Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide. Discovered 30 years ago, it is produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP has two ...major forms (α and β). It belongs to a group of peptides that all act on an unusual receptor family. These receptors consist of calcitonin receptor-like receptor (CLR) linked to an essential receptor activity modifying protein (RAMP) that is necessary for full functionality. CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. It is concluded that CGRP is an important peptide in mammalian biology, but it is too early at present to know if new medicines for disease treatment will emerge from our knowledge concerning this molecule.
Abstract
The Kelvin‐Helmholtz instability (KHI) at Earth's magnetopause and associated turbulence are suggested to play a role in the transport of mass and momentum from the solar wind into Earth's ...magnetosphere. We investigate electromagnetic turbulence observed in Kelvin‐Helmholtz vortices encountered at the dusk flank magnetopause by the Magnetospheric Multiscale (MMS) spacecraft under northward interplanetary magnetic field (IMF) conditions in order to reveal its generation process, mode properties, and role. A comparison with another MMS event at the dayside magnetopause with reconnection but no KHI signatures under a similar IMF condition indicates that while high‐latitude magnetopause reconnection excites a modest level of turbulence in the dayside low‐latitude boundary layer, the KHI further amplifies the turbulence, leading to magnetic energy spectra with a power law index −5/3 at magnetohydrodynamic scales even in its early nonlinear phase. The mode of the electromagnetic turbulence is analyzed with a single‐spacecraft method based on Ampère's law, developed by Bellan (2016,
https://doi.org/10.1002/2016JA022827
), for estimating wave vectors as a function of spacecraft frame frequency. The results suggest that the turbulence does not consist of propagating normal‐mode waves but is due to interlaced magnetic flux tubes advected by plasma flows in the vortices. The turbulence at sub‐ion scales in the early nonlinear phase of the KHI may not be the cause of the plasma transport across the magnetopause but rather a consequence of three‐dimensional vortex‐induced reconnection, the process that can cause an efficient transport by producing tangled reconnected field lines.
Plain Language Summary
Turbulence is ubiquitous in nature and plays an important role in material mixing and energy transport. Turbulence in space plasmas is characterized by fluctuations of flow velocity and/or electromagnetic fields over a broad frequency range and/or length scales and is believed to be the key to efficient plasma transport and heating. However, its generation mechanism is not fully understood because turbulence in space is often fully developed or already relaxed when observed. By analyzing high‐resolution plasma and electromagnetic field data taken by the Magnetospheric Multiscale spacecraft, we study the generation process of electromagnetic turbulence at the outer boundary of Earth's magnetosphere, called the magnetopause, where either a flow shear‐driven Kelvin‐Helmholtz instability or magnetic reconnection or both could drive turbulence. It is shown that while dayside reconnection generates a modest level of turbulence at the magnetopause near noon, the flow shear instability further amplifies the turbulence at the flank magnetopause. Our analysis also suggests that the turbulence may not be the primary cause of plasma transport from solar wind into the magnetosphere but rather a consequence of the flow shear‐induced reconnection that is likely the primary cause of plasma transport at the dayside flank under northward solar wind magnetic field conditions.
Key Points
The Kelvin‐Helmholtz instability (KHI) amplifies electromagnetic fluctuations in the magnetopause boundary layer
The turbulent fluctuations in the vortices may not be due to propagating waves but to magnetic structures, that is, interlaced flux tubes
The observed turbulent power law spectra at sub‐ion scales are consistent with those in kinetic simulations of KHI‐driven reconnection
We present an analysis of 55 central galaxies in clusters and groups with molecular gas masses and star formation rates lying between 10 8 and 10 11 M and 0.5 and 270 M yr − 1 , respectively. ...Molecular gas mass is correlated with star formation rate, H line luminosity, and central atmospheric gas density. Molecular gas is detected only when the central cooling time or entropy index of the hot atmosphere falls below ∼1 Gyr or ∼35 keV cm2, respectively, at a (resolved) radius of 10 kpc. These correlations indicate that the molecular gas condensed from hot atmospheres surrounding the central galaxies. We explore the origins of thermally unstable cooling by evaluating whether molecular gas becomes prevalent when the minimum of the cooling to free-fall time ratio ( t cool t ff ) falls below ∼10. We find that (1) molecular gas-rich systems instead lie between 10 < min ( t cool t ff ) < 25 , where t cool t ff = 25 corresponds approximately to cooling time and entropy thresholds of 1 Gyr and 35 keV cm 2 , respectively; (2) min ( t cool t ff ) is uncorrelated with molecular gas mass and jet power; and (3) the narrow range 10 < min ( t cool t ff ) < 25 can be explained by an observational selection effect, although a real physical effect cannot be excluded. These results and the absence of isentropic cores in cluster atmospheres are in tension with models that assume thermal instability ensues from linear density perturbations in hot atmospheres when t cool t ff 10 . Some of the molecular gas may instead have condensed from atmospheric gas lifted outward by buoyantly rising X-ray bubbles or by dynamically induced uplift (e.g., mergers, sloshing).
Purpose
Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary ...aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies.
Methods
A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus.
Results
Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for
Aspergillus
. Probable IAPA required the detection of galactomannan or positive
Aspergillus
culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between
Aspergillus
and the SARS-CoV-2-infected lung.
Conclusion
A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe
Aspergillus
disease, and may be of use to study CAPA.
We present accurate mass and thermodynamic profiles for 57 galaxy clusters observed with the Chandra X-ray Observatory. We investigate the effects of local gravitational acceleration in central ...cluster galaxies, and explore the role of the local free-fall time ( ) in thermally unstable cooling. We find that the radially averaged cooling time ( ) is as effective an indicator of cold gas, traced through its nebular emission, as the ratio / . Therefore, primarily governs the onset of thermally unstable cooling in hot atmospheres. The location of the minimum / , a thermodynamic parameter that many simulations suggest is key in driving thermal instability, is unresolved in most systems. Consequently, selection effects bias the value and reduce the observed range in measured / minima. The entropy profiles of cool-core clusters are characterized by broken power laws down to our resolution limit, with no indication of isentropic cores. We show, for the first time, that mass isothermality and the entropy profile slope imply a floor in / profiles within central galaxies. No significant departures of / below 10 are found. This is inconsistent with models that assume thermally unstable cooling ensues from linear perturbations at or near this threshold. We find that the inner cooling times of cluster atmospheres are resilient to active galactic nucleus (AGN)-driven change, suggesting gentle coupling between radio jets and atmospheric gas. Our analysis is consistent with models in which nonlinear perturbations, perhaps seeded by AGN-driven uplift of partially cooled material, lead to cold gas condensation.
Abstract
The long-period, highly eccentric Wolf-Rayet star binary system WR 140 has exceptionally well-determined orbital and stellar parameters. Bright, variable X-ray emission is generated in ...shocks produced by the collision of the winds of the WC7pd+O5.5fc component stars. We discuss the variations in the context of the colliding-wind model using broadband spectrometry from the RXTE, Swift, and NICER observatories obtained over 20 yr and nearly 1000 observations through three consecutive 7.94 yr orbits, including three periastron passages. The X-ray luminosity varies as expected with the inverse of the stellar separation over most of the orbit; departures near periastron are produced when cooling shifts to excess optical emission in C
iii
λ
5696 in particular. We use X-ray absorption to estimate mass-loss rates for both stars and to constrain the system morphology. The absorption maximum coincides closely with the inferior conjunction of the WC star and provides evidence of the ion-reflection mechanism that underlies the formation of collisionless shocks governed by magnetic fields probably generated by the Weibel instability. Comparisons with
K
-band emission and He
i
λ
10830 absorption show that both are correlated after periastron with the asymmetric X-ray absorption. Dust appears within a few days of periastron, suggesting formation within shocked gas near the stagnation point. The X-ray flares seen in
η
Car have not occurred in WR 140, suggesting the absence of large-scale wind inhomogeneities. Relatively constant soft emission revealed during the X-ray minimum is probably not from recombining plasma entrained in outflowing shocked gas.
X-ray luminosity, temperature, gas mass, total mass, and their scaling relations are derived for 94 early-type galaxies (ETGs) using archival Chandra X-ray Observatory observations. Consistent with ...earlier studies, the scaling relations, LX ∝ T4.5 0.2, M ∝ T2.4 0.2, and LX ∝ M2.8 0.3, are significantly steeper than expected from self-similarity. This steepening indicates that their atmospheres are heated above the level expected from gravitational infall alone. Energetic feedback from nuclear black holes and supernova explosions are likely heating agents. The tight LX-T correlation for low-luminosity systems (i.e., below 1040 erg s−1) are at variance with hydrodynamical simulations, which generally predict higher temperatures for low-luminosity galaxies. We also investigate the relationship between total mass and pressure, YX = Mg × T, finding . We explore the gas mass to total mass fraction in ETGs and find a range of 0.1%-1.0%. We find no correlation between the gas-to-total mass fraction with temperature or total mass. Higher stellar velocity dispersions and higher metallicities are found in hotter, brighter, and more massive atmospheres. X-ray core radii derived from β-model fitting are used to characterize the degree of core and cuspiness of hot atmospheres.
Hybrid multiscale agent-based models (ABMs) are unique in their ability to simulate individual cell interactions and microenvironmental dynamics. Unfortunately, the high computational cost of ...modeling individual cells, the inherent stochasticity of cell dynamics, and numerous model parameters are fundamental limitations of applying such models to predict tumor dynamics. To overcome these challenges, we have developed a coarse-grained two-scale ABM (cgABM) with a reduced parameter space that allows for an accurate and efficient calibration using a set of time-resolved microscopy measurements of cancer cells grown with different initial conditions. The multiscale model consists of a reaction-diffusion type model capturing the spatio-temporal evolution of glucose and growth factors in the tumor microenvironment (at tissue scale), coupled with a lattice-free ABM to simulate individual cell dynamics (at cellular scale). The experimental data consists of BT474 human breast carcinoma cells initialized with different glucose concentrations and tumor cell confluences. The confluence of live and dead cells was measured every three hours over four days. Given this model, we perform a time-dependent global sensitivity analysis to identify the relative importance of the model parameters. The subsequent cgABM is calibrated within a Bayesian framework to the experimental data to estimate model parameters, which are then used to predict the temporal evolution of the living and dead cell populations. To this end, a moment-based Bayesian inference is proposed to account for the stochasticity of the cgABM while quantifying uncertainties due to limited temporal observational data. The cgABM reduces the computational time of ABM simulations by 93% to 97% while staying within a 3% difference in prediction compared to ABM. Additionally, the cgABM can reliably predict the temporal evolution of breast cancer cells observed by the microscopy data with an average error and standard deviation for live and dead cells being 7.61±2.01 and 5.78±1.13, respectively.
Electron heating at Earth's quasiperpendicular bow shock has been surmised to be due to the combined effects of a quasistatic electric potential and scattering through wave-particle interaction. Here ...we report the observation of electron distribution functions indicating a new electron heating process occurring at the leading edge of the shock front. Incident solar wind electrons are accelerated parallel to the magnetic field toward downstream, reaching an electron-ion relative drift speed exceeding the electron thermal speed. The bulk acceleration is associated with an electric field pulse embedded in a whistler-mode wave. The high electron-ion relative drift is relaxed primarily through a nonlinear current-driven instability. The relaxed distributions contain a beam traveling toward the shock as a remnant of the accelerated electrons. Similar distribution functions prevail throughout the shock transition layer, suggesting that the observedacceleration and thermalization is essential to the cross-shock electron heating.
Cataracts account for over half of global blindness. Cataracts formations occur mainly due to aging and to the direct insults of oxidative stress and inflammation to the eye lens. The nuclear ...factor-erythroid-2-related factor 2 (Nrf2), a transcriptional factor for cell cytoprotection, is known as the master regulator of redox homeostasis. Nrf2 regulates nearly 600 genes involved in cellular protection against contributing factors of oxidative stress, including aging, disease, and inflammation. Nrf2 was reported to disrupt the oxidative stress that activates Nuclear factor-κB (NFκB) and proinflammatory cytokines. One of these cytokines is matrix metalloproteinase 9 (MMP-9), which participates in the decomposition of lens epithelial cells (LECs) extracellular matrix and has been correlated with cataract development. Thus, during inflammatory processes, MMP production may be attenuated by the Nrf2 pathway or by the Nrf2 inhibition of NFκB pathway activation. Moreover, plant-based polyphenols have garnered attention due to their presumed safety and efficacy, nutritional, and antioxidant effects. Polyphenol compounds can activate Nrf2 and inhibit MMP-9. Therefore, this review focuses on discussing Nrf2's role in oxidative stress and cataract formation, epigenetic effect in Nrf2 activity, and the association between Nrf2 and MMP-9 in cataract development. Moreover, we describe the protective role of flavonoids in cataract formation, targeting Nrf2 activation and MMP-9 synthesis inhibition as potential molecular targets in preventing cataracts.
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