Characterization of light production and transport in tellurium dioxide crystals

Simultaneous measurement of phonon and light signatures is an effective way to reduce the backgrounds and increase the sensitivity of CUPID, a next-generation bolometric neutrinoless double-beta decay (0νββ) experiment. Light emission in tellurium dioxide (TeO2) crystals, one of the candidate materials for CUPID, is dominated by faint Cherenkov radiation, and the high refractive index of TeO2 complicates light collection. Positive identification of 0νββ events therefore requires high-sensitivity light detectors and careful optimization of light transport. A detailed microphysical understanding of the optical properties of TeO2 crystals is essential for such optimization. We present a set of quantitative measurements of light production and transport in a cubic TeO2 crystal, verified with a complete optical model and calibrated against a UVT acrylic standard. We measure the optical surface properties of the crystal, and set stringent limits on the amount of room-temperature scintillation in TeO2 for β and α particles of 5.3 and 8 photons/MeV, respectively, at 90% confidence. The techniques described here can be used to optimize and verify the particle identification capabilities of CUPID

The association between muscular power from childhood to adulthood and adult measures of glucose homeostasis

This study aimed to assess whether the longitudinal association between childhood muscular fitness and adult measures of glucose homeostasis persist despite changes in muscular fitness across the life course. This prospective longitudinal study included 586 participants who had their muscular power (standing long jump distance), cardiorespiratory fitness (CRF), and waist circumference measured as children (aged 9, 12, 15 years) and again 20 years later as adults. In adulthood, these participants also provided a fasting blood sample which was tested for glucose and insulin. Glucose homeostasis measures including insulin resistance (HOMA2-IR) and beta cell function (HOMA2-β) were estimated. Child and adult muscular power levels were separated into thirds, and tracking groups (persistently low, decreasing, persistently moderate, increasing, and persistently high) were created. Sex-stratified multivariable linear regression models were used to examine the association between muscular power tracking groups and adult measures of glucose homeostasis. Compared with males with persistently high muscular power, males with increasing and persistently low muscular power had higher fasting insulin (increasing: β = 1.12 mU/L, P = .04; persistently low: β = 2.12 mU/L, P = .001) and HOMA2-β (increasing: β = 8.50%, P = .03; persistently low: β = 11.27%, P = .01) independent of CRF and males with persistently low muscular power had greater fasting insulin (β = 1.22 mU/L, P = .02) and HOMA2-IR (β = 0.14, P = .02) independent of waist circumference. Non-significant associations were present for females. For males, maintaining persistently high muscular power between childhood and adulthood could lead to a healthier adult glucose homeostasis profile

Thalidomide-induced Teratogenesis : History and Mechanisms

Peer reviewedPublisher PD

The association between grip strength measured in childhood, young- and mid-adulthood and prediabetes or type 2 diabetes in mid-adulthood

Background: Although low child and adult grip strength is associated with adverse cardiometabolic health, how grip strength across the life course associates with type 2 diabetes is unknown. This study identified the relative contribution of grip strength measured at specific life stages (childhood, young adulthood, mid-adulthood) with prediabetes or type 2 diabetes in mid-adulthood. Methods: Between 1985 and 2019, 263 participants had their grip strength measured using an isometric dynamometer in childhood (9-15 years), young adulthood (28-36 years) and mid-adulthood (38-49 years). In mid-adulthood, a fasting blood sample was collected and tested for glucose and glycated haemoglobin (HbA1c). Participants were categorized as having prediabetes or type 2 diabetes if fasting glucose levels were ≥ 5.6 mmol or if HbA1c levels were ≥ 5.7% (≥ 39 mmol/mol). A Bayesian relevant life course exposure model examined the association between lifelong grip strength and prediabetes or type 2 diabetes. Results: Grip strength at each time point was equally associated with prediabetes or type 2 diabetes in mid-adulthood (childhood: 37%, young adulthood: 36%, mid-adulthood: 28%). A one standard deviation increase in cumulative grip strength was associated with 34% reduced odds of prediabetes or type 2 diabetes in mid-adulthood (OR 0.66, 95% credible interval 0.40, 0.98). Conclusions: Greater grip strength across the life course could protect against the development of prediabetes and type 2 diabetes. Strategies aimed at increasing muscular strength in childhood and maintaining behaviours to improve strength into adulthood could improve future cardiometabolic health. The Association Between Grip Strength Measured in Childhood, Young- and Mid-adulthood and Prediabetes or Type 2 Diabetes in Mid-adulthood

Modal Analysis of Fluid Flows: An Overview

Simple aerodynamic configurations under even modest conditions can exhibit complex flows with a wide range of temporal and spatial features. It has become common practice in the analysis of these flows to look for and extract physically important features, or modes, as a first step in the analysis. This step typically starts with a modal decomposition of an experimental or numerical dataset of the flow field, or of an operator relevant to the system. We describe herein some of the dominant techniques for accomplishing these modal decompositions and analyses that have seen a surge of activity in recent decades. For a non-expert, keeping track of recent developments can be daunting, and the intent of this document is to provide an introduction to modal analysis in a presentation that is accessible to the larger fluid dynamics community. In particular, we present a brief overview of several of the well-established techniques and clearly lay the framework of these methods using familiar linear algebra. The modal analysis techniques covered in this paper include the proper orthogonal decomposition (POD), balanced proper orthogonal decomposition (Balanced POD), dynamic mode decomposition (DMD), Koopman analysis, global linear stability analysis, and resolvent analysis

An accurate test for homogeneity of odds ratios based on Cochran's Q-statistic

Background: A frequently used statistic for testing homogeneity in a meta-analysis of K independent studies is Cochran's Q. For a standard test of homogeneity the Q statistic is referred to a chi-square distribution with K - 1 degrees of freedom. For the situation in which the effects of the studies are logarithms of odds ratios, the chi-square distribution is much too conservative for moderate size studies, although it may be asymptotically correct as the individual studies become large. Methods: Using a mixture of theoretical results and simulations, we provide formulas to estimate the shape and scale parameters of a gamma distribution to t the distribution of Q. Results: Simulation studies show that the gamma distribution is a good approximation to the distribution for Q. Conclusions: : Use of the gamma distribution instead of the chi-square distribution for Q should eliminate inaccurate inferences in assessing homogeneity in a meta-analysis. (A computer program for implementing this test is provided.) This hypothesis test is competitive with the Breslow-Day test both in accuracy of level and in power

The association between muscular power from childhood to adulthood and adult measures of glucose homeostasis

This study aimed to assess whether the longitudinal association between childhood muscular fitness and adult measures of glucose homeostasis persist despite changes in muscular fitness across the life course. This prospective longitudinal study included 586 participants who had their muscular power (standing long jump distance), cardiorespiratory fitness (CRF), and waist circumference measured as children (aged 9, 12, 15 years) and again 20 years later as adults. In adulthood, these participants also provided a fasting blood sample which was tested for glucose and insulin. Glucose homeostasis measures including insulin resistance (HOMA2-IR) and beta cell function (HOMA2-beta) were estimated. Child and adult muscular power levels were separated into thirds, and tracking groups (persistently low, decreasing, persistently moderate, increasing, and persistently high) were created. Sex-stratified multivariable linear regression models were used to examine the association between muscular power tracking groups and adult measures of glucose homeostasis. Compared with males with persistently high muscular power, males with increasing and persistently low muscular power had higher fasting insulin (increasing: beta = 1.12 mU/L, P = .04; persistently low: beta = 2.12 mU/L, P = .001) and HOMA2-beta (increasing: beta = 8.50%, P = .03; persistently low: beta = 11.27%, P = .01) independent of CRF and males with persistently low muscular power had greater fasting insulin (beta = 1.22 mU/L, P = .02) and HOMA2-IR (beta = 0.14, P = .02) independent of waist circumference. Non-significant associations were present for females. For males, maintaining persistently high muscular power between childhood and adulthood could lead to a healthier adult glucose homeostasis profile

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

Situational Awareness of Influenza Activity Based on Multiple Streams of Surveillance Data Using Multivariate Dynamic Linear Model

BACKGROUND: Multiple sources of influenza surveillance data are becoming more available; however integration of these data streams for situational awareness of influenza activity is less explored. METHODS AND RESULTS: We applied multivariate time-series methods to sentinel outpatient and school absenteeism surveillance data in Hong Kong during 2004-2009. School absenteeism data and outpatient surveillance data experienced interruptions due to school holidays and changes in public health guidelines during the pandemic, including school closures and the establishment of special designated flu clinics, which in turn provided 'drop-in' fever counts surveillance data. A multivariate dynamic linear model was used to monitor influenza activity throughout epidemics based on all available data. The inferred level followed influenza activity closely at different times, while the inferred trend was less competent with low influenza activity. Correlations between inferred level and trend from the multivariate model and reference influenza activity, measured by the product of weekly laboratory influenza detection rates and weekly general practitioner influenza-like illness consultation rates, were calculated and compared with those from univariate models. Over the whole study period, there was a significantly higher correlation (rho = 0.82, p</=0.02) for the inferred trend based on the multivariate model compared to other univariate models, while the inferred trend from the multivariate model performed as well as the best univariate model in the pre-pandemic and the pandemic period. The inferred trend and level from the multivariate model was able to match, if not outperform, the best univariate model albeit with missing data plus drop-in and drop-out of different surveillance data streams. An overall influenza index combining level and trend was constructed to demonstrate another potential use of the method. CONCLUSIONS: Our results demonstrate the potential use of multiple streams of influenza surveillance data to promote situational awareness about the level and trend of seasonal and pandemic influenza activity.published_or_final_versio

Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection

Many new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals (GLUD1), humans and apes acquired a second GLUD gene (GLUD2) through retroduplication of GLUD1, which codes for an enzyme with unique, potentially brain-adapted properties. Here we show that whereas the GLUD1 parental protein localizes to mitochondria and the cytoplasm, GLUD2 is specifically targeted to mitochondria. Using evolutionary analysis and resurrected ancestral protein variants, we demonstrate that the enhanced mitochondrial targeting specificity of GLUD2 is due to a single positively selected glutamic acid-to-lysine substitution, which was fixed in the N-terminal mitochondrial targeting sequence (MTS) of GLUD2 soon after the duplication event in the hominoid ancestor ~18–25 million years ago. This MTS substitution arose in parallel with two crucial adaptive amino acid changes in the enzyme and likely contributed to the functional adaptation of GLUD2 to the glutamate metabolism of the hominoid brain and other tissues. We suggest that rapid, selectively driven subcellular adaptation, as exemplified by GLUD2, represents a common route underlying the emergence of new gene functions