4,282 research outputs found

    The Combination

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    When I first saw Druna, at a sad little makeshift refugee camp north of Mankerny on Sri Lanka’s East Coast, she was sitting in a square of hard red dirt, surrounded by a tangle of tent poles and metal stakes..

    Granular Structure Determined by Terahertz Scattering

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    Light-scattering in the terahertz region is demonstrated for granular matter. A quantum-cascade laser is used in a benchtop setup to determine the angle-dependent scattering of spherical grains as well as coffee powder and sugar grains. For the interpretation of the form factors for the scattering from single particles one has to go beyond the usual Rayleigh-Gans-Debye theory and apply calculations within Mie theory. In addition to single scattering also collective correlations can be identified and extracted as a static structure factor.Comment: 7 pages, 12 figure

    Structural basis for DNMT3A-mediated de novo DNA methylation.

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    DNA methylation by de novo DNA methyltransferases 3A (DNMT3A) and 3B (DNMT3B) at cytosines is essential for genome regulation and development. Dysregulation of this process is implicated in various diseases, notably cancer. However, the mechanisms underlying DNMT3 substrate recognition and enzymatic specificity remain elusive. Here we report a 2.65-ångström crystal structure of the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides, with the target sites separated by 14 base pairs within the same DNA duplex. The DNMT3A-DNA interaction involves a target recognition domain, a catalytic loop, and DNMT3A homodimeric interface. Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. Haematological cancer-associated somatic mutations of the substrate-binding residues decrease DNMT3A activity, induce CpG hypomethylation, and promote transformation of haematopoietic cells. Together, our study reveals the mechanistic basis for DNMT3A-mediated DNA methylation and establishes its aetiological link to human disease

    Systematic comparison of monoclonal versus polyclonal antibodies for mapping histone modifications by ChIP-seq.

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    BackgroundThe robustness of ChIP-seq datasets is highly dependent upon the antibodies used. Currently, polyclonal antibodies are the standard despite several limitations: They are non-renewable, vary in performance between lots and need to be validated with each new lot. In contrast, monoclonal antibody lots are renewable and provide consistent performance. To increase ChIP-seq standardization, we investigated whether monoclonal antibodies could replace polyclonal antibodies. We compared monoclonal antibodies that target five key histone modifications (H3K4me1, H3K4me3, H3K9me3, H3K27ac and H3K27me3) to their polyclonal counterparts in both human and mouse cells.ResultsOverall performance was highly similar for four monoclonal/polyclonal pairs, including when we used two distinct lots of the same monoclonal antibody. In contrast, the binding patterns for H3K27ac differed substantially between polyclonal and monoclonal antibodies. However, this was most likely due to the distinct immunogen used rather than the clonality of the antibody.ConclusionsAltogether, we found that monoclonal antibodies as a class perform equivalently to polyclonal antibodies for the detection of histone post-translational modifications in both human and mouse. Accordingly, we recommend the use of monoclonal antibodies in ChIP-seq experiments

    Methodologies for Designing Power-Aware Smart Card Systems

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    Smart cards are some of the smallest computing platforms in use today. They have limited resources, but a huge number of functional requirements. The requirement for multi-application cards increases the demand for high performance and security even more, whereas the limits given by size and energy consumption remain constant. We describe new methodologies for designing and implementing entire systems with regard to power awareness and required performance. To make use of this power-saving potential, also the higher layers of the system - the operating system layer and the application domain layer - are required to be designed together with the rest of the system. HW/SW co-design methodologies enable the gain of system-level optimization. The first part presents the abstraction of smart cards to optimize system architecture and memory system. Both functional and transactional-level models are presented and discussed. The proposed design flow and preliminary results of the evaluation are depicted. Another central part of this methodology is a cycle-accurate instruction-set simulator for secure software development. The underlaying energy model is designed to decouple instruction and data dependent energy dissipation, which leads to an independent characterization process and allows stepwise model refinement to increase estimation accuracy. The model has been evaluated for a high-performance smart card CPU and an use-case for secure software is given

    The roles of motivation and ability in controlling the consequences of stereotype suppression

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    Two experiments investigated the conditions under which previously suppressed stereotypes are applied in impression formation. In Experiment 1, the extent to which a previously suppressed racial stereotype influenced subsequent impressions depended on the race of the target who was subsequently encountered. Whereas impressions of race-unspecified targets were assimilated to the stereotype following its suppression, no such effects were observed when the target belonged to the racial group whose stereotype had been initially suppressed. These results demonstrate that when perceivers are motivated to avoid stereo-typing individuals, the influence of a stereotype that has been previously activated through suppression is minimized. Experiment 2 demonstrated that these processing goals effectively reduce the impact of suppression-activated stereotypes only when perceivers have sufficient capacity to enact the goals. These results suggest that both sufficient motivation and capacity are necessary to prevent heightened stereotyping following stereotype suppression

    Cognitive consequences of perceiving social exclusion

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    Although a great deal is now known about how people mentally represent individuals and groups, less attention has been paid to the question of how interpersonal relationships are represented in memory. Drawing on principles of categorization, this paper reports an investigation into how we mentally represent the relationships of others. In three experiments, evidence for assimilation effects following social exclusion (and subsequent categorization) is found. Experiment 1 uses a judgment paradigm to demonstrate that social exclusion influences the perception of interpersonal closeness. Experiments 2 and 3 employ a memory confusion paradigm to establish that representations of relationship partners are assimilated following the exclusion of a third party. © 2008 Elsevier Inc. All rights reserved

    Reactive and Regulative Temperament in Youths: Psychometric Evaluation of the Early Adolescent Temperament Questionnaire-Revised

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    The present study examined the psychometric properties of the self-report version of the Early Adolescent Temperament Questionnaire-Revised (EATQ-R), which is a scale for measuring reactive and regulative temperament traits, in a large sample of children and adolescents (N = 1,055). The results indicated that the internal consistency was acceptable for most EATQ-R temperament scales. Further, principal components analysis of the instrument yielded a structure with nine components, which generally reflected the temperament scales of the EATQ-R. The test–retest stability of the scale was moderate to good, whereas the parent–child agreement was rather low. Finally, the scale correlated in a theoretically meaningful way with children’s self-reports of personality and psychopathology. It can be concluded that the EATQ-R is a useful scale for measuring aspects of reactive and regulative temperament in children and adolescents, although there is certainly room for improving the instrument
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