. At a clinically relevant dose (1.0–1.8mg/kg, approx. 300–600ng/mL plasma), ATX would occupy >90% of NET and >85% of SERT. This extrapolation assumes comparable free fraction of ATX in humans and non-human primates.
Our data suggests that ATX at clinically relevant doses greatly occupies both NET and SERT. Thus, therapeutic modes of ATX action for treatment of depression and ADHD may be more complex than selective blockade of NET.
•We examine the in vivo selectivity of atomoxetine (ATX) with PET.•11CMRB and 11CAFM were used to evaluate ATX IC50 values for NET & SERT.•ATX at clinically relevant doses greatly occupies both NET and SERT.•ATX for treatment of depression and ADHD may be more complex than current thinking.•The implications on the therapeutic mechanisms of ATX are discussed.
The worm Caenorhabditis elegans is a model system for studying many aspects of biology, including host responses to bacterial pathogens, but it is not known to support replication of any virus. ...Plants and insects encode multiple Dicer enzymes that recognize distinct precursors of small RNAs and may act cooperatively. However, it is not known whether the single Dicer of worms and mammals is able to initiate the small RNA-guided RNA interference (RNAi) antiviral immunity as occurs in plants and insects. Here we show complete replication of the Flock house virus (FHV) bipartite, plus-strand RNA genome in C. elegans. We show that FHV replication in C. elegans triggers potent antiviral silencing that requires RDE-1, an Argonaute protein essential for RNAi mediated by small interfering RNAs (siRNAs) but not by microRNAs. This immunity system is capable of rapid virus clearance in the absence of FHV B2 protein, which acts as a broad-spectrum RNAi inhibitor upstream of rde-1 by targeting the siRNA precursor. This work establishes a C. elegans model for genetic studies of animal virus-host interactions and indicates that mammals might use a siRNA pathway as an antiviral response.
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