Various positioning techniques such as Wi-Fi positioning system have been proposed to use in situations where satellite navigation is unavailable. One such system, the muometric positioning system ...(muPS), was invented for navigation which operates in locations where even radio waves cannot reach such as underwater or underground. muPS takes advantage of a key feature of its probe, cosmic-ray muons, which travel straightforwardly at almost a speed of light in vacuum regardless of the matter they traverse. Similar to other positioning techniques, muPS is a technique to determine the position of a client's muPS receiver within the coordinate defined by reference detectors. This can be achieved either by using time-of-flight (ToF) or angle of arrival (AoA) measurements. The latter configuration (AoA), called the Vector-muPS has recently been invented and the present paper describes the developments of the first prototype of a vector muometric wireless navigation system (MuWNS-V) with this new vector-muPS concept and its demonstration. With MuWNS-V, the reference tracker and the receiver ran wirelessly with fully independent readout systems, and a positioning accuracy of 3.9 cm (RMS) has been achieved. We also evaluated the outcome of measuring continuous indoor localization of a moving receiver with this prototype. Our results indicated that further improvements in positioning accuracy will be attainable by acquiring higher angular resolution of the reference trackers. It is anticipated that "sub-cm level" navigation will be possible for muPS which could be applied to many situations such as future autonomous mobile robot operations.
Summary
The transition from active, invasive interventions to comfort care for critical care patients is often fraught with misunderstandings, conflict and moral distress. The most common issues that ...arise are ethical dilemmas around the equivalence of withholding and withdrawing life‐sustaining treatment; the doctrine of double effect; the balance between paternalism and shared decision‐making; legal challenges around best‐interest decisions for patients that lack capacity; conflict resolution; and practical issues during the limitation of treatment. The aim of this article is to address commonly posed questions on these aspects of end‐of‐life care in the intensive care unit, using best available evidence, and provide practical guidance to critical care clinicians in the UK. With the help of case vignettes, we clarify the disassociation of withdrawing and/or withholding treatment from euthanasia; offer practical suggestions for the use of sedation and analgesia around the end of life, dissipating concerns about hastening death; and advocate for the inclusion of family in decision‐making, when the patient does not have capacity. We propose a step‐escalation approach in cases of family conflict and advocate for incorporation of communication skills during medical and nursing training.
Drosophila Dicer-2 generates small interfering RNAs (siRNAs) from long double-stranded RNA (dsRNA), whereas Dicer-1 produces microRNAs (miRNAs) from pre-miRNA. What makes the two Dicers specific for ...their biological substrates? We find that purified Dicer-2 can efficiently cleave pre-miRNA, but that inorganic phosphate and the Dicer-2 partner protein R2D2 inhibit pre-miRNA cleavage. Dicer-2 contains C-terminal RNase III domains that mediate RNA cleavage and an N-terminal helicase motif, whose function is unclear. We show that Dicer-2 is a dsRNA-stimulated ATPase that hydrolyzes ATP to ADP; ATP hydrolysis is required for Dicer-2 to process long dsRNA, but not pre-miRNA. Wild-type Dicer-2, but not a mutant defective in ATP hydrolysis, can generate siRNAs faster than it can dissociate from a long dsRNA substrate. We propose that the Dicer-2 helicase domain uses ATP to generate many siRNAs from a single molecule of dsRNA before dissociating from its substrate.
► Dicer-2 cleaves pre-miRNA, but its product is shorter than the authentic miRNA ► The protein R2D2 and inorganic phosphate block pre-miRNA processing by Dicer-2 ► Dicer-2 is a double-stranded RNA-stimulated ATPase that hydrolyzes ATP to ADP ► Wild-type but not mutant Dicer-2 makes siRNAs faster than it dissociates from dsRNA
Salamanders, such as axolotls and newts, can regenerate complex tissues including entire limbs. But what mechanisms ensure that an amputated limb regenerates a limb, and not a tail or unpatterned ...tissue? An important concept in regeneration is positional memory-the notion that adult cells "remember" spatial identities assigned to them during embryogenesis (e.g., "head" or "hand") and use this information to restore the correct body parts after injury. Although positional memory is well documented at a phenomenological level, the underlying cellular and molecular bases are just beginning to be decoded. Herein, we review how major principles in positional memory were established in the salamander limb model, enabling the discovery of positional memory-encoding molecules, and advancing insights into their pattern-forming logic during regeneration. We explore findings in other amphibians, fish, reptiles, and mammals and speculate on conserved aspects of positional memory. We consider the possibility that manipulating positional memory in human cells could represent one route toward improved tissue repair or engineering of patterned tissues for therapeutic purposes.
Dust-enshrouded, starbursting, submillimeter galaxies (SMGs) at z ≥ 3 have been proposed as progenitors of z ≥ 2 compact quiescent galaxies (cQGs). To test this connection, we present a detailed ...spatially resolved study of the stars, dust, and stellar mass in a sample of six submillimeter-bright starburst galaxies at z ∼ 4.5. The stellar UV emission probed by HST is extended and irregular and shows evidence of multiple components. Informed by HST, we deblend Spitzer/IRAC data at rest-frame optical, finding that the systems are undergoing minor mergers with a typical stellar mass ratio of 1:6.5. The FIR dust continuum emission traced by ALMA locates the bulk of star formation in extremely compact regions (median re = 0.70 0.29 kpc), and it is in all cases associated with the most massive component of the mergers (median ). We compare spatially resolved UV slope (β) maps with the FIR dust continuum to study the infrared excess (IRX = LIR/LUV)-β relation. The SMGs display systematically higher IRX values than expected from the nominal trend, demonstrating that the FIR and UV emissions are spatially disconnected. Finally, we show that the SMGs fall on the mass-size plane at smaller stellar masses and sizes than the cQGs at z = 2. Taking into account the expected evolution in stellar mass and size between z = 4.5 and z = 2 due to the ongoing starburst and mergers with minor companions, this is in agreement with a direct evolutionary connection between the two populations.
Pentatricopeptide repeat (PPR) motifs are α-helical structures known for their modular recognition of single-stranded RNA sequences with each motif in a tandem array binding to a single nucleotide. ...Protein-only RNase P 1 (PRORP1) in Arabidopsis thaliana is an endoribonuclease that uses its PPR domain to recognize precursor tRNAs (pre-tRNAs) as it catalyzes removal of the 5'-leader sequence from pre-tRNAs with its NYN metallonuclease domain. To gain insight into the mechanism by which PRORP1 recognizes tRNA, we determined a crystal structure of the PPR domain in complex with yeast tRNAPhe at 2.85 Å resolution. The PPR domain of PRORP1 bound to the structurally conserved elbow of tRNA and recognized conserved structural features of tRNAs using mechanisms that are different from the established single-stranded RNA recognition mode of PPR motifs. The PRORP1 PPR domain-tRNAPhe structure revealed a conformational change of the PPR domain upon tRNA binding and moreover demonstrated the need for pronounced overall flexibility in the PRORP1 enzyme conformation for substrate recognition and catalysis. The PRORP1 PPR motifs have evolved strategies for protein-tRNA interaction analogous to tRNA recognition by the RNA component of ribonucleoprotein RNase P and other catalytic RNAs, indicating convergence on a common solution for tRNA substrate recognition.
We report our identification of the optical afterglow and host galaxy of the short-duration gamma-ray burst sGRB 160821B. The spectroscopic redshift of the host is z = 0.162, making it one of the ...lowest redshift short-duration gamma-ray bursts (sGRBs) identified by Swift. Our intensive follow-up campaign using a range of ground-based facilities as well as Hubble Space Telescope, XMM-Newton, and Swift, shows evidence for a late-time excess of optical and near-infrared emission in addition to a complex afterglow. The afterglow light curve at X-ray frequencies reveals a narrow jet, deg, that is refreshed at >1 day post-burst by a slower outflow with significantly more energy than the initial outflow that produced the main GRB. Observations of the 5 GHz radio afterglow shows a reverse shock into a mildly magnetized shell. The optical and near-infrared excess is fainter than AT2017gfo associated with GW170817, and is well explained by a kilonova with dynamic ejecta mass Mdyn = (1.0 0.6) × 10−3 M and a secular (post-merger) ejecta mass with Mpm = (1.0 0.6) × 10−2 M , consistent with a binary neutron star merger resulting in a short-lived massive neutron star. This optical and near-infrared data set provides the best-sampled kilonova light curve without a gravitational wave trigger to date.
Radiographic imaging of magma dynamics in a volcanic conduit provides detailed information about ascent and descent of magma, the magma flow rate, the conduit diameter and inflation and deflation of ...magma due to volatile expansion and release. Here we report the first radiographic observation of the ascent and descent of magma along a conduit utilizing atmospheric (cosmic ray) muons (muography) with dynamic radiographic imaging. Time sequential radiographic images show that the top of the magma column ascends right beneath the crater floor through which the eruption column was observed. In addition to the visualization of this magma inflation, we report a sequence of images that show magma descending. We further propose that the monitoring of temporal variations in the gas volume fraction of magma as well as its position in a conduit can be used to support existing eruption prediction procedures.
Central to measuring the impact of the COVID-19 pandemic on HIV is understanding the role of loss of access to essential HIV prevention and care services created by clinic and community-based ...organization closures. In this paper, we use a comprehensive list of HIV prevention services in four corridors of the US heavily impacted by HIV, developed as part of a large RCT, to illustrate the potential impact of service closure on LGBTQ+ youth.
We identified and mapped LGBTQ+ friendly services offering at least one of the following HIV-related services: HIV testing; STI testing; PrEP/PEP; HIV treatment and care; and other HIV-related services in 109 counties across four major interstate corridors heavily affected by HIV US Census regions: Pacific (San Francisco, CA to San Diego, CA); South-Atlantic (Washington, DC to Atlanta, GA); East-North-Central (Chicago, IL to Detroit, MI); and East-South-Central (Memphis, TN to New Orleans, LA).
There were a total of 831 LGBTQ+ youth-friendly HIV service providers across the 109 counties. There was a range of LGBTQ+ youth-friendly HIV-service provider availability across counties (range: 0-14.33 per 10,000 youth aged 13-24 (IQR: 2.13), median: 1.09); 9 (8.26%) analyzed counties did not have any LGBTQ+ youth-friendly HIV service providers. The Pearson correlation coefficient for the correlation between county HIV prevalence and LGBTQ+ youth-friendly HIV service provider density was 0.16 (p = 0.09), suggesting only a small, non-statistically significant linear relationship between a county's available LGBTQ+ youth-friendly HIV service providers and their HIV burden.
As the COVID-19 pandemic continues, we must find novel, affordable ways to continue to provide sexual health, mental health and other support services to LGBTQ+ youth.
Lungfishes belong to lobe-fined fish (Sarcopterygii) that, in the Devonian period, 'conquered' the land and ultimately gave rise to all land vertebrates, including humans
. Here we determine the ...chromosome-quality genome of the Australian lungfish (Neoceratodus forsteri), which is known to have the largest genome of any animal. The vast size of this genome, which is about 14× larger than that of humans, is attributable mostly to huge intergenic regions and introns with high repeat content (around 90%), the components of which resemble those of tetrapods (comprising mainly long interspersed nuclear elements) more than they do those of ray-finned fish. The lungfish genome continues to expand independently (its transposable elements are still active), through mechanisms different to those of the enormous genomes of salamanders. The 17 fully assembled lungfish macrochromosomes maintain synteny to other vertebrate chromosomes, and all microchromosomes maintain conserved ancient homology with the ancestral vertebrate karyotype. Our phylogenomic analyses confirm previous reports that lungfish occupy a key evolutionary position as the closest living relatives to tetrapods
, underscoring the importance of lungfish for understanding innovations associated with terrestrialization. Lungfish preadaptations to living on land include the gain of limb-like expression in developmental genes such as hoxc13 and sall1 in their lobed fins. Increased rates of evolution and the duplication of genes associated with obligate air-breathing, such as lung surfactants and the expansion of odorant receptor gene families (which encode proteins involved in detecting airborne odours), contribute to the tetrapod-like biology of lungfishes. These findings advance our understanding of this major transition during vertebrate evolution.
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