Suchergebnisse

While recent studies have identified higher than anticipated heterogeneity of mutation rate across genomic regions, mutations in exons and introns are assumed to be generated at the same rate. Here we find fewer somatic mutations in exons than expected from their sequence content and demonstrate that this is not due to purifying selection. Instead, we show that it is caused by higher mismatch-repair activity in exonic than in intronic regions. Our findings have important implications for understanding of mutational and DNA repair processes and knowledge of the evolution of eukaryotic genes, and they have practical ramifications for the study of evolution of both tumors and species. ; We acknowledge funding from Spanish Ministry of Economy and Competitiveness (SAF2015-66084-R, MINECO/FEDER, UE), La Fundació la Marató de TV3, EU H2020 Programme 2014-2020 under grant agreements no. 634143 (MedBioinformatics) and by the European Research Council (Consolidator Grant 682398). IRB Barcelona is a recipient of a Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO; Government of Spain) and is supported by CERCA (Generalitat de Catalunya). R. Sabarinathan is supported by an EMBO Long-Term Fellowship (ALTF 568-2014) co-funded by the European Commission (EMBOCOFUND2012, GA-2012-600394) support from Marie Curie Actions. A.Gonzalez-Perez is supported by a Ramón y Cajal contract

Purpose
This study aims to challenge the generic interpretation of Multilatinas as Latin American firms that have been able to internationalize because of highly competitive strategic capabilities. The authors test whether capabilities that international business researchers commonly associate with internationalization are necessary at different stages of the internationalization process to better understand the extent to which emerging market (EM) firms need to develop them.


Design/methodology/approach
International business research suggests a positive association between strategic capabilities and firm internalization. However, it remains unclear what specific capabilities are necessary and when they are necessary. These questions are particularly important in the context of the internationalization of firms from emerging economies, such as Latin America. The authors apply necessary condition analysis (NCA) on a sample of Latin American firms at different internationalization stages to test what strategic capabilities represent necessary conditions for becoming a Multilatina.


Findings
The findings suggest that only a few strategic capabilities are necessary for Latin American firms to become "Multilatinas". While entrepreneurial orientation and marketing and sales capabilities represent necessary conditions, EM firms may internationalize even though other capabilities are developed to a lesser extent. The authors reflect on how shifts in local markets and technology drive the emergence of different types of Multilatinas.


Research limitations/implications
Measuring strategic capabilities across multiple EM firms implies a risk that firm-specific aspects are not fully captured. While the authors focused on the comparative competitive strength of capabilities and took great care to minimize measurement error, the authors acknowledge possible bias. Also, while NCA does not require a minimum sample size, findings from our sample of firms from four countries may not generalize to the region or other EMs.


Originality/value
As a relatively new statistical technique, the use of NCA has spread rapidly. To the best of the authors' knowledge, the linkage between organizational capabilities and firm internationalization has not been tested from a necessary conditions perspective yet. The reflections on the "Multilatina" concept based on the notion of EM firms as configurations of strategic capabilities inform current debates on EM multinational enterprises.

Purpose
This paper aims to analyze how emerging market firms upgrade their capabilities by focusing on "uncommoditizing strategies" that enable them to achieve levels of international competitiveness beyond the comparative advantages of their home countries and serve markets with premium pricing, quality and reputation of products.


Design/methodology/approach
In this paper, the authors studied 18 Latin American companies across six countries. Latin America represents an ideal setting because many of these countries have traditionally developed using natural resource endowments, and their firms have tended to rely on these in their internationalization. To facilitate the analysis of each case and the comparisons across cases, the authors used the same analytical framework for the companies, identifying the sources of differentiation and cost efficiency strategies that enabled these firms to upgrade their capabilities and compete on the basis of premium pricing, quality and reputation.


Findings
The analysis identified a general framework that represents an abstraction of the actions taken by these companies over time. The proposed model consists of three main elements used to pursue uncommoditizing strategies: tropicalized innovation, global efficiency and coordinated control.


Originality/value
Recent research on emerging market firms has shown interest in how these firms upgrade their capabilities. This paper contributes to this stream of research by providing an overarching framework that not only bridged previous narrower studies but also explained how firms can develop uncommoditizing strategies to upgrade their capabilities. Further, this paper helps managers by providing a comprehensive yet succinct overview of the main strategies that they can use to help their firms to achieve international competitiveness.

PurposeThis paper aims to provide insights into the internationalization strategic responses to the COVID-19 pandemic by higher education institutions (HEIs) in Latin America.Design/methodology/approachThis study is based on information from eight leading Latin American private universities. The data were obtained from official sources such as institutional communications and university administrators.FindingsThe authors identify two main issues that HEIs should consider while responding to the pandemic. First, greater attention and resource allocation to the universities' main local stakeholders can affect traditional internationalization activities. Second, a focus on revitalizing foreign partnerships and strengthening "virtual internationalization" can help maintain and eventually increase international presence.Research limitations/implicationsWhile this study analyses how these Latin American HEIs responded during the initial stages of the COVID-19 outbreak, it is important to conduct follow-up studies to shed light on how HEIs are adapting to the COVID-19 crisis as it continues to unfold.Originality/valueThis study is based on unique information gathered from leading private, not-for-profit HEIs in Latin America, which, contrary to state-owned HEIs or other private institutions in developed economies, have exhibited different means and conditions to respond to the coronavirus outbreak. Finally, the authors contribute to the literature on the internationalization of HEIs by discussing the role of a significant disruptive event on the internationalization of higher education and, particularly, business schools.

This paper presents recent research experiences developed with the aim of manufacturing cranial prostheses in polymeric sheet using Incremental Sheet Forming (ISF) technologies. With this purpose, different approaches have been carried out in Single-Point Incremental Forming (SPIF) and Two-Point Incremental Forming (TPIF) in order to produce customized cranial implants using different polymeric materials. In this context, this research work provides a methodology to design and manufacture polymer customized cranial prostheses using the ISF technologies starting from a patient's computerized tomography (CT). The results demonstrate the potential of manufacturing polymeric cranial prostheses by ISF in terms of the high formability achievable and show the appropriate geometrical accuracy at affordable manufacturing costs provided by these processes ; The authors wish to thank the Spanish Government for its financial support through the research projects DPI2015-64047-R and DPI2016-77156-R and the University of Girona (Spain) for the support provided byMPCUdG2016/036

This article presents the decision-making based on, an analysis to select which is best option patent an invention. The selected countries were Mexico and United States. It is important to know the different processes that each country has to grant a patent, their costs, whether to patent in one country or more, the procedure for international protection. Something important to note is that many people do not have the information necessary to protect their inventions. The process and the time for which a patent assigned are too long or tedious for people. It is important to promote technological development of the country, but you have to identify what the needs are, involve society, private sector, and government.

PurposeThis study aims to build on embedded approaches to stakeholder management and examines how organizational decision-makers consider social responsibility toward proximal stakeholders in crises that encompass an entire system of stakeholder relationships.Design/methodology/approachWithin a criterion-based sample of eight Latin American private universities, this paper develops in-depth exploratory case studies to examine the prioritization of stakeholders in higher education institutions' decision-making during the outbreak of the COVID-19 crisis.FindingsContrary to the notion that during crises organizations prioritize stakeholders that provide resources that are critical to survival, this study finds that in contextual crises stakeholder management is informed by social responsibility. In addition, the findings suggest that crises may be tipping points for changes toward mission-driven approaches to governance.Practical implicationsAcknowledging the roles of social responsibility and proximity in stakeholder management during contextual crises allows for more informed governance of organizations that face disruptions in their system of stakeholder relations.Originality/valueThis study contributes unique insights into the decision-maker's prioritization of stakeholders during the COVID-19 crisis. The uncertainty associated with the emerging "new normal" allowed for an extreme test of socially embedded versus resource-oriented approaches to stakeholder management.

We use three semi-analytical models (SAMs) of galaxy formation and evolution run on the same 1 h(-1) Gpc MultiDark Planck2 cosmological simulation to investigate the properties of [O II] emission line galaxies at redshift z similar to 1. We compare model predictions with different observational data sets, including DEEP2-FIREFLY galaxies with absolute magnitudes. We estimate the [O II] luminosity (L[O II]) of our model galaxies using the public code GET EMLINES, which ideally assumes as input the instantaneous star formation rates (SFRs). This property is only available in one of the SAMs under consideration, while the others provide average SFRs, as most models do. We study the feasibility of inferring galaxies' L[O II] from average SFRs in post-processing. We find that the result is accurate for model galaxies with dust attenuated L[O II] less than or similar to 10(42.2) erg s(-1) ( 10(40.4) erg s(-1) remains overall unchanged on scales above 1 h(-1) Mpc, independently of the L[O II] computation. © 2020 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society ; GFandVGPacknowledge support from the University of Portsmouth through the Dennis Sciama Fellowship award. VGP acknowledges support from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement No 769130). DS is funded by the Spanish Ministry of Economy and Competitiveness (MINECO) under the 2014 Severo Ochoa Predoctoral Training Programme. DS also wants to thank the Mamua Cafe Bar-team for their kind (g)astronomical support. DS and FP acknowledge funding support from the MINECO grant AYA2014-60641-C2-1-P. AO acknowledges support from the Spanish Ministerio de Economia y Competitividad (MINECO) project No. AYA2015-66211-C2-P-2, and funding from the European Union Horizon 2020 research and innovation programme under grant agreement No. 734374. SAC acknowledges funding from Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET, PIP0387), Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT, PICT-2013-0317), and Universidad Nacional de La Plata (11-G124 and 11-G150), Argentina. CVMacknowledges CONICET, Argentina, for the supporting fellowship. AK is supported by the MINECO and the Fondo Europeo de Desarrollo Regional (FEDER, UE) in Spain through grant AYA2015-63810-P as well as by the MICIU/FEDER through grant number PGC2018-094975-C21. He further acknowledges support from the Spanish Red Consolider MultiDark FPA2017-90566-REDC and thanks Christopher Cross for sailing. ARHS acknowledges receipt of the Jim Buckee Fellowship at ICRAR-UWA. GF, VGP and DS wish to thank La Plata Astronomical Observatory for hosting the MultiDark Galaxies workshop in September 2016, during which this work was started. The authors thank the FIREFLY team and the anonymous referee for providing insightful comments. The analysis of DEEP2 data using the FIREFLY code was done on the Sciama High Performance Compute cluster which is supported by the ICG, SEPNet and the University of Portsmouth (UK). The CosmoSim database used in this paper is a service by the Leibniz-Institute for Astrophysics Potsdam (AIP). The MultiDark database was developed in cooperation with the Spanish MultiDark Consolider Project CSD200900064. The authors gratefully acknowledge the Gauss Centre for Supercomputing e.V. (www.gauss-centre.eu) and the Partnership for Advanced Supercomputing in Europe (PRACE, www.praceri.eu) for funding the MultiDark simulation project by providing computing time on the GCS Supercomputer SuperMUC at Leibniz Supercomputing Centre (LRZ, www.lrz.de).The authors thank New Mexico State University (USA) and Instituto de Astrof ' isica de Andalucia CSIC (Spain) for hosting the SKIES& UNIVERSES database for cosmological simulation products. This work has benefited from the publicly available software tools and packages: MATPLOTLIB14 2012-2016 (Hunter 2007); PYTHON SOFTWARE FOUNDATION15 19902017, version 2.7., PYTHONBREW16; we use whenever possible in this work a colour-blind friendly colour palette17 for our plots. ; Peer reviewed

Cromosomes; Marcadors pronòstics ; Cromosomas; Marcadores de pronóstico ; Chromosomes; Prognostic markers ; Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modification with an unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox is located primarily in heterochromatin, where it is involved in chromatin compaction. Knocking down LOXL2 reduces H3K4ox levels and causes chromatin decompaction, resulting in a sustained activation of the DNA damage response (DDR) and increased susceptibility to anticancer agents. This critical role that LOXL2 and oxidized H3 play in chromatin compaction and DDR suggests that functionally targeting LOXL2 could be a way to sensitize TNBC cells to conventional therapy. ; This work was supported by grants from Instituto de Salud Carlos III (ISCIII) FIS/FEDER (PI12/01250; CP08/00223; PI16/00253; and CB16/12/00449), MINECO (SAF2013-48849-C2-1-R) to SP, BFU2015-68354 to THS, Breast Cancer Research Foundation (BCRF-17-008) to JA, AGL2014-52395-C2-2-R to DA, Worldwide Cancer Research, Red Temática de Investigación Cooperativa en Cáncer (RD012/0036/005), Fundación Científica de la Asociación Española contra el Cáncer, and Fundació La Marató TV3. THS was supported by institutional funding (MINECO) through the Centres of Excellence Severo Ochoa award and the CERCA Programme of the Catalan Government, and SS-B, by a Fundació La Caixa fellowship. We thank La Caixa Foundation and Cellex Foundation for provide research facilities and equipment. GV has received funding from the MINECO (a "Juan de la Cierva Incorporation" fellowship; IJCI-2014-20723). SP was a recipient of a Miguel Servet contract (ISCIII/FIS), and AI, JPC-C, LP-G, and GS-B are supported by contracts from Worldwide Cancer Research, Fundació La Marató TV3, Fundació FERO, and a FI Fellowship from the Generalitat de ...

BACKGROUND: Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use. METHODS AND FINDINGS: We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown-rump length measured at 8-13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25-31), median height was 162 cm (IQR 157-168), median weight was 61 kg (IQR 55-68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487-2,222). The median pregnancy duration was 39 wk (IQR 38-40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8-16). The median birthweight was 3,300 g (IQR 2,980-3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts. CONCLUSIONS: This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world.

BACKGROUND: Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use. METHODS AND FINDINGS: We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown-rump length measured at 8-13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25-31), median height was 162 cm (IQR 157-168), median weight was 61 kg (IQR 55-68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487-2,222). The median pregnancy duration was 39 wk (IQR 38-40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8-16). The median birthweight was 3,300 g (IQR 2,980-3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements ...