Big system: Interactive graphics for the engineer

The BCS Interactive Graphics System (BIG System) approach to graphics was presented, along with several significant engineering applications. The BIG System precompiler, the graphics support library, and the function requirements of graphics applications are discussed. It was concluded that graphics standardization and a device independent code can be developed to assure maximum graphic terminal transferability

A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion.

The counterregulatory response to hypoglycemia, which restores normal blood glucose levels to ensure sufficient provision of glucose to the brain, is critical for survival. To discover underlying brain regulatory systems, we performed a genetic screen in recombinant inbred mice for quantitative trait loci (QTL) controlling glucagon secretion in response to neuroglucopenia. We identified a QTL on the distal part of chromosome 7 and combined this genetic information with transcriptomic analysis of hypothalami. This revealed Fgf15 as the strongest candidate to control the glucagon response. Fgf15 was expressed by neurons of the dorsomedial hypothalamus and the perifornical area. Intracerebroventricular injection of FGF19, the human ortholog of Fgf15, reduced activation by neuroglucopenia of dorsal vagal complex neurons, of the parasympathetic nerve, and lowered glucagon secretion. In contrast, silencing Fgf15 in the dorsomedial hypothalamus increased neuroglucopenia-induced glucagon secretion. These data identify hypothalamic Fgf15 as a regulator of glucagon secretion

The MASSIVE Survey - XII Connecting Stellar Populations of Early-Type Galaxies to Kinematics and Environment

We measure the stellar populations as a function of radius for 90 early-type galaxies (ETGs) in the MASSIVE survey, a volume-limited integral-field spectroscopic (IFS) galaxy survey targeting all northern-sky ETGs with absolute K-band magnitude M_K < -25.3 mag, or stellar mass M* 4x10^11 M_sun, within 108 Mpc. We are able to measure reliable stellar population parameters for individual galaxies out to 10-20 kpc (1-3 R_e) depending on the galaxy. Focusing on ~R_e (~10 kpc), we find significant correlations between the abundance ratios, sigma, and M* at large radius, but we also find that the abundance ratios saturate in the highest-mass bin. We see a strong correlation between the kurtosis of the line of sight velocity distribution (h4) and the stellar population parameters beyond R_e. Galaxies with higher radial anisotropy appear to be older, with metal-poorer stars and enhanced [alpha/Fe]. We suggest that the higher radial anisotropy may derive from more accretion of small satellites. Finally, we see some evidence for correlations between environmental metrics (measured locally and on >5 Mpc scales) and the stellar populations, as expected if satellites are quenched earlier in denser environments.Comment: 17 pages, 7 figures, Appendix not included here due to size constraints. Posted after responding to referee's comment

3D morphometric analysis of calcified cartilage properties using micro-computed tomography

Objective: Our aim is to establish methods for quantifying morphometric properties of calcified cartilage (CC) from micro-computed tomography (mu CT). Furthermore, we evaluated the feasibility of these methods in investigating relationships between osteoarthritis (OA), tidemark surface morphology and open subchondral channels (OSCCs). Method: Samples (n = 15) used in this study were harvested from human lateral tibial plateau (n = 8). Conventional roughness and parameters assessing local 3-dimensional (3D) surface variations were used to quantify the surface morphology of the CC. Subchondral channel properties (percentage, density, size) were also calculated. As a reference, histological sections were evaluated using Histopathological osteoarthritis grading (OARSI) and thickness of CC and subchondral bone (SCB) was quantified. Results: OARSI grade correlated with a decrease in local 3D variations of the tidemark surface (amount of different surface patterns (r(s) = -0.600, P = 0.018), entropy of patterns (EP) (r(s) = -0.648, P = 0.018), homogeneity index (HI) (r(s) = 0.555, P = 0.032)) and tidemark roughness (TMR) (r(s) = -0.579, P = 0.024). Amount of different patterns (ADP) and EP associated with channel area fraction (CAF) (r(p) = 0.876, P <0.0001; r(p) = 0.665, P = 0.007, respectively) and channel density (CD) (r(p) = 0.680, P = 0.011; r(p) = 0.582, P = 0.023, respectively). TMR was associated with CAF (r(p) = 0.926, P <0.0001) and average channel size (r(p) = 0.574, P = 0.025). CC topography differed statistically significantly in early OA vs healthy samples. Conclusion: We introduced a mu-CT image method to quantify 3D CC topography and perforations through CC. CC topography was associated with OARSI grade and OSCC properties; this suggests that the established methods can detect topographical changes in tidemark and CC perforations associated with OA. (c) 2018 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Cell type differences in activity of the Streptomyces bacteriophage ϕC31 integrase

Genomic integration by the Streptomyces bacteriophage ϕC31 integrase is a promising tool for non-viral gene therapy of various genetic disorders. We investigated the ϕC31 integrase recombination activity in T cell derived cell lines, primary T lymphocytes and CD34+ haematopoietic stem cells in comparison to mesenchymal stem cells and cell lines derived from lung-, liver- and cervix-tissue. In T cell lines, enhanced long-term expression above control was observed only with high amounts of integrase mRNA. Transfections of ϕC31 integrase plasmids were not capable of mediating enhanced long-term transgene expression in T cell lines. In contrast, moderate to high efficiency could be detected in human mesenchymal stem cells, human lung, liver and cervix carcinoma cell lines. Up to 100-fold higher levels of recombination product was found in ϕC31 integrase transfected A549 lung than Jurkat T cells. When the ϕC31 integrase activity was normalized to the intracellular integrase mRNA levels, a 16-fold difference was found. As one possible inhibitor of the ϕC31 integrase, we found 3- to 5-fold higher DAXX levels in Jurkat than in A549 cells, which could in addition to other yet unknown factors explain the observed discrepancy of ϕC31 integrase activity

Reactive Molecular Dynamics study on the first steps of DNA-damage by free hydroxyl radicals

We employ a large scale molecular simulation based on bond-order ReaxFF to simulate the chemical reaction and study the damage to a large fragment of DNA-molecule in the solution by ionizing radiation. We illustrate that the randomly distributed clusters of diatomic OH-radicals that are primary products of megavoltage ionizing radiation in water-based systems are the main source of hydrogen-abstraction as well as formation of carbonyl- and hydroxyl-groups in the sugar-moiety that create holes in the sugar-rings. These holes grow up slowly between DNA-bases and DNA-backbone and the damage collectively propagate to DNA single and double strand break.Comment: 6 pages and 8 figures. movies and simulations are available at: http://qmsimulator.wordpress.com

Immunophenotypic predictive profiling of BRCA1-associated breast cancer

The immunophenotypic predictive profile of BRCA1-associated cancers including major predictive markers, i.e., PARP-1, EGFR, c-kit, HER-2, and steroid hormones (ER/PR) that may have therapeutic relevance has not yet been reported in a comprehensive study. Using immunohistochemistry, we examined the expression of these proteins in a large cohort of BRCA1-associated breast cancers. PARP-1 immunoreactivity was found in 81.9%, EGFR in 43.6%, ER/PR in 17.9%, c-kit in 14.7%, and overexpression of HER-2 in 3.6% of cancers. For all markers studied, 8.2% of tumors were negative. Expression of only one predictive marker was found in 29.7% of cancers, and most frequently, it was PARP-1 (20.8%). In 62.1% of tumors, more than one predictive marker was expressed: PARP-1 and EGFR in 30.4%, PARP-1, and hormone receptors in 13.3% and PARP-1 with c-kit in 7.5% of all tumors. Coexpression of two or more other predictive markers was rare. There were significant differences in the median age at diagnosis of BRCA1-associated cancer between patients with ER+ vs. ER− and grades 1–2 vs. grade 3 tumors. These results demonstrate that BRCA1-associated cancers differ with respect to expression of proteins that are regarded as targets for specific therapies and that 92% of patients with BRCA1-associated cancers may benefit from one or several options for specific therapy (in addition to DNA damaging agents, e.g., cisplatin). About 8% of cancers which do not express therapeutic target proteins may not respond to such therapies. Knowledge of the immunophenotypic predictive profile may help with the recruitment of patients for trials of targeted therapies