Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylati

Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders

Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific diagnostic classifiers. This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic capabilities through the resolution of unsolved cases and the reclassification of variants of unknown clinical significance, and provides further insight into the molecular etiology of Mendelian conditions

Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders.

Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific diagnostic classifiers. This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic capabilities through the resolution of unsolved cases and the reclassification of variants of unknown clinical significance, and provides further insight into the molecular etiology of Mendelian conditions

The nature of discrimination learning in pigeons

The results from five experiments are considered in relation to two of Spence's (1937, 1938) proposals concerning discrimination learning. In Experiments 1 and 2, we investigated whether his ideas about the interaction between excitatory and inhibitory generalization gradients can be used to understand how animals solve a complex patterning discrimination. The results supported a development of his proposals as put forward by Pearce (1994), provided a modification was made to Pearce's rule for determining the shape of the generalization gradient. In Experiments 3, 4, and 5, we examined whether animals would pay more attention to stimuli that are relevant, rather than irrelevant, to the solution of a discrimination. The results supported this proposal for stimuli comprising visual patterns, but not for those comprising plain colors. The results also indicated that change of attention was a consequence of preliminary receptor-exposure acts, as envisaged by Spence, and not of more central changes in attention. Copyright 2008 Psychonomic Society, Inc

The effect of different ventilation modes on in-vehicle carbon monoxide exposure

In-vehicle carbon monoxide (CO) concentration profiles were monitored in a passenger vehicle driven along a heavily traveled route of a commercial/residential area of Beirut, Lebanon, under several ventilation modes. Trips were conducted during morning rush hours in spring and summer time. Concomitant monitoring of car-exterior CO level, ambient CO level and wind speed was also undertaken. The highest mean CO exposure was experienced for the “windows closed, vents closed” and “windows closed, AC on recirculation” ventilation settings, with mean CO levels of 37.4 and 30.8 ppm, respectively, exceeding the 1-h air quality guidelines. The exposure was less significant for other ventilation modes with respective mean values of 10.8 - 19ppm. Mean car-exterior CO levels were lower than the 1-h air quality guidelines, but exceeded the 8-h CO exposure guidelines. Ambient CO levels were low and non-representative of the personal exposure of individuals neither inside nor in the vicinity of road vehicles. In-vehicle CO levels revealed moderate to good correlations to out-vehicle CO levels for ventilation modes allowing for outdoor air intake, and no correlation to ambient CO levels and wind speed. Infiltration as a result of indoor–outdoor air exchange and intrusion from engine combustion/exhaust infiltration constituted the main sources of observed in-vehicle CO levels.<br/

Stimuli that signal the absence of reinforcement are paid more attention than are irrelevant stimuli

According to established theories of attention (e.g., Mackintosh, 1975; Sutherland & Mackintosh, 1971), simple discriminations of the form AX+ BX- result in an increase in attention to stimuli A and B, which are relevant to the outcome that follows them, at the expense of X, which is irrelevant. Experiments that have apparently shown such changes in attention have failed to determine whether attention is enhanced to both A and B, which signal reinforcement and nonreinforcement, respectively, or just to A. In Experiments 1 and 2, pigeons were trained with a number of discriminations of the kind AX+ BX-, before compounds that had been consistently nonreinforced were involved in a subsequent discrimination. Both experiments provided support for theories that propose that more attention is paid to stimuli that consistently signal nonreinforcement than to irrelevant stimuli in simple discriminations

A practical guide to conversation research: how to study what people say to each other

Conversation—a verbal interaction between two or more people—is a complex, pervasive, and consequential human behavior. Conversations have been studied across many academic disciplines. However, advances in recording and analysis techniques over the last decade have allowed researchers to more directly and precisely examine conversations, in natural contexts and at a larger scale than ever before, and these advances open new paths to understand humanity and the social world. Existing reviews of text analysis and conversation research have focused on text generated by a single author (e.g. product reviews, news articles, and public speeches), and thus leave open questions about the unique challenges presented by interactive conversation data (i.e., dialogue). In this article, we suggest approaches to overcome common challenges in the workflow of conversation science, including recording and transcribing conversations, structuring data (to merge turn-level and speaker-level datasets), extracting and aggregating linguistic features, estimating effects, and sharing data. This practical guide is meant to shed light on current best practices and empower more researchers to study conversations more directly—to expand the community of conversation scholars and contribute to a greater cumulative scientific understanding of the social world

21.6% monoPoly ^TM cells with in-situ interfacial oxide and poly-Si layers deposited by inline PECVD

10.1109/PVSC.2018.85472712018 IEEE 7th World Conference on Photovoltaic Energy Conversion, WCPEC 2018 - A Joint Conference of 45th IEEE PVSC, 28th PVSEC and 34th EU PVSEC2048-205