ABSTRACT
Natal supernova kicks, the linear momentum compact remnants receive during their formation, are an essential part of binary population synthesis (BPS) models. Although these kicks are well ...supported by evidence, their underlying distributions and incorporation into BPS models are uncertain. In this work, we investigate the nature of natal kicks using a previously proposed analytical prescription where the strength of the kick is given by $v_\text{k}=\alpha \frac{m_\text{ejecta}}{m_\text{remnant}}+\beta \, \mathrm{km\, s}^{-1}$ , for free parameters α and β. We vary the free parameters over large ranges of possible values, comparing these synthetic populations simultaneously against four constraints: the merger rate of compact binary neutron star (BNS) systems, the period–eccentricity distribution of Galactic BNSs, the velocity distribution of single-star pulsars, and the likelihood for low ejecta mass supernovae to produce low-velocity kicks. We find that different samples of the parameter space satisfy each test, and only 1 per cent of the models satisfy all four constraints simultaneously. Although we cannot identify a single best kick model, we report $\alpha =115^{+40}_{-55}\, \mathrm{km\, s}^{-1}, \beta =15^{+10}_{-15}\, \mathrm{km\, s}^{-1}$ as the centre of the region of the parameter space that fulfils all of our constraints, and expect $\beta \ge 0\, \mathrm{km\, s}^{-1}$ as a further constraint. We also suggest further observations that will enable future refinement of the kick model. A sensitive test for the kick model will be the redshift evolution of the BNS merger rate since this is effectively a direct measure of the delay-time distribution for mergers. For our best-fitting values, we find that the peak of the BNS merger rate is the present day.
The Forkhead boxO (FOXO) transcription factors regulate multiple cellular functions. FOXO1 and FOXO3 are highly expressed in granulosa cells of ovarian follicles. Selective depletion of the Foxo1 and ...Foxo3 genes in granulosa cells of mice reveals a novel ovarian-pituitary endocrine feedback loop characterized by: 1) undetectable levels of serum FSH but not LH, 2) reduced expression of the pituitary Fshb gene and its transcriptional regulators, and 3) ovarian production of a factor(s) that suppresses pituitary cell Fshb expression. Equally notable, and independent of FSH, microarray analyses and quantitative PCR document that depletion of Foxo1/3 alters the expression of specific genes associated with follicle growth vs. apoptosis by disrupting critical and selective regulatory interactions of FOXO1/3 with the activin or bone morphogenetic protein 2 (BMP2) pathways, respectively. As a consequence, both granulosa cell proliferation and apoptosis were decreased. These data provide the first evidence that FOXO1/3 divergently regulate follicle growth or death by interacting with the activin or BMP pathways in granulosa cells and by modulating pituitary FSH production.
An ideal material for photon harvesting must allow control of the exciton diffusion length and directionality. This is necessary in order to guide excitons to a reaction center, where their energy ...can drive a desired process. To reach this goal both of the following are required; short- and long-range structural order in the material and a detailed understanding of the excitonic transport. Here we present a strategy to realize crystalline chromophore assemblies with bespoke architecture. We demonstrate this approach by assembling anthracene dibenzoic acid chromophore into a highly anisotropic, crystalline structure using a layer-by-layer process. We observe two different types of photoexcited states; one monomer-related, the other excimer-related. By incorporating energy-accepting chromophores in this crystalline assembly at different positions, we demonstrate the highly anisotropic motion of the excimer-related state along the 010 direction of the chromophore assembly. In contrast, this anisotropic effect is inefficient for the monomer-related excited state.
Malaria is a leading cause of mortality and morbidity globally, and effective vaccines are urgently needed. Malaria vaccine approaches can be broadly grouped as pre‐erythrocytic, blood stage and ...transmission blocking. This review focuses on blood‐stage vaccines, and considers the evidence supporting the development of blood‐stage vaccines, the advantages and challenges of this approach, potential targets, human vaccine studies and future directions. There is a strong rationale for the development of vaccines based on antigens of blood‐stage parasites. Symptomatic malaria is caused by blood‐stage parasitemia and acquired immunity in humans largely targets blood‐stage antigens. Several candidate vaccines have proved efficacious in animal models and at least one vaccine showed partial efficacy in a clinical trial. At present, all leading candidate blood‐stage antigens are merozoite proteins, located on the merozoite surface or within the apical organelles. Major challenges and priorities include overcoming antigenic diversity, identification of protective epitopes, understanding the nature and targets of protective immune responses, and defining antigen combinations that give the greatest efficacy. Additionally, objective criteria and approaches are needed to prioritize the large number of candidate antigens, and strong candidates need to be tested in clinical trials as quickly as possible.
Short-wave infrared (SWIR) fluorescence could become the new gold standard in optical imaging for biomedical applications due to important advantages such as lack of autofluorescence, weak photon ...absorption by blood and tissues, and reduced photon scattering coefficient. Therefore, contrary to the visible and NIR regions, tissues become translucent in the SWIR region. Nevertheless, the lack of bright and biocompatible probes is a key challenge that must be overcome to unlock the full potential of SWIR fluorescence. Although rare-earth-based core-shell nanocrystals appeared as promising SWIR probes, they suffer from limited photoluminescence quantum yield (PLQY). The lack of control over the atomic scale organization of such complex materials is one of the main barriers limiting their optical performance. Here, the growth of either homogeneous (α-NaYF
) or heterogeneous (CaF
) shell domains on optically-active α-NaYF
:Yb:Er (with and without Ce
co-doping) core nanocrystals is reported. The atomic scale organization can be controlled by preventing cation intermixing only in heterogeneous core-shell nanocrystals with a dramatic impact on the PLQY. The latter reached 50% at 60 mW/cm
; one of the highest reported PLQY values for sub-15 nm nanocrystals. The most efficient nanocrystals were utilized for in vivo imaging above 1450 nm.
Gain-of-function p53 mutants such as p53-R175H form stable aggregates that accumulate in cells and play important roles in cancer progression. Selective degradation of gain-of-function p53 mutants ...has emerged as a highly attractive therapeutic strategy to target cancer cells harboring specific p53 mutations. We identified a small molecule called MCB-613 to cause rapid ubiquitination, nuclear export, and degradation of p53-R175H through a lysosome-mediated pathway, leading to catastrophic cancer cell death. In contrast to its effect on the p53-R175H mutant, MCB-613 causes slight stabilization of p53-WT and has weaker effects on other p53 gain-of-function mutants. Using state-of-the-art genetic and chemical approaches, we identified the deubiquitinase USP15 as the mediator of MCB-613's effect on p53-R175H, and established USP15 as a selective upstream regulator of p53-R175H in ovarian cancer cells. These results confirm that distinct pathways regulate the turnover of p53-WT and the different p53 mutants and open new opportunities to selectively target them.
Discussion of issues and development of consensus. Present the background, purpose, development process, format and definitions of the International Spinal Cord Injury Pain (ISCIP) Classification. An ...international group of spinal cord injury (SCI) and pain experts deliberated over 2 days, and then via e-mail communication developed a consensus classification of pain after SCI. The classification was reviewed by members of several professional organizations and their feedback was incorporated. The classification then underwent validation by an international group of clinicians with minimal exposure to the classification, using case study vignettes. Based upon the results of this study, further revisions were made to the ISCIP Classification. An overall structure and terminology has been developed and partially validated as a merger of and improvement on previously published SCI pain classifications, combined with basic definitions proposed by the International Association for the Study of Pain and pain characteristics described in published empiric studies of pain. The classification is designed to be comprehensive and to include pains that are directly related to the SCI pathology as well as pains that are common after SCI but are not necessarily mechanistically related to the SCI itself. The format and definitions presented should help experienced and non-experienced clinicians as well as clinical researchers classify pain after SCI.
ABSTRACT
We present a detailed exploration of the stellar mass versus gas-phase metallicity relation (MZR) using integral field spectroscopy data obtained from ∼1000 galaxies observed by the SAMI ...galaxy survey. These spatially resolved spectroscopic data allow us to determine the metallicity within the same physical scale (Reff) for different calibrators. The shape of the MZ relations is very similar between the different calibrators, while there are large offsets in the absolute values of the abundances. We confirm our previous results derived using the spatially resolved data provided by the CALIFA and MaNGA surveys: (1) we do not find any significant secondary relation of the MZR with either the star formation rate (SFR) or the specific SFR (SFR/M*) for any of the calibrators used in this study, based on the analysis of the individual residuals; (2) if there is a dependence with the SFR, it is weaker than the reported one (rc ∼ −0.3), it is confined to the low-mass regime (M* < 109 M⊙) or high-SFR regimes, and it does not produce any significant improvement in the description of the average population of galaxies. The aparent disagreement with published results based on single-fibre spectroscopic data could be due to (i) the interpretation of the secondary relation itself; (ii) the lower number of objects sampled at the low-mass regime by the current study; or (iii) the presence of extreme star-forming galaxies that drive the secondary relation in previous results.
Glucose-6-phosphate-dehydrogenase-deficiency (G6PDd) is a major risk factor for primaquine-induced haemolysis. There is a need for improved point-of-care and laboratory-based G6PD diagnostics to ...unsure safe use of primaquine.
G6PD activities of participants in a cross-sectional survey in Bangladesh were assessed using two novel quantitative assays, the modified WST-8 test and the CareStart™ G6PD Biosensor (Access Bio), The results were compared with a gold standard UV spectrophotometry assay (Randox). The handheld CareStart™ Hb instrument (Access Bio) is designed to be a companion instrument to the CareStart™ G6PD biosensor, and its performance was compared to the well-validated HemoCue™ method. All quantitative G6PD results were normalized with the HemoCue™ result.
A total of 1002 individuals were enrolled. The adjusted male median (AMM) derived by spectrophotometry was 7.03 U/g Hb (interquartile range (IQR): 5.38-8.69), by WST-8 was 7.03 U/g Hb (IQR: 5.22-8.16) and by Biosensor was 8.61 U/g Hb (IQR: 6.71-10.08). The AMM between spectrophotometry and WST-8 did not differ (p = 1.0) but differed significantly between spectrophotometry and Biosensor (p<0.01). Both, WST-8 and Biosensor were correlated with spectrophotometry (rs = 0.5 and rs = 0.4, both p<0.001). The mean difference in G6PD activity was -0.12 U/g Hb (95% limit of agreement (95% LoA): -5.45 to 5.20) between spectrophotometry and WST-8 and -1.74U/g Hb (95% LoA: -7.63 to 4.23) between spectrophotometry and Biosensor. The WST-8 identified 55.1% (49/89) and the Biosensor 19.1% (17/89) of individuals with G6PD activity <30% by spectrophotometry. Areas under the ROC curve did not differ significantly for the WST-8 and Biosensor irrespective of the cut-off activity applied (all p>0.05). Sensitivity and specificity for detecting G6PD activity <30% was 0.55 (95% confidence interval (95%CI): 0.44-0.66) and 0.98 (95%CI: 0.97-0.99) respectively for the WST-8 and 0.19 (95%CI: 0.12-0.29) and 0.99 (95%CI: 0.98-0.99) respectively for the Biosensor. Hb concentrations measured by HemoCue™ and CareStart™ Hb were strongly correlated (rs = 0.8, p<0.001, mean difference = 0.09 g Hb/dL, 95% LoA: -2.15 to 2.34).
WST-8 and the CareStart™ G6PD Biosensor represent advances in G6PD diagnostics in resource poor settings, but will require further development before clinical deployment. The CareStart™ Hb instrument produced a precise measure of haemoglobin concentration.
Abstract The red hypergiant VY CMa is famous for its very visible record of high-mass-loss events. Recent CO observations with the Atacama Large Millimeter/submillimeter Array (ALMA) revealed three ...previously unknown large-scale outflows (Singh et al). In this paper, we use the CO maps to investigate the motions of a cluster of four clumps close to the star, not visible in the optical or infrared images. We present their proper motions measured from two epochs of ALMA images and determine the line-of-sight velocities of the gas in emission at the clumps. We estimate their masses and ages, or time since ejection, and conclude that all four were ejected during VY CMa’s active period in the early 20th century. Together with two additional knots observed with the Hubble Space Telescope, VY CMa experienced at least six massive outflows during a 30 yr period, with a total mass lost ≥0.07 M ⊙ . The position–velocity map of the 12 CO emission reveals previously unnoticed attributes of the older outer ejecta. In a very narrow range of Doppler velocities, 12 CO absorption and emission causes some of this outer material to be quite opaque. At those frequencies the inner structure is hidden and we see only emission from an extended outer region. This fact produces a conspicuous but illusory dark spot if one attempts to subtract the continuum in a normal way.
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