Image Analysis Applied to Slices of History

During the last 10 years, TASC has undertaken several digital image enhancement projects based on nondestructive evaluation (NDE) applications. Most of these projects involved analyzing NDE imagery to determine why a critical part failed to operate as expected, or trying to recover from a failure which degraded NDE imagery or made it difficult to obtain. Examples include our studies of the Inertial Upper Stage nozzle nosecap following the unsuccessful launch of a Tracking Data Relay Satellite in the summer of 1983 [1] and our development of a video data image processing system to enhance, in real time, unevenly lit, poor-contrast signals from within the contaminated Number 2 reactor vessel at Three Mile Island [2]

The role of charged residues in the transmembrane helices of monocarboxylate transporter 1 and its ancillary protein basigin in determining plasma membrane expression and catalytic activity

Monocarboxylate transporters MCT1-MCT4 require basigin (CD147) or embigin (gp70), ancillary proteins with a glutamate residue in their single transmembrane (TM) domain, for plasma membrane (PM) expression and activity. Here we use site-directed mutagenesis and expression in COS cells or Xenopus oocytes to investigate whether this glutamate (Glu218 in basigin) may charge-pair with a positively charged TM-residue of MCT1. Such residues were predicted using a new molecular model of MCT1 based upon the published structure of the E. coli glycerol-3-phosphate transporter. No evidence was obtained for Arg306 (TM 8) of MCT1 and Glu218 of basigin forming a charge-pair; indeed E218Q-basigin could replace WT-basigin, although E218R-basigin was inactive. No PM expression of R306E-MCT1 or D302R-MCT1 was observed but D302R/R306D-MCT1 reached the PM, as did R306K-MCT1. However, both were catalytically inactive suggesting that Arg306 and Asp302 form a charge-pair in either orientation, but their precise geometry is essential for catalytic activity. Mutation of Arg86 to Glu or Gln within TM3 of MCT1 had no effect on plasma membrane expression or activity of MCT1. However, unlike WT-MCT1, these mutants enabled expression of E218R-basigin at the plasma membrane of COS cells. We propose that TM3 of MCT1 lies alongside the TM of basigin with Arg86 adjacent to Glu218 of basigin. Only when both these residues are positively charged (E218R-basigin with WT-MCT1) is this interaction prevented; all other residue pairings at these positions may be accommodated by charge-pairing or stabilization of unionized residues through hydrogen bonding or local distortion of the helical structure

Weak lensing of Type Ia Supernovae from the Dark Energy Survey

We consider the effects of weak gravitational lensing on observations of 196 spectroscopically confirmed Type Ia Supernovae (SNe Ia) from years 1 to 3 of the Dark Energy Survey (DES). We simultaneously measure both the angular correlation function and the non-Gaussian skewness caused by weak lensing. This approach has the advantage of being insensitive to the intrinsic dispersion of SNe Ia magnitudes. We model the amplitude of both effects as a function of σ8, and find σ8 =1.2+0.9−0.8⁠. We also apply our method to a subsample of 488 SNe from the Joint Light-curve Analysis (JLA; chosen to match the redshift range we use for this work), and find σ8 =0.8+1.1−0.7⁠. The comparable uncertainty in σ8 between DES–SN and the larger number of SNe from JLA highlights the benefits of homogeneity of the DES–SN sample, and improvements in the calibration and data analysis

High star formation rates as the origin of turbulence in early and modern disk galaxies

High spatial and spectral resolution observations of star formation and kinematics in early galaxies have shown that two-thirds are massive rotating disk galaxies with the remainder being less massive non-rotating objects. The line of sight averaged velocity dispersions are typically five times higher than in today's disk galaxies. This has suggested that gravitationally-unstable, gas-rich disks in the early Universe are fuelled by cold, dense accreting gas flowing along cosmic filaments and penetrating hot galactic gas halos. However these accreting flows have not been observed, and cosmic accretion cannot power the observed level of turbulence. Here we report on a new sample of rare high-velocity-dispersion disk galaxies we have discovered in the nearby Universe where cold accretion is unlikely to drive their high star-formation rates. We find that the velocity dispersion is most fundamentally correlated with their star-formation rates, and not their mass nor gas fraction, which leads to a new picture where star formation itself is the energetic driver of galaxy disk turbulence at all cosmic epochs.Comment: 9 pages, 2 figures, Supplimentary Info available at: http://pulsar.swin.edu.au/~agreen/nature/sigma_mean_arXiv.pdf. Accepted for publication in Natur

Factors influencing patient uptake of an exercise referral scheme: a qualitative study.

Exercise referral schemes aim to increase physical activity amongst inactive individuals with or at risk of long-term health conditions. Yet many patients referred to these schemes (by health professionals) fail to take up the exercise opportunities on offer. Understanding factors influencing uptake to exercise referral schemes may help improve future attendance. Using the Socio-Ecological Model as a framework, this qualitative study aimed to explore factors influencing uptake to an exercise referral scheme based in the North West of England. Semi-structured interviews were conducted with referred patients (n = 38) about their reasons for referral, interactions with referring health professionals, events following referral and ideas to improve future uptake. Data were analysed thematically and mapped onto the constructs of the Socio-Ecological Model. Factors reported to influence uptake included intrapersonal (past PA experiences, motivation, competing priorities), interpersonal (scheme explanations, support) and organizational influences (scheme promotion, communication between service, cost). Whilst several intrapersonal-level factors influenced patient decisions to uptake the exercise referral scheme, modifiable interpersonal and organizational factors were identified as potential targets for intervention. Recommendations are made for improving awareness of exercise referral schemes and for enhancing communication between referring practitioners, patients and referral scheme staff

Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in Caenorhabditis elegans through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic, and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate’s body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour

Mechanisms of attenuation of pulmonary V'O_{2} slow component in humans after prolonged endurance training

In this study we have examined the effect of prolonged endurance training program on the pulmonary oxygen uptake (V'O2 ) kinetics during heavy-intensity cycling-exercise and its impact on maximal cycling and running performance. Twelve healthy, physically active men (mean\ub1SD: age 22.33\ub11.44 years, V'O2peak 3198\ub1458 mL \ub7 min-1 ) performed an endurance training composed mainly of moderate-intensity cycling, lasting 20 weeks. Training resulted in a decrease (by 3c5%, P = 0.027) in V'O2 during prior low-intensity exercise (20 W) and in shortening of \u3c4 p of the V'O2 on-kinetics (30.1\ub15.9 s vs. 25.4\ub11.5 s, P = 0.007) during subsequent heavy-intensity cycling. This was accompanied by a decrease of the slow component of V'O2 on-kinetics by 49% (P = 0.001) and a decrease in the end-exercise V'O2 by 3c5% (P = 0.005). An increase (P = 0.02) in the vascular endothelial growth factor receptor 2 mRNA level and a tendency (P = 0.06) to higher capillary-to-fiber ratio in the vastus lateralis muscle were found after training (n = 11). No significant effect of training on the V'O2peak was found (P = 0.12). However, the power output reached at the lactate threshold increased by 19% (P = 0.01). The power output obtained at the V'O2peak increased by 14% (P = 0.003) and the time of 1,500-m performance decreased by 5% (P = 0.001). Computer modeling of the skeletal muscle bioenergetic system suggests that the training-induced decrease in the slow component of V'O2 on-kinetics found in the present study is mainly caused by two factors: an intensification of the each-step activation (ESA) of oxidative phosphorylation (OXPHOS) complexes after training and decrease in the "additional" ATP usage rising gradually during heavy-intensity exercise

Population mixing and incidence of cancers in adolescents and young adults between 1990 and 2013 in Yorkshire, UK

Purpose: Epidemiological evidence suggests a role for an infectious etiology for cancers in teenagers and young adults (TYAs). We investigated this by describing associations between infection transmission using the population mixing (PM) proxy and incidence of cancers in TYAs in Yorkshire, UK. Methods: We extracted cancer cases from the Yorkshire Specialist Register of Cancer in Children and Young People from 1990 to 2013 (n = 1929). Using multivariable Poisson regression models (adjusting for effects of deprivation and population density), we investigated whether PM was associated with cancer incidence. We included population mixing–population density interaction terms to examine for differences in effects of PM in urban and rural populations. Results: Nonsignificant IRRs were observed for leukemias (IRR 1.20, 95% CI 0.91–1.59), lymphomas (IRR 1.09, 95% CI 0.90–1.32), central nervous system tumors (IRR 1.06, 95% CI 0.80–1.40) and germ cell tumors (IRR 1.14, 95% CI 0.92–1.41). The association between PM and cancer incidence did not vary in urban and rural areas. Conclusions: Study results suggest PM is not associated with incidence of cancers among TYAs. This effect does not differ between rural and urban settings

Sequential Metabolism of 7-Dehydrocholesterol to Steroidal 5,7-Dienes in Adrenal Glands and Its Biological Implication in the Skin

Since P450scc transforms 7-dehydrocholesterol (7DHC) to 7-dehydropregnenolone (7DHP) in vitro, we investigated sequential 7DHC metabolism by adrenal glands ex vivo. There was a rapid, time- and dose-dependent metabolism of 7DHC by adrenals from rats, pigs, rabbits and dogs with production of more polar 5,7-dienes as detected by RP-HPLC. Based on retention time (RT), UV spectra and mass spectrometry, we identified the major products common to all tested species as 7DHP, 22-hydroxy-7DHC and 20,22-dihydroxy-7DHC. The involvement of P450scc in adrenal metabolic transformation was confirmed by the inhibition of this process by DL-aminoglutethimide. The metabolism of 7DHC with subsequent production of 7DHP was stimulated by forscolin indicating involvement of cAMP dependent pathways. Additional minor products of 7DHC metabolism that were more polar than 7DHP were identified as 17-hydroxy-7DHP (in pig adrenals but not those of rats) and as pregna-4,7-diene-3,20-dione (7-dehydroprogesterone). Both products represented the major identifiable products of 7DHP metabolism in adrenal glands. Studies with purified enzymes show that StAR protein likely transports 7DHC to the inner mitochondrial membrane, that 7DHC can compete effectively with cholesterol for the substrate binding site on P450scc and that the catalytic efficiency of 3βHSD for 7DHP (Vm/Km) is 40% of that for pregnenolone. Skin mitochondria are capable of transforming 7DHC to 7DHP and the 7DHP is metabolized further by skin extracts. Finally, 7DHP, its photoderivative 20-oxopregnacalciferol, and pregnenolone exhibited biological activity in skin cells including inhibition of proliferation of epidermal keratinocytes and melanocytes, and melanoma cells. These findings define a novel steroidogenic pathway: 7DHC→22(OH)7DHC→20,22(OH)27DHC→7DHP, with potential further metabolism of 7DHP mediated by 3βHSD or CYP17, depending on mammalian species. The 5–7 dienal intermediates of the pathway can be a source of biologically active vitamin D3 derivatives after delivery to or production in the skin, an organ intermittently exposed to solar radiation