From 2007 to 2013, the southeastern Bering Sea was dominated by extensive sea ice and below-average ocean temperatures. In 2014 there was a shift to reduced sea ice on the southern shelf and ...above-average ocean temperatures. These conditions continued in 2015 and 2016. During these three years, the spring bloom at mooring site M4 (57.9°N, 168.9°W) occurred primarily in May, which is typical of years without sea ice. At mooring site M2 (56.9°N, 164.1°W) the spring bloom occurred earlier especially in 2016. Higher chlorophyll fluorescence was observed at M4 than at M2. In addition, these three warm years continued the pattern near St. Matthew Island of high concentrations (>1 μM) of nitrite occurring during summer in warm years. Historically, the dominant parameters controlling sea-ice extent are winds and air temperature, with the persistence of frigid, northerly winds in winter and spring resulting in extensive ice. After mid-March 2014 and 2016 there were no cold northerly or northeasterly winds. Cold northerly winds persisted into mid-April in 2015, but did not result in extensive sea ice south of 58°N. The apparent mechanism that helped limit ice on the southeastern shelf was the strong advection of warm water from the Gulf of Alaska through Unimak Pass. This pattern has been uncommon, occurring in only one other year (2003) in a 37-year record of estimated transport through Unimak Pass. During years with no sea ice on the southern shelf (e.g. 2001-2005, 2014-2016), the depth-averaged temperature there was correlated to the previous summers ocean temperature.
Recent demonstrations of room-temperature lasing in optically pumped GeSn show promise for future CMOS compatible lasers for Si-photonics applications. However, challenges remain for electrically ...pumped devices. Investigation of the processes that limit device performance is therefore vital in aiding the production of future commercial devices. In this work, a combined experimental and modelling approach is utilised to explore the dominant loss processes in current devices. By manipulating the band structure of functioning devices using high hydrostatic pressure techniques at low temperature, the dominant carrier recombination pathways are identified. This reveals that 93
5% of the threshold current is attributable to defect-related recombination at a temperature, T = 85 K. Furthermore, carrier occupation of L-valley states (carrier leakage) is responsible for 1.1
0.3% of the threshold current, but this sharply increases to 50% with a decrease of just 30 meV in the L-
separation energy. This indicates that thermal broadening of a similar order may reproduce these adverse effects, limiting device performance at higher temperatures. Temperature dependent calculations show that carrier occupation of indirect valley L-states strongly affects the transparency carrier density and is therefore very sensitive to the Sn composition, leading to an effective operational temperature range for given Sn compositions and strain values. Recommendations for future device designs are proposed based on band structure and growth optimisations.
ABSTRACT
We report the results of optical follow-up observations of 29 gravitational-wave (GW) triggers during the first half of the LIGO–Virgo Collaboration (LVC) O3 run with the Gravitational-wave ...Optical Transient Observer (GOTO) in its prototype 4-telescope configuration (GOTO-4). While no viable electromagnetic (EM) counterpart candidate was identified, we estimate our 3D (volumetric) coverage using test light curves of on- and off-axis gamma-ray bursts and kilonovae. In cases where the source region was observable immediately, GOTO-4 was able to respond to a GW alert in less than a minute. The average time of first observation was 8.79 h after receiving an alert (9.90 h after trigger). A mean of 732.3 square degrees were tiled per event, representing on average 45.3 per cent of the LVC probability map, or 70.3 per cent of the observable probability. This coverage will further improve as the facility scales up alongside the localization performance of the evolving GW detector network. Even in its 4-telescope prototype configuration, GOTO is capable of detecting AT2017gfo-like kilonovae beyond 200 Mpc in favourable observing conditions. We cannot currently place meaningful EM limits on the population of distant ($\hat{D}_L = 1.3$ Gpc) binary black hole mergers because our test models are too faint to recover at this distance. However, as GOTO is upgraded towards its full 32-telescope, 2 node (La Palma & Australia) configuration, it is expected to be sufficiently sensitive to cover the predicted O4 binary neutron star merger volume, and will be able to respond to both northern and southern triggers.
We use numerical simulations to investigate how the statistical properties of dark matter (DM) haloes are affected by the baryonic processes associated with galaxy formation. We focus on how these ...processes influence the spin and shape of a large number of DM haloes covering a wide range of mass scales, from galaxies to clusters at z = 0, 1, extending to dwarf galaxies at z = 2. The haloes are extracted from the OverWhelmingly Large Simulations (OWLS), a suite of state-of-the-art high-resolution cosmological simulations run with a range of feedback prescriptions. We find that the median spin parameter in DM-only simulations is independent of mass, redshift and cosmology. At z = 0 baryons increase the spin of the DM in the central region (≤0.25 r
200) by up to 30 per cent when feedback is weak or absent. This increase can be attributed to the transfer of angular momentum from baryons to the DM, but is no longer present at z = 2. We also present fits to the mass dependence of the DM halo shape at both low and high redshift. At z = 0 the sphericity (triaxiality) is negatively (positively) correlated with halo mass and both results are independent of cosmology. Interestingly, these mass-dependent trends are markedly weaker at z = 2. While the cooling of baryons acts to make the overall DM halo more spherical, stronger feedback prescriptions (e.g. from active galactic nuclei) tend to reduce the impact of baryons by reducing the central halo mass concentration. More generally, we demonstrate a strongly positive (negative) correlation between halo sphericity (triaxiality) and galaxy formation efficiency, with the latter measured using the central halo baryon fraction. In conclusion, our results suggest that the effects of baryons on the DM halo spin and shape are minor when the effects of cooling are mitigated, as required by realistic models of galaxy formation, although they remain significant for the inner halo.
WALLABY – an SKA Pathfinder H i survey Koribalski, Bärbel S.; Staveley-Smith, L.; Westmeier, T. ...
Astrophysics and space science,
07/2020, Volume:
365, Issue:
7
Journal Article
Peer reviewed
The Widefield ASKAP L-band Legacy All-sky Blind surveY (
wallaby
) is a next-generation survey of neutral hydrogen (H
i
) in the Local Universe. It uses the widefield, high-resolution capability of ...the Australian Square Kilometer Array Pathfinder (ASKAP), a radio interferometer consisting of
36
×
12
-m dishes equipped with Phased-Array Feeds (PAFs), located in an extremely radio-quiet zone in Western Australia.
wallaby
aims to survey three-quarters of the sky (
−
90
∘
<
δ
<
+
30
∘
) to a redshift of
z
≲
0.26
, and generate spectral line image cubes at ∼30 arcsec resolution and ∼1.6 mJy beam
−1
per 4 km s
−1
channel sensitivity. ASKAP’s instantaneous field of view at 1.4 GHz, delivered by the PAF’s 36 beams, is about 30 sq deg. At an integrated signal-to-noise ratio of five,
wallaby
is expected to detect around half a million galaxies with a mean redshift of
z
∼
0.05
(∼200 Mpc). The scientific goals of
wallaby
include: (a) a census of gas-rich galaxies in the vicinity of the Local Group; (b) a study of the H
i
properties of galaxies, groups and clusters, in particular the influence of the environment on galaxy evolution; and (c) the refinement of cosmological parameters using the spatial and redshift distribution of low-bias gas-rich galaxies. For context we provide an overview of recent and planned large-scale H
i
surveys. Combined with existing and new multi-wavelength sky surveys,
wallaby
will enable an exciting new generation of panchromatic studies of the Local Universe. — First results from the
wallaby
pilot survey are revealed, with initial data products publicly available in the CSIRO ASKAP Science Data Archive (CASDA).
The human melanocortin-1 receptor (MC1R) is a G-protein coupled receptor involved in the regulation of pigmentation. Several MC1R variant alleles are associated with red hair, fair skin and increased ...skin cancer risk. We have performed a systematic functional analysis of nine common MC1R variants and correlated these results with the strength of the genetic association of each variant allele with pigmentation phenotypes. In vitro expression studies revealed that variant receptors with reduced cell surface expression, including V60L, D84E, R151C, I155T, R160W and R163Q, showed a corresponding impairment in cAMP coupling. The R142H and D294H variants demonstrated normal cell surface expression, but had reduced functional responses, indicating that altered G-protein coupling may be responsible for this loss of function. The V92M variant cAMP activation was equal to or higher than that for wild-type MC1R. In co-expression studies, the D84E, R151C, I155T and R160W variants showed a dominant negative effect on wild-type receptor cell surface expression, which was reflected in a decreased ability to elevate intracellular cAMP levels. The D294H variant also demonstrated a dominant negative effect on wild-type MC1R cAMP signalling, but had no effect on wild-type surface expression. Importantly, comparison of the in vitro receptor characteristics with skin and hair colour data of individuals both homozygous and heterozygous for MC1R variant alleles revealed parallels between variant MC1R cell surface expression, functional ability, dominant negative activity and their effects on human pigmentation. These findings show the first direct correlations between variant MC1R biochemical properties and pigmentation phenotype.
ABSTRACT
We use the latest parallaxes measurements from Gaia DR3 to obtain a geometric calibration of the tip of the red giant branch (TRGB) in Cousins I magnitudes as a standard candle for ...cosmology. We utilize the following surveys: SkyMapper DR3, APASS DR9, ATLAS Refcat2, and Gaia DR3 synthetic photometry to obtain multiple zero-point calibrations of the TRGB magnitude, $M_{I}^{TRGB}$. Our sample contains Milky Way halo stars at high galactic latitudes (|b| > 36) where the impact of metallicity, dust, and crowding are minimized. The magnitude of the TRGB is identified using Sobel edge detection, but this approach introduced a systematic offset. To address this issue, we utilized simulations with parsec isochrones and showed how to calibrate and remove this bias. Applying our method within the colour range where the slope of the TRGB is relatively flat for metal-poor halo stars (1.55 < (BP − RP) < 2.25), we find a weighted average $M_{I}^{TRGB} = -4.042 \pm 0.041$ (stat) ±0.031 (sys) mag. A geometric calibration of the Milky Way TRGB has the benefit of being independent of other distance indicators and will help probe systematics in the local distance ladder, leading to improved measurements of the Hubble constant.
The eukaryotic translation initiation factor 4E (eIF4E) is a potent oncogene that is found to be dysregulated in 30% of human cancer, including colorectal carcinogenesis (CRC). ISIS 183750 is a ...second‐generation antisense oligonucleotide (ASO) designed to inhibit the production of the eIF4E protein. In preclinical studies we found that EIF4e ASOs reduced expression of EIF4e mRNA and inhibited proliferation of colorectal carcinoma cells. An additive antiproliferative effect was observed in combination with irinotecan. We then performed a clinical trial evaluating this combination in patients with refractory cancer. No dose‐limiting toxicities were seen but based on pharmacokinetic data and tolerability the dose of irinotecan was reduced to 160 mg/m2 biweekly. Efficacy was evaluated in 15 patients with irinotecan‐refractory colorectal cancer. The median time of disease control was 22.1 weeks. After ISIS 183750 treatment, peripheral blood levels of eIF4E mRNA were decreased in 13 of 19 patients. Matched pre‐ and posttreatment tumor biopsies showed decreased eIF4E mRNA levels in five of nine patients. In tumor tissue, the intracellular and stromal presence of ISIS 183750 was detected by IHC in all biopsied patients. Although there were no objective responses stable disease was seen in seven of 15 (47%) patients who were progressing before study entry, six of whom were stable at the time of the week 16 CT scan. We were also able to confirm through mandatory pre‐ and posttherapy tumor biopsies penetration of the ASO into the site of metastasis.
What's new?
Antisense technologies offer a number of potential advantages over more traditional therapeutic approaches, including improved specificity. Here the authors treated individuals afflicted with chemo‐refractory colorectal cancer with an antisense oligonucleotide (ASO) against eIF4E, a critical translational factor often dysregulated in malignant tumors. Treatment was performed in combination with the chemotherapeutic irinotecan and halted disease progression in less than half of the treated individuals. The authors speculate based on detection of the ASO in tumor biopsies that stromal binding may reduce intracellular penetrance and lower effectiveness of the treatment.
Summary
Background
A high total body naevus count is the highest risk factor for melanoma; the phenotype of red hair colour, freckling and pale skin that burns easily, produced by MC1R R alleles, ...also predisposes to melanoma.
Objectives
To determine whether the known melanoma risk factors of high naevus count and red hair or MC1R R alleles act synergistically to increase melanoma risk.
Methods
The Brisbane Naevus Morphology Study involved 1267 participants from volunteers presenting at a melanoma unit, dermatology outpatient clinic, private dermatology clinics, the Brisbane Longitudinal Twin Study and the QSkin Study. We examined pigmentation characteristics, total body naevus ≥ 5 mm count, and MC1R, ASIP and CDKN2A genotype in participants with and without a personal history of melanoma, living in Queensland, Australia, which is an area of high ultraviolet radiation.
Results
Cases were older than controls (median 57 vs. 33 years). Compared with individuals with dark brown hair and zero to four naevi, individuals with red hair and ≥ 20 naevi had a melanoma odds ratio of 10·0 (95% confidence interval 4·2–24·3). Individuals with MC1R R/R genotype and ≥ 20 naevi (≥ 5 mm diameter) had a melanoma odds ratio of 25·1 (95% confidence interval 8·4–82·7) compared with wild‐type (WT)/WT individuals with zero to four naevi. The highest risk group is Australian men with the MC1R R/R genotype and ≥ 20 moles, who have an absolute risk of melanoma to age 75 years of 23·3%, compared with 0·8% for men with the WT/WT genotype and zero to four naevi.
Conclusions
Patients who live in areas of high ultraviolet radiation, and have many large naevi and the red hair colour phenotype, particularly those with the MC1R R/R genotype, have a high risk of melanoma above the threshold recommended for screening in other cancers. Therefore, they should undergo intensive physician‐led surveillance.
What's already known about this topic?
A high number of acquired melanocytic naevi, the red hair phenotype and MC1R R alleles all independently increase melanoma risk.
Women with atypical naevi have an increasing melanoma risk gradient from darker hair to lighter hair.
Women with many naevi have an increasing melanoma risk gradient from those with no elements of the red hair phenotype, to those with freckles but not red hair, to those with red hair.
What does this study add?
In Queensland, Australia, people with ≥ 20 naevi (≥ 5 mm diameter) and MC1R R/R genotype have a 25‐fold increased melanoma risk, relative to people with zero to four naevi and the MC1R WT/WT genotype.
In Queensland, individuals with ≥ 20 naevi and the MC1R R/R genotype have an absolute melanoma risk to age 75 years of 23·3% for men and 19·3% for women. This effect is independent of CDKN2A genotype.
Further research is required to determine the effect of areas of lower ultraviolet radiation, as this study took place in the Queensland, Australia, which is an area of high ultraviolet radiation.
MC1R R/r genotype is associated with increased total body naevus count but this is not the case for R/R.
What is the translational message?
Patients with many large naevi and the red hair colour phenotype, particularly those with an MC1R R/R genotype, have an unusually high risk of melanoma.
In a high ultraviolet environment, this risk exceeds the threshold recommended for screening in other cancers, and such individuals should undergo intensive, regular, physician‐led surveillance.
Patients with many large naevi but with non‐red colour hair may benefit further from clinical MC1R genotyping.
Plain language summary available online
Linked Comment: Ribero. Br J Dermatol 2019; 181:889–890.
Respond to this article
Hair morphology is highly differentiated between populations and among people of European ancestry. Whereas hair morphology in East Asian populations has been studied extensively, relatively little ...is known about the genetics of this trait in Europeans. We performed a genome-wide association scan for hair morphology (straight, wavy, curly) in three Australian samples of European descent. All three samples showed evidence of association implicating the Trichohyalin gene (TCHH), which is expressed in the developing inner root sheath of the hair follicle, and explaining ∼6% of variance (p = 1.5 × 10−31). These variants are at their highest frequency in Northern Europeans, paralleling the distribution of the straight-hair EDAR variant in Asian populations.
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