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.
We present Atacama Large Millimeter Array 850 m continuum observations of the Orion Nebula Cluster that provide the highest angular resolution (∼0 1 40 au) and deepest sensitivity (∼0.1 mJy) of the ...region to date. We mosaicked a field containing ∼225 optical or near-IR-identified young stars, ∼60 of which are also optically identified "proplyds." We detect continuum emission at 850 m toward ∼80% of the proplyd sample, and ∼50% of the larger sample of previously identified cluster members. Detected objects have fluxes of ∼0.5-80 mJy. We remove submillimeter flux due to free-free emission in some objects, leaving a sample of sources detected in dust emission. Under standard assumptions of isothermal, optically thin disks, submillimeter fluxes correspond to dust masses of ∼0.5-80 Earth masses. We measure the distribution of disk sizes, and find that disks in this region are particularly compact. Such compact disks are likely to be significantly optically thick. The distributions of submillimeter flux and inferred disk size indicate smaller, lower-flux disks than in lower-density star-forming regions of similar age. Measured disk flux is correlated weakly with stellar mass, contrary to studies in other star-forming regions that found steeper correlations. We find a correlation between disk flux and distance from the massive star θ1 Ori C, suggesting that disk properties in this region are influenced strongly by the rich cluster environment.
This paper studies the throughput of large-scale decentralized wireless networks with physical layer security constraints. In particular, we are interested in the question of how much throughput ...needs to be sacrificed for achieving a certain level of security. We consider random networks where the legitimate nodes and the eavesdroppers are distributed according to independent two-dimensional Poisson point processes. The transmission capacity framework is used to characterize the area spectral efficiency of secure transmissions with constraints on both the quality of service (QoS) and the level of security. This framework illustrates the dependence of the network throughput on key system parameters, such as the densities of legitimate nodes and eavesdroppers, as well as the QoS and security constraints. One important finding is that the throughput cost of achieving a moderate level of security is quite low, while throughput must be significantly sacrificed to realize a highly secure network. We also study the use of a secrecy guard zone, which is shown to give a significant improvement on the throughput of networks with high security requirements.
Primary haemostasis: newer insights Berndt, M. C.; Metharom, P.; Andrews, R. K.
Haemophilia,
20/May , Letnik:
20, Številka:
s4
Journal Article
Recenzirano
Odprti dostop
Summary
At the same time as biophysical and omics approaches are drilling deeper into the molecular details of platelets and other blood cells, as well as their receptors and mechanisms of ...regulation, there is also an increasing awareness of the functional overlap between human vascular systems. Together, these studies are redefining the intricate networks linking haemostasis and thrombosis with inflammation, infectious disease, cancer/metastasis and other vascular pathophysiology. The focus of this state‐of‐the‐art review is some of the newer advances relevant to primary haemostasis. Of particular interest, platelet‐specific primary adhesion‐signalling receptors and associated activation pathways control platelet function in flowing blood and provide molecular links to other systems. Platelet glycoprotein (GP)Ibα of the GPIb‐IX‐V complex and GPVI not only initiate platelet aggregation and thrombus formation by primary interactions with von Willebrand factor and collagen, respectively, but are also involved in coagulation, leucocyte engagement, bacterial or viral interactions, and are relevant as potential risk markers in a range of human diseases. Understanding these systems in unprecedented detail promises significant advances in evaluation of individual risk, in new diagnostic or therapeutic possibilities and in monitoring the response to drugs or other treatment.
Context. Massive stars and their stellar winds are important for a number of feedback processes. The mass lost in the stellar wind can help determine the end-point of the star as a neutron star (NS) ...or a black hole (BH). However, the impact of mass loss on the post-main sequence evolutionary stage of massive stars is not well understood. Westerlund 1 is an ideal astrophysical laboratory in which to study massive stars and their winds in great detail over a large range of different evolutionary phases. Aims. We aim to study the radio emission from Westerlund 1, in order to measure radio fluxes from the population of massive stars, and determine mass-loss rates and spectral indices where possible. Methods. Observations were carried out in 2015 and 2016 with the Australia Telescope Compact Array (ATCA) at 5.5 and 9 GHz using multiple configurations, with maximum baselines ranging from 750 m to 6 km. Results. Thirty stars are detected in the radio from the fully concatenated dataset, ten of which are Wolf-Rayet stars (WRs) (predominantly late type WN stars), five yellow hypergiants (YHGs), four red supergiants (RSGs), one luminous blue variable (LBV), the sgBe star W9, and several OB supergiants. New source detections in the radio are found for five WR stars, and five OB supergiants. These detections lead to evidence for three new OB supergiant binary candidates, which is inferred from derived spectral index limits. Conclusions. Spectral indices and index limits were determined for massive stars in Westerlund 1. For cluster members found to have partially optically thick emission, mass-loss rates were calculated. Under the approximation of a thermally emitting stellar wind and a steady mass-loss rate, clumping ratios were then estimated for eight WRs. Diffuse radio emission was detected throughout the cluster. Detections of knots of radio emission with no known stellar counterparts indicate the highly clumped structure of this intra-cluster medium, likely shaped by a dense cluster wind.
Essentials
Dimeric high‐affinity collagen receptor glycoprotein VI (GPVI) is present on resting platelets.
Spatio‐temporal organization of platelet GPVI‐dimers was evaluated using advanced ...microscopy.
Upon platelet adhesion to collagenous substrates, GPVI‐dimers coalesce to form clusters.
Clustering of GPVI‐dimers may increase avidity and facilitate platelet activation
Summary
Background
Platelet glycoprotein VI (GPVI) binding to subendothelial collagen exposed upon blood vessel injury initiates thrombus formation. Dimeric GPVI has high affinity for collagen, and occurs constitutively on resting platelets.
Objective
To identify higher‐order oligomerization (clustering) of pre‐existing GPVI dimers upon interaction with collagen as a mechanism to initiate GPVI‐mediated signaling.
Methods
GPVI was located by use of fluorophore‐conjugated GPVI dimer‐specific Fab (antigen‐binding fragment). The tested substrates include Horm collagen I fibers, soluble collagen III, GPVI‐specific collagen peptides, and fibrinogen. GPVI dimer clusters on the platelet surface interacting with these substrates were visualized with complementary imaging techniques: total internal reflection fluorescence microscopy to monitor real‐time interactions, and direct stochastic optical reconstruction microscopy (dSTORM), providing relative quantification of GPVI cluster size and density. Confocal microscopy was used to locate GPVI dimer clusters, glycoprotein Ib, integrin α2β1, and phosphotyrosine.
Results
Upon platelet adhesion to all collagenous substrates, GPVI dimers coalesced to form clusters; notably clusters formed along the fibers of Horm collagen. dSTORM revealed that GPVI density within clusters depended on the substrate, collagen III being the most effective. Clusters on fibrinogen‐adhered platelets were much smaller and more numerous; whether these are pre‐existing oligomers of GPVI dimers or fibrinogen‐induced is not clear. Some GPVI dimer clusters colocalized with areas of phosphotyrosine, indicative of signaling activity. Integrin α2β1 was localized to collagen fibers close to GPVI dimer clusters. GPVI clustering depends on a dynamic actin cytoskeleton.
Conclusions
Platelet adhesion to collagen induces GPVI dimer clustering. GPVI clustering increases both avidity for collagen and the proximity of GPVI‐associated signaling molecules, which may be crucial for the initiation and persistence of signaling.
Essentials
Relationship of acquired von Willebrand disease (VWD) and platelet dysfunction is explored.
Patients with ventricular assist devices and on extracorporeal membrane oxygenation are ...investigated.
Acquired VWD and platelet receptor shedding is demonstrated in the majority of patients.
Loss of platelet adhesion receptors glycoprotein (GP) Ibα and GPVI may increase bleeding risk.
Summary
Background
Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are associated with bleeding that is not fully explained by anticoagulant or antiplatelet use. Exposure of platelets to elevated shear in vitro leads to increased shedding.
Objectives
To investigate whether loss of platelet receptors occurs in vivo, and the relationship with acquired von Willebrand syndrome (AVWS).
Methods
Platelet counts, coagulation tests and von Willebrand factor (VWF) analyses were performed on samples from 21 continuous flow VAD (CF‐VAD), 20 ECMO, 12 heart failure and seven aortic stenosis patients. Levels of platelet receptors were measured by flow cytometry or ELISA.
Results
The loss of high molecular weight VWF multimers was observed in 18 of 19 CF‐VAD and 14 of 20 ECMO patients, consistent with AVWS. Platelet receptor shedding was demonstrated by elevated soluble glycoprotein (GP) VI levels in plasma and significantly reduced surface GPIbα and GPVI levels in CF‐VAD and ECMO patients as compared with healthy donors. Platelet receptor levels were also significantly reduced in heart failure patients.
Conclusions
These data link AVWS and increased platelet receptor shedding in patients with CF‐VADs or ECMO for the first time. Loss of the platelet surface receptors GPIbα and GPVI in heart failure, CF‐VAD and ECMO patients may contribute to ablated platelet adhesion/activation, and limit thrombus formation under high/pathologic shear conditions.
This research is concerned with the following environmental research questions: socio-ecological system complexity, especially when valuing ecosystem services; ecosystems stock and services flow ...sustainability and valuation; the incorporation of scale issues when valuing ecosystem services; and the integration of knowledge from diverse disciplines for governance and decision making. In this case study, we focused on ecosystem services that can be jointly supplied but independently valued in economic terms: healthy climate (via carbon sequestration and storage), food (via fisheries production in nursery grounds), and nature recreation (nature watching and enjoyment). We also explored the issue of ecosystem stock and services flow, and we provide recommendations on how to value stock and flows of ecosystem services via accounting and economic values respectively. We considered broadly comparable estuarine systems located on the English North Sea coast: the Blackwater estuary and the Humber estuary. In the past, these two estuaries have undergone major land-claim. Managed realignment is a policy through which previously claimed intertidal habitats are recreated allowing the enhancement of the ecosystem services provided by saltmarshes. In this context, we investigated ecosystem service values, through biophysical estimates and welfare value estimates. Using an optimistic (extended conservation of coastal ecosystems) and a pessimistic (loss of coastal ecosystems because of, for example, European policy reversal) scenario, we find that context dependency, and hence value transfer possibilities, vary among ecosystem services and benefits. As a result, careful consideration in the use and application of value transfer, both in biophysical estimates and welfare value estimates, is advocated to supply reliable information for policy making.
•We investigate socio-ecological system complexity for informed decision making.•We provide recommendations on how to value stock and flows of ecosystem services.•We transfer biophysical data and welfare value estimates between estuaries.•Context dependency and value transfer possibilities vary among ecosystem services.•Results imply a need for careful use of value transfer for informed decision making.
Essentials
The platelet thrombin receptor, PAR4, is an emerging anti‐thrombotic drug target.
We examined the anti‐platelet & anti‐thrombotic effects of PAR4 inhibition in human blood.
PAR4 inhibition ...impaired platelet procoagulant activity in isolated cells and during thrombosis.
Our study shows PAR4 is required for platelet procoagulant function & thrombosis in human blood.
Summary
Background
Thrombin‐induced platelet activation is important for arterial thrombosis. Thrombin activates human platelets predominantly via protease‐activated receptor (PAR)1 and PAR4. PAR1 has higher affinity for thrombin, and the first PAR1 antagonist, vorapaxar, was recently approved for use as an antiplatelet agent. However, vorapaxar is contraindicated in a significant number of patients, owing to adverse bleeding events. Consequently, there is renewed interest in the role of platelet PAR4 in the setting of thrombus formation.
Objectives
To determine the specific antiplatelet effects of inhibiting PAR4 function during thrombus formation in human whole blood.
Methods and Results
We developed a rabbit polyclonal antibody against the thrombin cleavage site of PAR4, and showed it to be a highly specific inhibitor of PAR4‐mediated platelet function. This function‐blocking anti‐PAR4 antibody was used to probe for PAR4‐dependent platelet functions in human isolated platelets in the absence and presence of concomitant PAR1 inhibition. The anti‐PAR4 antibody alone was sufficient to abolish the sustained elevation of cytosolic calcium level and consequent phosphatidylserine exposure induced by thrombin, but did not significantly inhibit integrin αIIbβ3 activation, α‐granule secretion, or aggregation. In accord with these in vitro experiments on isolated platelets, selective inhibition of PAR4, but not of PAR1, impaired thrombin activity (fluorescence resonance energy transfer‐based thrombin sensor) and fibrin formation (anti‐fibrin antibody) in an ex vivo whole blood flow thrombosis assay.
Conclusions
These findings demonstrate that PAR4 is required for platelet procoagulant function during thrombus formation in human blood, and suggest PAR4 inhibition as a potential target for the prevention of arterial thrombosis.
Context.
Protoplanetary disks in dense, massive star-forming regions are strongly affected by their environment. How this environmental impact changes over time is an important constraint on disk ...evolution and external photoevaporation models.
Aims.
We characterize the dust emission from 179 disks in the core of the young (0.5 Myr) NGC 2024 cluster. By studying how the disk mass varies within the cluster, and comparing these disks to those in other regions, we aim to determine how external photoevaporation influences disk properties over time.
Methods.
Using the Atacama Large Millimeter/submillimeter Array, a 2.9′× 2.9′ mosaic centered on NGC 2024 FIR 3 was observed at 225 GHz with a resolution of 0.25″, or ~100 AU. The imaged region contains 179 disks identified at IR wavelengths, seven new disk candidates, and several protostars.
Results.
The overall detection rate of disks is 32 ± 4%. Few of the disks are resolved, with the exception of a giant (
R
= 300 AU) transition disk. Serendipitously, we observe a millimeter flare from an X-ray bright young stellar object (YSO), and resolve continuum emission from a Class 0 YSO in the FIR 3 core. Two distinct disk populations are present: a more massive one in the east, along the dense molecular ridge hosting the FIR 1-5 YSOs, with a detection rate of 45 ± 7%. In the western population, towards IRS 1, only 15 ± 4% of disks are detected.
Conclusions.
NGC 2024 hosts two distinct disk populations. Disks along the dense molecular ridge are young (0.2–0.5 Myr) and partly shielded from the far ultraviolet radiation of IRS 2b; their masses are similar to isolated 1–3 Myr old SFRs. The western population is older and at lower extinctions, and may be affected by external photoevaporation from both IRS 1 and IRS 2b. However, it is possible these disks had lower masses to begin with.
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