The inverse-Compton ghost HDF 130 and the giant radio galaxy 6C 0905+3955: matching an analytic model for double radio source evolution

We present new GMRT observations of HDF 130, an inverse-Compton (IC) ghost of a giant radio source that is no longer being powered by jets. We compare the properties of HDF 130 with the new and important constraint of the upper limit of the radio flux density at 240 MHz to an analytic model. We learn what values of physical parameters in the model for the dynamics and evolution of the radio luminosity and X-ray luminosity (due to IC scattering of the cosmic microwave background (CMB)) of a Fanaroff-Riley II (FR II) source are able to describe a source with features (lobe length, axial ratio, X-ray luminosity, photon index and upper limit of radio luminosity) similar to the observations. HDF 130 is found to agree with the interpretation that it is an IC ghost of a powerful double-lobed radio source, and we are observing it at least a few Myr after jet activity (which lasted 5--100 Myr) has ceased. The minimum Lorentz factor of injected particles into the lobes from the hotspot is preferred to be $\gamma\sim10^3$ for the model to describe the observed quantities well, assuming that the magnetic energy density, electron energy density, and lobe pressure at time of injection into the lobe are linked by constant factors according to a minimum energy argument, so that the minimum Lorentz factor is constrained by the lobe pressure. We also apply the model to match the features of 6C 0905+3955, a classical double FR II galaxy thought to have a low-energy cutoff of $\gamma\sim10^4$ in the hotspot due to a lack of hotspot inverse-Compton X-ray emission. The models suggest that the low-energy cutoff in the hotspots of 6C 0905+3955 is $\gamma\gtrsim 10^3$, just slightly above the particles required for X-ray emission.Comment: 9 pages, 3 figure

Hardness variation in inconel 718 produced by laser directed energy deposition

Directed energy deposition (DED) of Inconel 718 is of critical importance for the repair of aerospace components, which have tight tolerances for certification, particularly on mechanical properties. Significant hardness variation has been seen throughout DED manufactured Inconel 718 components, suggestive of variation in mechanical properties, which must be understood such that the variation can either be removed, or implemented within the design in line with regulatory guidance. In this work, γʹ precipitation was theorised to be the cause of hardness variation throughout the component, despite Inconel 718 conventionally being regarded as a γʺ strengthened alloy. A simple precipitation potential model based on a moving heat source was found to correlate with the measured hardness and explain the hardness distribution observed. In addition, it has been shown that sections under a critical thickness of 2 mm never reach the peak hardness in the as-built condition. This understanding allows for the development of in-situ heat treatment strategies to be developed for microstructural, and hence, mechanical property optimisation, necessary for repair technologies where post processing steps are limited

Hardness variation in inconel 718 produced by laser directed energy deposition

Directed energy deposition (DED) of Inconel 718 is of critical importance for the repair of aerospace components, which have tight tolerances for certification, particularly on mechanical properties. Significant hardness variation has been seen throughout DED manufactured Inconel 718 components, suggestive of variation in mechanical properties, which must be understood such that the variation can either be removed, or implemented within the design in line with regulatory guidance. In this work, γʹ precipitation was theorised to be the cause of hardness variation throughout the component, despite Inconel 718 conventionally being regarded as a γʺ strengthened alloy. A simple precipitation potential model based on a moving heat source was found to correlate with the measured hardness and explain the hardness distribution observed. In addition, it has been shown that sections under a critical thickness of 2 mm never reach the peak hardness in the as-built condition. This understanding allows for the development of in-situ heat treatment strategies to be developed for microstructural, and hence, mechanical property optimisation, necessary for repair technologies where post processing steps are limited

Sexual dimorphism in postcranial skeletal shape suggests male‐biased specialization for physical competition in anthropoid primates

Sexual dimorphism often arises as a response to selection on traits that improve a male's ability to physically compete for access to mates. In primates, sexual dimorphism in body mass and canine size is more common in species with intense male–male competition. However, in addition to these traits, other musculoskeletal adaptations may improve male fighting performance. Postcranial traits that increase strength, agility, and maneuverability may also be under selection. To test the hypothesis that males, as compared to females, are more specialized for physical competition in their postcranial anatomy, we compared sex‐specific skeletal shape using a set of functional indices predicted to improve fighting performance. Across species, we found significant sexual dimorphism in a subset of these indices, indicating the presence of skeletal shape sexual dimorphism in our sample of anthropoid primates. Mean skeletal shape sexual dimorphism was positively correlated with sexual dimorphism in body size, an indicator of the intensity of male–male competition, even when controlling for both body mass and phylogenetic relatedness. These results suggest that selection on male fighting ability has played a role in the evolution of postcranial sexual dimorphism in primates

Carbon uptake and distribution in Spark Plasma Sintering (SPS) processed Sm(Co, Fe, Cu, Zr)z

Spark Plasma Sintering (SPS) rapidly consolidates high-melting point powders between carbon dies, but carbon can pose a risk for many materials. Carbon uptake in SPS and conventional, pressure-less sintered (CS) Sm(Co, Fe, Cu, Zr)z has been analysed using Electron Probe Micro-Analysis (EPMA) to produce high-detail elemental distribution maps. Field's metal was used as mounting material to avoid introducing carbon into the samples. The distribution maps show high surface carbon levels in the SPS-processed Sm(Co, Fe, Cu, Zr)z to a depth of 10 μm. Much less carbon was observed in CS Sm(Co, Fe, Cu, Zr)z. Furthermore, elemental carbon analysis (LECO-C) confirmed carbon was most abundant at the surface in SPS-processed Sm(Co, Fe, Cu, Zr)z but also at higher levels internally, when compared to the CS sample. It is inferred that the carbon contamination is due to the contact between the powder and the graphite die/paper at elevated temperatures during SPS process. The measured levels of carbon in the SPS-processed sample are not expected to significantly impact the magnetic properties of Sm(Co, Fe, Cu, Zr)z. These results may have implications for other powder materials processed by SPS with properties sensitive to carbon

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma

Background: Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells. Methods: In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival. Results: A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported. Conclusions: Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.). Copyright © 2021 Massachusetts Medical Society

Peperiksaan Perkhidmatan Penolong Pegawai Sains C29 Kertas II (Hospital Universiti Sains Malaysia) 28 November 2018

Tarikh : 28 November 2018 (Rabu) Masa : 9.00 pagi – 11.30 pagi (2 ½ jam) Tempat : Kampus Kesihata

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation

Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease

Background--Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. Methods and Results--To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol. Conclusions--Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression