julilili42/papers huggingface dataset:
Long-Term Effect of GPi-DBS in a Patient With Generalized Dystonia Due to GLUT1 Deficiency Syndrome
2018-05-30

Treatment outcomes from pallidal deep brain stimulation are highly heterogeneous reflecting the phenotypic and etiologic spectrum of dystonia. Treatment stratification to neurostimulation therapy primarily relies on the phenotypic motor presentation; however, etiology including genetic factors are increasingly recognized as modifiers of treatment outcomes. Here, we describe a 53 year-old female patient with a progressive generalized dystonia since age 25. The patient underwent deep brain stimulation of the globus pallidus internus (GPi-DBS) at age 44. Since the clinical phenotype included mobile choreo-dystonic features, we expected favorable therapeutic outcome from GPi-DBS. Although mobile dystonia components were slightly improved in the long-term outcome from GPi-DBS the overall therapeutic response 9 years from implantation was limited when comparing "stimulation off" and "stimulation on" despite of proper electrode localization and sufficient stimulation programming. In order to further understand the reason for this limited motor symptom response, we aimed to clarify the etiology of generalized dystonia in this patient. Genetic testing identified a novel heterozygous pathogenic <i>SLC2A1</i> mutation as cause of glucose transporter type 1 deficiency syndrome (GLUT1-DS). This case report presents the first outcome of GPi-DBS in a patient with GLUT1-DS, and suggests that genotype relations may increasingly complement phenotype-based therapy stratification of GPi-DBS in dystonia.
Dissemination of Cartographic Knowledge: 6th International Symposium of the ICA Commission on the History of Cartography, 2016. Edited by Mirela Altic, Imre Josef Demhardt and Soetkin Vervust.
2018-05-30

"Dissemination of Cartographic Knowledge: 6th International Symposium of the ICA Commission on the History of Cartography, 2016. Edited by Mirela Altic, Imre Josef Demhardt and Soetkin Vervust.." Imago Mundi, 70(2), pp. 239–240
Die älteste tschechische Übersetzung von Märchen aus Tausendundeine Nacht
2018-05-30

Summary This paper deals with a manuscript from the library of the Regional Museum in Chrudim (East Bohemia) which contains a Czech translation of some of the tales of ‘One Thousand and One Nights’. The manuscript was written at the end of the 18 th century in a rather peculiar orthography and belongs to a group of manuscripts which were evidently written by a single person, the painter Josef Ceregetti (1722–1779). The language used in these manuscripts is the literary Czech of that time, with some influence from spoken language. By comparison of the French text of Galland and two contemporary German translations with the Czech text I show that the author seems to have been working with the German translation from the year 1730. The Czech translation was probably intended for a local circle of intellectuals, mainly clerics, and never reached a broader public.
BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells
2018-05-31

The transcription factor BCL11B is essential for development of the nervous and the immune system, and Bcl11b deficiency results in structural brain defects, reduced learning capacity, and impaired immune cell development in mice. However, the precise role of BCL11B in humans is largely unexplored, except for a single patient with a BCL11B missense mutation, affected by multisystem anomalies and profound immune deficiency. Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B. Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency. Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo. A further frameshift mutation was transmitted from a similarly affected mother. Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient. Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice. Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice. Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. In addition, we suggest that missense mutations affecting specific sites within zinc-finger domains might result in distinct and more severe clinical outcomes.
Dependency parsing of learner English
2018-05-31

Abstract Current syntactic annotation of large-scale learner corpora mainly resorts to “standard parsers” trained on native language data. Understanding how these parsers perform on learner data is important for downstream research and application related to learner language. This study evaluates the performance of multiple standard probabilistic parsers on learner English. Our contributions are three-fold. Firstly, we demonstrate that the common practice of constructing a gold standard – by manually correcting the pre-annotation of a single parser – can introduce bias to parser evaluation. We propose an alternative annotation method which can control for the annotation bias. Secondly, we quantify the influence of learner errors on parsing errors, and identify the learner errors that impact on parsing most. Finally, we compare the performance of the parsers on learner English and native English. Our results have useful implications on how to select a standard parser for learner English.
Development, Optimization, and Structure–Activity Relationships of Covalent-Reversible JAK3 Inhibitors Based on a Tricyclic Imidazo[5,4-d]pyrrolo[2,3-b]pyridine Scaffold
2018-05-31

Janus kinases are major drivers of immune signaling and have been the focus of anti-inflammatory drug discovery for more than a decade. Because of the invariable colocalization of JAK1 and JAK3 at cytokine receptors, the question if selective JAK3 inhibition is sufficient to effectively block downstream signaling has been highly controversial. Recently, we discovered the covalent-reversible JAK3 inhibitor FM-381 (23) featuring high isoform and kinome selectivity. Crystallography revealed that this inhibitor induces an unprecedented binding pocket by interactions of a nitrile substituent with arginine residues in JAK3. Herein, we describe detailed structure-activity relationships necessary for induction of the arginine pocket and the impact of this structural change on potency, isoform selectivity, and efficacy in cellular models. Furthermore, we evaluated the stability of this novel inhibitor class in in vitro metabolic assays and were able to demonstrate an adequate stability of key compound 23 for in vivo use.
A diffusion model analysis of the response-effect compatibility effect.
2018-05-31

Humans act goal-oriented, and this idea is at the core of ideomotor theory (IT), which claims that actions are selected by mentally anticipating the sensory consequences brought about by the respective bodily movement (i.e., their action effects). Evidence for this effect anticipation mainly derives from the response-effect (R-E) compatibility (REC) paradigm: In the spatial domain, for example, a left response is produced faster (and sometimes less error-prone) if followed by a compatible left rather than an incompatible right action effect. In the present study, we employed the diffusion model to elucidate the reasons for this observation. To this end, we reanalyzed data from the seminal study by Kunde (2001) and from a new experiment. The overall results suggest that REC affects drift rate. This result fits well with conceptualizing REC as an endogenously created case of stimulus-response compatibility (SRC). Several consequences of this view are discussed against the background of available empirical results. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Real-Time Monitoring of Growth and Orientational Alignment of Pentacene on Epitaxial Graphene for Organic Electronics
2018-05-31

The interaction between a graphene layer and pentacene (PEN) molecules leads to the formation of a lying-down phase, which can improve charge transport for organic vertical field effect transistors and enhance the optical absorption for increased light harvesting in organic solar cells. Here, we present a comprehensive study of PEN growth on epitaxial graphene on silicon carbide (SiC). Simultaneous grazing-incidence small- and wide-angle X-ray scattering (GISAXS/GIWAXS) were used in situ for real-time monitoring of the PEN crystal growth with millisecond time resolution to identify two distinct anisotropic growth stages after the nucleation of the first monolayer (ML). In the first stage up to 1.5 nm, we observe rapid growth of pentacene domains along the (010) and (001) facets. This growth behavior is saturating after 1.5 nm. In a second stage, this is followed by continuous lateral crystal growth in only one in-plane direction (100) forming needle-shaped domains. In the second stage, an uninterrupted linear growth of the lying-down PEN phase is found based on the (001) diffraction up to 15 nm. Ex situ atomic force microscopy and polarized confocal Raman microscopy were used to further support the real-time observations of aligned PEN films on graphene.
The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson’s Disease
2018-06-01

While mitochondrial dysfunction is emerging as key in Parkinson's disease (PD), a central question remains whether mitochondria are actual disease drivers and whether boosting mitochondrial biogenesis and function ameliorates pathology. We address these questions using patient-derived induced pluripotent stem cells and Drosophila models of GBA-related PD (GBA-PD), the most common PD genetic risk. Patient neurons display stress responses, mitochondrial demise, and changes in NAD+ metabolism. NAD+ precursors have been proposed to ameliorate age-related metabolic decline and disease. We report that increasing NAD+ via the NAD+ precursor nicotinamide riboside (NR) significantly ameliorates mitochondrial function in patient neurons. Human neurons require nicotinamide phosphoribosyltransferase (NAMPT) to maintain the NAD+ pool and utilize NRK1 to synthesize NAD+ from NAD+ precursors. Remarkably, NR prevents the age-related dopaminergic neuronal loss and motor decline in fly models of GBA-PD. Our findings suggest NR as a viable clinical avenue for neuroprotection in PD and other neurodegenerative diseases.
First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury
2018-06-01

Background. Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery. Objective. This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia. Methods. Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks). Results. ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining &gt;10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia. Conclusions. ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.
Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species
2018-06-01

Using a comparative genomics approach, it was possible to determine the potential of the genus Amycolatopsis to produce a huge diversity of secondary metabolites. Furthermore, the analysis demonstrates that horizontal and vertical gene transfer play an important role in the acquisition and maintenance of valuable secondary metabolites. Our results cast light on the interconnections between secondary metabolite gene clusters and provide a way to prioritize biosynthetic pathways in the search and discovery of novel compounds.
Characterization of cancer genomic heterogeneity by next-generation sequencing advances precision medicine in cancer treatment
2018-06-01

Abstract Cancer is a heterogeneous disease with unique genomic and phenotypic features that differ between individual patients and even among individual tumor regions. In recent years, large-scale genomic studies and new next-generation sequencing technologies have uncovered more scientific details about tumor heterogeneity, with significant implications for the choice of specific molecular biomarkers and clinical decision making. Genomic heterogeneity significantly contributes to the generation of a diverse cell population during tumor development and progression, representing a determining factor for variation in tumor treatment response. It has been considered a prominent contributor to therapeutic failure, and increases the likelihood of resistance to future therapies in most common cancers. The understanding of molecular heterogeneity in cancer is a fundamental component of precision oncology, enabling the identification of genomic alteration of key genes and pathways that can be targeted therapeutically. Here, we review the emerging knowledge of tumor genomics and heterogeneity, as well as potential implications for precision medicine in cancer treatment and new therapeutic discoveries. An analysis and interpretation of the TCGA database was included.
A Universal Spin–Mass Relation for Brown Dwarfs and Planets
2018-06-01

Abstract While brown dwarfs show similarities to stars early in their lives, their spin evolutions are much more akin to those of planets. We have used light curves from the K2 mission to measure new rotation periods for 18 young brown dwarfs in the Taurus star-forming region. Our sample spans masses from 0.02 to 0.08 M ⊙ and has been characterized extensively in the past. To search for periods, we utilize three different methods (autocorrelation, periodogram, Gaussian processes). The median period for brown dwarfs with disks is twice as long as for those without (3.1 versus 1.6 days), a signature of rotational braking by the disk, albeit with small numbers. With an overall median period of 1.9 days, brown dwarfs in Taurus rotate slower than their counterparts in somewhat older (3–10 Myr) star-forming regions, consistent with spin-up of the latter due to contraction and angular momentum conservation, a clear sign that disk braking overall is inefficient and/or temporary in this mass domain. We confirm the presence of a linear increase of the typical rotation period as a function of mass in the substellar regime. The rotational velocities, when calculated forward to the age of the solar system, assuming angular momentum conservation, fit the known spin–mass relation for solar system planets and extra-solar planetary-mass objects. This spin–mass trend holds over six orders of magnitude in mass, including objects from several different formation paths. Our result implies that brown dwarfs by and large retain their primordial angular momentum through the first few Myr of their evolution.
Efficient Data Plane Protection for SDN
2018-06-01

Software-defined networks (SDN) usually require intervention of a controller to restore connectivity in case of link or node failures. To avoid this dependence, a fast failover function enables switches to locally detect a failure and deviate affected traffic. In this paper, we develop fast reroute (FRR) methods leveraging that feature and the principle of loop-free alternates (LFAs) from IP networks for network-wide configuration. We explain how LFAs, remote LFAs, and novel explicit-path LFAs may be implemented with OpenFlow so that SDN with general destination-based routing can be protected. An advanced loop detection and termination function is suggested to prevent loops that may be caused by FRR in case of severe failures. We evaluate the FRR methods on a large set of representative network topologies and compare them with existing FRR methods. Classic rLFAs from IP networks generate many loops in case of node failures so that they are not appropriate for SDN. One developed protection method is particularly suitable for SDN as it can protect all flows in a network against any single link and node failure. The solution is efficient because it secures most traffic also in case of dual failures, leads to short backup paths, and requires in most networks only a few additional forwarding entries per node. The latter is important as OpenFlow switches can accommodate only a moderate number of forwarding entries in their flow tables.
Rendering Physically Correct Raindrops on Windshields for Robustness Verification of Camera-based Object Recognition
2018-06-01

Recent developments in the field of autonomous cars indicate the appearance of those vehicles on the streets of every city in the near future. This urban driving requires zero error tolerance. In order to guarantee safety requirements self-driving cars and the used software have to pass exhaustive tests under as many different conditions as possible. The more versatile the considered influences and the more thorough the tests made under those influences, the safer the car will drive under real conditions. Unfortunately, it is very time and resource intensive to record the same test set of images over and over again, every time producing, or hoping for, specific conditions; especially when using real test vehicles. This is where environment simulation comes into play. This research investigates the simulation of environmental influences which may affect the sensors used in autonomous vehicles, in particular how raindrops resting on a windshield affect cameras as they may occlude large parts of the field of view. We propose a novel method to render these raindrops using Continuous Nearest Neighbor search leveraging the benefits of R-trees. The 3D scene in front of the camera, which is generated from stereo images, reflects physically correct in these drops. This leads to near photo-realistic simulated results. The derived images may be used to extend the training data sets used for machine learning without being forced to capture new real pictures.
Development of speech rhythm in first language: The role of syllable intensity variability
2018-06-01

The opening-closing alternations of the mouth were viewed as the articulatory basis of speech rhythm. Such articulatory cycles have been observed to highly correlate with the intensity curve of the speech signal. Analysis of the intensity variability in English monolingual children and adults revealed that (1) adults showed significantly smaller intensity variability than children, and (2) intensity variability decreased from intermediate-aged children to older children. Maturation of articulatory motor control is likely to be the main reason for the reduced variability in articulatory cycles, and hence smaller intensity variability in adults and older children.
Structural stress response of segmented natural shells: a numerical case study on the clypeasteroid echinoidEchinocyamus pusillus
2018-06-01

The skeleton of Echinocyamus pusillus is considered as an exceptional model organism for structural strength and skeletal integrity within the echinoids as demonstrated by the absence of supportive collagenous fibres between single plates and the high preservation potential of their skeletons. The structural principles behind this remarkably stable, multi-plated, light-weight construction remain hardly explored. In this study, high-resolution X-ray micro-computed tomography, finite-element analysis and physical crushing tests are used to examine the structural mechanisms of this echinoid's skeleton. The virtual model of E. pusillus shows that the material is heterogeneously distributed with high material accumulations in the internal buttress system and at the plate boundaries. Finite-element analysis indicates that the heterogeneous material distribution has no effect on the skeleton's strength. This numerical approach also demonstrates that the internal buttress system is of high significance for the overall skeletal stability of this flattened echinoid. Results of the finite-element analyses with respect to the buttress importance were evaluated by physical crushing tests. These uniaxial compression experiments support the results of the simulation analysis. Additionally, the crushing tests demonstrate that organic tissues do not significantly contribute to the skeletal stability. The strength of the echinoid shell, hence, predominantly relies on the structural design.
A Distributed Control Architecture for a Loosely Coupled Virtual Power Plant
2018-06-01

The increasing share of renewable energy with volatile production results in higher variability of prices for electrical energy. Optimized operating schedules, e.g., for industrial units, can yield a considerable reduction of energy costs by shifting processes with high power consumption to times with low energy prices. We present a distributed control architecture for virtual power plants (VPPs) where VPP participants benefit from flexible adaptation of schedules to price forecasts while maintaining control of their operating schedule. An aggregator trades at the energy market on behalf of the participants and benefits from more detailed and reliable load profiles within the VPP.
Distributed Controller Communication in Virtual Power Plants Using Smart Meter Gateways
2018-06-01

A virtual power plant (VPP) is a distributed power plant aggregating the capacity of multiple small distributed energy resources (DERs) and acts as a single entity at the energy markets. The VPP needs a secure communication infrastructure to monitor, coordinate, and control the DERs. This work describes how a smart meter gateway (SMGW) according to the German regulations can be used to provide a secure communication channel between the central VPP aggregator and distributed DER controllers.