Abstract
We present intensity-corrected
Herschel
maps at 100, 160, 250, 350, and 500
μ
m for 56 isolated low-mass clouds. We determine the zero-point corrections for
Herschel
Photodetector Array ...Camera and Spectrometer (PACS) and Spectral Photometric Imaging Receiver (SPIRE) maps from the
Herschel
Science Archive (HSA) using
Planck
data. Since these HSA maps are small, we cannot correct them using typical methods. Here we introduce a technique to measure the zero-point corrections for small
Herschel
maps. We use radial profiles to identify offsets between the observed HSA intensities and the expected intensities from
Planck
. Most clouds have reliable offset measurements with this technique. In addition, we find that roughly half of the clouds have underestimated HSA-SPIRE intensities in their outer envelopes relative to
Planck
, even though the HSA-SPIRE maps were previously zero-point corrected. Using our technique, we produce corrected
Herschel
intensity maps for all 56 clouds and determine their line-of-sight average dust temperatures and optical depths from modified blackbody fits. The clouds have typical temperatures of ∼14–20 K and optical depths of ∼10
−5
–10
−3
. Across the whole sample, we find an anticorrelation between temperature and optical depth. We also find lower temperatures than what was measured in previous
Herschel
studies, which subtracted out a background level from their intensity maps to circumvent the zero-point correction. Accurate
Herschel
observations of clouds are key to obtaining accurate density and temperature profiles. To make such future analyses possible, intensity-corrected maps for all 56 clouds are publicly available in the electronic version.
Collagen type IV (Col IV) is a basement membrane protein associated with early blood vessel morphogenesis and is essential for blood vessel stability. Defects in vascular Col IV deposition are the ...basis of heritable disorders, such as small vessel disease, marked by cerebral hemorrhage and drastically shorten lifespan. To date, little is known about how endothelial cells regulate the intracellular transport and selective secretion of Col IV in response to angiogenic cues, leaving a void in our understanding of this critical process. Our aim was to identify trafficking pathways that regulate Col IV deposition during angiogenic blood vessel development. We have identified the GTPase Rab10 as a major regulator of Col IV vesicular trafficking during vascular development using both in vitro imaging and biochemistry as well as in vivo models. Knockdown of Rab10 reduced de novo Col IV secretion in vivo and in vitro. Mechanistically, we determined that Rab10 is an indirect mediator of Col IV secretion, partnering with atypical Rab25 to deliver the enzyme lysyl hydroxylase 3 (LH3) to Col IV-containing vesicles staged for secretion. Loss of Rab10 or Rab25 results in depletion of LH3 from Col IV-containing vesicles and rapid lysosomal degradation of Col IV. Furthermore, we demonstrate that Rab10 is Notch responsive, indicating a novel connection between permissive Notch-based vessel maturation programs and vesicle trafficking. Our results illustrate both a new trafficking-based component in the regulated secretion of Col IV and how this vesicle trafficking program interfaces with Notch signaling to fine-tune basement membrane secretion during blood vessel development.
Objective
Despite the absolute requirement of Delta/Notch signaling to activate lateral inhibition during early blood vessel development, many mechanisms remain unclear about how this system is ...regulated. Our objective was to determine the involvement of Epsin 15 Homology Domain Containing 2 (EHD2) in delta‐like ligand 4 (Dll4) endocytosis during Notch activation.
Approach and Results
Using both in vivo and in vitro models, we demonstrate that EHD2 is a novel modulator of Notch activation in endothelial cells through controlling endocytosis of Dll4. In vitro, EHD2 localized to plasma membrane‐bound Dll4 and caveolae. Chemical disruption of caveolae complexes resulted in EHD2 failing to organize around Dll4 as well as loss of Dll4 internalization. Reduced Dll4 internalization blunted Notch activation in endothelial cells. In vivo, EHD2 is primarily expressed in the vasculature, colocalizing with junctional marker VE‐cadherin and Dll4. Knockout of EHD2 in zebrafish produced a significant increase in dysmorphic sprouts in zebrafish intersomitic vessels during development and a reduction in downstream Notch signaling.
Conclusions
Overall, we demonstrate that EHD2 is necessary for Dll4 transcytosis and downstream Notch activation.
We present intensity-corrected Herschel maps at 100, 160, 250, 350, and 500 m for 56 isolated low-mass clouds. We determine the zero-point corrections for Herschel Photodetector Array Camera and ...Spectrometer (PACS) and Spectral Photometric Imaging Receiver (SPIRE) maps from the Herschel Science Archive (HSA) using Planck data. Since these HSA maps are small, we cannot correct them using typical methods. Here we introduce a technique to measure the zero-point corrections for small Herschel maps. We use radial profiles to identify offsets between the observed HSA intensities and the expected intensities from Planck. Most clouds have reliable offset measurements with this technique. In addition, we find that roughly half of the clouds have underestimated HSA-SPIRE intensities in their outer envelopes relative to Planck, even though the HSA-SPIRE maps were previously zero-point corrected. Using our technique, we produce corrected Herschel intensity maps for all 56 clouds and determine their line-of-sight average dust temperatures and optical depths from modified blackbody fits. The clouds have typical temperatures of ∼14-20 K and optical depths of ∼10−5-10−3. Across the whole sample, we find an anticorrelation between temperature and optical depth. We also find lower temperatures than what was measured in previous Herschel studies, which subtracted out a background level from their intensity maps to circumvent the zero-point correction. Accurate Herschel observations of clouds are key to obtaining accurate density and temperature profiles. To make such future analyses possible, intensity-corrected maps for all 56 clouds are publicly available in the electronic version.
Metal hydrides are known as a potential efficient, low-risk option for high-density hydrogen storage since the late 1970s. In this paper, the present status and the future perspectives of the use of ...metal hydrides for hydrogen storage are discussed. Since the early 1990s, interstitial metal hydrides are known as base materials for Ni – metal hydride rechargeable batteries. For hydrogen storage, metal hydride systems have been developed in the 2010s 1 for use in emergency or backup power units, i. e. for stationary applications.
With the development and completion of the first submarines of the U212 A series by HDW (now Thyssen Krupp Marine Systems) in 2003 and its export class U214 in 2004, the use of metal hydrides for hydrogen storage in mobile applications has been established, with new application fields coming into focus.
In the last decades, a huge number of new intermetallic and partially covalent hydrogen absorbing compounds has been identified and partly more, partly less extensively characterized.
In addition, based on the thermodynamic properties of metal hydrides, this class of materials gives the opportunity to develop a new hydrogen compression technology. They allow the direct conversion from thermal energy into the compression of hydrogen gas without the need of any moving parts. Such compressors have been developed and are nowadays commercially available for pressures up to 200 bar. Metal hydride based compressors for higher pressures are under development. Moreover, storage systems consisting of the combination of metal hydrides and high-pressure vessels have been proposed as a realistic solution for on-board hydrogen storage on fuel cell vehicles.
In the frame of the “Hydrogen Storage Systems for Mobile and Stationary Applications” Group in the International Energy Agency (IEA) Hydrogen Task 32 “Hydrogen-based energy storage”, different compounds have been and will be scaled-up in the near future and tested in the range of 500 g to several hundred kg for use in hydrogen storage applications.
•Latest developments in the application of hydride technology.•Investigations on both stationary and mobile applications.•Special attention to metal hydride compressors.•Heat storage and H2 compression especially noted in the Outlook.
To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen ...can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF.
Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial.
Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV).
Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 μm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome.
Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24.
Of the 349 participants randomized (intensive arm, n = 174; relaxed arm, n = 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P = 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P = 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P = 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 standard deviation, 5.9) than those in the intensive group (mean, 17 standard deviation, 6.5; P = 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P = 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P = 0.005).
Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.
During July 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 variant infections, including vaccine breakthrough infections, occurred after large public gatherings in ...Provincetown, Massachusetts, USA, prompting a multistate investigation. Public health departments identified primary and secondary cases by using coronavirus disease surveillance data, case investigations, and contact tracing. A primary case was defined as SARS-CoV-2 detected <14 days after travel to or residence in Provincetown during July 3-17. A secondary case was defined as SARS-CoV-2 detected <14 days after close contact with a person who had a primary case but without travel to or residence in Provincetown during July 3-August 10. We identified 1,098 primary cases and 30 secondary cases associated with 26 primary cases among fully and non-fully vaccinated persons. Large gatherings can have widespread effects on SARS-CoV-2 transmission, and fully vaccinated persons should take precautions, such as masking, to prevent SARS-CoV-2 transmission, particularly during substantial or high transmission.
Abstract Background Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 ...pandemic in the UK. Objectives Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme. Methods Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping. Results People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups’ 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon. Conclusions Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty.
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