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Whole-Genome Sequencing Reveals Breast Cancers with Mismatch Repair Deficiency
Davies, Helen,Morganella, Sandro,Purdie, Colin A.,Jang, Se Jin,Borgen, Elin,Russnes, Hege,Glodzik, Dominik,Zou, Xueqing,Viari, Alain,Richardson, Andrea L.,Børresen-Dale, Anne-Lise,Thompson, Alastair,E American Association for Cancer Research 2017 Cancer Research Vol.77 No.18
<P>The effectiveness of PD-1 blockade against DNA mismatch repair-deficient cancers makes it paramount to reliably identify the relatively rare cases beyond those with Lynch syndrome–associated colon cancers.</P><P>Mismatch repair (MMR)–deficient cancers have been discovered to be highly responsive to immune therapies such as PD-1 checkpoint blockade, making their definition in patients, where they may be relatively rare, paramount for treatment decisions. In this study, we utilized patterns of mutagenesis known as mutational signatures, which are imprints of the mutagenic processes associated with MMR deficiency, to identify MMR-deficient breast tumors from a whole-genome sequencing dataset comprising a cohort of 640 patients. We identified 11 of 640 tumors as MMR deficient, but only 2 of 11 exhibited germline mutations in MMR genes or Lynch Syndrome. Two additional tumors had a substantially reduced proportion of mutations attributed to MMR deficiency, where the predominant mutational signatures were related to APOBEC enzymatic activity. Overall, 6 of 11 of the MMR-deficient cases in this cohort were confirmed genetically or epigenetically as having abrogation of MMR genes. However, IHC analysis of MMR-related proteins revealed all but one of 10 samples available for testing as MMR deficient. Thus, the mutational signatures more faithfully reported MMR deficiency than sequencing of MMR genes, because they represent a direct pathophysiologic readout of repair pathway abnormalities. As whole-genome sequencing continues to become more affordable, it could be used to expose individually abnormal tumors in tissue types where MMR deficiency has been rarely detected, but also rarely sought. <I>Cancer Res; 77(18); 4755–62. ©2017 AACR</I>.</P>
Deliberately Unequal Gene Sampling, A Design of Molecular Studies Tested in Lepidoptera
Soowon Cho,Andreas Zwick,Jerome Regier,Charles Mitter,Michael Cummings,Jianxiu Yao,Zaile Du,Hong Zhao,Akito Kawahara,Susan Weller,Donald Davis,Joaquin Baixeras,John Brown,Cynthia Parr 한국응용곤충학회 2010 한국응용곤충학회 학술대회논문집 Vol.2010 No.05
Seeking to improve the weak resolution of deeper divergences in an initial study based on five nuclear genes (6.6kb total) in 123 exemplars, we nearly tripled the total sequence (to 26 genes, 18.4 kb total) in one third (41) of the taxa. The expanded, deliberately incomplete data matrix consistently increased bootstrap support for previously-identified groupings, while introducing no contradictory groupings of the kind that missing data have been predicted to produce. To test the relative effectiveness of “more genes” versus “more taxa” sind that we compared two largely complete matrices, the initial 5 gene × 123 taxon and the 26 gene × 41 taxon data sets, that contain roughly equal amounts of sequence. The “more genes” data set yielded consistently, sometimes dramatically higher bootstrap support that is generally not attributable to taxon number alone. We also found that a gene-rich taxon subset provides reassuring evidence of strong underlying signal that is not obvious in subsequent larger analyses, helping to encourage and guide the search for deep relationships amid the noise of expanded taxon sampling.
CONSUMPTION AND CULTURAL CAPITAL FOR SELF-PRESENTATION IN THE WORKPLACE
Connie Mak,Andrea Davies,Christiana Tsaousi 글로벌지식마케팅경영학회 2018 Global Marketing Conference Vol.2018 No.07
Consumption practices for self-construction and impression management have been widely studied. However, most research adopts snap-shot, cross-sectional views and focuses mainly on leisure and home settings, giving little attention to the mundane context of workplace. Building on the works of Goffman and Bourdieu, this study takes an over-time view to understand how professionals acquire cultural capital related resources and practices for impression management over their career life. Based on retrospective narrative inquiries (Davies & Fitchett, 2015) and a novel on-route walking-with interview (Richardson, 2015) to capture bodily and other affective resonances, this paper reports on our analysis so far with ten senior executives in Hong Kong, as part of an on-going study. Mutability and agency are key to understand the biographical evolution of cultural capital for impression management. Exclusive resources and practices, such as grooming styles and dining choices, are found as ‘class-markers’ in the workplace (Bourdieu 1984), which also keep changing over people’s career life. With thin cultural capital, junior executives can only rely on extrinsic ‘sign vehicles’ (Goffman 1959) such as appearance and surface diligence to extend their work identity (Belk, 1988; Tian and Belk 2005). Over time, when cultural capital is accumulated through accrued learning and socialization (Bourdieu, 1977; Skeggs, 2004), senior executives climb up the career ladder by building up embodied habitus to differentiate themselves through more intrinsic competence and practices, such as discourse and decisive judgement. The study also reflects the field-specific nature of cultural capital (Bourdieu & Wacquant, 1992) and finds that resources valued in one field could become liabilities or capital shocks in another. Such ‘embodied hysteresis’ is found attributable to the rupture between the changing field conditions (McDonough & Polzer, 2012) and we example how executives struggle with self-field incongruity when switching workplaces. Lastly, the study reveals that the workplace is itself a potent ground for learning embodied competences for workplace consumption and practices. Secondary socialization through observation of the referenced others and continuous self-reflection is found to be a crucial source of acquiring cultural capital for self-presentation.
Macaulay, E,Nichol, R C,Bacon, D,Brout, D,Davis, T M,Zhang, B,Bassett, B A,Scolnic, D,Mö,ller, A,D’Andrea, C B,Hinton, S R,Kessler, R,Kim, A G,Lasker, J,Lidman, C,Sako, M,Smith, M,Sullivan, M,Abbo Oxford University Press 2019 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.486 No.2
<B>ABSTRACT</B><P>We present an improved measurement of the Hubble constant (H0) using the ‘inverse distance ladder’ method, which adds the information from 207 Type Ia supernovae (SNe Ia) from the Dark Energy Survey (DES) at redshift 0.018 < z < 0.85 to existing distance measurements of 122 low-redshift (z < 0.07) SNe Ia (Low-z) and measurements of Baryon Acoustic Oscillations (BAOs). Whereas traditional measurements of H0 with SNe Ia use a distance ladder of parallax and Cepheid variable stars, the inverse distance ladder relies on absolute distance measurements from the BAOs to calibrate the intrinsic magnitude of the SNe Ia. We find H0 = 67.8 ± 1.3 km s−1 Mpc−1 (statistical and systematic uncertainties, 68 per cent confidence). Our measurement makes minimal assumptions about the underlying cosmological model, and our analysis was blinded to reduce confirmation bias. We examine possible systematic uncertainties and all are below the statistical uncertainties. Our H0 value is consistent with estimates derived from the Cosmic Microwave Background assuming a ΛCDM universe.</P>
( Anthony Horton ),( Brian Sullivan ),( Katie Charles ),( Thasha Mcintosh ),( Andrea Davis ),( Ziad Gellad ),( Rahul Shimpi ),( C Prakash Gyawali ),( Amit Patel ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2020 Journal of Neurogastroenterology and Motility (JNM Vol.26 No.4
Background/Aims Esophageal baseline impedance (BI) can be extracted from pH-impedance tracings as mean nocturnal baseline impedance (MNBI), and from high-resolution impedance manometry (HRIM), but it is unknown if values are similar between acquisition methods across HRIM manufacturers. We aim to assess correlations between MNBI and BI from HRIM (BI-HRIM) from 2 HRIM manufacturers in the setting of physiologic acid exposure time (AET). Methods HRIM and pH-impedance monitoring demonstrating physiologic AET (< 4%) off proton pump inhibitors were required. BI-HRIM was extracted as the average from 5 cm and 10 cm above the lower esophageal sphincter. Distal BI-HRIM (DBI-HRIM) was also extracted from the most distal channel (Medtronic studies). MNBI was extracted from 6 channels. Concordance between BI-HRIM across manufacturers with MNBI was analyzed. Results Thirty-six patients met the inclusion criteria (59.6 ± 1.7 years; 22% female; body mass index 30.5 ± 0.7; AET 1.6 ± 0.2%). Although MNBI was similar at all channels (P ≥ 0.18), Diversatek BI-HRIM was lower than Medtronic BI-HRIM (P = 0.003). Overall, BI-HRIM correlated with MNBI at corresponding recording sites, 7 cm and 9 cm (P < 0.05), but not at other sites (P ≥ 0.19). Pearson’s correlations > 0.5 were seen at MNBI at 7 cm for both systems, and at 9 cm for Medtronic. DBI-HRIM correlated with MNBI at 3 cm and 5 cm (P < 0.03), but not at other locations (P > 0.1). Conclusions While numeric differences exist between manufacturers, BI-HRIM correlates with MNBI from corresponding channels in patients with physiologic AET. Comparison with AET elevation is needed to determine correlations between pathologic MNBI with BI-HRIM across manufacturers. The optimal HRIM channels from which BI values should be extracted also warrants further study. (J Neurogastroenterol Motil 2020;26:455-462)