The disks that orbit young stars are the essential conduits and reservoirs of material for star and planet formation. Their structures, meaning the spatial variations of the disk physical conditions, ...reflect the underlying mechanisms that drive those formation processes. Observations of the solids and gas in these disks, particularly at high resolution, provide fundamental insights on their mass distributions, dynamical states, and evolutionary behaviors. Over the past decade, rapid developments in these areas have largely been driven by observations with the Atacama Large Millimeter/submillimeter Array (ALMA). This review highlights the state of observational research on disk structures, emphasizing the following three key conclusions that reflect the main branches of the field:
Relationships among disk structure properties are also linked to the masses, environments, and evolutionary states of their stellar hosts.
There is clear, qualitative evidence for the growth and migration of disk solids, although the implied evolutionary timescales suggest the classical assumption of a smooth gas disk is inappropriate.
Small-scale substructures with a variety of morphologies, locations, scales, and amplitudes-presumably tracing local gas pressure maxima-broadly influence the physical and observational properties of disks.
The last point especially is reshaping the field, with the recognition that these disk substructures likely trace active sites of planetesimal growth or are the hallmarks of planetary systems at their formation epoch.
The second meeting of the Emergency Committee convened by the WHO Director-General under the International Health Regulations (2005) regarding the outbreak of novel coronavirus 2019 in the People's ...Republic of China on January 30, 2020, declared COVID-19 outbreak as Public Health Emergency of International Concern (PHEIC)5. In the Emergency department in General Hospital, she was afebrile with a pulse rate of 82/min, blood pressure 130/80 mmHg, temperature 98.5°F and oxygen saturation 96 per cent while the patient was breathing ambient air. On day 1 of illness, the total white blood cell count was towards the low normal side, but on days 5 and 20, the count showed a rise which was consistent with a viral infection.
This review addresses the state of research that employs astronomical (remote sensing) observations of solids ("dust") in young circumstellar disks to learn about planet formation. The intention is ...for it to serve as an accessible, introductory, pedagogical resource for junior scientists interested in the subject. After some historical background and a basic observational primer, the focus is shifted to the three fundamental topics that broadly define the field: (1) demographics-the relationships between disk properties and the characteristics of their environments and hosts; (2) structure-the spatial distribution of disk material and its associated physical conditions and composition; and (3) evolution-the signposts of key changes in disk properties, including the growth and migration of solids and the impact of dynamical interactions with young planetary systems. Based on the state-of-the-art results in these areas, suggestions are made for potentially fruitful lines of work in the near future.
Traumatic brain injury (TBI) is a major cause for long-term disability, yet the treatments available that improve outcomes after TBI limited. Neuroinflammatory responses are key contributors to ...determining patient outcomes after TBI. Transplantation of mesenchymal stem cells (MSCs), which release trophic and pro-repair cytokines, represents an effective strategy to reduce inflammation after TBI. One such pro-repair cytokine is interleukin-10 (IL-10), which reduces pro-inflammatory markers and trigger alternative inflammatory markers, such as CD163. In this study, we tested the therapeutic effects of MSCs that were engineered to overexpress IL-10 when transplanted into rats following TBI in the medial frontal cortex.
Thirty-six hours following TBI, rats were transplanted with MSCs and then assessed for 3 weeks on a battery of behavioral tests that measured motor and cognitive abilities. Histological evaluation was then done to measure the activation of the inflammatory response. Additionally, immunomodulatory effects were evaluated by immunohistochemistry and Western blot analyses.
A significant improvement in fine motor function was observed in rats that received transplants of MSCs engineered to overexpress IL-10 (MSCs + IL-10) or MSCs alone compared to TBI + vehicle-treated rats. Although tissue spared was unchanged, anti-inflammatory effects were revealed by a reduction in the number of glial fibrillary acidic protein cells and CD86 cells in both TBI + MSCs + IL-10 and TBI + MSC groups compared to TBI + vehicle rats. Microglial activation was significantly increased in the TBI + MSC group when compared to the sham + vehicle group. Western blot data suggested a reduction in tumor necrosis factor-alpha in the TBI + MSCs + IL-10 group compared to TBI + MSC group. Immunomodulatory effects were demonstrated by a shift from classical inflammation expression (CD86) to an alternative inflammation state (CD163) in both treatments with MSCs and MSCs + IL-10. Furthermore, co-labeling of both CD86 and CD163 was detected in the same cells, suggesting a temporal change in macrophage expression.
Overall, our findings suggest that transplantation of MSCs that were engineered to overexpress IL-10 can improve functional outcomes by providing a beneficial perilesion environment. This improvement may be explained by the shifting of macrophage expression to a more pro-repair state, thereby providing a possible new therapy for treating TBI.
The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global ...perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression.
Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ identification and quantification p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes-sphingolipids and glycerophospholipids-that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer's Disease Neuroimaging Initiative ADNI, N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that summarized the relative importance of each metabolite to severity of AD pathology and disease progression (Endophenotype Association Score in Early Alzheimer's Disease EASE-AD). Finally, we mapped the main metabolite classes emerging from our analyses to key biological pathways implicated in AD pathogenesis. We found that distinct sphingolipid species including sphingomyelin (SM) with acyl residue sums C16:0, C18:1, and C16:1 (SM C16:0, SM C18:1, SM C16:1) and hydroxysphingomyelin with acyl residue sum C14:1 (SM (OH) C14:1) were consistently associated with severity of AD pathology at autopsy and AD progression across prodromal and preclinical stages. Higher log-transformed blood concentrations of all four sphingolipids in cognitively normal individuals were significantly associated with increased risk of future conversion to incident AD: SM C16:0 (hazard ratio HR = 4.430, 95% confidence interval CI = 1.703-11.520, p = 0.002), SM C16:1 (HR = 3.455, 95% CI = 1.516-7.873, p = 0.003), SM (OH) C14:1 (HR = 3.539, 95% CI = 1.373-9.122, p = 0.009), and SM C18:1 (HR = 2.255, 95% CI = 1.047-4.855, p = 0.038). The sphingolipid species identified map to several biologically relevant pathways implicated in AD, including tau phosphorylation, amyloid-β (Aβ) metabolism, calcium homeostasis, acetylcholine biosynthesis, and apoptosis. Our study has limitations: the relatively small number of brain tissue samples may have limited our power to detect significant associations, control for heterogeneity between groups, and replicate our findings in independent, autopsy-derived brain samples.
We present a novel framework to identify biologically relevant brain and blood metabolites associated with disease pathology and progression during the prodromal and preclinical stages of AD. Our results show that perturbations in sphingolipid metabolism are consistently associated with endophenotypes across preclinical and prodromal AD, as well as with AD pathology at autopsy. Sphingolipids may be biologically relevant biomarkers for the early detection of AD, and correcting perturbations in sphingolipid metabolism may be a plausible and novel therapeutic strategy in AD.
We present a survey at subarcsecond resolution of the 340 GHz dust continuum emission from 50 nearby protoplanetary disks, based on new and archival observations with the Submillimeter Array. The ...observed visibility data were modeled with a simple prescription for the radial surface brightness profile. The results were used to extract intuitive, empirical estimates of the emission "size" for each disk, , defined as the radius that encircles a fixed fraction of the total continuum luminosity, . We find a significant correlation between the sizes and luminosities, such that , providing a confirmation and quantitative characterization of a putative trend that was noted previously. This correlation suggests that these disks have roughly the same average surface brightness interior to their given effective radius, ∼0.2 Jy arcsec−2 (or 8 K in brightness temperature). The same trend remains, but the 0.2 dex of dispersion perpendicular to this relation essentially disappears, when we account for the irradiation environment of each disk with a crude approximation of the dust temperatures based on the stellar host luminosities. We consider two (not mutually exclusive) explanations for the origin of this size-luminosity relationship. Simple models of the growth and migration of disk solids can account for the observed trend for a reasonable range of initial conditions, but only on timescales that are much shorter than the nominal ages present in the sample. An alternative scenario invokes optically thick emission concentrated on unresolved scales, with filling factors of a few tens of percent, which is perhaps a manifestation of localized particle traps.
Minimum inhibitory concentrations (MICs) are defined as the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation, and minimum ...bactericidal concentrations (MBCs) as the lowest concentration of antimicrobial that will prevent the growth of an organism after subculture on to antibiotic-free media. MICs are used by diagnostic laboratories mainly to confirm resistance, but most often as a research tool to determine the in vitro activity of new antimicrobials, and data from such studies have been used to determine MIC breakpoints. MBC determinations are undertaken less frequently and their major use has been reserved for isolates from the blood of patients with endocarditis. Standardized methods for determining MICs and MBCs are described in this paper. Like all standardized procedures, the method must be adhered to and may not be adapted by the user. The method gives information on the storage of standard antibiotic powder, preparation of stock antibiotic solutions, media, preparation of inocula, incubation conditions, and reading and interpretation of results. Tables giving expected MIC ranges for control NCTC and ATCC strains are also supplied.
The Disk Substructures at High Angular Resolution Project (DSHARP) provides a large sample of protoplanetary disks with substructures that could be induced by young forming planets. To explore the ...properties of planets that may be responsible for these substructures, we systematically carry out a grid of 2D hydrodynamical simulations, including both gas and dust components. We present the resulting gas structures, including the relationship between the planet mass, as well as (1) the gaseous gap depth/width and (2) the sub/super-Keplerian motion across the gap. We then compute dust continuum intensity maps at the frequency of the DSHARP observations. We provide the relationship between the planet mass, as well as (1) the depth/width of the gaps at millimeter intensity maps, (2) the gap edge ellipticity and asymmetry, and (3) the position of secondary gaps induced by the planet. With these relationships, we lay out the procedure to constrain the planet mass using gap properties, and study the potential planets in the DSHARP disks. We highlight the excellent agreement between observations and simulations for AS 209 and the detectability of the young solar system analog. Finally, under the assumption that the detected gaps are induced by young planets, we characterize the young planet population in the planet mass-semimajor axis diagram. We find that the occurrence rate for >5 MJ planets beyond 5-10 au is consistent with direct imaging constraints. Disk substructures allow us to probe a wide-orbit planet population (Neptune to Jupiter mass planets beyond 10 au) that is not accessible to other planet searching techniques.
The possibility that Arctic sea ice loss weakens mid-latitude westerlies, promoting more severe cold winters, has sparked more than a decade of scientific debate, with apparent support from ...observations but inconclusive modelling evidence. Here we show that sixteen models contributing to the Polar Amplification Model Intercomparison Project simulate a weakening of mid-latitude westerlies in response to projected Arctic sea ice loss. We develop an emergent constraint based on eddy feedback, which is 1.2 to 3 times too weak in the models, suggesting that the real-world weakening lies towards the higher end of the model simulations. Still, the modelled response to Arctic sea ice loss is weak: the North Atlantic Oscillation response is similar in magnitude and offsets the projected response to increased greenhouse gases, but would only account for around 10% of variations in individual years. We further find that relationships between Arctic sea ice and atmospheric circulation have weakened recently in observations and are no longer inconsistent with those in models.
The Disk Substructures at High Angular Resolution Project (DSHARP) is the largest homogeneous high-resolution (∼0 035, or ∼5 au) disk continuum imaging survey with the Atacama Large ...Millimeter/submillimeter Array (ALMA) so far. In the coming years, many more disks will be mapped with ALMA at similar resolution. Interpreting the results in terms of the properties and quantities of the emitting dusty material is, however, a very non-trivial task. This is in part due to the uncertainty in the dust opacities, an uncertainty that is not likely to be resolved any time soon. It is also partly due to the fact that, as the DSHARP survey has shown, these disk often contain regions of intermediate to high optical depth, even at millimeter wavelengths and at relatively large radius in the disk. This makes the interpretation challenging, in particular if the grains are large and have a large albedo. On the other hand, the highly structured features seen in the DSHARP survey, of which strong indications were already seen in earlier observations, provide a unique opportunity to study the dust growth and dynamics. To provide continuity within the DSHARP project, its follow-up projects, and projects by other teams interested in these data, we present here the methods and opacity choices used within the DSHARP collaboration to link the measured intensity I to dust surface density d.
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