julilili42/papers huggingface dataset:
Notch1-Cyclin E-p27kip1 and RAD17 form a network of proteins which control cellular proliferation and DNA damage response in cholangiocarcinoma
2018-01-01

Cholangiocellular cancers are characterized by a high degree of genetic instability, which is believed to contribute to the heterogeneous malignant phenotype and the resistance towards therapeutic interventions. Previously we had shown that expression of the intracellular domain of Notch1 (NICD) protein leads to the formation of progenitor derived CCC in mice. NICD overexpressing CCC are characterized by high expression of Cyclin E and greatly increased levels of DNA damage. Cyclin E exerts its oncogenic function through the acceleration of the cell cycle (together with cdk2) and through its ability to induce replicative stress and DNA damage. Cyclin E/cdk2 complexes are in turn inhibited by the cyclin kinase inhibitor (cki) p27kip1. p27 is an established prognostic marker in CCC and many tumors show reduced expression of this protein which correlates with poor prognosis. We recently identified a new function of p27 in CCC cells in directly regulating the response to DNA damage. p27 binds RAD17 an essential protein which loads DNA damage response complexes (9 – 1-1 and MRN) onto DNA. Upon DNA damage the p27-RAD17 complex dissociates after phosphorylation of rad17 by the ATM&ATR kinase. Dissociation from p27 is an essential step in the DNA damage response pathway. We therefore hypothesize that Notch1-Cyclin E-p27 and RAD17 together form a network of proteins which control cellular proliferation and DNA damage response in cholangiocarcinoma.
Inhibition of Collagen Related Peptide Induced Platelet Activation and Apoptosis by Ceritinib
2018-01-01

Background/Aims: The anaplastic lymphoma (tyrosine) kinase (ALK) inhibitor ceritinib triggers apoptosis of tumor cells and eryptosis of erythrocytes. Blood platelets may similarly enter a state resembling apoptosis, which could be triggered by activation with collagen related peptide (CRP). CRP-induced platelet apoptosis is characterized by cell membrane scrambling with phosphatidylserine exposure to the platelet surface and cell shrinkage, preceded by externalization of Ca2+ channel Orai1, increase of cytosolic Ca2+-activity ([Ca2+]i), formation of reactive oxygen species (ROS), and caspase activation. The present study explored whether ceritinib triggers platelet apoptosis and/or modifies the CRP induced apoptosis. Methods: Platelets isolated from wild-type mice were exposed for 30 minutes to ceritinib (1.5 μg/ml) without or with 2.5 – 15 min pretreatment with CRP (2 μg/ml or 5 μg/ml). Flow cytometry was employed to estimate cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, ROS abundance from 2’,7’-dichlorodihydrofluorescein diacetate fluorescence, platelet degranulation from P-selectin abundance, integrin activation from αIIbβ3 integrin abundance, caspase activity utilizing an Active Caspase-3 Staining kit, phosphatidylserine abundance from annexin-V-binding, platelet volume from forward scatter and aggregation utilizing staining with CD9-APC and CD9-PE. Results: In the absence of CRP, ceritinib slightly, but significantly decreased [Ca2+]i without significantly modifying the other measured parameters. CRP significantly increased [Ca2+]i, ROS abundance, P-selectin abundance, activated αIIbβ3 integrin, annexin-V-binding, caspase activity as well as aggregation and decreased cell volume, all effects significantly blunted in the presence of ceritinib. Conclusions: The present observations uncover a novel, unexpected effect of ceritinib, i.e. inhibition of CRP-induced platelet activation and apoptosis.
Intraspinal intradural nodular fasciitis mimicking glioblastoma metastasis: a case report
2018-01-01

We report the case of a 78-year-old male patient suffering from right temporal glioblastoma with radiographic meningeal tumor spread. During the further course of the disease he developed a rapidly progressive paraplegia. An magnetic resonance imaging scan showed a contrast enhancing an intraspinal intradural lesion with compression of the myelon on segment Th 8/9. With a high suspicion of a spinal metastasis of the known glioblastoma, emergency spinal decompression and resection of the intradural mass was performed. However, histopathological evaluation revealed nodular fasciitis without any signs of glial origin.
Simulation of short-pulse DPOAEs using a hydrodynamic time-domain cochlea model: The effect of interchanging the elicitors
2018-01-01

Distortion-product otoacoustic emissions (DPOAEs) are used in clinics and research to noninvasively ascertain the functional state of the cochlea. According to a widely accepted model, the cubic distortion product at 2f1 - f2 consists of a nonlinear-distortion component, which is generated in the overlap region of the two primary tones, and a coherent-reflection component arising at the tonotopic place of the distortion-product frequency. Pulsing the f2 primary in the presence of a f1 tone enables the separation of the two DPOAE components in time-domain recordings due to their different latencies. However, short-pulse DPOAE responses show larger amplitudes and shorter latencies when interchanging the temporal arrangement of the primary tones, i.e. triggering DPOAE generation with a f1 short pulse in the presence of a f2 tone. The present work utilizes a one-dimensional implementation of a nonlinear hydrodynamic cochlea model for the human cochlea to simulate cochlear distortion products for the two short-pulse acquisition paradigms. Matrix formulation of the equations of motion was used to compute the solution directly in the time domain. The properties of the simulated cochlear distortion products closely match experimental data from normal-hearing subjects. The results suggest that the temporal arrangement of the primary tones has a distinct influence on the mechanoelectrical transduction near the f2 place which is reflected by changes in the DPOAE responses.
CHAPTER 3. Modulation of Calcium Overload and Calpain Activity
2018-01-01

Fluxes of calcium ions (Ca2+) in rod photoreceptors are major regulators of steady-state and light-evoked intracellular reactions to stimuli. The homeostasis of Ca2+ is regulated by channels and pumps localized at the plasma membrane and in intracellular organelles. Photoreceptor degeneration is frequently associated with Ca2+ homeostasis disruption and stimulation of Ca2+ activated proteases, such as calpains. These events trigger molecular pathways leading to cell death. In this chapter we discuss Ca2+ channels and pumps as well as calpains as potential targets of new therapies for retinal degeneration.
A spectral decomposition for the block counting process and the fixation line of the beta(3,1)-coalescent
2018-01-01

A spectral decomposition for the generator of the block counting process of the -coalescent is provided. This decomposition is strongly related to Riordan matrices and particular Fuss–Catalan numbers. The result is applied to obtain formulas for the distribution function and the moments of the absorption time of the -coalescent restricted to a sample of size . We also provide the analog spectral decomposition for the fixation line of the -coalescent. The main tools in the proofs are generating functions and Siegmund duality. Generalizations to the -coalescent with parameter are discussed leading to fractional differential or integral equations.
Convergence or Divergence? Educational Discrepancies in Work-Care Arrangements of Mothers with Young Children in Germany
2018-01-01

This study examines how educational differences in work-care patterns among mothers with young children in Germany changed between 1997 and 2013. Since the mid-2000s, Germany has undergone a paradigm shift in parental leave and childcare policies. Our comparative analysis of East and West Germany provides new evidence on whether the long-standing gender regime differences interact with recent developments of social class inequalities in the changing family policy context. The analyses include pooled binary and multinomial logistic regressions based on 17,764 observations of 8604 children below the age of three years from the German Socio-Economic Panel Study (SOEP). The findings point to growing educational divergence in work-care arrangements in East and West Germany: employment and day-care use increased more strongly among families with medium and highly educated mothers compared to those with low education. This has critical implications for the latter’s economic security. The decline in the use of informal childcare options was, however, fairly homogenous.
Offshoring and volatility of demand
2018-01-01

In this paper we explore the role that demand uncertainty plays for the offshoring decision, and the role that offshoring plays for domestic volatility of employment. Offshoring is modeled as in Antras & Helpman (2004), but we assume complete contracts. Firms are heterogeneous as in Melitz (2003). Uncertainty arises through recurring firm-specific shocks to demand. The presence of a cost of firing or hiring as in Bagliano & Bertola (2004) generates an intertemporal element to a firm’s employment decision in its domestic and offshore production. In this environment, offshoring is driven by differential labor market exibility as well as by wage differences. Our most important results are: 1) If the foreign labor market features a high exibility, measured relative to its wage rate, compared to the domestic labor market, then higher uncertainty has a pro-offshoring effect. And 2), under this same condition, offshoring increases volatility in domestic employment of offshoring firms and the volatility of offshore employment of these same firms is larger than volatility of domestic employment.
Searching Neutrinoless Double Beta Decay with Gerda Phase II
2018-01-01

An observation of neutrinoless double beta ([Formula: see text]) decay would allow to shed light onto the nature of neutrinos. Gerda (GERmanium Detector Array) aims to discover this process in a background-free search using [Formula: see text]Ge. The experiment is located at the Laboratori Nazionali del Gran Sasso (LNGS) of the Istituto Nazionale di Fisica Nucleare (INFN) in Italy. Bare, isotopically enriched, high purity germanium detectors are operated in liquid argon. Gerda follows a staged approach. In Phase II 35.6 kg of enriched germanium detectors are operated since December 2015. The application of active background rejection methods, such as a liquid argon scintillation light read-out and pulse shape discrimination of germanium detector signals, allows to reduce the background index to the intended level of [Formula: see text] cts/(keV⋅kg⋅yr). No evidence for the [Formula: see text] decay has been found in 23.2 kg⋅yr of Phase II data, and together with data from Phase I the up-to-date most stringent half-life limit for this process in [Formula: see text]Ge has been established, at a median sensitivity of 5.8⋅10[Formula: see text][Formula: see text]yr the 90[Formula: see text]% C.L. lower limit is 8.0⋅10[Formula: see text][Formula: see text]yr.
COAST - Customizable Online Syllable Enhancement in Texts. A flexible framework for automatically enhancing reading materials
2018-01-01

This paper presents COAST, a web-based application to easily and automatically enhance syllable structure, word stress, and spacing in texts, that was designed in close collaboration with learning therapists to ensure its practical relevance. Such syllable-enhanced texts are commonly used in learning therapy or private tuition to promote the recognition of syllables in order to improve reading and writing skills. In a state of the art solutions for automatic syllable enhancement, we put special emphasis on syllable stress and support specific marking of the primary syllable stress in words. Core features of our tool are i) a highly customizable text enhancement and template functionality, and ii) a novel crowd-sourcing mechanism that we employ to address the issue of data sparsity in language resources. We successfully tested COAST with real-life practitioners in a series of user tests validating the concept of our framework.
Automatic Input Enrichment for Selecting Reading Material: An Online Study with English Teachers
2018-01-01

Input material at the appropriate level is crucial for language acquisition. Automating the search for such material can systematically and efficiently support teachers in their pedagogical practice. This is the goal of the computational linguistic task of automatic input enrichment (Chinkina & Meurers, 2016): It analyzes and re-ranks a collection of texts in order to prioritize those containing target linguistic forms. In the online study described in the paper, we collected 240 responses from English teachers in order to investigate whether they preferred automatic input enrichment over web search when selecting reading material for class. Participants demonstrated a general preference for the material provided by an automatic input enrichment system. It was also rated significantly higher than the texts retrieved by a standard web search engine with regard to the representation of linguistic forms and equivalent with regard to the relevance of the content to the topic. We discuss the implications of the results for language teaching and consider the potential strands of future research.
It’s been a decade
2018-01-01

The Swiss Young Neurosurgeons Society (SYNS) comes to life in 2008, creating a community renowned for its unique spirit, a platform dedicated to lifelong teaching and learning. In 2008, a small group of Swiss residents found a cross-canton training platform to provide dedicated, affordable courses organized by residents to directly support their peers. After almost 10 years, SYNS thrives on its unique, familial spirit cultivating a direct contact with teachers as well as with their supporters. The society provides up to four annual training courses and serves as an open platform for residents to exchange experiences and to represent their members’ interests on a national and international level.
Computed diffusion weighted imaging (cDWI) and voxelwise-computed diffusion weighted imaging (vcDWI) for oncologic liver imaging: A pilot study
2018-01-01

Measuring higher upper b-values seems to lead to more precise computed high b-value images and a decrease of CV. vcDWI provides a comparable lesion contrast to b = 1500s/mm<sup>2</sup> and offers additionally the reduction of T2 shine-through effects. For vcDWI, measuring b = 1000s/mm<sup>2</sup> as upper b-value seems to be necessary to guarantee good lesion visibility in the liver based on our preliminary results.
The prevalence of repair in studies of language evolution
2018-01-01

Fay et al, 2017; Byun et al, in press), many still fail to consider just what interaction offers emerging communication systems.That is, while it's been acknowledged that face-to-face interaction in communication games is beneficial in its approximation of natural language use (Macuch Silva & Roberts, 2016;Nölle et al, 2017), there remains a lack of detailed analysis of what this type of interaction affords participants, and how those affordances impact the evolving language.To this end, here we will expose one particular process that occurs in interaction: repair, or the processes by which we can indicate misunderstanding and resolve problems in communication (Schegloff, Jefferson, & Sacks, 1977;Jefferson, 1972).Though it is often not explicitly analyzed, repair is a relevant aspect of interaction to consider for its effects on the evolution of a communication system as well as how it demonstrates the moment-to-moment processing and negotiation of alignment in emerging communication.We present data from various studies of language evolution in which we document how repair is carried out, the types of repair present, and their effect on novel signaling.All studies in this collection utilized referential communication tasks -some iterated over simulated generations and other repeating interactions between two individuals.However, they differ in modality (of stimuli and communication).The data collection includes: silent gesture communication of written nouns and verbs; non-linguistic vocalizations and
Sonidegib, a Novel Inhibitor of Suicidal Erythrocyte Death
2018-01-01

Background/Aims: The Hedgehog pathway disrupting drug sonidegib is used in the treatment of basal cell carcinoma. Side effects of sonidegib include anemia, which could result either from impaired erythropoiesis or from loss of erythrocytes e.g. due to suicidal erythrocyte death or eryptosis, which is characterized by cell membrane scrambling with phosphatidylserine translocation to the cell surface and by cell shrinkage. Eryptosis is stimulated by cell stress, including energy depletion, hyperosmotic shock, oxidative stress and excessive increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored, whether sonidegib exerts an effect on eryptosis. Methods: Human erythrocytes have been treated with energy depletion (glucose withdrawal for 48 hours), hyperosmotic shock (addition of 550 mM sucrose for 6 hours), oxidative stress (addition of 0.3 mM tert-butylhydroperoxide [tBOOH] for 50 min) or Ca2+ ionophore ionomycin (1 μM for 60 min) in absence and presence of sonidegib (2-6 μg/ ml). After treatment flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, and cell volume from forward scatter. Hemolysis was estimated from the hemoglobin concentration in the supernatant. Results: In the absence of cell stress exposure to sonidegib did not significantly modify annexin-V-binding or forward scatter, but triggered hemolysis. Energy depletion, hyperosmotic shock, oxidative stress and ionomycin, all markedly and significantly increased the percentage of annexin-V-binding erythrocytes, and decreased the forward scatter. Sonidegib significantly blunted the effect of energy depletion, hyperosmotic shock, and oxidative stress, but not of ionomycin on annexin-V-binding. Sonidegib further significantly blunted the effect of energy depletion, but not of hyperosmotic shock, oxidative stress, and ionomycin on forward scatter. Conclusions: Sonidegib is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion, hyperosmotic shock and oxidative stress.
Neutron anisotropic evaporation and scission emission in fission
2018-01-01

Experimental neutron distributions have been investigated in the spontaneous fission of 252 Cf at IPHC in Strasbourg. The CORA experiment associating the CODIS twin ionisation chamber and the neutron multi-detector DEMON aimed to solve an long-standing problem in fission: the possible emission of scission neutrons and/or the presence of a dynamical anisotropy in the neutron evaporation by the moving fission fragments. A new method allowing to establish the dynamical anisotropy in an independent way is presented. The results obtained from a comparison with simulations based on GEANT4 are shown.
Multi-photon luminescence of single gold nanoparticles: Exploring the dynamics of plasmons and electron hole pairs
2018-01-01

We investigate the dynamics of the multi-photon excitation of single, isolated gold nanoparticles and show that the one/two/three emission can be actively switched by changing the excitation pulse duration.
CHAPTER 6. Modulation of cGMP-signalling to Prevent Retinal Degeneration
2018-01-01

In the photoreceptors of the retina, the second-messenger molecule cyclic guanosine monophosphate (cGMP) occupies centre stage in the phototransduction cascade. Remarkably, cGMP is also involved in hereditary photoreceptor degeneration caused by a variety of different genetic insults. This provides an entry point for the development of inhibitory cGMP analogues for a mutation-independent treatment. Here, we outline how cGMP signalling can be targeted for the treatment of retinal degeneration, how inhibitory cGMP analogues may be designed and formulated, and how test systems of rising complexity can be used to identify new compounds with photoreceptor neuroprotective properties. In this context, we cite the European Union-funded DRUGSFORD project and provide an example for the efficacy of a specific cGMP analogue to prevent photoreceptor loss and preserve retinal function.
Children’s comprehension of pronouns and definites
2018-01-01

We present an experiment which tests children’s comprehension of the requirementsof use of pronouns and definites. An adult-like use of definites and pronouns imposes differentbut related requirements. In the case of definites, a unique referent is required in the context,whereas in the case of a pronoun, the referent in the context has to be salient. In this experiment,we use a novel word task to test three-year-olds’ sensitivity to these requirements. Ourresults show that children are adult-like in their sensitivity to salience in their comprehensionof pronouns, compared to definites. However, they failed to show sensitivity to the uniquenessrequirement on the use of definites.Keywords: pronouns, definiteness, language acquisition, salience, uniqueness, familiarity.
2018-01-01

Supernova remnants exhibit shock fronts (shells) that can accelerate charged particles up to very high energies. In the past decade, measurements of a handful of shell-type supernova remnants in very high-energy gamma rays have provided unique insights into the acceleration process. Among those objects, RX J1713.7−3946 (also known as G347.3−0.5) has the largest surface brightness, allowing us in the past to perform the most comprehensive study of morphology and spatially resolved spectra of any such very high-energy gamma-ray source. Here we present extensive new H.E.S.S. measurements of RX J1713.7−3946, almost doubling the observation time compared to our previous publication. Combined with new improved analysis tools, the previous sensitivity is more than doubled. The H.E.S.S. angular resolution of 0.048° (0.036° above 2 TeV) is unprecedented in gamma-ray astronomy and probes physical scales of 0.8 (0.6) parsec at the remnant’s location. The new H.E.S.S. image of RX J1713.7−3946 allows us to reveal clear morphological differences between X-rays and gamma rays. In particular, for the outer edge of the brightest shell region, we find the first ever indication for particles in the process of leaving the acceleration shock region. By studying the broadband energy spectrum, we furthermore extract properties of the parent particle populations, providing new input to the discussion of the leptonic or hadronic nature of the gamma-ray emission mechanism.Key words: acceleration of particles / cosmic rays / ISM: supernova remnants / gamma rays: general / astroparticle physic★ All images (FITS files)are available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/612/A6† Deceased.
2018-01-01

Shell-type supernova remnants (SNRs) are considered prime candidates for the acceleration of Galactic cosmic rays (CRs) up to the knee of the CR spectrum at E ≈ 3 × 10 eV. Our Milky Way galaxy hosts more than 350 SNRs discovered at radio wavelengths and at high energies, of which 220 fall into the H.E.S.S. Galactic Plane Survey (HGPS) region. Of those, only 50 SNRs are coincident with a H.E.S.S source and in 8 cases the very high-energy (VHE) emission is firmly identified as an SNR. The H.E.S.S. GPS provides us with a legacy for SNR population study in VHE γ-rays and we use this rich data set to extract VHE flux upper limits from all undetected SNRs. Overall, the derived flux upper limits are not in contradiction with the canonical CR paradigm. Assuming this paradigm holds true, we can constrain typical ambient density values around shell-type SNRs to n ≤ 7 cm and electron-to-proton energy fractions above 10 TeV to ε ≤ 5 × 10 . Furthermore, comparisons of VHE with radio luminosities in non-interacting SNRs reveal a behaviour that is in agreement with the theory of magnetic field amplification at shell-type SNRs.