Bcl-2/Bax protein ratio predicts 5-fluorouracil sensitivity independently of p53 status

p53 tumour-suppressor gene is involved in cell growth control, arrest and apoptosis. Nevertheless cell cycle arrest and apoptosis induction can be observed in p53-defective cells after exposure to DNA-damaging agents such as 5-fluorouracil (5-FU) suggesting the importance of alternative pathways via p53-independent mechanisms. In order to establish relationship between p53 status, cell cycle arrest, Bcl-2/Bax regulation and 5-FU sensitivity, we examined p53 mRNA and protein expression and p53 protein functionality in wild-type (wt) and mutant (mt) p53 cell lines. p53 mRNA and p53 protein expression were determined before and after exposure to equitoxic 5-FU concentration in six human carcinoma cell lines differing in p53 status and displaying marked differences in 5-FU sensitivity, with IC 50 values ranging from 0.2–22.6 mM. 5-FU induced a rise in p53 mRNA expression in mt p53 cell lines and in human papilloma virus positive wt p53 cell line, whereas significant decrease in p53 mRNA expression was found in wt p53 cell line. Whatever p53 status, 5-FU altered p53 transcriptional and translational regulation leading to up-regulation of p53 protein. In relation with p53 functionality, but independently of p53 mutational status, after exposure to 5-FU equitoxic concentration, all cell lines were able to arrest in G1. No relationship was evidenced between G1 accumulation ability and 5-FU sensitivity. Moreover, after 5-FU exposure, Bax and Bcl-2 proteins regulation was under p53 protein control and a statistically significant relationship (r= 0.880,P= 0.0097) was observed between Bcl-2/Bax ratio and 5-FU sensitivity. In conclusion, whatever p53 status, Bcl-2 or Bax induction and Bcl-2/Bax protein ratio were correlated to 5-FU sensitivity. © 2000 Cancer Research Campaig

COSMOGRAIL: XVII. Time delays for the quadruply imaged quasar PG 1115+080

Indexación: Scopus.Acknowledgements. The authors would like to thank R. Gredel for his help in setting up the program at the ESO MPIA 2.2 m telescope, and the anonymous referee for his or her comments on this work. This work is supported by the Swiss National Fundation. This research made use of Astropy, a community-developed core Python package for Astronomy (Astropy Collaboration et al. 2013, 2018) and the 2D graphics environment Matplotlib (Hunter 2007). K.R. acknowledge support from PhD fellowship FIB-UV 2015/2016 and Becas de Doctorado Nacional CONICYT 2017 and thanks the LSSTC Data Science Fellowship Program, her time as a Fellow has benefited this work. M.T. acknowledges support by the DFG grant Hi 1495/2-1. G. C.-F. C. acknowledges support from the Ministry of Education in Taiwan via Government Scholarship to Study Abroad (GSSA). D. C.-Y. Chao and S. H. Suyu gratefully acknowledge the support from the Max Planck Society through the Max Planck Research Group for S. H. Suyu. T. A. acknowledges support by the Ministry for the Economy, Development, and Tourism’s Programa Inicativa Científica Milenio through grant IC 12009, awarded to The Millennium Institute of Astrophysics (MAS).We present time-delay estimates for the quadruply imaged quasar PG 1115+080. Our results are based on almost daily observations for seven months at the ESO MPIA 2.2 m telescope at La Silla Observatory, reaching a signal-to-noise ratio of about 1000 per quasar image. In addition, we re-analyze existing light curves from the literature that we complete with an additional three seasons of monitoring with the Mercator telescope at La Palma Observatory. When exploring the possible source of bias we considered the so-called microlensing time delay, a potential source of systematic error so far never directly accounted for in previous time-delay publications. In 15 yr of data on PG 1115+080, we find no strong evidence of microlensing time delay. Therefore not accounting for this effect, our time-delay estimates on the individual data sets are in good agreement with each other and with the literature. Combining the data sets, we obtain the most precise time-delay estimates to date on PG 1115+080, with Δt(AB) = 8.3+1.5 -1.6 days (18.7% precision), Δt(AC) = 9.9+1.1 -1.1 days (11.1%) and Δt(BC) = 18.8+1.6 -1.6 days (8.5%). Turning these time delays into cosmological constraints is done in a companion paper that makes use of ground-based Adaptive Optics (AO) with the Keck telescope. © ESO 2018.https://www.aanda.org/articles/aa/abs/2018/08/aa33287-18/aa33287-18.htm

Characterization of Color Production in Xalla´s Palace Complex, Teotihuacan

A multi-analytical approach was used to characterize color remains from Xalla, a Teotihuacan palace complex (project Teotihuacan, Elite and Government. Excavations in Xalla led by Linda R. Manzanilla). Color samples were obtained from polished lithic instruments and pigment ores. Those samples were analyzed combining microscopic and spectroscopic techniques. Our results coincide with previous studies in Teotihuacan, with the chromatic palette displaying a predominance of iron oxides such as hematite, yellow ochre and natural earths, as well as malachite, celadonite and glauconite. We have enlarged the corpus of raw materials with the characterization of jarosite and bone white and mica as aggregate. The identification of raw materials crossed with functional analysis of polished lithic artefacts suggests a production and application process for the pigmenting materials that were divided in four phases, from the crushing of the raw material to the application and finishing of the painted surfaces

The Big Three Perfectionism Scale: A new measure of perfectionism

This article introduces a new measure of dispositional perfectionism: the Big Three Perfectionism Scale (BTPS). The BTPS assesses three higher-order global factors (rigid perfectionism, self-critical perfectionism, narcissistic perfectionism) via 10 lower-order perfectionism facets (self-oriented perfectionism, self-worth contingencies, concern over mistakes, doubts about actions, self-criticism, socially prescribed perfectionism, other-oriented perfectionism, hypercriticism, grandiosity, entitlement). The present investigation examined the structure of the BTPS using exploratory factor analysis in Study 1 (288 undergraduates), and confirmatory factor analyses in Study 2 (352 community adults) and Study 3 (290 undergraduates). Additionally, in Study 3 the relationships among the BTPS, other measures of perfectionism, and the five-factor model of personality were investigated. Overall, findings provide first evidence for the reliability and validity of the BTPS as a multidimensional measure of perfectionism

COSMOGRAIL XVIII: time delays of the quadruply lensed quasar WFI2033-4723

We present new measurements of the time delays of WFI2033-4723. The data sets used in this work include 14 years of data taken at the 1.2m Leonhard Euler Swiss telescope, 13 years of data from the SMARTS 1.3m telescope at Las Campanas Observatory and a single year of high-cadence and high-precision monitoring at the MPIA 2.2m telescope. The time delays measured from these different data sets, all taken in the R-band, are in good agreement with each other and with previous measurements from the literature. Combining all the time-delay estimates from our data sets results in Dt_AB = 36.2-0.8+0.7 days (2.1% precision), Dt_AC = -23.3-1.4+1.2 days (5.6%) and Dt_BC = -59.4-1.3+1.3 days (2.2%). In addition, the close image pair A1-A2 of the lensed quasars can be resolved in the MPIA 2.2m data. We measure a time delay consistent with zero in this pair of images. We also explore the prior distributions of microlensing time-delay potentially affecting the cosmological time-delay measurements of WFI2033-4723. There is however no strong indication in our measurements that microlensing time delay is neither present nor absent. This work is part of a H0LiCOW series focusing on measuring the Hubble constant from WFI2033-4723.Comment: Submitted to Astronomy and Astrophysic

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Current empirical assessment methods for adolescents and children who sexually abuse others

The assessment of adolescents and children who commit sexually abusive behavior is a complex and challenging task. Incorporating empirically based assessment methods into psychosexual evaluations promises appropriate coverage of relevant domains, sound interpretation of the meaning of data, reduced clinician biases and error, and greater certainty in decision-making. In this paper we review empirically-based assessment methods currently available for use in psychosexual assessment of adolescents and children who sexually abuse others. Our review describes the robustness of these measures and provides guidance for their appropriate use in assessment. The review highlighted that several empirically-based measures are suitable for clinical use with adolescents, but very little is available to guide assessment of children\u27s abusive behavior per se. </i

Interpersonal and affective dimensions of psychopathic traits in adolescents : development and validation of a self-report instrument

We report the development and psychometric evaluations of a self-report instrument designed to screen for psychopathic traits among mainstream community adolescents. Tests of item functioning were initially conducted with 26 adolescents. In a second study the new instrument was administered to 150 high school adolescents, 73 of who had school records of suspension for antisocial behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity α = .73, Self-Centredness α = .70, Callous-Unemotional α = .69, and Manipulativeness α = .83). In a third study involving 328 high school adolescents, 130 with records of suspension for antisocial behaviour, competing measurement models were evaluated using confirmatory factor analysis. The superiority of a first-order model represented by four correlated factors that was invariant across gender and age was confirmed. The findings provide researchers and clinicians with a psychometrically strong, self-report instrument and a greater understanding of psychopathic traits in mainstream adolescents