Non-resonant new physics search at the LHC for the b → cτν anomalies

Motivated by the →$\overline{}$ anomalies, we study non-resonant searches for new physics at the large hadron collider (LHC) by considering final states with an energetic and hadronically decaying τ lepton, a b-jet and large missing transverse momentum (→ℎ$\overline{}$+$^{miss}$$_{T}$). Such searches can be useful to probe new physics contributions to →$\overline{}$. They are analyzed not only within the dimension-six effective field theory (EFT) but also in explicit leptoquark (LQ) models with the LQ non-decoupled. The former is realized by taking a limit of large LQ mass in the latter. It is clarified that the LHC sensitivity is sensitive to the LQ mass for (1) TeV even in the search of →ℎ$\overline{}$+$^{miss}$$_{T}$. Although the LQ models provide a weaker sensitivity than the EFT limit, it is found that the non-resonant search of →ℎ$\overline{}$+$^{miss}$$_{T}$ can improve the sensitivity by ≈ 40% versus a conventional mono-τ search (→ℎ$\overline{}$+$^{miss}$$_{T}$) in the whole LQ mass region. Consequently, it is expected that most of the parameter regions suggested by the →$\overline{}$⎯ anomalies can be probed at the HL-LHC. Also, it is shown that R$_{2}$ LQ scenario is accessible entirely once the LHC Run 2 data are analyzed. In addition, we discuss a charge selection of τh to further suppress the standard-model background, and investigate the angular correlations among b, τ and the missing transverse momentum to discriminate the LQ scenarios

Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer onco- and suppressor gene changes

BACKGROUND: A subset of lung adenocarcinomas harboring an EML4-ALK fusion gene resulting in dominant oncogenic activity has emerged as a target for specific therapy. EML4-ALK fusion confers a characteristic histology and is detected more frequently in never or light smokers and younger patients. METHODS: To gain insights into etiology and carcinogenic mechanisms we conducted analyses to compare allelotypes of 35 ALK fusion-positive and 95 -negative tumours using single nucleotide polymorphism (SNP) arrays and especially designed software which enabled precise global genomic profiling. RESULTS: Overall aberration numbers (gains + losses) of chromosomal alterations were 8.42 and 9.56 in tumours with and without ALK fusion, respectively, the difference not being statistically significant, although patterns of gain and loss were distinct. Interestingly, among selected genomic regions, oncogene-related examples such as 1p34.3(MYCL1), 7q11.2(EGFR), 7p21.1, 8q24.21(MYC), 16p13.3, 17q12(ERBB2) and 17q25.1 showed significantly less gain. Also, changes in tumour suppressor gene-related regions, such as 9p21.3 (CDKN2A) 9p23-24.1 (PTPRD), 13q14.2 (RB1), were significantly fewer in tumours with ALK fusion. CONCLUSION: Global genomic comparison with SNP arrays showed tumours with ALK fusion to have fewer alterations in oncogenes and suppressor genes despite a similar overall aberration frequency, suggesting very strong oncogenic potency of ALK activation by gene fusion

Clinically Relevant Characterization of Lung Adenocarcinoma Subtypes Based on Cellular Pathways: An International Validation Study

Lung adenocarcinoma (AD) represents a predominant type of lung cancer demonstrating significant morphologic and molecular heterogeneity. We sought to understand this heterogeneity by utilizing gene expression analyses of 432 AD samples and examining associations between 27 known cancer-related pathways and the AD subtype, clinical characteristics and patient survival. Unsupervised clustering of AD and gene expression enrichment analysis reveals that cell proliferation is the most important pathway separating tumors into subgroups. Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component. Additionally, we find that tumors with any solid component have decreased survival as compared to tumors without a solid component. These results lead to the potential to use a relatively simple pathological examination of a tumor in order to determine its aggressiveness and the patient's prognosis. Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment. We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87) and Europe (N = 89) using the identical analytic procedures

北海道の女性労働者における抑うつの因子構造に関する研究

北海道の女性労働者586名に質問紙票(CES-D:the Center for Epidemiologic Study Depression Scale)を用いた抑うつ調査を実施した。一般職域の従業員542名と栄養士144名の2群に分けてCES-D(20質問項目)の因子構造を比較・検討した結果、以下の諸点が明らかとなった。1)一般職域従業員の探索的(因子数を指定しない)因子分析では、直交回転法、斜交回転法のいずれにおいても、第1因子:「不安6項目・孤立4項目」、第2因子:「抑うつ6項目」、第3因子:「生活に対する満足4項目」の3因子に縮約された。2)栄養士の探索的因子分析では、直交回転法では因子構造が同定できず、斜交回転法では6因子構造が示唆されたものの相関係数が1.0を越えるなど構造に不安定さがみとめられた。3)栄養士の確認的(因子数を3に指定した斜交回転法)因子分析では、第1因子:「不安6項目・抑うつ6項目」、第2因子:「孤立4項目」、第3因子:「生活に対する満足4項目」に集約された。4)一般職域従業員と栄養士の因子構造では、第3因子の「生活に対する満足4項目」は同じ質問項目で構成され、第1因子の「不安6項目」についても共通していた。また、一般職域従業員の第1因子の「孤立4項目」は栄養士の第2因子の「孤立4項目」と等しく、栄養士の第1因子の「抑うつ6項目」は一般職域従業員の第2因子の「抑うつ6項目」と対応していた。5)一般職域従業員、栄養士ともに第1因子の「不安6項目」を中核として共有し、それに「孤立4項目」が付随すると一般職域従業員の因子構造となり、「抑うつ6項目」が付随すると栄養士の因子構造となることが示唆された。以上のことから、北海道内女性労働者のCES-Dは、潜在的に「不安6項目」、「孤立4項目」、「抑うつ6項目」、「生活に対する満足4項目」の4因子で構成されていることが推察された

Research priorities for freshwater mussel conservation assessment

Freshwater mussels are declining globally, and effective conservation requires prioritizing research and actions to identify and mitigate threats impacting mussel species. Conservation priorities vary widely, ranging from preventing imminent extinction to maintaining abundant populations. Here, we develop a portfolio of priority research topics for freshwater mussel conservation assessment. To address these topics, we group research priorities into two categories: intrinsic or extrinsic factors. Intrinsic factors are indicators of organismal or population status, while extrinsic factors encompass environmental variables and threats. An understanding of intrinsic factors is useful in monitoring, and of extrinsic factors are important to understand ongoing and potential impacts on conservation status. This dual approach can guide conservation status assessments prior to the establishment of priority species and implementation of conservation management actions.NF-R was supported by a post-doctoral fellowship (Xunta de Galicia Plan I2C 2017-2020, 09.40.561B.444.0) from the government of the autonomous community of Galicia. BY was supported by the Ministry of Science and Higher Education (no. 0409-2016-0022). DLS was supported by the G. E. Hutchinson Chair at the Cary Institute of Ecosystem Studies. AO was supported by the Russian Foundation for Basic Research (no. 17-44-290016). SV was funded by European Investment Funds by FEDER/COMPETE/POCI- Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT-Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013. NF-R is very grateful to the University of Oklahoma Biological Survey for providing space to work in the U.S. and especially to Vaughn Lab members. Authors are very grateful to Akimasa Hattori, Allan K. Smith, Andrew Roberts, Daniel Graf, David Stagliano, David T. Zanatta, Dirk Van Damme, Ekaterina Konopleva, Emilie Blevins, Ethan Nedeau, Frankie Thielen, Gregory Cope, Heinrich Vicentini, Hugh Jones, Htilya Sereflisan, Ilya Vikhrev, John Pfeiffer, Karen Mock, Mary Seddon, Katharina Stockl, Katarzyna Zajac, Kengo Ito, Marie Capoulade, Marko Kangas, Michael Lange, Mike Davis, Pirkko-Liisa Luhta, Sarina Jepsen, Somsak Panha, Stephen McMurray, G. Thomas Watters, Wendell R. Haag, and Yoko Inui for their valuable contribution in the initial selection and description of extrinsic and intrinsic factors. We also wish to thank Dr. Amanda Bates, Chase Smith, and two anonymous reviewers for comments on earlier drafts of this manuscript. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government

Differential Pathogenesis of Lung Adenocarcinoma Subtypes Involving Sequence Mutations, Copy Number, Chromosomal Instability, and Methylation

Lung adenocarcinoma (LAD) has extreme genetic variation among patients, which is currently not well understood, limiting progress in therapy development and research. LAD intrinsic molecular subtypes are a validated stratification of naturally-occurring gene expression patterns and encompass different functional pathways and patient outcomes. Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors.The LAD molecular subtypes (Bronchioid, Magnoid, and Squamoid) were tested for association with gene mutations and DNA copy number alterations using statistical methods and published cohorts (n = 504). A novel validation (n = 116) cohort was assayed and interrogated to confirm subtype-alteration associations. Gene mutation rates (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and genomewide DNA methylation were significantly different among tumors of the molecular subtypes. Secondary analyses compared subtypes by integrated alterations and patient outcomes. Tumors having integrated alterations in the same gene associated with the subtypes, e.g. mutation, deletion and underexpression of STK11 with Magnoid, and mutation, amplification, and overexpression of EGFR with Bronchioid. The subtypes also associated with tumors having concurrent mutant genes, such as KRAS-STK11 with Magnoid. Patient overall survival, cisplatin plus vinorelbine therapy response and predicted gefitinib sensitivity were significantly different among the subtypes.The lung adenocarcinoma intrinsic molecular subtypes co-occur with grossly distinct genomic alterations and with patient therapy response. These results advance the understanding of lung adenocarcinoma etiology and nominate patient subgroups for future evaluation of treatment response

Radiosensitization of tumor cells through endoplasmic reticulum stress induced by PEGylated nanogel containing gold nanoparticles

High atomic number molecules, such as gold and platinum, are known to enhance the biological effect of X-irradiation. This study was aimed to determine the radiosensitizing potential of PEGylated nanogel containing gold nanoparticles (GNG) and the cellular mechanism involved. GNG pretreatment increased the levels of reproductive cell death and apoptosis induced by X-irradiation. GNG accumulated in cytoplasm and increased the expression of endoplasmic reticulum (ER) stress-related protein. GNG suppressed the repair capacity of DNA after X-irradiation by down-regulating DNA repair-related proteins. Our results suggest that GNG radiosensitized cells by enhancing apoptosis and impairing DNA repair capacity via ER stress induction