Regulation of signaling genes by TGFβ during entry into dauer diapause in C. elegans

BACKGROUND: When resources are scant, C. elegans larvae arrest as long-lived dauers under the control of insulin/IGF- and TGFβ-related signaling pathways. However, critical questions remain regarding the regulation of this developmental event. How do three dozen insulin-like proteins regulate one tyrosine kinase receptor to control complex events in dauer, metabolism and aging? How are signals from the TGFβ and insulin/IGF pathways integrated? What gene expression programs do these pathways regulate, and how do they control complex downstream events? RESULTS: We have identified genes that show different levels of expression in a comparison of wild-type L2 or L3 larvae (non-dauer) to TGFβ mutants at similar developmental stages undergoing dauer formation. Many insulin/IGF pathway and other known dauer regulatory genes have changes in expression that suggest strong positive feedback by the TGFβ pathway. In addition, many insulin-like ligand and novel genes with similarity to the extracellular domain of insulin/IGF receptors have altered expression. We have identified a large group of regulated genes with putative binding sites for the FOXO transcription factor, DAF-16. Genes with DAF-16 sites upstream of the transcription start site tend to be upregulated, whereas genes with DAF-16 sites downstream of the coding region tend to be downregulated. Finally, we also see strong regulation of many novel hedgehog- and patched-related genes, hormone biosynthetic genes, cell cycle genes, and other regulatory genes. CONCLUSIONS: The feedback regulation of insulin/IGF pathway and other dauer genes that we observe would be predicted to amplify signals from the TGFβ pathway; this amplification may serve to ensure a decisive choice between "dauer" and "non-dauer", even if environmental cues are ambiguous. Up and down regulation of insulin-like ligands and novel genes with similarity to the extracellular domain of insulin/IGF receptors suggests opposing roles for several members of these large gene families. Unlike in adults, most genes with putative DAF-16 binding sites are upregulated during dauer entry, suggesting that DAF-16 has different activity in dauer versus adult metabolism and aging. However, our observation that the position of putative DAF-16 binding sites is correlated with the direction of regulation suggests a novel method of achieving gene-specific regulation from a single pathway. We see evidence of TGFβ-mediated regulation of several other classes of regulatory genes, and we discuss possible functions of these genes in dauer formation

Effect of various dopant elements on primary graphite growth

Five spheroidal graphite cast irons were investigated, a usual ferritic grade and four pearlitic alloys containing Cu and doped with Sb, Sn and Ti. These alloys were remelted in a graphite crucible, leading to volatilization of the magnesium added for spheroidization and to carbon saturation of the liquid. The alloys were then cooled down and maintained at a temperature above the eutectic temperature. During this step, primary graphite could develop showing various features depending on the doping elements added. The largest effects were that of Ti which greatly reduces graphite nucleation and growth, and that of Sb which leads to rounded agglomerates instead of lamellar graphite. The samples have been investigated with secondary ion mass spectrometry to enlighten distribution of elements in primary graphite. SIMS analysis showed almost even distribution of elements, including Mg and Al (from the inoculant) in the ferritic grade, while uneven distribution was evident in all doped alloys. Investigations are going on to clarify if the uneven distribution is associated with structural defects in the graphite precipitates

Search for the electric dipole moment of the electron with thorium monoxide

The electric dipole moment of the electron (eEDM) is a signature of CP-violating physics beyond the Standard Model. We describe an ongoing experiment to measure or set improved limits to the eEDM, using a cold beam of thorium monoxide (ThO) molecules. The metastable $H {}^3\Delta_1$ state in ThO has important advantages for such an experiment. We argue that the statistical uncertainty of an eEDM measurement could be improved by as much as 3 orders of magnitude compared to the current experimental limit, in a first-generation apparatus using a cold ThO beam. We describe our measurements of the $H$ state lifetime and the production of ThO molecules in a beam, which provide crucial data for the eEDM sensitivity estimate. ThO also has ideal properties for the rejection of a number of known systematic errors; these properties and their implications are described.Comment: v2: Equation (11) correcte

HALOGAS observations of NGC 5023 and UGC 2082: Modeling of non-cylindrically symmetric gas distributions in edge-on galaxies

In recent years it has become clear that the vertical structure of disk galaxies is a key ingredient for understanding galaxy evolution. In particular, the presence and structure of extra-planar gas has been a focus of research. The Hydrogen Accretion in LOcal GAlaxieS (HALOGAS) survey aims to provide a census on the rate of cold neutral gas accretion in nearby galaxies as well as a statistically significant set of galaxies that can be investigated for their extra-planar gas properties. In order to better understand the the vertical structure of the neutral hydrogen in the two edge-on HALOGAS galaxies NGC 5023 and UGC 2082 we construct detailed tilted ring models. The addition of distortions resembling arcs or spiral arms significantly improves the fit of the models to these galaxies. In the case of UGC 2082 no vertical gradient in rotational velocity is required in either symmetric models nor non-symmetric models to match the observations. The best fitting model features two arcs of large vertical extent that may be due to accretion. In the case of NGC 5023 a vertical gradient is required in symmetric models (dV/dz =$-14.9\pm3.8$ km s$^{-1}$ kpc$^{-1}$) and its magnitude is significantly lowered when non-symmetric models are considered (dV/dz =$-9.4\pm3.8$ km s$^{-1}$ kpc$^{-1}$). Additionally it is shown that the underlying disk of NGC 5023 can be made symmetric, in all parameters except the warp, in non-symmetric models. In comparison to the "classical" modeling these models fit the data significantly better with a limited addition of free parameters.Comment: 27 Pages, 22 Figures. Accepted for publication in MNRA

Charge Ordering and Ferroelectricity in Half-doped Manganites

By means of density-functional simulations for half-doped manganites, such as pseudocubic Pr0.5Ca0.5MnO3 and bilayer PrCa2Mn2O7, we discuss the occurrence of ferroelectricity and we explore its crucial relation to the crystal structure and to peculiar charge/spin/orbital ordering effects. In pseudocubic Pr0.5Ca0.5MnO3, ferroelectricity is induced in the Zener polaron type structure, where Mn ions are dimerized. In marked contrast, in bilayer PrCa2Mn2O7, it is the displacements of apical oxygens bonded to either Mn3+ or Mn4+ ions that play a key role in the rising of ferroelectricity. Importantly, local dipoles due to apical oxygens are also intimately linked to charge and orbital ordering patterns in MnO2 planes, which in turn contribute to polarization. Finally, an important outcome of our work consists in proposing Born effective charges as a valid mean to quantify charge disproportionation effects, in terms of anisotropy and size of electronic clouds around Mn ions.Comment: 5 pages, 2 figures, submitted for publicatio

Stability of the r-modes in white dwarf stars

Stability of the r-modes in rapidly rotating white dwarf stars is investigated. Improved estimates of the growth times of the gravitational-radiation driven instability in the r-modes of the observed DQ Her objects are found to be longer (probably considerably longer) than 6x10^9y. This rules out the possibility that the r-modes in these objects are emitting gravitational radiation at levels that could be detectable by LISA. More generally it is shown that the r-mode instability can only be excited in a very small subset of very hot (T>10^6K), rather massive (M>0.9M_sun) and very rapidly rotating (P_min<P<1.2P_min) white dwarf stars. Further, the growth times of this instability are so long that these conditions must persist for a very long time (t>10^9y) to allow the amplitude to grow to a dynamically significant level. This makes it extremely unlikely that the r-mode instability plays a significant role in any real white dwarf stars.Comment: 5 Pages, 5 Figures, revte

Cancer-related pain in head and neck cancer survivors: longitudinal findings from the Head and Neck 5000 clinical cohort

\ua9 The Author(s) 2024.Purpose: Reports suggest pain is common in head and neck cancer (HNC). However, past studies are limited by small sample sizes and design and measurement heterogeneity. Using data from the Head and Neck 5000 longitudinal cohort, we investigated pain over a year post-diagnosis. We assessed: temporal trends; compared pain across HNC treatments, stages, sites and by HPV status; and identified subgroups of patients at increased risk of pain. Methods: Sociodemographic and clinical data and patient-reported pain (measured by EORTC QLQ-C30 and QLQ-H&amp;N35) were collected at baseline (pre-treatment), 4- and 12- months. Using mixed effects multivariable regression, we investigated time trends and identified associations between (i) clinically-important general pain and (ii) HN-specific pain and clinical, socio-economic, and demographic variables. Results: 2,870 patients were included. At baseline, 40.9% had clinically-important general pain, rising to 47.6% at 4-months and declining to 35.5% at 12-months. HN-specific pain followed a similar pattern (mean score (sd): baseline 26.4 (25.10); 4-months. 28.9 (26.55); 12-months, 17.2 (19.83)). Across time, general and HN-specific pain levels were increased in: younger patients, smokers, and those with depression and comorbidities at baseline, and more advanced, oral cavity and HPV negative cancers. Conclusions: There is high prevalence of general pain in people living with HNC. We identified subgroups more often reporting general and HN-specific pain towards whom interventions could be targeted. Implications for cancer survivors: Greater emphasis should be placed on identifying and treating pain in HNC. Systematic pain screening could help identify those who could benefit from an early pain management plan

The system parameters of DW Ursae Majoris

We present new constraints on the system parameters of the SW Sextantis star DW Ursae Majoris, based on ultraviolet (UV) eclipse observations with the Hubble Space Telescope. Our data were obtained during a low state of the system, in which the UV light was dominated by the hot white dwarf (WD) primary. Eclipse analysis, using the full Roche lobe geometry, allows us to set firm limits on the masses and radii of the system components and the distance between them: 0.67 \leq M_1/M_sun \leq 1.06, 0.008 \leq R_1/R_sun \leq 0.014, M_2/M_sun > 0.16, R_2/R_sun > 0.28 and a/R_sun > 1.05. For q = M_2/M_1 < 1.5 the inclination must satisfy i > 71 degrees. Using Smith & Dhillon's mass-period relation for CV secondaries, our estimates for the system parameters become M_1/M_sun = 0.77 \pm 0.07, R_1/R_sun = 0.012 \pm 0.001, M_2/M_sun = 0.30 \pm 0.10, R_2/R_sun = 0.34 \pm 0.04, q =0.39 \pm 0.12, i = 82 \pm 4 degrees and a/R_sun = 1.14 \pm 0.06. We have also estimated the spectral type of the secondary, M3.5 \pm 1.0, and distance to the system, d =930 \pm 160 pc, from time-resolved I- and K-band photometry. Finally, we have repeated Knigge et al.'s WD model atmosphere fit to the low-state UV spectrum of DW UMa in order to account for the higher surface gravity indicated by our eclipse analysis. In this way we obtained a second estimate for the distance, d = 590 \pm 100 pc, which allows us to obtain a second estimate for the spectral type of the secondary, M7 \pm 2.0. We conclude that the true value for the distance and spectral type will probably be in between the values obtained by the two methods.Comment: 23 pages including 5 figures and 3 tables. Accepted for publication in Ap

Correlates of unmet needs and psychological distress in adolescent and young adults who have a parent diagnosed with cancer.

Objective. Young people who have a parent with cancer experience elevated levels of psychological distress and unmet needs. In this study we examined the associations between demographics, cancer variables, and family functioning; and levels of distress and unmet needs amongst young people who have a parent diagnosed with cancer. Methods. Young people aged 12 -24 with a parent with cancer (n=255) completed the Offspring Cancer Needs Instrument (unmet needs), the Kessler-10 (distress), and the Family Relationship Index (family functioning), along with measures of demographics and cancer variables (such as: age, sex, time since cancer diagnosis). Variables associated with distress and unmet needs (including unmet need domains) were assessed using multiple linear regression. Results. Being female and older, having more unmet cancer needs and poorer family functioning was associated with increased distress. Having a father with cancer, a shorter time since diagnosis, and poor family functioning were associated with increased unmet needs. Family conflict and expressiveness were particularly important components of family functioning. Having a parent relapse with cancer was also associated with unmet needs in the domains of practical assistance, ‘time out’, and support from other young people who have been through something similar. Conclusions. Delineating factors associated with increased distress and unmet needs assists in identifying at risk young people allowing improved assessment and tailoring of support to improve the psychosocial outcomes of young people impacted by parental cancer.beyondblu

Large-Scale Distributed Bayesian Matrix Factorization using Stochastic Gradient MCMC

Despite having various attractive qualities such as high prediction accuracy and the ability to quantify uncertainty and avoid over-fitting, Bayesian Matrix Factorization has not been widely adopted because of the prohibitive cost of inference. In this paper, we propose a scalable distributed Bayesian matrix factorization algorithm using stochastic gradient MCMC. Our algorithm, based on Distributed Stochastic Gradient Langevin Dynamics, can not only match the prediction accuracy of standard MCMC methods like Gibbs sampling, but at the same time is as fast and simple as stochastic gradient descent. In our experiments, we show that our algorithm can achieve the same level of prediction accuracy as Gibbs sampling an order of magnitude faster. We also show that our method reduces the prediction error as fast as distributed stochastic gradient descent, achieving a 4.1% improvement in RMSE for the Netflix dataset and an 1.8% for the Yahoo music dataset