150 research outputs found
CASE REPORT: 17 YEARS SURVIVAL RATE AFTER RADICAL RESECTION OF CEREBELLAR PILOCYTIC ASTROCYTOMA
A case report is presented to approve 17 years survival after Nafziger- Town operation of a boy, aged 5, 5 years, diagnosed with cerebellar pilocytic astrocytoma. Ventriculo- peritoneal (VP) shunt is applied a week before the radical operation. Pre and postoperative (17 years after) computed tomographic scans (CT) as well as histological verification.A case report is presented to approve 17 years survival after Nafziger- Town operation of a boy, aged 5, 5 years, diagnosed with cerebellar pilocytic astrocytoma. Ventriculo- peritoneal (VP) shunt is applied a week before the radical operation. Pre and postoperative (17 years after) computed tomographic scans (CT) as well as histological verification
Adding a New Dimension to DNA Melting Curves.
to be published in Europhysics LettersInternational audienceStandard DNA melting curves record the separation of the two strands versus temperature, but they do not provide any information on the location of the opening. We introduce an experimental method which adds a new dimension to the melting curves of short DNA sequences by allowing us to record the degree of opening in several positions along the molecule all at once. This adds the spatial dimension to the melting curves and allows a precise investigation of the role of the base-pair sequence on the fluctuations and denaturation of the DNA double helix. We illustrate the power of the method by investigating the influence of an AT rich region on the fluctuations of neighboring domains
Explaining Deep Learning Models Through Rule-Based Approximation and Visualization
This paper describes a novel approach to the problem of developing explainable machine learning models. We consider a Deep Reinforcement Learning (DRL) model representing a highway path planning policy for autonomous highway driving. The model constitutes a mapping from the continuous multidimensional state space characterizing vehicle positions and velocities to a discrete set of actions in longitudinal and lateral direction. It is obtained by applying a customized version of the Double Deep Q-Network (DDQN) learning algorithm. The main idea is to approximate the DRL model with a set of IF…THEN rules that provide an alternative interpretable model, which is further enhanced by visualizing the rules. This concept is rationalized by the universal approximation properties of the rule-based models with fuzzy predicates. The proposed approach includes a learning engine composed of 0-order fuzzy rules, which generalize locally around the prototypes by using multivariate function models. The adjacent (in the data space) prototypes, which correspond to the same action are further grouped and merged into so-called "MegaClouds" reducing significantly the number of fuzzy rules. The input selection method is based on ranking the density of the individual inputs. Experimental results show that the specific DRL agent can be interpreted by approximating with families of rules of different granularity. The method is computationally efficient and can be potentially extended to addressing the explainability of the broader set of fully connected deep neural network model
RSC remodeling of oligo-nucleosomes: an atomic force microscopy study
RSC is an essential chromatin remodeling factor that is required for the
control of several processes including transcription, repair and replication.
The ability of RSC to relocate centrally positioned mononucleosomes at the end
of nucleosomal DNA is firmly established, but the data on RSC action on
oligo-nucleosomal templates remains still scarce. By using Atomic Force
Microscopy (AFM) imaging, we have quantitatively studied the RSC- induced
mobilization of positioned di- and trinucleosomes as well as the directionality
of mobilization on mononucleosomal template labeled at one end with
streptavidin. AFM imaging showed only a limited set of distinct configurational
states for the remodeling products. No stepwise or preferred directionality of
the nucleosome motion was observed. Analysis of the corresponding reaction
pathways allows deciphering the mechanistic features of RSC-induced nucleosome
relocation. The final outcome of RSC remodeling of oligosome templates is the
packing of the nucleosomes at the edge of the template, providing large
stretches of DNA depleted of nucleosomes. This feature of RSC may be used by
the cell to overcome the barrier imposed by the presence of nucleosomes
The dynamics of individual nucleosomes controls the chromatin condensation pathway: direct AFM visualization of variant chromatin
Chromatin organization and dynamics is studied in this work at scales ranging
from single nucleosome to nucleosomal array by using a unique combination of
biochemical assays, single molecule imaging technique and numerical modeling.
We demonstrate that a subtle modification in the nucleosome structure induced
by the histone variant H2A.Bbd drastically modifies the higher order
organization of the nucleosomal arrays. Importantly, as directly visualized by
AFM, conventional H2A nucleosomal arrays exhibit specific local organization,
in contrast to H2A.Bbd arrays, which show "beads on a string" structure. The
combination of systematic image analysis and theoretical modeling allows a
quantitative description relating the observed gross structural changes of the
arrays to their local organization. Our results strongly suggest that
higher-order organization of H1-free nucleosomal arrays is mainly determined by
the fluctuation properties of individual nucleosomes. Moreover, numerical
simulations suggest the existence of attractive interactions between
nucleosomes to provide the degree of compaction observed for conventional
chromatin fibers.Comment: Biophys J. in pres
Interference Mapping in 3D for High-Density Indoor IoT Deployments
Deployment of practical Internet of Things (IoT) in the context of 5G can be hindered by substantial interference and spectrum limitations, especially in the unlicensed frequency bands. Due to the high density of such devices in indoor scenarios, the need for interference characterization which facilitates more effective spectrum utilization is further emphasized. This chapter studies the influence of diverse scenarios for the dense placement of interferers on the spectrum occupancy through the use of 3D interference maps for two popular IoT technologies—LoRa and Wi-Fi. The experiments are performed with software-defined radio (SDR) platforms in real time and an automated positioning tool which provides the measurements to characterize the interference in 3D space. The findings demonstrate a nonuniform character of the interference and the significant impact of fading within the width, height, and length of the examined area. They suggest the role of dynamic relocation for realistic IoT scenarios
Extensive characterization of NF-κB binding uncovers non-canonical motifs and advances the interpretation of genetic functional traits
Background
Genetic studies have provided ample evidence of the influence of non-coding DNA polymorphisms on trait variance, particularly those occurring within transcription factor binding sites. Protein binding microarrays and other platforms that can map these sites with great precision have enhanced our understanding of how a single nucleotide polymorphism can alter binding potential within an in vitro setting, allowing for greater predictive capability of its effect on a transcription factor binding site.
Results
We have used protein binding microarrays and electrophoretic mobility shift assay-sequencing (EMSA-Seq), a deep sequencing based method we developed to analyze nine distinct human NF-κB dimers. This family of transcription factors is one of the most extensively studied, but our understanding of its DNA binding preferences has been limited to the originally described consensus motif, GGRRNNYYCC. We highlight differences between NF-κB family members and also put under the spotlight non-canonical motifs that have so far received little attention. We utilize our data to interpret the binding of transcription factors between individuals across 1,405 genomic regions laden with single nucleotide polymorphisms. We also associated binding correlations made using our data with risk alleles of disease and demonstrate its utility as a tool for functional studies of single nucleotide polymorphisms in regulatory regions.
Conclusions
NF-κB dimers bind specifically to non-canonical motifs and these can be found within genomic regions in which a canonical motif is not evident. Binding affinity data generated with these different motifs can be used in conjunction with data from chromatin immunoprecipitation-sequencing (ChIP-Seq) to enable allele-specific analyses of expression and transcription factor-DNA interactions on a genome-wide scale.Wellcome Trust (London, England) (grant 075491/Z/04)European Commission (Seventh Framework Programme FP7/2007-2013: Model-In (222008))European Commission (Seventh Framework Programme FP7 ITN Network INTEGER (214902))Medical Research Council (Canada) (MRC project grant G0700818
Kinky DNA in solution: Small-angle-scattering study of a nucleosome positioning sequence
DNA is a flexible molecule, but the degree of its flexibility is subject to debate. The commonly-accepted
persistence length of lp ≈ 500Å is inconsistent with recent studies on short-chain DNA that show much greater
flexibility but do not probe its origin. We have performed x-ray and neutron small-angle scattering on a short
DNA sequence containing a strong nucleosome positioning element and analyzed the results using a modified
Kratky-Porod model to determine possible conformations. Our results support a hypothesis from Crick and Klug
in 1975 that some DNA sequences in solution can have sharp kinks, potentially resolving the discrepancy. Our
conclusions are supported by measurements on a radiation-damaged sample, where single-strand breaks lead to
increased flexibility and by an analysis of data from another sequence, which does not have kinks, but where our
method can detect a locally enhanced flexibility due to an AT domain.Spanish Ministry of Economy, Industry and Competitiveness (BES-2013-065453, EEBB-I-2015-09973, FIS2012-38827). S.C.L. and UC-154 are grateful for the support of Junta de Castilla y Leon (Spain) Nanofibersafe BU079U16. D.A. acknowledges funding from the Agence Nationale de la Recherche through ANR-12-BSV5-0017-01 “Chrome” and ANR-17-CE11-0019-03 “Chrom3D” grants. N.T. acknowledges support by the project Advanced Materials and Devices (MIS 5002409, Competitiveness, Entrepreneurship and Innovation, NSRF 2014-2020) cofinanced by Greece and the European Regional Development Fund
The incorporation of the novel histone variant H2AL2 confers unusual structural and functional properties of the nucleosome
In this work we have studied the properties of the novel mouse histone variant H2AL2. H2AL2 was used to reconstitute nucleosomes and the structural and functional properties of these particles were studied by a combination of biochemical approaches, atomic force microscopy (AFM) and electron cryo-microscopy. DNase I and hydroxyl radical footprinting as well as micrococcal and exonuclease III digestion demonstrated an altered structure of the H2AL2 nucleosomes all over the nucleosomal DNA length. Restriction nuclease accessibility experiments revealed that the interactions of the H2AL2 histone octamer with the ends of the nucleosomal DNA are highly perturbed. AFM imaging showed that the H2AL2 histone octamer was complexed with only ∼130 bp of DNA. H2AL2 reconstituted trinucleosomes exhibited a type of a ‘beads on a string’ structure, which was quite different from the equilateral triangle 3D organization of conventional H2A trinucleosomes. The presence of H2AL2 affected both the RSC and SWI/SNF remodeling and mobilization of the variant particles. These unusual properties of the H2AL2 nucleosomes suggest a specific role of H2AL2 during mouse spermiogenesis
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