Readout technologies for directional WIMP Dark Matter detection

The measurement of the direction of WIMP-induced nuclear recoils is a compelling but technologically challenging strategy to provide an unambiguous signature of the detection of Galactic dark matter. Most directional detectors aim to reconstruct the dark-matter-induced nuclear recoil tracks, either in gas or solid targets. The main challenge with directional detection is the need for high spatial resolution over large volumes, which puts strong requirements on the readout technologies. In this paper we review the various detector readout technologies used by directional detectors. In particular, we summarize the challenges, advantages and drawbacks of each approach, and discuss future prospects for these technologies

Discovery of 36 eclipsing EL CVn binaries found by the Palomar Transient Factory

We report the discovery and analysis of 36 new eclipsing EL CVn-type binaries, consisting of a core helium-composition pre-white dwarf and an early-type main-sequence companion, more than doubling the known population of these systems. We have used supervised machine learning methods to search 0.8 million lightcurves from the Palomar Transient Factory, combined with SDSS, Pan-STARRS and 2MASS colours. The new systems range in orbital periods from 0.46-3.8 d and in apparent brightness from ~14-16 mag in the PTF $R$ or $g^{\prime}$ filters. For twelve of the systems, we obtained radial velocity curves with the Intermediate Dispersion Spectrograph at the Isaac Newton Telescope. We modelled the lightcurves, radial velocity curves and spectral energy distributions to determine the system parameters. The radii (0.3-0.7 $\mathrm{R_{\odot}}$) and effective temperatures (8000-17000 K) of the pre-He-WDs are consistent with stellar evolution models, but the masses (0.12-0.28 $\mathrm{M_{\odot}}$) show more variance than models predicted. This study shows that using machine learning techniques on large synoptic survey data is a powerful way to discover substantial samples of binary systems in short-lived evolutionary stages

Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study

The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotypes. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptome of non-transformed (MCF10A) and cancerous (MCF7 and Hs578T) BC cells. The total number of transcripts altered was MCF10A 75 (70 up-regulated), MCF7 24 (14 up-regulated) and Hs578T 328 (156 up-regulated). Only the cancer-associated gene TAGLN was altered by FA in all three cell lines. In MCF10A and Hs578T cells, FA treatment decreased pathways associated with apoptosis, cell death and senescence, but increased those associated with cell proliferation. The folate transporters SLC19A1, SLC46A1 and FOLR1 were differentially expressed between cell lines tested. However, the level of expression was not altered by FA treatment. These findings suggest that physiological concentrations of FA can induce cell type-specific changes in gene regulation in a manner that is consistent with proliferative phenotype. This has implications for understanding the role of FA in BC risk. In addition, these findings support the suggestion the differences in gene expression induced by FA may involve differential activities of folate transporters. Together these findings indicate the need for further studies of the effect of FA on BC

Differential pathways to adult metabolic dysfunction following poor nutrition at two critical developmental periods in sheep

Epidemiological and experimental studies suggest early nutrition has long-term effects on susceptibility to obesity, cardiovascular and metabolic diseases. Small and large animal models confirm the influence of different windows of sensitivity, from fetal to early postnatal life, on offspring phenotype. We showed previously that undernutrition in sheep either during the first month of gestation or immediately after weaning induces differential, sex-specific changes in adult metabolic and cardiovascular systems. The current study aims to determine metabolic and molecular changes that underlie differences in lipid and glucose metabolism induced by undernutrition during specific developmental periods in male and female sheep. Ewes received 100% (C) or 50% nutritional requirements (U) from 1–31 days gestation, and 100% thereafter. From weaning (12 weeks) to 25 weeks, offspring were then fed either ad libitum (CC, UC) or were undernourished (CU, UU) to reduce body weight to 85% of their individual target. From 25 weeks, all offspring were fed ad libitum. A cohort of late gestation fetuses were studied after receiving either 40% nutritional requirements (1–31 days gestation) or 50% nutritional requirements (104–127 days gestation). Post-weaning undernutrition increased in vivo insulin sensitivity, insulin receptor and glucose transporter 4 expression in muscle, and lowered hepatic methylation at the delta-like homolog 1/maternally expressed gene 3 imprinted cluster in adult females, but not males. Early gestational undernutrition induced lower hepatic expression of gluconeogenic factors in fetuses and reduced in vivo adipose tissue insulin sensitivity in adulthood. In males, undernutrition in early gestation increased adipose tissue lipid handling mechanisms (lipoprotein lipase, glucocorticoid receptor expression) and hepatic methylation within the imprinted control region of insulin-like growth factor 2 receptor in adulthood. Therefore, undernutrition during development induces changes in mechanisms of lipid and glucose metabolism which differ between tissues and sexes dependent on the period of nutritional restriction. Such changes may increase later life obesity and dyslipidaemia risk

Readout technologies for directional WIMP Dark Matter detection

The measurement of the direction of WIMP-induced nuclear recoils is a compelling but technologically challenging strategy to provide an unambiguous signature of the detection of Galactic dark matter. Most directional detectors aim to reconstruct the dark-matter-induced nuclear recoil tracks, either in gas or solid targets. The main challenge with directional detection is the need for high spatial resolution over large volumes, which puts strong requirements on the readout technologies. In this paper we review the various detector readout technologies used by directional detectors. In particular, we summarize the challenges, advantages and drawbacks of each approach, and discuss future prospects for these technologies

Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later Adiposity

Objective: fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans.Research design and methods: using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5? from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ?5% and a 5–95% range ?10%, we related methylation status to maternal pregnancy diet and to child’s adiposity at age 9 years. Replication was sought in a second independent cohort.Results: in cohort 1, retinoid X receptor-? (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [?] 17% per SD change in methylation [95% CI 4–31], P = 0.009, n = 64, and ? = 20% [9–32], P < 0.001, n = 66, respectively) and %fat mass (? = 10% [1–19], P = 0.023, n = 64 and ? =12% [4–20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (? = 6% [2–10] and ? = 4% [1–7], respectively, both P = 0.002, n = 239).Conclusions: our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic diseas

Progressive, Transgenerational Changes in Offspring Phenotype and Epigenotype following Nutritional Transition

Induction of altered phenotypes during development in response to environmental input involves epigenetic changes. Phenotypic traits can be passed between generations by a variety of mechanisms, including direct transmission of epigenetic states or by induction of epigenetic marks de novo in each generation. To distinguish between these possibilities we measured epigenetic marks over four generations in rats exposed to a sustained environmental challenge. Dietary energy was increased by 25% at conception in F0 female rats and maintained at this level to generation F3. F0 dams showed higher pregnancy weight gain, but lower weight gain and food intake during lactation than F1 and F2 dams. On gestational day 8, fasting plasma glucose concentration was higher and β-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPARα and carnitine palmitoyl transferase-1 mRNA expression. PEPCK mRNA expression was inversely related to the methylation of specific CpG dinucleotides in its promoter. DNA methyltransferase (Dnmt) 3a2, but not Dnmt1 or Dnmt3b, expression increased and methylation of its promoter decreased from F1 to F3 generations. These data suggest that the regulation of energy metabolism during pregnancy and lactation within a generation is influenced by the maternal phenotype in the preceding generation and the environment during the current pregnancy. The transgenerational effects on phenotype were associated with altered DNA methylation of specific genes in a manner consistent with induction de novo of epigenetic marks in each generation

A new class of large-amplitude radial-mode hot subdwarf pulsators

Using high-cadence observations from the Zwicky Transient Facility at low Galactic latitudes, we have discovered a new class of pulsating, hot compact stars. We have found four candidates, exhibiting blue colors (g − r ≤ −0.1 mag), pulsation amplitudes of >5%, and pulsation periods of 200–475 s. Fourier transforms of the light curves show only one dominant frequency. Phase-resolved spectroscopy for three objects reveals significant radial velocity, T eff, and log(g) variations over the pulsation cycle, which are consistent with large-amplitude radial oscillations. The mean T eff and log(g) for these stars are consistent with hot subdwarf B (sdB) effective temperatures and surface gravities. We calculate evolutionary tracks using MESA and adiabatic pulsations using GYRE for low-mass, helium-core pre-white dwarfs (pre-WDs) and low-mass helium-burning stars. Comparison of low-order radial oscillation mode periods with the observed pulsation periods show better agreement with the pre-WD models. Therefore, we suggest that these new pulsators and blue large-amplitude pulsators (BLAPs) could be members of the same class of pulsators, composed of young ≈0.25–0.35 M ⊙ helium-core pre-WDs.Published versio

Lipidomic Analysis of Plasma from Healthy Men and Women Shows Phospholipid Class and Molecular Species Differences between Sexes

The phospholipid composition of lipoproteins is determined by the specificity of hepatic phospholipid biosynthesis. Plasma phospholipid 20:4n-6 and 22:6n-3 concentrations are higher in women than in men. We used this sex difference in a lipidomics analysis of the impact of endocrine factors on the phospholipid class and molecular species composition of fasting plasma from young men and women. Diester species predominated in all lipid classes measured. 20/54 Phosphatidylcholine (PtdCho) species were alkyl ester, 15/48 phosphatidylethanolamine (PtdEtn) species were alkyl ester, and 12/48 PtdEtn species were alkenyl ester. There were no significant differences between sexes in the proportions of alkyl PtdCho species. The proportion of alkyl ester PtdEtn species was greater in women than men, while the proportion of alkenyl ester PtdEtn species was greater in men than women. None of the phosphatidylinositol (PtdIns) or phosphatidylserine (PtdSer) molecular species contained ether-linked fatty acids. The proportion of PtdCho16:0_22:6, and the proportions of PtdEtn O-16:0_20:4 and PtdEtn O-18:2_20:4 were greater in women than men. There were no sex differences in PtdIns and PtdSer molecular species compositions. These findings show that plasma phospholipids can be modified by sex. Such differences in lipoprotein phospholipid composition could contribute to sexual dimorphism in patterns of health and disease