julilili42/papers huggingface dataset:
Tetraparesis and sensorimotor axonal polyneuropathy due to co-occurrence of Pompe disease and hereditary ATTR amyloidosis
2020-11-13

Abstract Introduction/aims Hereditary transthyretin amyloidosis with polyneuropathy (hATTRPN) is an autosomal dominant multi-organ disorder manifesting in the third to fifth decade with the key clinical features of distal and painful sensory loss of the lower limbs and autonomic dysregulation. Motor neuropathy and cardiomyopathy evolve in the course of the disease. Pompe disease is an autosomal recessive disease leading to decreased levels of lysosomal enzyme acid α-glucosidase and proximal muscle weakness. We report the clinical features and diagnostic workup in the rare case of a patient with ATTR amyloidosis and late-onset Pompe disease, both genetically confirmed. Methods We performed a detailed clinical assessment, exome sequencing, and biochemical measurements. Results The patient presented with a distal, painful hypaesthesia of both legs, a cardiomyopathy, and a muscle weakness in the form of a girdle-type pattern of the arms and legs at the beginning and a spreading to distal muscle groups in the course of disease. Discussion This study highlights the importance of searching for co-occurrence of rare monogenetic neuromuscular diseases, especially in cases in which all clinical features can be readily explained by a single gene defect.
Radio/X-ray correlations and variability in the X-ray binary LS I +61°303
2020-11-13

ABSTRACT The high-mass X-ray binary LS I +61°303 exhibits variability in its radio and X-ray emissions, ranging from minute to hour time-scales. At such short time-scales, not much is known about the possible correlations between these two emissions from this source, which might offer hints to their origin. Here, we study the relationship between these emissions using simultaneous X-ray and radio monitoring. We present new radio observations using the Arcminute Microkelvin Imager Large Array telescope at two frequency bands, 13–15.5 and 15.5–18 GHz. We also describe new X-ray observations performed using the XMM–Newton telescope. These X-ray and radio observations overlapped for five hours. We find for the first time that the radio and X-ray emission are correlated up to 81 with their few per cent variability correlated up to 40 . We discuss possible physical scenarios that produces the observed correlations and variability in the radio and X-ray emission of LS I +61°303.
The Impact of Neuron Morphology on Cortical Network Architecture
2020-11-13

It has become increasingly clear that the neurons in the cerebral cortex are not randomly interconnected. This wiring specificity can result from synapse formation mechanisms that interconnect neurons depending on their activity or genetically defined identity. Here we report that in addition to these synapse formation mechanisms, the structural composition of the neuropil provides a third prominent source by which wiring specificity emerges in cortical networks. This structurally determined wiring specificity reflects the packing density, morphological diversity and similarity of the dendritic and axonal processes. The higher these three factors are, the more recurrent the topology of the networks. Conversely, low density, diversity and similarity yield feedforward networks. These principles predict connectivity patterns from subcellular to network scales that are remarkably consistent with empirical observations from a rich body of literature. Thus, cortical network architectures reflect the specific morphological properties of their constituents to much larger degrees than previously thought.
Selective cyclization modes of methyl 3′-heteroarylamino-2′-(2,5-dichlorothiophene-3-carbonyl)acrylates. Synthesis of model (thienyl)pyrazolo- and triazolo[1,5-α]pyrimidines
2020-11-13

Abstract Interaction of methyl 3-ethoxy-2-(2,5-dichloro-3-thenoyl)acrylate ( I ) with 3-aminopyrazole and 3-amino-1,2,4-triazole generated the respective pyrazolo[1,5-α]pyrimidine ( 4 ) and triazolo[1,5-α]pyrimidine ( 7 ). The formation of 4 entails selective and consecutive displacement of the 3-ethoxy and methoxy (ester) anions in I by 3-NH 2 and 1-NH of 3-aminopyrazole. On the other hand, the formation of 7 implies selective displacement of 3-ethoxy in I by the ring-NH followed by cyclocondensation involving the keto group in I and 3-NH 2 of aminotriazole. This latter selective displacement sequence is also followed by 3-amino-5-hydroxypyrazole in its reaction with I . The structures of the new compounds are supported by microanalytical and spectral data.
Multiple-pulse damage thresholds of retinal explants in the ns-time regime
2020-11-13

The data situation of laser-induced damage measurements after multiple-pulse irradiation in the ns-time regime is limited. Since the laser safety standard is based on damage experiments, it is crucial to determine damage thresholds. For a better understanding of the underlying damage mechanism after repetitive irradiation, we generate damage thresholds for pulse sequences up to N = 20 000 with 1.8 ns-pulses using a square-core fiber and a pulsed Nd:YAG laser. Porcine retinal pigment epithelial layers were used as tissue samples, irradiated with six pulse sequences and evaluated for damage by fluorescence microscopy. The damage thresholds decreased from 31.16 μJ for N = 1 to 11.56 μJ for N = 20 000. The reduction indicates photo-chemical damage mechanisms after reaching a critical energy dose.
Are text comprehension and calculation processes in word problem solving sequential or interactive? An eye-tracking study in children
2020-11-13

The difficulty of a word problem is influenced by both linguistic and arithmetic processes. However, whether these processes are sequential or interactive is a matter of debate. Little is known about how attention changes when faced with different linguistic and arithmetic task characteristics, both in relation to the entire problem and to specific components (i.e., numerical and textual elements). To address this gap, we conducted a study monitoring the eye movements of children aged 10-13 years during word problem solving. We manipulated linguistic and arithmetic task characteristics independently, focusing on the mathematical factor operation (addition/subtraction) and the linguistic factors consistency (consistent/inconsistent) and nominalization (verbalized/nominalized). The results revealed that eye movements generally increased as linguistic difficulty (e.g., nominalization) or arithmetic difficulty (e.g., operation) increased. Thereby, specific parts of the text were differentially affected based on the task characteristics. Increasing arithmetic difficulty led to a shift in eye movements towards numerical elements, while increasing linguistic difficulty resulted in a shift towards textual elements. Interestingly, the increase in arithmetic difficulty also influenced processing in the linguistic domain. For example, textual parts of the word problem received more attention when arithmetic difficulty increased, but not vice versa. This suggests that text comprehension and calculation processes in word problem-solving are not separate and not sequential; instead, they partially rely on shared processing components.
Dislocating NPs to the Right: Anything Goes? Semantic and Pragmatic Constraints
2020-11-13

In our paper we investigate the semantics and pragmatics of the NP-right dislocation (RD) in German, concentrating in particular on the conditions under which dislocation is possible. We argue that semantic properties of the NP are relevant for the possibility of having an NP dislocated: it has to have a type denotation. This requirement allows particular definite NPs as well as kind-referring terms and excludes quantified NPs. We propose a semantic account of RD in terms of ‘separate performatives’ thereby explaining the distributional facts. Furthermore, we show how the function of RD as a discourse topic marker endorses the requirement of the type denotation for the RD-NP.
TüEyeQ, a rich IQ test performance data set with eye movement, educational and socio-demographic information
2020-11-13

We present the TüEyeQ data set - to the best of our knowledge - the most comprehensive data set generated on a culture fair intelligence test (CFT 20-R), i.e., an IQ Test, consisting of 41 single tasks, taken by 315 individuals aged between 18 and 30 years. In addition to socio-demographic and educational information, the data set also includes the eye movements of the individuals while taking the IQ test. Along with distributional information we also highlight the potential for predictive analysis on the TüEyeQ data set and report the most important covariates for predicting the performance of a subject on a given task along with their influence on the prediction.
Universal and Existential Perfect in German
2020-11-13

This article is about three interrelated things: the German Present Perfect, durative adverbs (bis ’until’, seit ’since’) and Extended-Now-adverbs (schon oft ’often ever since’, schon immer). For the Perfect and durative adverbs, an interrelation has always been suggested in the literature: there are universal/ existential ambiguities in Perfect-sentences containing durative adverbs. These ambiguities are claimed to disappear if there is no Perfect. The traditional conclusion is that there must be an intimate interrelation between the Perfect and durative adverbs. I will show with authentic data from the web that this is false, the universal/ existential ambiguities are not limited to the Perfect. - As for the Perfect and Extended-Nowadverbs, the literature has not claimed that there is an interrelation. But I will show that there is a very intimate one. The behavior of Extended-Now-adverbs makes the traditional Reichenbachian Perfect-semantics untenable and suggests instead that the correct Perfectsemantics is the Extended-Now-theory. As for the mentioned universal/ existential ambiguities connected to durative adverbs, there are actually two different kinds of them. The first one I call "simple universal/ existential-ambiguity"; it is associated with lang ’for’ and for. John has been in Boston for two weeks is ambiguous between the two weeks being somewhere in the past (this is called the existential reading) and the two weeks being in the past but abutting speech time (this is called the universal reading). I will analyze this in terms of underspecification: somewhere within the Extended-Now-interval denoted by the Perfect, the event takes place. The second of the aforementioned universal/ existential ambiguities associated with durative adverbs I call "complex universal/ existential-ambiguity". It is associated with bis ’until’, seit ’since’, until, and since. John has been in Boston since Tuesday is ambiguous between him being there all the time (universal reading) and him being there at least once (existential reading). So far, the literature has only acknowledged this ambiguity for since and (marginally) for seit ’since’, and only in combination with the Perfect. I will show with authentic data that this ambiguity exists with all durative adverbs and with all tenses. I will analyze it as a scope ambiguity of the durative adverb and a possibly covert frequency adverb.
Lost in translation: the pitfalls of Ensembl Gene annotations between human genome assemblies and their impact on diagnostics
2020-11-13

Abstract Background The GRCh37 human genome assembly is still widely used in genomics despite the fact an updated human genome assembly (GRCh38) has been available for many years. A particular issue with relevant ramifications for clinical genetics currently is the case of the GRCh37 Ensembl gene annotations which has been archived, and thus not updated, since 2013. These Ensembl GRCh37 gene annotations are just as ubiquitous as the former assembly and are the default gene models used and preferred by the majority of genomic projects internationally. In this study, we highlight the issue of genes with discrepant annotations, that have been recognized as protein coding in the new but not the old assembly. These genes are ignored by all genomic resources that still rely on the archived and outdated gene annotations. Moreover, the majority if not all of these discrepant genes (DGs) are automatically discarded and ignored by all variant prioritization tools that rely on the GRCh37 Ensembl gene annotations. Methods We performed bioinformatics analysis identifying Ensembl genes with discrepant annotations between the two most recent human genome assemblies, hg37, hg38, respectively. Clinical and phenotype gene curations have been obtained and compared for this gene set. Furthermore, matching RefSeq transcripts have also been collated and analyzed. Results We found hundreds of genes (N=267) that were reclassified as “protein-coding” in the new hg38 assembly. Notably, 169 of these genes also had a discrepant HGNC gene symbol between the two assemblies. Most genes had RefSeq matches (N=199/267) including all the genes with defined phenotypes in Ensembl genes GRCh38 assembly (N=10). However, many protein-coding genes remain missing from the current known RefSeq gene models (N=68) Conclusion We found many clinically relevant genes in this group of neglected genes and we anticipate that many more will be found relevant in the future. For these genes, the inaccurate label of “non-protein-coding” hinders the possibility of identifying any causal sequence variants that overlap them. In addition, Important additional annotations such as evolutionary constraint metrics are also not calculated for these genes for the same reason, further relegating them into oblivion.
Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory Study
2020-11-13

<strong>Slightly processed raw data for the paper 'Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory Study'</strong> The processing include a spike removal to allow an interpolation to a common wavenumber axis. Always three files belong to each other: wavenumber axis file (wx_XYZ), spectral intensity file (spec_XYZ) and metadata file (meta_XYZ). The ‘XYZ’ refers to the samples measured (see the publication and its SI for details).
Wave optical simulation of retinal images in laser safety evaluations
2020-11-14

Abstract Lasers with wavelengths in the visible and near infrared region, pose a potential hazard to vision as the radiation can be focused on the retina. The laser safety standard IEC 60825–1:2014 provides limits and evaluation methods to perform a classification for such systems. An important parameter is the retinal spot size which is described by the angular subtense of the apparent source. In laser safety evaluations, the radiation is often described as a Gaussian beam and the image on the retina is calculated using the wave optical propagation through a thin lens. For coherent radiation, this method can be insufficient as the diffraction effects of the pupil aperture influence the retinal image. In this publication, we analyze these effects and propose a general analytical calculation method for the angular subtense. The proposed formula is validated for collimated and divergent Gaussian beams.
Gene expression profiling of malaria parasites reveals common virulence gene expression in adult first-time infected patients and severe cases
2020-11-14

Abstract Sequestration of Plasmodium falciparum -infected erythrocytes to host endothelium through the parasite-derived Pf EMP1 adhesion proteins is central to the development of malaria pathogenesis. Pf EMP1 proteins have diversified and expanded to encompass many sequence variants conferring each parasite a similar array of human endothelial receptor binding phenotypes. Here, we analyzed RNA-seq profiles of parasites isolated from 32 P. falciparum infected adult travelers returning to Germany. Patients were categorized into either malaria naïve (n=15) or pre-exposed (n=17), and into severe (n=8) or non-severe (n=24) cases. For differential expression analysis of Pf EMP1-encoding var gene transcripts were de novo assembled from RNA-seq data and, in parallel, var expressed sequence tags were analyzed and used to predict the encoded domain composition of the transcripts. Both approaches showed in concordance that severe malaria was associated with Pf EMP1 containing the endothelial protein C receptor (EPCR)-binding CIDRα1 domain, whereas CD36-binding Pf EMP1 was linked to non-severe malaria outcomes. First-time infected adults were more likely to develop severe symptoms and tended to be infected for a longer period. Thus, parasites with more pathogenic Pf EMP1 variants are more common in patients with a naïve immune status and/or adverse inflammatory host responses to first infections favors growth of EPCR-binding parasites.
AUXIN RESPONSE FACTOR 6(ARF6)andARF8promote Gibberellin-mediated hypocotyl xylem expansion and cambium homeostasis
2020-11-14

Abstract During secondary growth, the thickening of plant organs, wood (xylem) and bast (phloem) are continuously produced by the vascular cambium. In Arabidopsis hypocotyl and root, we can distinguish two phases of secondary growth based on cell morphology and production rate. The first phase, in which xylem and phloem are equally produced, precedes the xylem expansion phase in which xylem formation is enhanced and xylem fibers differentiate. It is known that Gibberellins (GA) trigger this developmental transition via the degradation of DELLA proteins and that the cambium master regulator BREVIPEDICELLUS/KNAT1 (BP/KNAT1) and the receptor like kinases ERECTA and ERL1 regulate this process downstream of GA. However, our understandings on the regulatory network underlying GA-mediated secondary growth, are still limited. Here, we demonstrate that DELLA-mediated xylem expansion is mainly achieved through RGA and GAI and that RGA and GAI promote cambium senescence. We further show that AUXIN RESPONSE FACTOR (ARF6) and ARF8, which physically interact with DELLAs, specifically repress phloem proliferation and induce cambium senescence during the xylem expansion phase. Moreover, the inactivation of BP in arf6 arf8 background revealed an essential role for ARF6 and ARF8 in cambium establishment and maintenance. Overall, our results shed light on a pivotal hormone cross-talk between GA and auxin in the context of plant secondary growth.
SensitizingStaphylococcus aureusto antibacterial host defense by decoding and blocking the lipid flippase MprF
2020-11-14

Abstract The pandemic of antibiotic resistance represents a major human health threat demanding new antimicrobial strategies. MprF is the synthase and flippase of the phospholipid lysyl-phosphatidylglycerol that increases virulence and resistance of methicillin-resistant Staphylococcus aureus (MRSA) and other pathogens to cationic host defense peptides and antibiotics. With the aim to design MprF inhibitors that could sensitize MRSA to both, human antimicrobials and antibiotics and support the clearance of staphylococcal infections with minimal selection pressure, we developed MprF-targeting monoclonal antibodies, which bound and blocked the MprF flippase subunit. Antibody M-C7.1 targeted a specific loop in the flippase domain that proved to be exposed at both sides of the bacterial membrane, thereby enhancing the mechanistic understanding into bacterial lipid translocation. M-C7.1 rendered MRSA susceptible to host antimicrobial peptides and antibiotics such as daptomycin. Moreover, it impaired MRSA survival in human phagocytes, which recommends MprF inhibitors for new anti-MRSA approaches. MprF-directed monoclonal antibodies provide a proof of concept for development of precisely targeted anti-virulence approaches, which block bacterial antimicrobial resistance mechanisms.
Biphasic cortical macro‐ and microstructural changes in autosomal dominant Alzheimer's disease
2020-11-16

Abstract INTRODUCTION A biphasic model for brain structural changes in preclinical Alzheimer's disease (AD) could reconcile some conflicting and paradoxical findings in observational studies and anti‐amyloid clinical trials. METHODS In this study we tested this model fitting linear versus quadratic trajectories and computed the timing of the inflection points vertexwise of cortical thickness and cortical diffusivity—a novel marker of cortical microstructure—changes in 389 participants from the Dominantly Inherited Alzheimer Network. RESULTS In early preclinical AD, between 20 and 15 years before estimated symptom onset, we found increases in cortical thickness and decreases in cortical diffusivity followed by cortical thinning and cortical diffusivity increases in later preclinical and symptomatic stages. The inflection points 16 to 19 years before estimated symptom onset are in agreement with the start of tau biomarker alterations. DISCUSSION These findings confirm a biphasic trajectory for brain structural changes and have direct implications when interpreting magnetic resonance imaging measures in preventive AD clinical trials.
A Gain‐of‐Function Variant in Dopamine D2 Receptor and Progressive Chorea and Dystonia Phenotype
2020-11-16

ABSTRACT Background We describe a 4‐generation Dutch pedigree with a unique dominantly inherited clinical phenotype of a combined progressive chorea and cervical dystonia carrying a novel heterozygous dopamine D2 receptor ( DRD2 ) variant. Objectives The objective of this study was to identify the genetic cause of the disease and to further investigate the functional consequences of the genetic variant. Methods After detailed clinical and neurological examination, whole‐exome sequencing was performed. Because a novel variant in the DRD2 gene was found as the likely causative gene defect in our pedigree, we sequenced the DRD2 gene in a cohort of 121 Huntington‐like cases with unknown genetic cause (Germany). Moreover, functional characterization of the DRD2 variant included arrestin recruitment, G protein activation, and G protein‐mediated inhibition of adenylyl cyclase determined in a cell model, and G protein‐regulated inward‐rectifying potassium channels measured in midbrain slices of mice. Result We identified a novel heterozygous variant c.634A &gt; T, p.Ile212Phe in exon 5 of DRD2 that cosegregated with the clinical phenotype. Screening of the German cohort did not reveal additional putative disease‐causing variants. We demonstrated that the D2 S/L ‐I 212 F receptor exhibited increased agonist potency and constitutive activation of G proteins in human embryonic kidney 239 cells as well as significantly reduced arrestin3 recruitment. We further showed that the D2 S ‐I 212 F receptor exhibited aberrant receptor function in mouse midbrain slices. Conclusions Our results support an association between the novel p.Ile212Phe variant in DRD2 , its modified D2 receptor activity, and the hyperkinetic movement disorder reported in the 4‐generation pedigree. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.