The Lick Observatory Supernova Search

We report here the current status of the Lick Observatory Supernova Search (LOSS) with the Katman Automatic Imaging Telescope (KAIT). The progress on both the hardware and the software of the system is described, and we present a list of recent discoveries. LOSS is the world' most successful search engine for nearby supernovae.Comment: 4 pages, 1 figure, Submitted to the proceedings of the 10th Annual October Astrophysics Conference in Maryland on Cosmic Explosion

Large-scale functional inference for skin-expressing lncRNAs using expression and sequence information

Long noncoding RNAs (lncRNAs) regulate the expression of protein-coding genes and have been shown to play important roles in inflammatory skin diseases. However, we still have limited understanding of the functional impact of lncRNAs in skin, partly due to their tissue specificity and lower expression levels compared with protein-coding genes. We compiled a comprehensive list of 18,517 lncRNAs from different sources and studied their expression profiles in 834 RNA-Seq samples from multiple inflammatory skin conditions and cytokine-stimulated keratinocytes. Applying a balanced random forest to predict involvement in biological functions, we achieved a median AUROC of 0.79 in 10-fold cross-validation, identifying significant DNA binding domains (DBDs) for 39 lncRNAs. G18244, a skin-expressing lncRNA predicted for IL-4/IL-13 signaling in keratinocytes, was highly correlated in expression with F13A1, a protein-coding gene involved in macrophage regulation, and we further identified a significant DBD in F13A1 for G18244. Reflecting clinical implications, AC090198.1 (predicted for IL-17 pathway) and AC005332.6 (predicted for IFN-γ pathway) had significant negative correlation with the SCORAD metric for atopic dermatitis. We also utilized single-cell RNA and spatial sequencing data to validate cell type specificity. Our research demonstrates lncRNAs have important immunological roles and can help prioritize their impact on inflammatory skin diseases.</p

Service users’ first accounts of experiencing endings from a psychological service or therapy: a systematic review and meta-ethnographic synthesis

Purpose: To review and synthesis the qualitative literature on service users’ experiences of endings from a psychological service or therapy. Methods: A systematic search of the peer-reviewed literature was conducted. Studies were identified using specific inclusion criteria and included in the synthesis. A modified CASP tool was used to critically appraise the quality of the papers. A meta-ethnographic approach was used to synthesize the findings from the included studies. Results: Twelve papers were identified which met the inclusion criteria. The interpretation of findings suggested three key themes: anticipation of ending, service user control and sense of responsibility. Studies were geographically spread and of high quality. Conclusions: The review highlights the importance of service users’ perspectives in understanding the experiences of endings. The findings complement existing literature and provide new interpretations. Considerations for practice in the UK were limited however the review does provide directions for future research

Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity

The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a five-year survival rate of 15%, identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a mutational signature defined by a high prevalence of A to C transversions at AA dinucleotides. Statistical analysis of exome data identified significantly mutated 26 genes. Of these genes, four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include chromatin modifying factors and candidate contributors: SPG20, TLR4, ELMO1, and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 reveal increased cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis

Mapping Copy Number Variation by Population Scale Genome Sequencing

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.Organismic and Evolutionary Biolog

Large-scale functional inference for skin-expressing lncRNAs using expression and sequence information

Long noncoding RNAs (lncRNAs) regulate the expression of protein-coding genes and have been shown to play important roles in inflammatory skin diseases. However, we still have limited understanding of the functional impact of lncRNAs in skin, partly due to their tissue specificity and lower expression levels compared with protein-coding genes. We compiled a comprehensive list of 18,517 lncRNAs from different sources and studied their expression profiles in 834 RNA-Seq samples from multiple inflammatory skin conditions and cytokine-stimulated keratinocytes. Applying a balanced random forest to predict involvement in biological functions, we achieved a median AUROC of 0.79 in 10-fold cross-validation, identifying significant DNA binding domains (DBDs) for 39 lncRNAs. G18244, a skin-expressing lncRNA predicted for IL-4/IL-13 signaling in keratinocytes, was highly correlated in expression with F13A1, a protein-coding gene involved in macrophage regulation, and we further identified a significant DBD in F13A1 for G18244. Reflecting clinical implications, AC090198.1 (predicted for IL-17 pathway) and AC005332.6 (predicted for IFN-γ pathway) had significant negative correlation with the SCORAD metric for atopic dermatitis. We also utilized single-cell RNA and spatial sequencing data to validate cell type specificity. Our research demonstrates lncRNAs have important immunological roles and can help prioritize their impact on inflammatory skin diseases.</p

Estimation of Stellar Metal Abundance. II : A Recalibration of the Ca II K Technique, and the Autocorrelation Function Method

Original article can be found at: http://www.iop.org/EJ/journal/aj Copyright American Astronomical Society DOI: 10.1086/300727 [Full text of this article is not available in the UHRA]We have recalibrated a method for the estimation of stellar metal abundance, parameterized as [Fe/H], based on medium-resolution (1–2 Å) optical spectra (the majority of which cover the wavelength range 3700–4500 Å). The equivalent width of the Ca II K line (3933 Å) as a function of [Fe/H] and broadband B-V color, as predicted from spectrum synthesis and model atmosphere calculations, is compared with observations of 551 stars with high-resolution abundances available from the literature (a sevenfold increase in the number of calibration stars that were previously available). A second method, based on the Fourier autocorrelation function technique first described by Ratnatunga & Freeman, is used to provide an independent estimate of [Fe/H], as calibrated by comparison with 405 standard-star abundances. Metallicities based on a combination of the two techniques for dwarfs and giants in the color range 0.30 ≤ (B-V)0 ≤ 1.2 exhibit an external 1 σ scatter of approximately 0.10–0.20 dex over the abundance range -4.0 ≤ [Fe/H] ≤ 0.5. Particular attention has been given to the determination of abundance estimates at the metal-rich end of the calibration, where our previous attempt suffered from a considerable zero-point offset. Radial velocities, accurate to approximately 10 km s-1, are reported for all 551 calibration stars.Peer reviewe

Genetic and Clonal Dissection of Murine Small Cell Lung Carcinoma Progression by Genome Sequencing

SummarySmall cell lung carcinoma (SCLC) is a highly lethal, smoking-associated cancer with few known targetable genetic alterations. Using genome sequencing, we characterized the somatic evolution of a genetically engineered mouse model (GEMM) of SCLC initiated by loss of Trp53 and Rb1. We identified alterations in DNA copy number and complex genomic rearrangements and demonstrated a low somatic point mutation frequency in the absence of tobacco mutagens. Alterations targeting the tumor suppressor Pten occurred in the majority of murine SCLC studied, and engineered Pten deletion accelerated murine SCLC and abrogated loss of Chr19 in Trp53; Rb1; Pten compound mutant tumors. Finally, we found evidence for polyclonal and sequential metastatic spread of murine SCLC by comparative sequencing of families of related primary tumors and metastases. We propose a temporal model of SCLC tumorigenesis with implications for human SCLC therapeutics and the nature of cancer-genome evolution in GEMMs