The expanding remnant from SN 1987A is an excellent laboratory for investigating the physics of supernovae explosions. There is still a large number of outstanding questions, such as the reason for ...the asymmetric radio morphology, the structure of the pre-supernova environment, and the efficiency of particle acceleration at the supernova shock. We explore these questions using three-dimensional simulations of the expanding remnant between days 820 and 10,000 after the supernova. We combine a hydrodynamical simulation with semi-analytic treatments of diffusive shock acceleration and magnetic field amplification to derive radio emission as part of an inverse problem. Simulations show that an asymmetric explosion, combined with magnetic field amplification at the expanding shock, is able to replicate the persistent one-sided radio morphology of the remnant. We use an asymmetric Truelove & McKee progenitor with an envelope mass of 10 M sub(middot in circle) and an energy of 1.5 x 10 super(44)J. A termination shock in the progenitor's stellar wind at a distance of 0."43-0."51 provides a good fit to the turn on of radio emission around day 1200. For the H II region, a minimum distance of 0."63 + or - 0."01 and maximum particle number density of (7.11 + or - 1.78) x 10 super(7) m super(-3) produces a good fit to the evolving average radius and velocity of the expanding shocks from day 2000 to day 7000 after explosion. The model predicts a noticeable reduction, and possibly a temporary reversal, in the asymmetric radio morphology of the remnant after day 7000, when the forward shock left the eastern lobe of the equatorial ring.
The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually ...present with the acute complications of bone marrow failure
. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion
. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)
. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.
Photodissociation of carbon dioxide (CO₂) has long been assumed to proceed exclusively to carbon monoxide (CO) and oxygen atom (O) primary products. However, recent theoretical calculations suggested ...that an exit channel to produce C + O₂ should also be energetically accessible. Here we report the direct experimental evidence for the C + O₂ channel in CO₂ photodissociation near the energetic threshold of the C(³P) + O₂(X³Σg⁻) channel with a yield of 5 ± 2% using vacuum ultraviolet laser pump-probe spectroscopy and velocity-map imaging detection of the C(³PJ) product between 101.5 and 107.2 nanometers. Our results may have implications for nonbiological oxygen production in CO₂-heavy atmospheres.
Summary
Background
The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results.
Aim
To assess in a meta‐analysis, the ...diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC.
Methods
Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random‐effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac‐based FOBT (gFOBT) and immunochemical‐based FOBT (iFOBT).
Results
Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3–79.4%), 93.6% (95% CI 90.7–95.7%), 11.1 (95% CI 7.8–15.8) and 0.3 (95% CI 0.2–0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9–87.0%), 93.6% (95% CI 90.7–95.7%), 12.6 (95% CI 8.8–18.1) and 0.2 (95% CI 0.1–0.3). The area‐under‐curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC.
Conclusion
Faecal occult blood tests, both guaiac‐ and immunochemical‐based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel.
Central compact objects (CCOs) constitute a population of radio-quiet, slowly spinning (> or =, slanted 100 ms) young neutron stars with anomalously high thermal X-ray luminosities. Their spin-down ...properties imply weak dipole magnetic fields (~10 super(10-11) G) and characteristic ages much greater than the ages of their host supernova remnants (SNRs). However, CCOs may posses strong "hidden" internal magnetic fields that may re-emerge on timescales of > ~10 kyr, with the neutron star possibly activating as a radio pulsar in the process. This suggests that the immediate descendants of CCOs may be masquerading as slowly spinning "old" radio pulsars. We present an X-ray survey of all ordinary radio pulsars within 6 kpc that are positionally coincident with Galactic SNRs in order to test the possible connection between the supposedly old but possibly very young pulsars and the SNRs. None of the targets exhibit anomalously high thermal X-ray luminosities, suggesting that they are genuine old ordinary pulsars unrelated to the superposed SNRs. This implies that CCOs are either latent radio pulsars that activate long after their SNRs dissipate or they remain permanently radio-quiet. The true descendants of CCOs remain at large.
There is an urgent issue on huge quantities of wastage generation in construction. There should not be lack of environmental support from construction stakeholders. The current implementation of ...prefabrication seems unable to provide satisfactory results to the construction industry. This paper provides a feasibility analysis in adopting prefabrication in construction activities. Advantages, hindrances and future development on prefabrication's applications are provided based on a questionnaire survey. The suitability in adopting prefabrication of various project types is also examined. Furthermore, a financial analysis is also investigated by a local case study. It found that wastage generation can reduce up to 100% after adopting prefabrication, in which up to 84.7% can be saved on wastage reduction.
We report the first molecular line survey of Supernova 1987A in the millimetre wavelengthrange. In the Atacama Large Millimeter/submillimeter Array (ALMA) 210–300 and 340–360 GHz spectra, we detected ...cold (20–170 K) CO,28SiO, HCO+and SO, with weaker linesof29SiO from ejecta. This is the first identification of HCO+and SO in a young supernovaremnant. We find a dip in the J=6–5 and 5–4 SiO line profiles, suggesting that the ejectamorphology is likely elongated. The difference of the CO and SiO line profiles is consistent withhydrodynamic simulations, which show that Rayleigh–Taylor instabilities cause mixing of gas,with heavier elements much more disturbed, making more elongated structure. We obtainedisotopologue ratios of28SiO/29SiO>13,28SiO/30SiO>14 and12CO/13CO>21, with themost likely limits of28SiO/29SiO>128,28SiO/30SiO>189. Low29Si and30Si abundancesin SN 1987A are consistent with nucleosynthesis models that show inefficient formation ofneutron-rich isotopes in a low-metallicity environment, such as the Large Magellanic Cloud.The deduced large mass of HCO+(∼5×10−6M) and small SiS mass (<6×10−5M)might be explained by some mixing of elements immediately after the explosion. The mixingmight have caused some hydrogen from the envelope to sink into carbon- and oxygen-richzones after the explosion, enabling the formation of a substantial mass of HCO+. Oxygenatoms may have penetrated into silicon and sulphur zones, suppressing formation of SiS. OurALMA observations open up a new window to investigate chemistry, dynamics and explosivenucleosynthesis in supernovae.
Neuroblastoma, the most common solid tumor of young children, frequently presents with aggressive metastatic disease and for these children the 5-year survival rates are dismal. Metastasis, the ...movement of cancer cells from one site to another, involves remodeling of the cytoskeleton including altered microtubule dynamics. The microtubule-destabilizing protein, stathmin, has recently been shown to mediate neuroblastoma metastasis although precise functions remain poorly defined. In this study we investigated stathmin's contribution to the metastatic process and potential mechanism(s) by which it exerts these effects. Stathmin suppression significantly reduced neuroblastoma cell invasion of 3D tumor spheroids into an extracellular matrix. Moreover, inhibiting stathmin expression significantly reduced transendothelial migration in two different neuroblastoma cell lines in vitro. Inhibition of ROCK, a key regulator of cell migration, in neuroblastoma cells highlighted that stathmin regulates transendothelial migration through ROCK signaling. Reduced stathmin expression in neuroblastoma cells significantly increased the activation of the RhoA small GTPase. Notably, re-expression of either wild type or a phospho-mimetic stathmin mutant (4E) made defective in tubulin binding returned cell migration and transendothelial migration back to control levels, indicating that stathmin may influence these processes in neuroblastoma cells independent of tubulin binding. Finally, stathmin suppression in neuroblastoma cells significantly reduced whole body, lung, kidney and liver metastases in an experimental metastases mouse model. In conclusion, stathmin suppression interferes with the metastatic process via RhoA/ROCK signaling in neuroblastoma cells. These findings highlight the importance of stathmin to the metastatic process and its potential as a therapeutic target for the treatment of neuroblastoma.
To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of ...AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.
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•Clinical outcome in AML correlates with LSC-associated miRNA expression•miR-126 targets multiple components of the PI3K/AKT/MTOR signaling pathway•miR-126 promotes chemotherapy resistance by preserving LSC in a quiescent state•miR-126 governs opposing self-renewal outcomes in normal and malignant stem cells
Lechman et al. show that miR-126 targets the PI3K/AKT/MTOR signaling pathway to preserve quiescence, increase self-renewal, and promote chemotherapy resistance of acute myeloid leukemia stem cells (LSC). Reducing the miR-126 level impairs LSC maintenance in contrast to expanding normal hematopoietic stem cells.
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