358 research outputs found
Stability of central finite difference schemes for the Heston PDE
This paper deals with stability in the numerical solution of the prominent
Heston partial differential equation from mathematical finance. We study the
well-known central second-order finite difference discretization, which leads
to large semi-discrete systems with non-normal matrices A. By employing the
logarithmic spectral norm we prove practical, rigorous stability bounds. Our
theoretical stability results are illustrated by ample numerical experiments
Tecnologias digitais no processo de alfabetização: analisando o uso do laboratório de informática nos anos iniciais
Este artigo discute tecnologias digitais na alfabetização, onde os estudantes as utilizam para desenvolver seus conhecimentos. Iniciamos com breves considerações sobre o uso das tecnologias na educação e as implicações na alfabetização. Em seguida, apresentamos resultados de uma pesquisa qualitativa, realizada com 15 professores que atuam nas salas de aula de alfabetização de 1º e 2º anos do Ensino Fundamental e professores de laboratório de informática de seis escolas no Município de Curitiba – PR. O propósito deste estudo foi analisar e investigar o impacto do uso do laboratório de informática no processo de alfabetização dos educandos nos anos iniciais. Este trabalho de pesquisa junto aos professores alfabetizadores permitiu que se elencassem duas categorias de análise preliminar: Uso e Planejamento para o Laboratório de Informática; Contribuições para Aprendizagem e Alfabetização no Laboratório de Informática. As reflexões baseiam-se nos estudos de Almeida (2005; 1998); Kenski (2012), Leite, Colello e Arantes (2010), Lucena (2002), Masetto(2000), Moran (2007), Nóvoa (2010), Pretto (2000), Sancho e Hernandez (2006), Soares (2004; 1998), Valente (1999; 1998). O resultado apontou que os professores alfabetizadores utilizam o laboratório de informática nas práticas educativas e que há saberes e habilidades que os alfabetizandos adquirem fazendo uso deste ambiente como melhora na leitura e na oralidade,reconhecimento de letras, registro de letras, palavras e textos, coordenação motora, atenção, raciocínio e nas suas produções
Evidence for tidal interaction and a supergiant HI shell in the Local Group dwarf galaxy NGC 6822
We present a wide-field, high spatial and velocity resolution map of the
entire extended HI distribution of the Local Group dwarf galaxy NGC 6822. The
observations were obtained with the Australia Telescope Compact Array in
mosaicing mode. The interstellar medium of NGC 6822 is shaped by the presence
of numerous H{\sc i} holes and shells, including a supergiant shell, and the
effects of tidal interaction, in the form of a tidal arm and an infalling or
interacting HI complex. The HI shell is situated outside the optical galaxy and
occupies roughly a quarter of the area of the main HI disk. It measures 2.0
times 1.4 kpc, making it one of the largest supergiant HI shells ever found.
The giant hole shows no signs of expansion and no obvious creation mechanism is
evident from our data. If star formation was the cause, an energy equivalent of
\~100 supernovae (10^53 erg) is needed to create the hole. We derive an upper
limit for the age of order 100 Myr. The presence of a possible tidal arm
indicates that NGC 6822 may recently have undergone some interaction. An HI
complex located in the north-west of the galaxy may be the interaction partner.
We argue that it is likely that these features were created about 100 Myr ago
in an event that also enhanced the star formation rateComment: Accepted for publication in Astrophysical Journal Letters (needs
emulateapj5.sty, included
Reliability of panel-based mutational signatures for immune-checkpoint-inhibition efficacy prediction in non-small cell lung cancer
OBJECTIVES: Mutational signatures (MS) are gaining traction for deriving therapeutic insights for immune checkpoint inhibition (ICI). We asked if MS attributions from comprehensive targeted sequencing assays are reliable enough for predicting ICI efficacy in non-small cell lung cancer (NSCLC).METHODS: Somatic mutations of m = 126 patients were assayed using panel-based sequencing of 523 cancer-related genes. In silico simulations of MS attributions for various panels were performed on a separate dataset of m = 101 whole genome sequenced patients. Non-synonymous mutations were deconvoluted using COSMIC v3.3 signatures and used to test a previously published machine learning classifier.RESULTS: The ICI efficacy predictor performed poorly with an accuracy of 0.51 -0.09 +0.09, average precision of 0.52 -0.11 +0.11, and an area under the receiver operating characteristic curve of 0.50 -0.09 +0.10. Theoretical arguments, experimental data, and in silico simulations pointed to false negative rates (FNR) related to panel size. A secondary effect was observed, where deconvolution of small ensembles of point mutations lead to reconstruction errors and misattributions. CONCLUSION: MS attributions from current targeted panel sequencing are not reliable enough to predict ICI efficacy. We suggest that, for downstream classification tasks in NSCLC, signature attributions be based on whole exome or genome sequencing instead.</p
Rotation Curves of Spiral Galaxies
Rotation curves of spiral galaxies are the major tool for determining the
distribution of mass in spiral galaxies. They provide fundamental information
for understanding the dynamics, evolution and formation of spiral galaxies. We
describe various methods to derive rotation curves, and review the results
obtained. We discuss the basic characteristics of observed rotation curves in
relation to various galaxy properties, such as Hubble type, structure,
activity, and environment.Comment: 40 pages, 6 gif figures; Ann. Rev. Astron. Astrophys. Vol. 39, p.137,
200
MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven Neuroblastoma Formation.
Roughly half of all high-risk neuroblastoma patients present with MYCN amplification. The molecular consequences of MYCN overexpression in this aggressive pediatric tumor have been studied for decades, but thus far, our understanding of the early initiating steps of MYCN-driven tumor formation is still enigmatic. We performed a detailed transcriptome landscaping during murine TH-MYCN-driven neuroblastoma tumor formation at different time points. The neuroblastoma dependency factor MEIS2, together with ASCL1, was identified as a candidate tumor-initiating factor and shown to be a novel core regulatory circuit member in adrenergic neuroblastomas. Of further interest, we found a KEOPS complex member (gm6890), implicated in homologous double-strand break repair and telomere maintenance, to be strongly upregulated during tumor formation, as well as the checkpoint adaptor Claspin (CLSPN) and three chromosome 17q loci CBX2, GJC1 and LIMD2. Finally, cross-species master regulator analysis identified FOXM1, together with additional hubs controlling transcriptome profiles of MYCN-driven neuroblastoma. In conclusion, time-resolved transcriptome analysis of early hyperplastic lesions and full-blown MYCN-driven neuroblastomas yielded novel components implicated in both tumor initiation and maintenance, providing putative novel drug targets for MYCN-driven neuroblastoma
Galaxy Populations and Evolution in Clusters IV: Deep HI Observations of Dwarf Ellipticals in the Virgo Cluster
We present in this paper the deepest Arecibo HI observations of Virgo cluster
dwarf ellipticals (dEs) taken to date. Based on this data we argue that a
significant fraction of Virgo cluster dEs recently underwent evolution. Our new
observations consist of HI 21-cm line observations for 22 classified dE
galaxies with optical radial velocities consistent with membership in the Virgo
cluster. Cluster members VCC 390 and VCC 1713 are detected with HI masses M(HI)
= 6*10^7 M_solar and 8*10^7 M_solar, respectively, while M(HI) in the remaining
20 dE galaxies have upper limits as low as 5*10^5 M_solar. We combine our
results with those for 27 other Virgo cluster dEs with HI observations in the
literature, 7 of which have HI detection claims. New optical images from the
WIYN telescope of 5 of these HI-detected dEs, along with archival data, suggest
that seven of the claimed detections are real, yielding a ~ 15% detection rate.
These HI-detected classified dEs are preferentially located near the periphery
of the Virgo cluster. Three Virgo dEs have observed HI velocity widths > 200
km/s, possibly indicating the presence of a large dark matter content, or
transient extended HI. We discuss the possible origins of these objects and
argue that they originate from field galaxies accreted onto high angular
momentum orbits by Virgo in the last few Gyr. As a result these galaxies are
slowly transformed within the cluster by gradual gas stripping processes,
associated truncation of star formation, and passive fading of stellar
populations. Low-mass early-type cluster galaxies are therefore currently being
produced as the product of cluster environmental effects. We utilize our
results to estimate the recent (past 1-3 Gyr) average mass accretion rate into
the Virgo cluster, finding dM/dt ~ 50 M_solar/year.Comment: Accepted to ApJ, 21 page
The Netherlands Arrhythmogenic Cardiomyopathy Registry:design and status update
BACKGROUND: Clinical research on arrhythmogenic cardiomyopathy (ACM) is typically limited by small patient numbers, retrospective study designs, and inconsistent definitions. AIM: To create a large national ACM patient cohort with a vast amount of uniformly collected high-quality data that is readily available for future research. METHODS: This is a multicentre, longitudinal, observational cohort study that includes (1) patients with a definite ACM diagnosis, (2) at-risk relatives of ACM patients, and (3) ACM-associated mutation carriers. At baseline and every follow-up visit, a medical history as well information regarding (non-)invasive tests is collected (e. g. electrocardiograms, Holter recordings, imaging and electrophysiological studies, pathology reports, etc.). Outcome data include (non-)sustained ventricular and atrial arrhythmias, heart failure, and (cardiac) death. Data are collected on a research electronic data capture (REDCap) platform in which every participating centre has its own restricted data access group, thus empowering local studies while facilitating data sharing. DISCUSSION: The Netherlands ACM Registry is a national observational cohort study of ACM patients and relatives. Prospective and retrospective data are obtained at multiple time points, enabling both cross-sectional and longitudinal research in a hypothesis-generating approach that extends beyond one specific research question. In so doing, this registry aims to (1) increase the scientific knowledge base on disease mechanisms, genetics, and novel diagnostic and treatment strategies of ACM; and (2) provide education for physicians and patients concerning ACM, e. g. through our website ( www.acmregistry.nl ) and patient conferences
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INSPIRE: A European training network to foster research and training in cardiovascular safety pharmacology
Safety pharmacology is an essential part of drug development aiming to identify, evaluate and investigate undesirable pharmacodynamic properties of a drug primarily prior to clinical trials. In particular, cardiovascular adverse drug reactions (ADR) have halted many drug development programs. Safety pharmacology has successfully implemented a screening strategy to detect cardiovascular liabilities, but there is room for further refinement. In this setting, we present the INSPIRE project, a European Training Network in safety pharmacology for Early Stage Researchers (ESRs), funded by the European Commission's H2020-MSCA-ITN programme. INSPIRE has recruited 15 ESR fellows that will conduct an individual PhD-research project for a period of 36 months. INSPIRE aims to be complementary to ongoing research initiatives. With this as a goal, an inventory of collaborative research initiatives in safety pharmacology was created and the ESR projects have been designed to be complementary to this roadmap. Overall, INSPIRE aims to improve cardiovascular safety evaluation, either by investigating technological innovations or by adding mechanistic insight in emerging safety concerns, as observed in the field of cardio-oncology. Finally, in addition to its hands-on research pillar, INSPIRE will organize a number of summer schools and workshops that will be open to the wider community as well. In summary, INSPIRE aims to foster both research and training in safety pharmacology and hopes to inspire the future generation of safety scientists
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