The goal of the quench and partition (Q&P) process for steel heat treatment is to enrich austenite with carbon during a partitioning treatment after initial quenching below the martensite start ...temperature (Ms). Two proposed mechanisms for austenite carbon enrichment during partitioning include carbon transport from martensite and/or the formation of carbide-free bainite. Theoretical calculations show experimentally measured austenite fractions are difficult to explain based upon a mechanism involving solely bainite formation. Carbon partitioning from martensite provides a more satisfactory explanation, although the formation of bainite during partitioning cannot be completely excluded.
OBJECTIVE: To validate the FRAIL scale. DESIGN: Longitudinal study. SETTING: Community. PARTICIPANTS: Representative sample of African Americans age 49 to 65 years at onset of study. MEASUREMENTS: ...The 5-item FRAIL scale (Fatigue, Resistance, Ambulation, Illnesses, & Loss of Weight), at baseline and activities of daily living (ADLs), instrumental activities of daily living (IADLs), mortality, short physical performance battery (SPPB), gait speed, one-leg stand, grip strength and injurious falls at baseline and 9 years. Blood tests for CRP, SIL6R, STNFR1, STNFR2 and 25 (OH) vitamin D at baseline. RESULTS: Cross-sectionally the FRAIL scale correlated significantly with IADL difficulties, SPPB, grip strength and one-leg stand among participants with no baseline ADL difficulties (N=703) and those outcomes plus gait speed in those with no baseline ADL dependencies (N=883). TNFR1 was increased in pre-frail and frail subjects and CRP in some subgroups. Longitudinally (N=423 with no baseline ADL difficulties or N=528 with no baseline ADL dependencies), and adjusted for the baseline value for each outcome, being pre-frail at baseline significantly predicted future ADL difficulties, worse one-leg stand scores, and mortality in both groups, plus IADL difficulties in the dependence-excluded group. Being frail at baseline significantly predicted future ADL difficulties, IADL difficulties, and mortality in both groups, plus worse SPPB in the dependence-excluded group. CONCLUSION: This study has validated the FRAIL scale in a late middle-aged African American population. This simple 5-question scale is an excellent screening test for clinicians to identify frail persons at risk of developing disability as well as decline in health functioning and mortality.
Interstellar dust and starlight are modeled for the galaxies of the project "Key Insights on Nearby Galaxies: A Far-Infrared Survey with Herschel." The galaxies were observed by the Infrared Array ...Camera and the Multiband Imaging Photometer for Spitzer on Spitzer Space Telescope, and the Photodetector Array Camera and Spectrometer and the Spectral and Photometric Imaging Receiver on Herschel Space Observatory. With data from 3.6 to 500 m, dust models are strongly constrained. Using a physical dust model, for each pixel in each galaxy we estimate (1) dust surface density, (2) dust mass fraction in polycyclic aromatic hydrocarbons (PAHs), (3) distribution of starlight intensities heating the dust, (4) total infrared (IR) luminosity emitted by the dust, and (5) IR luminosity originating in subregions with high starlight intensity. The dust models successfully reproduce the observed global and resolved spectral energy distributions. With the angular resolution of Herschel, we obtain well-resolved maps (available online) for the dust properties. As in previous studies, we find the PAH fraction to be an increasing function of metallicity, with a threshold oxygen abundance Z/Z 0.1, but we find the data to be fitted best with increasing linearly with above a threshold value of 0.15(O/H) . We obtain total dust masses for each galaxy by summing the dust mass over the individual map pixels; these "resolved" dust masses are consistent with the masses inferred from a model fit to the global photometry. The global dust-to-gas ratios obtained from this study are found to correlate with galaxy metallicities. Systems with Z/Z 0.5 have most of their refractory elements locked up in dust, whereas in systems with Z/Z 0.3 most of these elements tend to remain in the gas phase. Within galaxies, we find that is suppressed in regions with unusually warm dust with . With knowledge of one long-wavelength flux density ratio (e.g., f160/f500), the minimum starlight intensity heating the dust ( ) can be estimated to within ∼50%, despite a variation in of more than two orders of magnitude. For the adopted dust model, dust masses can be estimated to within ∼0.2 dex accuracy using the f160/f500 flux ratio and the integrated dust luminosity, and to ∼0.07 dex accuracy using the 500 m luminosity alone. There are additional systematic errors arising from the choice of dust model, but these are hard to estimate. These calibrated prescriptions for estimating starlight heating intensity and dust mass may be useful for studies of high-redshift galaxies.
Atom probe tomography and transmission electron microscopy (TEM) have been used to determine the location and distribution of carbon and alloying elements associated with the complex structural ...changes that occur at the atomic and nanoscale in 4340 steel after quenching to martensite and tempering at 325, 450 or 575°C. Tempering at 325°C resulted in carbide formation without partitioning of chromium, manganese, molybdenum, aluminum, nickel or phosphorus, but with early-stage silicon rejection from the carbide. TEM verified the presence of cementite and the Bagaryatsky orientation relationship with the tempered martensite matrix and detected complex precipitate structures. Tempering at 450 or 575°C developed concentrations of all alloying elements at ferrite–cementite interfaces: chromium, manganese and molybdenum partitioned into the cementite, and silicon, aluminum, nickel and phosphorus were clearly rejected from the cementite. These results provide direct evidence for staged cementite growth, where early-stage growth likely occurs under paraequilibrium conditions, followed by initial silicon redistribution and subsequent alloying element redistribution during late-stage growth. Tempering at 575°C induced spheroidization of the cementite, loss of the Bagaryatsky orientation relationship, and phosphorus concentrations at Cottrell atmospheres within the cementite and at ferrite–cementite interfaces, correlating with early observations of the retardation of spheroidization by phosphorus.
Isoprene emitted by vegetation is an important precursor of secondary organic aerosol (SOA), but the mechanism and yields are uncertain. Aerosol is prevailingly aqueous under the humid conditions ...typical of isoprene-emitting regions. Here we develop an aqueous-phase mechanism for isoprene SOA formation coupled to a detailed gas-phase isoprene oxidation scheme. The mechanism is based on aerosol reactive uptake coefficients (γ) for water-soluble isoprene oxidation products, including sensitivity to aerosol acidity and nucleophile concentrations. We apply this mechanism to simulation of aircraft (SEAC4RS) and ground-based (SOAS) observations over the southeast US in summer 2013 using the GEOS-Chem chemical transport model. Emissions of nitrogen oxides (NOx ≡ NO + NO2) over the southeast US are such that the peroxy radicals produced from isoprene oxidation (ISOPO2) react significantly with both NO (high-NOx pathway) and HO2 (low-NOx pathway), leading to different suites of isoprene SOA precursors. We find a mean SOA mass yield of 3.3 % from isoprene oxidation, consistent with the observed relationship of total fine organic aerosol (OA) and formaldehyde (a product of isoprene oxidation). Isoprene SOA production is mainly contributed by two immediate gas-phase precursors, isoprene epoxydiols (IEPOX, 58 % of isoprene SOA) from the low-NOx pathway and glyoxal (28 %) from both low- and high-NOx pathways. This speciation is consistent with observations of IEPOX SOA from SOAS and SEAC4RS. Observations show a strong relationship between IEPOX SOA and sulfate aerosol that we explain as due to the effect of sulfate on aerosol acidity and volume. Isoprene SOA concentrations increase as NOx emissions decrease (favoring the low-NOx pathway for isoprene oxidation), but decrease more strongly as SO2 emissions decrease (due to the effect of sulfate on aerosol acidity and volume). The US Environmental Protection Agency (EPA) projects 2013–2025 decreases in anthropogenic emissions of 34 % for NOx (leading to a 7 % increase in isoprene SOA) and 48 % for SO2 (35 % decrease in isoprene SOA). Reducing SO2 emissions decreases sulfate and isoprene SOA by a similar magnitude, representing a factor of 2 co-benefit for PM2.5 from SO2 emission controls.
Homologous recombination repair deficiency (HRD) is a frequent feature of high-grade serous ovarian, fallopian tube and peritoneal carcinoma (HGSC) and is associated with sensitivity to PARP ...inhibitor (PARPi) therapy. HRD testing provides an opportunity to optimise PARPi use in HGSC but methodologies are diverse and clinical application remains controversial.
To define best practice for HRD testing in HGSC the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project that incorporated a systematic review approach. The main aims were to (i) define the term ‘HRD test’; (ii) provide an overview of the biological rationale and the level of evidence supporting currently available HRD tests; (iii) provide recommendations on the clinical utility of HRD tests in clinical management of HGSC.
A broad range of repair genes, genomic scars, mutational signatures and functional assays are associated with a history of HRD. Currently, the clinical validity of HRD tests in ovarian cancer is best assessed, not in terms of biological HRD status per se, but in terms of PARPi benefit. Clinical trials evidence supports the use of BRCA mutation testing and two commercially available assays that also incorporate genomic instability for identifying subgroups of HGSCs that derive different magnitudes of benefit from PARPi therapy, albeit with some variation by clinical scenario. These tests can be used to inform treatment selection and scheduling but their use is limited by a failure to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies. Existing tests lack negative predictive value and inadequately address the complex and dynamic nature of the HRD phenotype.
Currently available HRD tests are useful for predicting likely magnitude of benefit from PARPis but better biomarkers are urgently needed to better identify current homologous recombination proficiency status and stratify HGSC management.
•Homologous recombination repair deficiency (HRD) is a common feature of high-grade serous gynaecological cancers (HGSC).•Currently, the clinical validity of HRD tests in ovarian cancer is best assessed in terms of PARPi benefit.•Germline and somatic BRCA mutation and genomic instability tests help to predict likely magnitude of benefit from a PARPi.•Existing HRD tests fail to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies.•HRD is a dynamic entity and better biomarkers that capture current homologous recombination proficiency status are needed.
We present the discovery of the optical afterglow and host galaxy of the Swift short-duration gamma-ray burst (SGRB) GRB 181123B. Observations with Gemini-North starting 9.1 hr after the burst reveal ...a faint optical afterglow with i 25.1 mag at an angular offset of 0 59 0 16 from its host galaxy. Using grizYJHK observations, we measure a photometric redshift of the host galaxy of . From a combination of Gemini and Keck spectroscopy of the host galaxy spanning 4500-18000 , we detect a single emission line at 13390 , inferred as Hβ at z = 1.754 0.001 and corroborating the photometric redshift. The host galaxy properties of GRB 181123B are typical of those of other SGRB hosts, with an inferred stellar mass of 9.1 × 109 M , a mass-weighted age of 0.9 Gyr, and an optical luminosity of 0.9L*. At z = 1.754, GRB 181123B is the most distant secure SGRB with an optical afterglow detection and one of only three at z > 1.5. Motivated by a growing number of high-z SGRBs, we explore the effects of a missing z > 1.5 SGRB population among the current Swift sample on delay time distribution (DTD) models. We find that lognormal models with mean delay times of 4-6 Gyr are consistent with the observed distribution but can be ruled out to 95% confidence, with an additional one to five Swift SGRBs recovered at z > 1.5. In contrast, power-law models with ∝t−1 are consistent with the redshift distribution and can accommodate up to 30 SGRBs at these redshifts. Under this model, we predict that 1/3 of the current Swift population of SGRBs is at z > 1. The future discovery or recovery of existing high-z SGRBs will provide significant discriminating power on their DTDs and thus their formation channels.
Abstract We report on X-ray (NICER/NuSTAR/MAXI/Swift) and radio (MeerKAT) timing and spectroscopic analysis from a 3 month monitoring campaign in 2022 of a high-intensity outburst of the dipping ...neutron star low-mass X-ray binary 1A 1744−361. The 0.5–6.8 keV NICER X-ray hardness–intensity and color–color diagrams of the observations throughout the outburst suggest that 1A 1744−361 spent most of its outburst in an atoll-state, but we show that the source exhibited Z-state-like properties at the peak of the outburst, similar to a small sample of other atoll-state sources. A timing analysis with NICER data revealed several instances of an ≈8 Hz quasiperiodic oscillation (QPO; fractional rms amplitudes of ∼5%) around the peak of the outburst, the first from this source, which we connect to the normal branch QPOs seen in the Z-state. Our observations of 1A 1744−361 are fully consistent with the idea of the mass accretion rate being the main distinguishing parameter between atoll- and Z-states. Radio monitoring data by MeerKAT suggests that the source was at its radio-brightest during the outburst peak, and that the source transitioned from the “island” spectral state to the “banana” state within ∼3 days of the outburst onset, launching transient jet ejecta. The observations present the strongest evidence for radio flaring, including jet ejecta, during the island-to-banana spectral state transition at low accretion rates (atoll-state). The source also exhibited Fe xxv , Fe xxvi K α , and K β X-ray absorption lines, whose origins likely lie in an accretion disk atmosphere.
Tau, a microtubule-associated protein, is implicated in the pathogenesis of Alzheimer's Disease (AD) in regard to both neurofibrillary tangle formation and neuronal network hyperexcitability. The ...genetic ablation of tau substantially reduces hyperexcitability in AD mouse lines, induced seizure models, and genetic in vivo models of epilepsy. These data demonstrate that tau is an important regulator of network excitability. However, developmental compensation in the genetic tau knock-out line may account for the protective effect against seizures. To test the efficacy of a tau reducing therapy for disorders with a detrimental hyperexcitability profile in adult animals, we identified antisense oligonucleotides that selectively decrease endogenous tau expression throughout the entire mouse CNS--brain and spinal cord tissue, interstitial fluid, and CSF--while having no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced tau protein had less severe seizures than control mice. Total tau protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of tau. Our results demonstrate that endogenous tau is integral for regulating neuronal hyperexcitability in adult animals and suggest that an antisense oligonucleotide reduction of tau could benefit those with epilepsy and perhaps other disorders associated with tau-mediated neuronal hyperexcitability.
The key component of a microstructural diffusion MRI ‘super-scanner’ is a dedicated high-strength gradient system that enables stronger diffusion weightings per unit time compared to conventional ...gradient designs. This can, in turn, drastically shorten the time needed for diffusion encoding, increase the signal-to-noise ratio, and facilitate measurements at shorter diffusion times. This review, written from the perspective of the UK National Facility for In Vivo MR Imaging of Human Tissue Microstructure, an initiative to establish a shared 300 mT/m-gradient facility amongst the microstructural imaging community, describes ten advantages of ultra-strong gradients for microstructural imaging. Specifically, we will discuss how the increase of the accessible measurement space compared to a lower-gradient systems (in terms of Δ, b-value, and TE) can accelerate developments in the areas of 1) axon diameter distribution mapping; 2) microstructural parameter estimation; 3) mapping micro-vs macroscopic anisotropy features with gradient waveforms beyond a single pair of pulsed-gradients; 4) multi-contrast experiments, e.g. diffusion-relaxometry; 5) tractography and high-resolution imaging in vivo and 6) post mortem; 7) diffusion-weighted spectroscopy of metabolites other than water; 8) tumour characterisation; 9) functional diffusion MRI; and 10) quality enhancement of images acquired on lower-gradient systems. We finally discuss practical barriers in the use of ultra-strong gradients, and provide an outlook on the next generation of ‘super-scanners’.
•Improved estimation of axon diameter in vivo.•Better fitting of complex microstructure models.•Improved characterisation of tumours.•Facilitation of multi-contrast MRI experiments.
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