The Evolution of Far-infrared CO Emission from Protostars

We investigate the evolution of far-IR CO emission from protostars observed with Herschel/PACS for 50 sources from the combined sample of HOPS and DIGIT Herschel key programs. From the uniformly sampled spectral energy distributions, whose peaks are well sampled, we computed the L_(bol), T_(bol), and L_(bol)/L_(smm) for these sources to search for correlations between far-IR CO emission and protostellar properties. We find a strong and tight correlation between far-IR CO luminosity (L_(CO)^(fir)) and the bolometric luminosity L_(bol) of the protostars with L_(CO)^(fir) α L_(bol)^(0.7). We, however, do not find a strong correlation between L_(CO)^(fir) and protostellar evolutionary indicators, T_(bol) and L(bol)/L(smm). FIR CO emission from protostars traces the currently shocked gas by jets/outflows, and far-IR CO luminosity, L_(CO)^(fir), is proportional to the instantaneous mass-loss rate, M_(out). The correlation between L_(CO)^(fir) and L_(bol), then, is indicative of instantaneous M_(out) tracking instantaneous M_(acc). The lack of a correlation between L_(CO)^(fir) and evolutionary indicators T_(bol) and L_(bol)/L_(smm) suggests that M_(out) and, therefore, M_(acc) do not show any clear evolutionary trend. These results are consistent with mass accretion/ejection in protostars being episodic. Taken together with the previous finding that the time-averaged mass-ejection/accretion rate declines during the protostellar phase, our results suggest that the instantaneous accretion/ejection rate of protostars is highly time variable and episodic, but the amplitude and/or frequency of this variability decreases with time such that the time-averaged accretion/ejection rate declines with system age

Apheresis for collection of Ebola convalescent plasma in Liberia

Purpose: This report describes initiation of apheresis capability in Liberia, Africa to support a clinical trial of convalescent plasma therapy for Ebola Virus Disease. Methods: A bloodmobile was outfitted in the United States as a four-bed apheresis unit with capabilities including pathogen reduction, electronic blood establishment computer system, designated areas for donor counseling and laboratory testing, and onboard electrical power generation. After air transport to Liberia, the bloodmobile was positioned at ELWA Hospital, Monrovia, and connected to the hospital's power grid. Liberian staff were trained to conduct donor screening, which included questionnaire and onsite blood typing and transfusion transmitted infection (TTI) testing, and plasma collection and processing. Results: The bloodmobile was operational within 3 weeks after arrival of the advance team. Of 101 donors who passed the pre-screening questionnaire, 32 were deferred. Twenty-eight of ninty-nine tested survivors were deferred for positive transfusion transmitted infection (TTI) tests; twenty-one were positive for hepatitis B, hepatitis C, or human immunodeficiency virus. The majority of donors had type O blood; all but one were Rh positive. Forty-three survivors donated at least once; eighty-nine apheresis attempts resulted in eighty-one successful collections. Conclusions: Apheresis capability was emergently established in Liberia to support an efficacy trial of Ebola Convalescent Plasma. Extensive cooperation among multinational team members, engineers, logisticians, and blood safety technical personnel at the operational site was required to surmount challenges to execution posed by logistical factors. The high proportion of positive TTI tests supported the use of a pathogen reduction system to enhance product safety

ERK1/2 signaling dominates over RhoA signaling in regulating early changes in RNA expression induced by endothelin-1 in neonatal rat cardiomyocytes

Cardiomyocyte hypertrophy is associated with changes in gene expression. Extracellular signal-regulated kinases 1/2 (ERK1/2) and RhoA [activated by hypertrophic agonists (e.g. endothelin-1)] regulate gene expression and are implicated in the response, but their relative significance in regulating the cardiomyocyte transcriptome is unknown. Our aim was to establish the significance of ERK1/2 and/or RhoA in the early cardiomyocyte transcriptomic response to endothelin-1.Cardiomyocytes were exposed to endothelin-1 (1 h) with/without PD184352 (to inhibit ERK1/2) or C3 transferase (C3T, to inhibit RhoA). RNA expression was analyzed using microarrays and qPCR. ERK1/2 signaling positively regulated approximately 65% of the early gene expression response to ET-1 with a small (approximately 2%) negative effect, whereas RhoA signaling positively regulated approximately 10% of the early gene expression response to ET-1 with a greater (approximately 14%) negative contribution. Of RNAs non-responsive to endothelin-1, 66 or 448 were regulated by PD184352 or C3T, respectively, indicating that RhoA had a more significant effect on baseline RNA expression. mRNAs upregulated by endothelin-1 encoded a number of receptor ligands (e.g. Ereg, Areg, Hbegf) and transcription factors (e.g. Abra/Srf) that potentially propagate the response.ERK1/2 dominates over RhoA in the early transcriptomic response to endothelin-1. RhoA plays a major role in maintaining baseline RNA expression but, with upregulation of Abra/Srf by endothelin-1, RhoA may regulate changes in RNA expression over longer times. Our data identify ERK1/2 as a more significant node than RhoA in regulating the early stages of cardiomyocyte hypertrophy

The Evolution of Far-infrared CO Emission from Protostars

We investigate the evolution of far-IR CO emission from protostars observed with Herschel/PACS for 50 sources from the combined sample of HOPS and DIGIT Herschel key programs. From the uniformly sampled spectral energy distributions, whose peaks are well sampled, we computed the L_(bol), T_(bol), and L_(bol)/L_(smm) for these sources to search for correlations between far-IR CO emission and protostellar properties. We find a strong and tight correlation between far-IR CO luminosity (L_(CO)^(fir)) and the bolometric luminosity L_(bol) of the protostars with L_(CO)^(fir) α L_(bol)^(0.7). We, however, do not find a strong correlation between L_(CO)^(fir) and protostellar evolutionary indicators, T_(bol) and L(bol)/L(smm). FIR CO emission from protostars traces the currently shocked gas by jets/outflows, and far-IR CO luminosity, L_(CO)^(fir), is proportional to the instantaneous mass-loss rate, M_(out). The correlation between L_(CO)^(fir) and L_(bol), then, is indicative of instantaneous M_(out) tracking instantaneous M_(acc). The lack of a correlation between L_(CO)^(fir) and evolutionary indicators T_(bol) and L_(bol)/L_(smm) suggests that M_(out) and, therefore, M_(acc) do not show any clear evolutionary trend. These results are consistent with mass accretion/ejection in protostars being episodic. Taken together with the previous finding that the time-averaged mass-ejection/accretion rate declines during the protostellar phase, our results suggest that the instantaneous accretion/ejection rate of protostars is highly time variable and episodic, but the amplitude and/or frequency of this variability decreases with time such that the time-averaged accretion/ejection rate declines with system age

Ebola virus disease: an update on post-exposure prophylaxis

The massive outbreak of Ebola virus disease in west Africa between 2013 and 2016 resulted in intense efforts to evaluate the efficacy of several specific countermeasures developed through years of preclinical work, including the first clinical trials for therapeutics and vaccines. In this Review, we discuss how the experience and data generated from that outbreak have helped to advance the understanding of the use of these countermeasures for post-exposure prophylaxis against Ebola virus infection. In future outbreaks, post-exposure prophylaxis could play an important part in reducing community transmission of Ebola virus by providing more immediate protection than does immunisation as well as providing additional protection for health-care workers who are inadvertently exposed over the course of their work. We propose provisional guidance for use of post-exposure prophylaxis in Ebola virus disease and identify the priorities for future preparedness and further research

Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease

β-Blockers reduce mortality and improve symptoms in people with heart disease. However, current clinically available β-blockers have poor selectivity for the cardiac β1-adrenoceptor (AR) over the lung β2-AR. Unwanted β2-blockade risks causing life-threatening bronchospasm and a reduction in the efficacy of β2-agonist emergency rescue therapy. Thus current life-prolonging β-blockers are contraindicated in people with both heart disease and asthma. Here we describe NDD-713 and NDD-825, novel highly β1-selective neutral antagonists with good pharmaceutical properties that can potentially overcome this limitation. Radioligand binding studies and functional assays using human receptors expressed in CHO cells demonstrate that NDD-713 and NDD-825 have nanomolar β1-AR affinity, greater than 500-fold β1-AR vs β2-AR selectivity and no agonism. Studies in conscious rats demonstrated that they are orally bioavailable and cause pronounced β1-mediated reduction of heart rate while showing no effect on β2-mediated hindquarters vasodilatation. The compounds also have good disposition properties and show no adverse toxicological effects. They potentially offer a truly cardioselective β-blocker therapy for the large number of people with heart and respiratory, or peripheral vascular comorbidities

A Phase 2a clinical trial of Molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus

Molnupiravir (800 mg dose) accelerated SARS-CoV-2 RNA clearance in patients with COVID-19 compared to placebo

Investigating Protostellar Accretion-Driven Outflows Across the Mass Spectrum: JWST NIRSpec IFU 3-5~μ\mum Spectral Mapping of Five Young Protostars

Investigating Protostellar Accretion (IPA) is a Cycle 1 JWST program using the NIRSpec+MIRI IFUs to obtain 2.9--28 $\mu$m spectral cubes of five young protostars with luminosities of 0.2 to 10,000 L$_{\odot}$ in their primary accretion phase. This paper introduces the NIRSpec 2.9--5.3 $\mu$m data of the inner 840-9000 au with spatial resolutions from 28-300 au. The spectra show rising continuum emission, deep ice absorption, emission from H$_{2}$, H~I, and [Fe~II], and the CO fundamental series in emission and absorption. Maps of the continuum emission show scattered light cavities for all five protostars. In the cavities, collimated jets are detected in [Fe~II] for the four $< 320$~L$_{\odot}$ protostars, two of which are additionally traced in Br-$\alpha$. Knots of [Fe~II] emission are detected toward the most luminous protostar, and knots of [FeII] emission with dynamical times of $< 30$~yrs are found in the jets of the others. While only one jet is traced in H$_2$, knots of H$_2$ and CO are detected in the jets of four protostars. H$_2$ is seen extending through the cavities showing they are filled by warm molecular gas. Bright H$_2$ emission is seen along the walls of a single cavity, while in three cavities, narrow shells of H$_2$ emission are found, one of which has an [Fe~II] knot at its apex. These data show cavities containing collimated jets traced in atomic/ionic gas surrounded by warm molecular gas in a wide-angle wind and/or gas accelerated by bow shocks in the jets.Comment: 30 pages, 11 figure