Functional Characterization of CLPTM1L as a Lung Cancer Risk Candidate Gene in the 5p15.33 Locus

Cleft Lip and Palate Transmembrane Protein 1-Like (CLPTM1L), resides in a region of chromosome 5 for which copy number gain has been found to be the most frequent genetic event in the early stages of non-small cell lung cancer (NSCLC). This locus has been found by multiple genome wide association studies to be associated with lung cancer in both smokers and non-smokers. CLPTM1L has been identified as an overexpressed protein in human ovarian tumor cell lines that are resistant to cisplatin, which is the only insight thus far into the function of CLPTM1L. Here we find CLPTM1L expression to be increased in lung adenocarcinomas compared to matched normal lung tissues and in lung tumor cell lines by mechanisms not exclusive to copy number gain. Upon loss of CLPTM1L accumulation in lung tumor cells, cisplatin and camptothecin induced apoptosis were increased in direct proportion to the level of CLPTM1L knockdown. Bcl-xL accumulation was significantly decreased upon loss of CLPTM1L. Expression of exogenous Bcl-xL abolished sensitization to apoptotic killing with CLPTM1L knockdown. These results demonstrate that CLPTM1L, an overexpressed protein in lung tumor cells, protects from genotoxic stress induced apoptosis through regulation of Bcl-xL. Thus, this study implicates anti-apoptotic CLPTM1L function as a potential mechanism of susceptibility to lung tumorigenesis and resistance to chemotherapy

New trends in the economic systems management in the context of modern global challenges

New trends in the economic systems management in the context of modern global challenges: collective monograph / scientific edited by M. Bezpartochnyi, in 2 Vol. // VUZF University of Finance, Business and Entrepreneurship. – Sofia: VUZF Publishing House “St. Grigorii Bogoslov”, 2020. – Vol. 1. – 309 p

COMAP Early Science: III. CO Data Processing

We describe the first season COMAP analysis pipeline that converts raw detector readouts to calibrated sky maps. This pipeline implements four main steps: gain calibration, filtering, data selection, and map-making. Absolute gain calibration relies on a combination of instrumental and astrophysical sources, while relative gain calibration exploits real-time total-power variations. High efficiency filtering is achieved through spectroscopic common-mode rejection within and across receivers, resulting in nearly uncorrelated white noise within single-frequency channels. Consequently, near-optimal but biased maps are produced by binning the filtered time stream into pixelized maps; the corresponding signal bias transfer function is estimated through simulations. Data selection is performed automatically through a series of goodness-of-fit statistics, including $\chi^2$ and multi-scale correlation tests. Applying this pipeline to the first-season COMAP data, we produce a dataset with very low levels of correlated noise. We find that one of our two scanning strategies (the Lissajous type) is sensitive to residual instrumental systematics. As a result, we no longer use this type of scan and exclude data taken this way from our Season 1 power spectrum estimates. We perform a careful analysis of our data processing and observing efficiencies and take account of planned improvements to estimate our future performance. Power spectrum results derived from the first-season COMAP maps are presented and discussed in companion papers.Comment: Paper 3 of 7 in series. 26 pages, 23 figures, submitted to Ap

COMAP Early Science: IV. Power Spectrum Methodology and Results

We present the power spectrum methodology used for the first-season COMAP analysis, and assess the quality of the current data set. The main results are derived through the Feed-feed Pseudo-Cross-Spectrum (FPXS) method, which is a robust estimator with respect to both noise modeling errors and experimental systematics. We use effective transfer functions to take into account the effects of instrumental beam smoothing and various filter operations applied during the low-level data processing. The power spectra estimated in this way have allowed us to identify a systematic error associated with one of our two scanning strategies, believed to be due to residual ground or atmospheric contamination. We omit these data from our analysis and no longer use this scanning technique for observations. We present the power spectra from our first season of observing and demonstrate that the uncertainties are integrating as expected for uncorrelated noise, with any residual systematics suppressed to a level below the noise. Using the FPXS method, and combining data on scales $k=0.051-0.62 \,\mathrm{Mpc}^{-1}$ we estimate $P_\mathrm{CO}(k) = -2.7 \pm 1.7 \times 10^4\mu\textrm{K}^2\mathrm{Mpc}^3$, the first direct 3D constraint on the clustering component of the CO(1-0) power spectrum in the literature.Comment: Paper 4 of 7 in series. 18 pages, 11 figures, as accepted in Ap

The Vanishing of the Primary Emission Region in PKS 1510-089

In 2021 July, PKS 1510-089 exhibited a significant flux drop in the high-energy γ-ray (by a factor 10) and optical (by a factor 5) bands and remained in this low state throughout 2022. Similarly, the optical polarization in the source vanished, resulting in the optical spectrum being fully explained through the steady flux of the accretion disk and the broad-line region. Unlike the aforementioned bands, the very-high-energy γ-ray and X-ray fluxes did not exhibit a significant flux drop from year to year. This suggests that the steady-state very-high-energy γ-ray and X-ray fluxes originate from a different emission region than the vanished parts of the high-energy γ-ray and optical jet fluxes. The latter component has disappeared through either a swing of the jet away from the line of sight or a significant drop in the photon production efficiency of the jet close to the black hole. Either change could become visible in high-resolution radio images

DNA methylation patterns of Brachypodium distachyon chromosomes and their alteration by 5-azacytidine treatment

Sequential immunolocalisation of 5-methylcytosine (5-MeC) and fluorescence in situ hybridisation with chromosome-specific BAC clones were performed on Brachypodium distachyon mitotic metaphase chromosomes to determine specific DNA methylation patterns of each chromosome in the complement. In the majority of cells examined, chromosomes Bd4 and Bd5, which bear the loci of 5S and 35S ribosomal DNA, respectively, had characteristic 5-MeC patterns. In contrast, the distribution of 5-MeC along the metacentric chromosome pairs Bd1, Bd2 and Bd3 was more variable. There were numerous differences in distribution of methylated sites between homologous chromosomes as well as between chromosome arms. Some chromosome sites, such as pericentromeric regions, were highly methylated in all chromosomes. Additionally, the influence of a hypomethylating agent, 5-azacytidine, on B. distachyon chromosome methylation patterns was confirmed. It was found that some chromosome pairs underwent demethylation more easily than others, but there was no apparent regularity in demethylation of particular chromosome segments