julilili42/papers huggingface dataset:
SLC 2A3 single‐nucleotide polymorphism and duplication influence cognitive processing and population‐specific risk for attention‐deficit/hyperactivity disorder
2017-02-22

Background Attention‐deficit/hyperactivity disorder ( ADHD ) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome‐wide screening approach for copy number variants ( CNV s) in ADHD implicated a duplication of SLC 2A3 , encoding glucose transporter‐3 ( GLUT 3). GLUT 3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory–inhibitory balance impacting both brain development and activity‐dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT 3 dysfunction in ADHD . Methods Case–control association analyses of SLC 2A3 single‐nucleotide polymorphisms ( SNP s) and CNV s were conducted in several European cohorts of patients with childhood and adult ADHD ( SNP , n = 1,886 vs. 1,988; CNV , n = 1,692 vs. 1,721). These studies were complemented by SLC 2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Results Meta‐analysis of all cohorts detected an association of SNP rs12842 with ADHD . While CNV analysis detected a population‐specific enrichment of SLC 2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC 2A3 m RNA expression in peripheral blood cells and altered event‐related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD , and an underestimation of energy units of high‐caloric food. Conclusions Taken together, our results indicate that both common and rare SLC 2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk.
Direct push sensing in wetland (geo)archaeology: High-resolution reconstruction of buried canal structures ( Fossa Carolina , Germany)
2017-02-22

(Geo)archaeological trenching techniques in floodplain and wetland environments are challenging due to the impact of groundwater inflow and highly unstable trench edges. Alternatively, classical driving core techniques often correspond with the contraction of organic layers and bias in height accuracies. Here, we present the application of direct push sensing techniques for minimal-invasive (geo)archaeological surveys in zones affected by a high groundwater table, especially when high-resolution parameterization of buried (geo)archaeological structures is required. Two of these direct push applications are electrical conductivity logging and the measurement of colorimetric proxies in unconsolidated sediments. The tools provide multi-proxy information about layer structure, texture, and organic parameters. The high sensing speed allows recording a large data set with high vertical and lateral resolution. In this study we exemplary provide results of a buried canal structure within a valley in SW Germany. We present a high-resolution cross-section from a zone of high groundwater table. The canal is part of Charlemagne's summit canal (Fossa Carolina), an Early Medieval hydro-engineering project bridging the Central European Watershed. We compare the direct push sensing data with driving core samples and discuss prediction and generation options of parameter transfer from multiple one-dimensional logs to a two-dimensional canal cross-section of high-resolution. In this context, we use in situ-obtained colorimetric data and electrical conductivity as proxies for (geo)archaeological site characterization. We model organic fills of the canal by direct push logs and robust sediment data. Given the cost and time effectiveness of such tools, (geo)archaeological site information of high-depth accuracy was grown rapidly, compared to less densely performed drillings that require an additional high effort in laboratory analyses. The Carolingian excavation depth is 6 m below current surface. There is evidence for multiple organic layers in the trench fills, which reveal aquatic to semi-terrestrial stillwater deposition and, therefore, evidence of multiple Carolingian and post-Carolingian ponds. We have evidence for a conceptual width of the deep-buried artificial water course of at least 3–4 m. This allows a passage of Carolingian cargo scows with a payload of several tons in this central zone of the canal.
Double parton scattering in pair production of J/ψ mesons at the LHC revisited
2017-02-22

Double parton scattering (DPS) is studied at the example of \\npair-production in the LHCb and ATLAS experiments of the Large Hadron Collider\\n(LHC) at centre-of-mass energies of 7, 8, and 13 TeV. We report\\ntheoretical predictions delivered to the LHCb and ATLAS collaborations adjusted\\nfor the fiducial volumes of the corresponding measurements during Run I and\\nprovide new predictions at 13 TeV collision energy. It is shown that DPS can\\nlead to noticeable contributions in the distributions of longitudinal variables\\nof the di- system, especially at 13 TeV. The increased DPS rate in\\ndouble production at high energies will open up more possibilities for\\nthe separation of single parton scattering (SPS) and DPS contributions in\\nfuture studies.\\n
Towards semi-inclusive deep inelastic scattering at next-to-next-to-leading order
2017-02-22

In this paper, we compute the first set of corrections\\nto semi-inclusive deep inelastic scattering structure functions. We start by\\nstudying the impact of the contribution of the partonic subprocesses that open\\nat this order for the longitudinal structure function. We perform the full\\ncalculation analytically, and obtain the expression of the factorized cross\\nsection at this order. Special care is given to the study of their flavour\\ndecomposition structure. We analyze the phenomenological effect of the\\ncorrections finding that, even though expected to be small a priori, it turns\\nout to be sizable with respect to the previous order know, calling for a full\\nNNLO calculation.\\n
Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders
2017-02-23

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (<3 months), and are thus more frequent than previously reported; (ii) distinct phenotypes can be seen within the late onset group, including myoclonic-atonic epilepsy (two patients), Lennox-Gastaut not emerging from West syndrome (two patients), and focal epilepsies with an electrical status epilepticus during slow sleep-like EEG pattern (six patients); and (iii) West syndrome constitutes a common phenotype with a major recurring mutation (p.Arg853Gln: two new and four previously reported children). Other known phenotypes include Ohtahara syndrome, epilepsy of infancy with migrating focal seizures, and intellectual disability or autism without epilepsy. To assess the response to antiepileptic therapy, we retrospectively reviewed the treatment regimen and the course of the epilepsy in 66 patients for which well-documented medical information was available. We find that the use of sodium channel blockers was often associated with clinically relevant seizure reduction or seizure freedom in children with early infantile epilepsies (<3 months), whereas other antiepileptic drugs were less effective. In contrast, sodium channel blockers were rarely effective in epilepsies with later onset (≥3 months) and sometimes induced seizure worsening. Regarding the genetic findings, truncating mutations were exclusively seen in patients with late onset epilepsies and lack of response to sodium channel blockers. Functional characterization of four selected missense mutations using whole cell patch-clamping in tsA201 cells-together with data from the literature-suggest that mutations associated with early infantile epilepsy result in increased sodium channel activity with gain-of-function, characterized by slowing of fast inactivation, acceleration of its recovery or increased persistent sodium current. Further, a good response to sodium channel blockers clinically was found to be associated with a relatively small gain-of-function. In contrast, mutations in patients with late-onset forms and an insufficient response to sodium channel blockers were associated with loss-of-function effects, including a depolarizing shift of voltage-dependent activation or a hyperpolarizing shift of channel availability (steady-state inactivation). Our clinical and experimental data suggest a correlation between age at disease onset, response to sodium channel blockers and the functional properties of mutations in children with SCN2A-related epilepsy.
Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies
2017-02-23

α-Synuclein misfolding and aggregation is a hallmark in Parkinson’s disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced α-synuclein toxicity in vitro and in vivo, in Drosophila and in mice. Glycation affected primarily the N-terminal region of α-synuclein, reducing membrane binding, impaired the clearance of α-synuclein, and promoted the accumulation of toxic oligomers that impaired neuronal synaptic transmission. Strikingly, using glycation inhibitors, we demonstrated that normal clearance of α-synuclein was re-established, aggregation was reduced, and motor phenotypes in Drosophila were alleviated. Altogether, our study demonstrates glycation constitutes a novel drug target that can be explored in synucleinopathies as well as in other neurodegenerative conditions.
Specific and Novel microRNAs Are Regulated as Response to Fungal Infection in Human Dendritic Cells
2017-02-23

Within the last two decades, the incidence of invasive fungal infections has been significantly increased. They are characterized by high mortality rates and are often caused by <i>Candida albicans</i> and <i>Aspergillus fumigatus</i>. The increasing number of infections underlines the necessity for additional anti-fungal therapies, which require extended knowledge of gene regulations during fungal infection. MicroRNAs are regulators of important cellular processes, including the immune response. By analyzing their regulation and impact on target genes, novel therapeutic and diagnostic approaches may be developed. Here, we examine the role of microRNAs in human dendritic cells during fungal infection. Dendritic cells represent the bridge between the innate and the adaptive immune systems. Therefore, analysis of gene regulation of dendritic cells is of particular significance. By applying next-generation sequencing of small RNAs, we quantify microRNA expression in monocyte-derived dendritic cells after 6 and 12 h of infection with <i>C. albicans</i> and <i>A. fumigatus</i> as well as treatment with lipopolysaccharides (LPS). We identified 26 microRNAs that are differentially regulated after infection by the fungi or LPS. Three and five of them are specific for fungal infections after 6 and 12 h, respectively. We further validated interactions of miR-132-5p and miR-212-5p with immunological relevant target genes, such as <i>FKBP1B, KLF4</i>, and <i>SPN</i>, on both RNA and protein level. Our results indicate that these microRNAs fine-tune the expression of immune-related target genes during fungal infection. Beyond that, we identified previously undiscovered microRNAs. We validated three novel microRNAs via qRT-PCR. A comparison with known microRNAs revealed possible relations with the miR-378 family and miR-1260a/b for two of them, while the third one features a unique sequence with no resemblance to known microRNAs. In summary, this study analyzes the effect of known microRNAs in dendritic cells during fungal infections and proposes novel microRNAs that could be experimentally verified.
Development of a Chromatic Pupillography Protocol for the First Gene Therapy Trial in Patients With CNGA3-Linked Achromatopsia
2017-02-23

Chromatic pupillography demonstrated significant reduced pupil responses to stimuli addressing primarily cone function, an increased sensitivity to rod-favoring stimuli and evidence for disinhibition of intrinsically photosensitive retinal ganglion cells in CNGA3-ACHM patients. A final protocol was established based on these findings. These conclusions may be useful for the objective assessment of efficacy gained by gene therapy or other innovative interventions in this hereditary retinal disorder.
Evaluating blood eosinophils and exacerbation history to predict ICS response in COPD
2017-02-23

Inhaled corticosteroids (ICS) are used to reduce the rate of COPD exacerbations (EX). Debate continues over use of blood eosinophils (EOS) to predict ICS response, with some suggesting a cut-off of ≥2% (Pascoe S et al. Lancet Respir Med 2015;3:435 – 42). In the WISDOM study (NCT00975195), this response was driven by patients with higher EOS levels (≥4% or ≥300 cells/μL) (Watz H et al. Lancet Respir Med 2016;4:390 – 8]).
The challenge of very rare childhood cancers in developed and developing countries
2017-02-23

Introduction: The improvements made in the field of pediatric oncology in the last decades due to the propensity to develop national and international cooperative protocols have not been historically seen for a number of very rare pediatric neoplasms whose common denominator lies in their having been treated as orphan diseases. For several years now, this situation has fortunately been gradually changing, and various projects dedicated to these rare diseases have been developed in several countries.Areas covered: This paper describes the schemes dedicated to rare pediatric tumors in countries with different development levels, with a particular reference to the EXPeRT (European Cooperative Study Group for Pediatric Rare Tumors) project.Expert opinion: Experience gained in recent years on rare tumors in childhood underscores the importance of cooperation and networking. Further efforts are now needed to extend research and improve the quality of patients care. The pediatric study groups that have invested their resources in this area must now strive to obtain institutional recognition and to seek new partnerships with adult medical oncology centers, organizations concerned with biological-genetic studies, and partners such as pharmaceutical industries, regulatory authorities, and international funding commissions.
Standardizing and benchmarking data analysis for calcium imaging
2017-02-23

Two-photon laser scanning microscopy with fluorescent calcium indicators is used widely to measure the activity of large populations of neurons. Extracting biologically relevant signals of interest without manual intervention remains a challenge. Two key problems are identifying image regions corresponding to individual neurons, and then detecting the timing of individual spikes from their derived fluorescence traces. The neuroscience community still lacks automated and agreed-upon solutions to these problems. Motivated by algorithm benchmarking efforts in computer vision and machine learning, we built two web-based benchmarking systems, Neurofinder (http://neurofinder.codeneuro.org) and Spikefinder (http://spikefinder.codeneuro.org), to compare algorithm performance on standardized datasets. Both were built with modular and modern open-source tools, allowing easy reuse for other data analysis problems. Neurofinder considers the problem of identifying neuron somata in fluorescence movies. We assembled a collection of training datasets from multiple labs in a standardized format, each with labeled regions defined manually, in some cases guided by activity-independent anatomical markers. Algorithm results are submitted through a web application and evaluated on independent test data, for which labels have not been made public. Evaluation metrics separately assess accuracy of neuronal locations and shapes. Submitted results are stored in a database and metrics are presented in a leaderboard. Spikefinder considers the problem of detecting spike times from fluorescence traces, building on a recent quantitative comparison of existing spike inference algorithms (Theis et al. 2016). Here, we assembled training data with simultaneously measured calcium traces and electrophysiologically-recorded action potentials. Performance of submitted algorithms is evaluated on a test dataset using several metrics including correlation, information gain, and standard measures from signal detection. Both challenges are currently running with publicly contributed algorithms. We hope this approach will both improve our understanding of how current algorithms perform, and generate new crowd-sourced solutions to current and future analysis problems.
Color terms in ancient Egyptian and Coptic
2017-02-23

The examination of the ancient Egyptian-Coptic color terms, their grammatical identification, their range of usage, and their etymologies permit the following conclusions: There are four BCTs, all verbs, ‘black,’ ‘white,’ ‘red’ and ‘green,’ as traditionally translated. The focus of ‘red’ is in the red range and not in the middle of the red-with-yellow range. The focus of ‘green’ lies in the green range and not in the middle of the green-with-blue range nor in the pale green range. In the final, Coptic, stage, the partition of the red range into ‘deep red’ and ‘light-red’ must be assumed. The traditional written language allowed additional place for further verbal color terms, but these never entered the colloquial language as BCTs. Among these alternatives, the use of ‘lapis lazuli-colored, blue’ is strikingly common; that of ‘charcoal-like, black’ and ‘golden’ is less common. Egyptian did not develop a BCT for either blue or yellow. Basically Egyptian-Coptic remained at B&K Stage IIIa.
Lung-Function Profile Before and After the First Moderate to Severe Exacerbation During the WISDOM Study
2017-02-23

In the WISDOM study (NCT00975195), daily home spirometry measured the time course of lung-function changes throughout the study. The aim of this post-hoc analysis was to address the lung-function profile leading up to, during, and following the first moderate-to-severe exacerbation.
A goal-driven deep learning approach for V1 system identification
2017-02-23

Understanding sensory processing in the visual system results from accurate predictions of its neural responses to any kind of stimulus. Although great effort has been devoted to the task, we still lack a full characterization of primary visual cortex (V1) computations and their role in higher cognitive functional tasks (e.g. object recognition) in response to naturalistic stimuli. While previous goal-driven deep learning models have provided unprecedented performance on visual ventral stream predictions and revealed hierarchical correspondence, no study has used the representations learned by those models to predict single cell spike counts in V1. We introduce a novel model (Fig. 1A) that leverages these learned representations to build a linearized model with Poisson noise. We separately use the representations of each convolutional layer of a near-state of the art convolutional neural network (CNN) trained on object recognition to fit a model that predicts V1 responses to naturalistic stimuli. When fitted to data collected from neurons across cortical layers in V1 from an awake, fixating monkey, we found that, as we expected, intermediate early layers in the CNN provided better performance on held out data (Fig. 1B). Additionally we show that, using the best predictive layers, our model significantly outperforms classical and current state-of-the-art methods on V1 identification (Fig. 1C). When exploring the properties of the best predictive layers in the CNN, we found striking similarities with known V1 computation. Our model is not only interpretable, but also interpolates between recent subunit-based hierarchical models and goal-driven deep learning models leading to results that argue in favor of shared representations in the brain.
Discrimination in lexical decision
2017-02-24

In this study we present a novel set of discrimination-based indicators of language processing derived from Naive Discriminative Learning (ndl) theory. We compare the effectiveness of these new measures with classical lexical-distributional measures-in particular, frequency counts and form similarity measures-to predict lexical decision latencies when a complete morphological segmentation of masked primes is or is not possible. Data derive from a re-analysis of a large subset of decision latencies from the English Lexicon Project, as well as from the results of two new masked priming studies. Results demonstrate the superiority of discrimination-based predictors over lexical-distributional predictors alone, across both the simple and primed lexical decision tasks. Comparable priming after masked corner and cornea type primes, across two experiments, fails to support early obligatory segmentation into morphemes as predicted by the morpho-orthographic account of reading. Results fit well with ndl theory, which, in conformity with Word and Paradigm theory, rejects the morpheme as a relevant unit of analysis. Furthermore, results indicate that readers with greater spelling proficiency and larger vocabularies make better use of orthographic priors and handle lexical competition more efficiently.
Fandom Biases Retrospective Judgments Not Perception
2017-02-24

Abstract Attitudes and motivations have been shown to affect the processing of visual input, indicating that observers may see a given situation each literally in a different way. Yet, in real-life, processing information in an unbiased manner is considered to be of high adaptive value. Attitudinal and motivational effects were found for attention, characterization, categorization, and memory. On the other hand, for dynamic real-life events, visual processing has been found to be highly synchronous among viewers. Thus, while in a seminal study fandom as a particularly strong case of attitudes did bias judgments of a sports event, it left the question open whether attitudes do bias prior processing stages. Here, we investigated influences of fandom during the live TV broadcasting of the 2013 UEFA-Champions-League Final regarding attention, event segmentation, immediate and delayed cued recall, as well as affect, memory confidence, and retrospective judgments. Even though we replicated biased retrospective judgments, we found that eye-movements, event segmentation, and cued recall were largely similar across both groups of fans. Our findings demonstrate that, while highly involving sports events are interpreted in a fan dependent way, at initial stages they are processed in an unbiased manner.