We present X-ray and radio observations of the Fast Blue Optical Transient CRTS-CSS161010 J045834−081803 (CSS161010 hereafter) at t = 69-531 days. CSS161010 shows luminous X-ray (Lx ∼ 5 × 1039 erg ...s−1) and radio (L ∼ 1029 erg s−1 Hz−1) emission. The radio emission peaked at ∼100 days post-transient explosion and rapidly decayed. We interpret these observations in the context of synchrotron emission from an expanding blast wave. CSS161010 launched a mildly relativistic outflow with velocity Γβc ≥ 0.55c at ∼100 days. This is faster than the non-relativistic AT 2018cow (Γβc ∼ 0.1c) and closer to ZTF18abvkwla (Γβc ≥ 0.3c at 63 days). The inferred initial kinetic energy of CSS161010 (Ek 1051 erg) is comparable to that of long gamma-ray bursts, but the ejecta mass that is coupled to the mildly relativistic outflow is significantly larger ( ). This is consistent with the lack of observed γ-rays. The luminous X-rays were produced by a different emission component to the synchrotron radio emission. CSS161010 is located at ∼150 Mpc in a dwarf galaxy with stellar mass M* ∼ 107 M and specific star formation rate sSFR ∼ 0.3 Gyr−1. This mass is among the lowest inferred for host galaxies of explosive transients from massive stars. Our observations of CSS161010 are consistent with an engine-driven aspherical explosion from a rare evolutionary path of a H-rich stellar progenitor, but we cannot rule out a stellar tidal disruption event on a centrally located intermediate-mass black hole. Regardless of the physical mechanism, CSS161010 establishes the existence of a new class of rare (rate < 0.4% of the local core-collapse supernova rate) H-rich transients that can launch mildly relativistic outflows.
Femtosecond transient absorption spectroscopy and microscopy were employed to study exciton dynamics in suspended and Si3N4 substrate-supported monolayer and few-layer MoS2 2D crystals. Exciton ...dynamics for the monolayer and few-layer structures were found to be remarkably different from those of thick crystals when probed at energies near that of the lowest energy direct exciton (A exciton). The intraband relaxation rate was enhanced by more than 40 fold in the monolayer in comparison to that observed in the thick crystals, which we attributed to defect assisted scattering. Faster electron–hole recombination was found in monolayer and few-layer structures due to quantum confinement effects that lead to an indirect–direct band gap crossover. Nonradiative rather than radiative relaxation pathways dominate the dynamics in the monolayer and few-layer MoS2. Fast trapping of excitons by surface trap states was observed in monolayer and few-layer structures, pointing to the importance of controlling surface properties in atomically thin crystals such as MoS2 along with controlling their dimensions.
The myelin sheaths wrapped around axons by oligodendrocytes are crucial for brain function. In ischaemia myelin is damaged in a Ca(2+)-dependent manner, abolishing action potential propagation. This ...has been attributed to glutamate release activating Ca(2+)-permeable N-methyl-D-aspartate (NMDA) receptors. Surprisingly, we now show that NMDA does not raise the intracellular Ca(2+) concentration (Ca(2+)i) in mature oligodendrocytes and that, although ischaemia evokes a glutamate-triggered membrane current, this is generated by a rise of extracellular K(+) and decrease of membrane K(+) conductance. Nevertheless, ischaemia raises oligodendrocyte Ca(2+)i, Mg(2+)i and H(+)i, and buffering intracellular pH reduces the Ca(2+)i and Mg(2+)i increases, showing that these are evoked by the rise of H(+)i. The H(+)-gated Ca(2+)i elevation is mediated by channels with characteristics of TRPA1, being inhibited by ruthenium red, isopentenyl pyrophosphate, HC-030031, A967079 or TRPA1 knockout. TRPA1 block reduces myelin damage in ischaemia. These data suggest that TRPA1-containing ion channels could be a therapeutic target in white matter ischaemia.
Trials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in ...preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.
We conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.
A total of 11,016 patients underwent randomization (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval CI, 0.71 to 0.96; P = 0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P = 0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P = 0.001).
Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.).
Abstract The most common way to discover extragalactic fast transients, which fade within a few nights in the optical, is via follow-up of gamma-ray burst and gravitational-wave triggers. However, ...wide-field surveys have the potential to identify rapidly fading transients independently of such external triggers. The volumetric survey speed of the Zwicky Transient Facility (ZTF) makes it sensitive to objects as faint and fast fading as kilonovae, the optical counterparts to binary neutron star mergers, out to almost 200 Mpc. We introduce an open-source software infrastructure, the ZTF REaltime Search and Triggering, ZTFReST , designed to identify kilonovae and fast transients in ZTF data. Using the ZTF alert stream combined with forced point-spread-function photometry, we have implemented automated candidate ranking based on their photometric evolution and fitting to kilonova models. Automated triggering, with a human in the loop for monitoring, of follow-up systems has also been implemented. In 13 months of science validation, we found several extragalactic fast transients independently of any external trigger, including two supernovae with post-shock cooling emission, two known afterglows with an associated gamma-ray burst (ZTF20abbiixp, ZTF20abwysqy), two known afterglows without any known gamma-ray counterpart (ZTF20aajnksq, ZTF21aaeyldq), and three new fast-declining sources (ZTF20abtxwfx, ZTF20acozryr, ZTF21aagwbjr) that are likely associated with GRB200817A, GRB201103B, and GRB210204A. However, we have not found any objects that appear to be kilonovae. We constrain the rate of GW170817-like kilonovae to R < 900 Gpc −3 yr −1 (95% confidence). A framework such as ZTFReST could become a prime tool for kilonova and fast-transient discovery with the Vera Rubin Observatory.
Cigarette smoke (CS) inhalation causes an early inflammatory response in rodent airways by stimulating capsaicin-sensitive sensory neurons that express transient receptor potential cation channel, ...subfamily V, member 1 (TRPV1) through an unknown mechanism that does not involve TRPV1. We hypothesized that 2 alpha,beta-unsaturated aldehydes present in CS, crotonaldehyde and acrolein, induce neurogenic inflammation by stimulating TRPA1, an excitatory ion channel coexpressed with TRPV1 on capsaicin-sensitive nociceptors. We found that CS aqueous extract (CSE), crotonaldehyde, and acrolein mobilized Ca2+ in cultured guinea pig jugular ganglia neurons and promoted contraction of isolated guinea pig bronchi. These responses were abolished by a TRPA1-selective antagonist and by the aldehyde scavenger glutathione but not by the TRPV1 antagonist capsazepine or by ROS scavengers. Treatment with CSE or aldehydes increased Ca2+ influx in TRPA1-transfected cells, but not in control HEK293 cells, and promoted neuropeptide release from isolated guinea pig airway tissue. Furthermore, the effect of CSE and aldehydes on Ca2+ influx in dorsal root ganglion neurons was abolished in TRPA1-deficient mice. These data identify alpha,beta-unsaturated aldehydes as the main causative agents in CS that via TRPA1 stimulation mediate airway neurogenic inflammation and suggest a role for TRPA1 in the pathogenesis of CS-induced diseases.
The pharmacology of TRP channels Holzer, Peter; Izzo, Angelo A
British journal of pharmacology,
20/May , Letnik:
171, Številka:
10
Journal Article
Recenzirano
Odprti dostop
This themed issue of the British Journal of Pharmacology contains review and research articles on recent advances in transient receptor potential (TRP) channel pharmacology. The review articles, ...written by a panel of distinguished experts, address the rapid progress in TRP channel research in fields as diverse as oncology, urology, dermatology, migraine, inflammation and pain. These reviews are complemented by original research reports focusing, among others, on the emerging roles of TRPV1 in osteoporosis and cystitis and on evodiamine as a lead structure for the development of potent TRPV1 agonists/desensitizers. Other papers highlight the differences in TRPV3 pharmacology between recombinant and native systems, the mechanisms of TRPM3 activation/inhibition and TRPP2 as a target of naringenin, a dietary flavonoid with anticancer actions. New therapeutic opportunities in pain may arise from the strategy to combine TRP channel and cell membrane impermeant sodium channel blockers to inhibit sensory nerve activity.
Linked Articles
This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐10
Abstract We present Hubble Space Telescope ultraviolet and infrared observations of eight fast radio burst (FRB) host galaxies with subarcsecond localizations, including the hosts of three known ...repeating FRBs. We quantify their spatial distributions and locations with respect to their host galaxy light distributions, finding that they occur at moderate host-normalized offsets of 1.4 r e (0.6, 2.1 r e ; 68% interval) and on fainter regions of their hosts in terms of IR light but overall trace the radial distribution of IR light in their galaxies. The FRBs in our tested distribution do not clearly trace the distributions of any other transient population with known progenitors and are statistically distinct from the locations of LGRBs, H-poor SLSNe, SGRBs, and Ca-rich transients. We further find that most FRBs are not in regions of elevated local star formation rates and stellar mass surface densities in comparison to the mean global values of their hosts. We also place upper limits on the IR flux at the FRB positions of m IR ≳ 24.8–27.6 AB mag, constraining both satellite and background galaxies to luminosities well below the host luminosity of FRB 121102. We find that 5/8 FRB hosts exhibit clear spiral arm features in IR light, and that the positions of all well-localized FRBs located in such hosts are consistent with their spiral arms, although not on their brightest regions. Our results do not strongly support the primary progenitor channel of FRBs being connected with either the most massive (stripped-envelope) stars or events that require kicks and long delay times (neutron star mergers).
Driven by the large-scale integration of distributed power resources, grid-connected voltage-source converters (VSCs) are increasingly required to operate as grid-forming units to regulate the system ...voltage/frequency and emulate the inertia. While various grid-forming control schemes have been reported, their transient behaviors under large-signal disturbances are still not fully explored. This article addresses this issue by presenting a design-oriented transient stability analysis of the grid-forming VSCs. First, four typical grid-forming control schemes, namely, the power-synchronization control (PSC), the basic droop control, the droop control with low-pass filters (LPFs), and the virtual synchronous generator (VSG) control, are systematically reviewed, whose dynamics are characterized by a general large-signal model. Based on this model, a comparative analysis on the transient stabilities of different control schemes is then carried out. It reveals that the PSC and the basic droop control can retain a stable operation as long as there are equilibrium points, due to their noninertial transient responses, while the droop control with LPFs and the VSG control can be destabilized even if the equilibrium points exist, due to the lack of damping on their inertial transient responses. With the phase portrait, the underlying stability mechanism is explicitly elaborated, and the quantitative impacts of the controller gains and the virtual inertia are clearly identified. Subsequently, controller design guidelines are proposed to enhance the system damping as well as the transient stability. Finally, experimental results are provided to verify the theoretical analysis.
The voltage-frequency coupled transient stability and risk assessment issues of weak grid-connected large-scale renewable energy plants (REPs) during low voltage ride through (LVRT) have received ...little attention to date. The shape and mechanism of voltage-frequency coupled transient instability during LVRT are investigated in detail by the voltage-vector-triangle graphic (VTG) method utilized in this article, which avoids complex mathematical calculations. In addition, the margin of the transmission line's voltage angle (MTVA) is defined in this article and is then used to quantitatively assess the transient instability risk of the large-scale REPs during LVRT. Furthermore, the expressions of the MTVA are deduced under different conditions and the major influencing factors, which resulted in instability risk, are determined correspondingly. On this basis, the transient instability risk assessment standard of the large-scale REPs is built and the instability risk minimized scheduling strategy is proposed in this article, which does not change the internal control structure and parameters of the REPs during LVRT. Finally, both the correctness of the VTG method and the risk assessment standard, and the effectiveness of the scheduling strategy proposed in this article are validated by experiments and simulations.
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