bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metastasenchirurgie beim Harnblasenkarzinom: Sinn oder Unsinn
Authors: Garstka Nathalie , Shariat Shahrokh François 
Published: February 2020

ZusammenfassungDas Outcome eines lymphknotenpositiven oder fernmetastasierten Urothelkarzinoms (mUC) der Harnblase ist schlecht. Eine cisplatinbasierte Chemotherapie wie Gemcitabin/Cisplatin oder akzeleriertes MVAC (Methotrexat, Vinblastin, Adriamycin und Cisplatin) bilden den Standard in der systemischen Erstlinientherapie des mUC. Alternativ kann seit 2016 in diesem Setting eine Immuntherapie angeboten werden. Somit stehen z. B. in der Erstlinie cisplatinungeeigneten Patienten die Checkpointinhibitoren Atezolizumab oder Pembrolizumab zur Verfügung, sofern sie einen positiven PD-L1-Status aufweisen. Eine Metastasen gezielte operative Therapie wird bereits erfolgreich bei verschiedenen urologischen Tumoren, wie dem Hoden- oder dem Nierenzellkarzinom, eingesetzt, um das Überleben zu verlängern und/oder die Lebensqualität zu verbessern. In diesem Artikel soll der Stellenwert der Metastasenchirurgie beim mUC der Harnblase evaluiert werden.
The approach of partial stabilisation in design of discrete-time robust guidance laws against manoeuvering targets
Authors: Shafiei M.H. , Vazirpour N. 
Published: February 2020

ABSTRACTIn this paper, a robust three-dimensional guidance law against manoeuvering targets is designed using the approach of discrete-time partial stabilisation. In the proposed method, the equations of the guidance problem are divided into two subsystems where the asymptotic stability is desired only for the first one. The control input of the second subsystem is designed such that the collision to be ensured in a short time. Despite recent advances in technology and implementation of digital controllers, the design of guidance laws with the approach of discrete-time partial stabilisation has not been done, till now. One of the advantages of this paper is to design a discrete-time guidance law even with the difficulties of the discrete-time Lyapunov theorem. Moreover, the Lyapunov function is chosen based on the physics of the guidance problem (making the rate of line of sight (LOS) rotation close to zero), and it is shown that it is not possible to asymptotically stabilise the system in the case of manoeuvering targets. Nevertheless, to guarantee the collision with the target, it is enough to limit the rotation rate of LOS to a small value. Finally, simulation results are given to show the appropriate performance of the proposed guidance law.
Conceptual metaphors in poetry interpretation: a psycholinguistic approach
Authors: RASSE CARINA , ONYSKO ALEXANDER , CITRON FRANCESCA M. M. 
Published: February 2020

ABSTRACTPsycholinguistic research has shown that conceptual metaphors influence how people produce and understand language (e.g., Gibbs, 1994, 2017a; Kövecses, 2015; Jacobs & Kinder, 2017). So far, investigations have mostly paid attention to non-poetic metaphor comprehension. This focus stems from the original discovery of Conceptual Metaphor Theory that much of everyday, non-poetic language is metaphorical. The present study aims to expand this focus and explores whether people access conceptual metaphors during poetry interpretation. To answer this question, we conducted a psycholinguistic experiment in which 38 participants, all native speakers of English, completed two tasks. In each task, participants read excerpts of poetry containing conceptual metaphors before selecting or rating items that indicated their implicit and explicit awareness of the conceptual metaphors. The results of both tasks show that participants retrieve conceptual metaphors when reading poetry. This provides empirical evidence in favor of the idea that crucial aspects of poetic thought and language arise from conceptual metaphor.
Ranking Dutch intensifiers: a usage-based approach
Authors: RICHTER MICHAEL , VAN HOUT ROELAND 
Published: February 2020

ABSTRACTThe present approach estimates the strength of intensifiers in Dutch by computing their information values in a language corpus, that is, contextual information content (Cohen Priva, 2008; Piantadosi, Tily, & Gibson, 2011) and Shannon Information (Shannon & Weaver, 1948), to respectively explain the use value and the expressive value of intensifiers when they intensify a predicative adjective. Conflicting strength values help in understanding the high number of intensifiers commonly available in particular languages and the constant need for adding new ones. Our approach underlines the relevance of two measures of information content (IC) for ranking intensifiers: (i) IC in context: the more combinatorial or transitional options an intensifier has, the higher its contextual information content and consequently its use value; and (ii) IC in relation to all alternative intensifiers: the higher the surprisal value that the occurrence of an intensifier evokes, the higher its expressive value. We shall investigate the validity of these two measures by researching a large corpus of Dutch tweets and shall test whether the values of these two measures can predict the stacking order in sequences of intensifiers.
False Memories: The Other Side of Forgetting
Authors: Turk Katherine W. , Palumbo Rocco , Deason Rebecca G. , Marin Anna , Elshaar Ala’a , Gosselin Emma , O’Connor Maureen K. , Tripodis Yorghos , Budson Andrew E. 
Published: February 2020

AbstractObjective:To measure caregivers’ and clinicians’ perception of false memories in the lives of patients with memory loss due to Alzheimer’s disease (AD) and mild cognitive impairment (MCI) using a novel false memories questionnaire. Our hypotheses were that false memories are occurring as often as forgetting according to clinicians and family members.Method:This prospective, questionnaire-based study consisting of 20 false memory questions paired with 20 forgetting questions had two forms: one for clinicians and the other for family members of older subjects. In total, 226 clinicians and 150 family members of 49 patients with AD, 44 patients with MCI, and 57 healthy older controls (OCs) completed the questionnaire.Results:False memories occurred nearly as often as forgetting according to clinicians and family members of patients with MCI and AD. Family members of OCs and patients with MCI reported fewer false memories compared to those of the AD group. As Mini-Mental State Examination scores decreased, the mean score increased for both forgetting and false memories. Among clinicians, correlations were observed between the dementia severity of patients seen with both forgetting and false memories questionnaire scores as well as with the impact of forgetting and false memories on daily life.Conclusion:Patients with AD experience false memories almost as frequently as they do forgetting. Given how common false memories are in AD patients, additional work is needed to understand the clinical implications of these false memories on patients’ daily lives. The novel false memories questionnaire developed may be a valuable tool.
Seismic Attenuation and Velocity Measurements of the Uppermost Mantle Beneath the Central and Eastern United States and Implications for the Temperature of the North American Lithosphere
Authors: Yassminh Rayan , Laphim Parichat , Sandvol Eric 
Published: February 2020

AbstractWe constructed a detailed map of the uppermost mantle seismic structure beneath the Central and Eastern United States (CEUS) using the International Seismological Centre Bulletin and seismic waveforms from USArray. Identical Pn and Sn travel time data sets were inverted to tomographically image the uppermost mantlePwave (Pn) velocity,Swave (Sn) velocity, and the velocity ratio (VPn/VSn). Furthermore, we modified the two‐station method in order to limit the contributions of site response and estimate the effective attenuation of Sn phase (Q−1Sn).Lower Q values generally correspond with lower velocities in terms of both Pn and Sn wave speeds (e.g., New England and the Mississippi Embayment), but some regions, including southern Georgia, eastern South Carolina, and the New Madrid Seismic Zone, show high velocity and low QSnvalues. This can be explained by scattering attenuation of the Sn phase. To estimate the uppermost mantle temperature, a constrained grid‐search algorithm was conducted using the observed VSn, VPn, and QSnwith the calculated velocities of specific compositional models. The uppermost mantle temperature result shows ~300–500 °C beneath the northern midcontinent and 1100 °C beneath New England. Although our temperature results appear to be well resolved, we found that VPn, VSn, and QSnare not enough to constrain the detailed uppermost mantle composition model. Our results highlight significant temperature heterogeneity in the uppermost mantle across the CEUS and is consistent with there not being any melt within the uppermost mantle beneath the CEUS.
Effects of Coupling Between Wave‐Induced Fluid Flow and Elastic Scattering on P‐Wave Dispersion and Attenuation in Rocks With Aligned Fractures
Authors: Guo Junxin , Gurevich Boris 
Published: February 2020

AbstractFracture‐background wave‐induced fluid flow (FB‐WIFF) and elastic scattering are considered two important mechanisms for P‐wave dispersion and attenuation in the fractured and porous fluid‐saturated rock. While numerous theoretical models have been proposed to study these two mechanisms, their coupling effects are seldom studied. Hence, in this work, we investigate the coupling between these two mechanisms theoretically based on the Biot equations of dynamic poroelasticity. The P wave is assumed to propagate perpendicular to the fracture plane in the fluid‐saturated porous rock with aligned penny‐shaped fractures. The general solutions are first obtained from the governing equations, then the expressions for the coefficients of the general solutions are derived using the boundary conditions. To illustrate the influencing factors on the coupling between FB‐WIFF and elastic scattering, a numerical example is given. The results show that the coupling strength between FB‐WIFF and elastic scattering are greatly influenced by the ratio of fluid viscosity to background permeability. With the decrease of this ratio, the coupling strength becomes stronger. Furthermore, the coupling effects are also affected by the fracture radius and thickness. However, the fracture density and fluid bulk modulus have negligible influence on the coupling effects. This new model shows good agreement with other theories. Furthermore, comparison of this new model with the linear superposition of FB‐WIFF and elastic scattering indicates the strong nonlinear coupling between these two mechanisms when their characteristic frequencies are close. Finally, the extension of this model and implications of our results for seismic exploration and sonic logging are discussed.
Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma
Authors: Bilich Tatjana , Nelde Annika , Bauer Jens , Walz Simon , Roerden Malte , Salih Helmut R. , Weisel Katja , Besemer Britta , Marcu Ana , Lübke Maren , Schuhmacher Juliane , Neidert Marian C. , Rammensee Hans-Georg , Stevanović Stefan , Walz Juliane S. 
Published: February 2020

AbstractThe B-cell maturation antigen (BCMA) is currently being evaluated as promising tumor-associated surface antigen for T-cell-based immunotherapy approaches, such as CAR T cells and bispecific antibodies, in multiple myeloma (MM). Cytotoxic T cells bearing BCMA-specific T-cell receptors might further allow targeting HLA-presented antigens derived from the intracellular domain of BCMA. By analyzing a mass spectrometry-acquired immunopeptidome dataset of primary MM samples and MM cell lines for BCMA-derived HLA ligands, we identified the naturally presented HLA-B*18-restricted ligand P(BCMA)B*18. Additionally, P(BCMA)B*18 was identified on primary CLL samples, thereby expanding the range for possible applications. P(BCMA)B*18 induced multifunctional BCMA-specific cells de novo from naïve CD8+ T cells of healthy volunteers. These T cells exhibited antigen-specific lysis of autologous peptide-loaded cells. Even in the immunosuppressive context of MM, we detected spontaneous memory T-cell responses against P(BCMA)B*18 in patients. By applying CTLA-4 and PD-1 inhibition in vitro we induced multifunctional P(BCMA)B*18-specific CD8+ T cells in MM patients lacking preexisting BCMA-directed immune responses. Finally, we could show antigen-specific lysis of autologous peptide-loaded target cells and even MM.1S cells naturally presenting P(BCMA)B*18 using patient-derived P(BCMA)B*18-specific T cells. Hence, this BCMA-derived T-cell epitope represents a promising target for T-cell-based immunotherapy and monitoring following immunotherapy in B-cell malignancy patients.
Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis
Authors: Dinh Phuong-Uyen C. , Paudel Dipti , Brochu Hayden , Popowski Kristen D. , Gracieux M. Cyndell , Cores Jhon , Huang Ke , Hensley M. Taylor , Harrell Erin , Vandergriff Adam C. , George Arianna K. , Barrio Raina T. , Hu Shiqi , Allen Tyler A. , Blackburn Kevin , Caranasos Thomas G. , Peng Xinxia , Schnabel Lauren V. , Adler Kenneth B. , Lobo Leonard J. , Goshe Michael B. , Cheng Ke 
Published: February 2020

AbstractIdiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis.
Iron whiskers on asteroid Itokawa indicate sulfide destruction by space weathering
Authors: Matsumoto Toru , Harries Dennis , Langenhorst Falko , Miyake Akira , Noguchi Takaaki 
Published: February 2020

AbstractExtraterrestrial iron sulfide is a major mineral reservoir of the cosmochemically and astrobiologically important elements iron and sulfur. Sulfur depletion on asteroids is a long-standing, yet unresolved phenomenon that is of fundamental importance for asteroid evolution and sulfur delivery to the Earth. Understanding the chemistry of such environments requires insight into the behavior of iron sulfides exposed to space. Here we show that troilite (FeS) grains recovered from the regolith of asteroid 25143 Itokawa have lost sulfur during long-term space exposure. We report the wide-spread occurrence of metallic iron whiskers as a decomposition product formed through irradiation of the sulfide by energetic ions of the solar wind. Whisker growth by ion irradiation is a novel and unexpected aspect of space weathering. It implies that sulfur loss occurs rapidly and, furthermore, that ion irradiation plays an important role in the redistribution of sulfur between solids and gas of the interstellar medium.
Quantum scale organic semiconductors for SERS detection of DNA methylation and gene expression
Authors: Ganesh Swarna , Venkatakrishnan Krishnan , Tan Bo 
Published: February 2020

AbstractCancer stem cells (CSC) can be identified by modifications in their genomic DNA. Here, we report a concept of precisely shrinking an organic semiconductor surface-enhanced Raman scattering (SERS) probe to quantum size, for investigating the epigenetic profile of CSC. The probe is used for tag-free genomic DNA detection, an approach towards the advancement of single-molecule DNA detection. The sensor detected structural, molecular and gene expression aberrations of genomic DNA in femtomolar concentration simultaneously in a single test. In addition to pointing out the divergences in genomic DNA of cancerous and non-cancerous cells, the quantum scale organic semiconductor was able to trace the expression of two genes which are frequently used as CSC markers. The quantum scale organic semiconductor holds the potential to be a new tool for label-free, ultra-sensitive multiplexed genomic analysis.
Targeting the CK1α/CBX4 axis for metastasis in osteosarcoma
Authors: Wang Xin , Qin Ge , Liang Xiaoting , Wang Wen , Wang Zhuo , Liao Dan , Zhong Li , Zhang Ruhua , Zeng Yi-Xin , Wu Yuanzhong , Kang Tiebang 
Published: February 2020

AbstractOsteosarcoma, an aggressive malignant cancer, has a high lung metastasis rate and lacks therapeutic target. Here, we reported that chromobox homolog 4 (CBX4) was overexpressed in osteosarcoma cell lines and tissues. CBX4 promoted metastasis by transcriptionally up-regulating Runx2 via the recruitment of GCN5 to the Runx2 promoter. The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα. Consistently, CK1α suppressed cell migration and invasion through inhibition of CBX4. There was a reverse correlation between CK1α and CBX4 in osteosarcoma tissues, and CK1α was a valuable marker to predict clinical outcomes in osteosarcoma patients with metastasis. Pyrvinium pamoate (PP) as a selective activator of CK1α could inhibit osteosarcoma metastasis via the CK1α/CBX4 axis. Our findings indicate that targeting the CK1α/CBX4 axis may benefit osteosarcoma patients with metastasis.
Structure of the processive human Pol δ holoenzyme
Authors: Lancey Claudia , Tehseen Muhammad , Raducanu Vlad-Stefan , Rashid Fahad , Merino Nekane , Ragan Timothy J. , Savva Christos G. , Zaher Manal S. , Shirbini Afnan , Blanco Francisco J. , Hamdan Samir M. , De Biasio Alfredo 
Published: February 2020

AbstractIn eukaryotes, DNA polymerase δ (Pol δ) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. We present the high-resolution cryo-EM structure of the human processive Pol δ–DNA–PCNA complex in the absence and presence of FEN1. Pol δ is anchored to one of the three PCNA monomers through the C-terminal domain of the catalytic subunit. The catalytic core sits on top of PCNA in an open configuration while the regulatory subunits project laterally. This arrangement allows PCNA to thread and stabilize the DNA exiting the catalytic cleft and recruit FEN1 to one unoccupied monomer in a toolbelt fashion. Alternative holoenzyme conformations reveal important functional interactions that maintain PCNA orientation during synthesis. This work sheds light on the structural basis of Pol δ’s activity in replicating the human genome.
Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency
Authors: Bell Emma , Curry Edward W. , Megchelenbrink Wout , Jouneau Luc , Brochard Vincent , Tomaz Rute A. , Mau King Hang T. , Atlasi Yaser , de Souza Roshni A. , Marks Hendrik , Stunnenberg Hendrik G. , Jouneau Alice , Azuara Véronique 
Published: February 2020

AbstractClusters of enhancers, referred as to super-enhancers (SEs), control the expression of cell identity genes. The organisation of these clusters, and how they are remodelled upon developmental transitions remain poorly understood. Here, we report the existence of two types of enhancer units within SEs typified by distinctive CpG methylation dynamics in embryonic stem cells (ESCs). We find that these units are either prone for decommissioning or remain constitutively active in epiblast stem cells (EpiSCs), as further established in the peri-implantation epiblast in vivo. Mechanistically, we show a pivotal role for ESRRB in regulating the activity of ESC-specific enhancer units and propose that the developmentally regulated silencing of ESRRB triggers the selective inactivation of these units within SEs. Our study provides insights into the molecular events that follow the loss of ESRRB binding, and offers a mechanism by which the naive pluripotency transcriptional programme can be partially reset upon embryo implantation.
Selective EMC subunits act as molecular tethers of intracellular organelles exploited during viral entry
Authors: Bagchi Parikshit , Torres Mauricio , Qi Ling , Tsai Billy 
Published: February 2020

AbstractAlthough viruses must navigate the complex host endomembrane system to infect cells, the strategies used to achieve this is unclear. During entry, polyomavirus SV40 is sorted from the late endosome (LE) to the endoplasmic reticulum (ER) to cause infection, yet how this is accomplished remains enigmatic. Here we find that EMC4 and EMC7, two ER membrane protein complex (EMC) subunits, support SV40 infection by promoting LE-to-ER targeting of the virus. They do this by engaging LE-associated Rab7, presumably to stabilize contact between the LE and ER. These EMC subunits also bind to the ER-resident fusion machinery component syntaxin18, which is required for SV40-arrival to the ER. Our data suggest that EMC4 and EMC7 act as molecular tethers, inter-connecting two intracellular compartments to enable efficient transport of a virus between these compartments. As LE-to-ER transport of cellular cargos is unclear, our results have broad implications for illuminating inter-organelle cargo transport.
Elucidating the mechanism of heterogeneous Wacker oxidation over Pd-Cu/zeolite Y by transient XAS
Authors: Imbao Jerick , van Bokhoven Jeroen A. , Clark Adam , Nachtegaal Maarten 
Published: February 2020

AbstractThe heterogenization of Wacker catalysts using chloride-free systems can potentially be a good alternative for the commercial homogeneous Wacker oxidation of ethylene, which utilizes excessive aqueous chloride solvents. However, the mechanism of the heterogeneous system has not been clarified, preventing the rational design of better catalysts. Here, we report a transient X-ray absorption spectroscopic (XAS) investigation of the heterogeneous Wacker oxidation over Pd-Cu/zeolite Y coupled with kinetic studies and chemometric analysis. Insight is obtained by operando quickXAS allowing the quantitative determination of rates and thereby revealing a rapid redox reaction involving copper. Our work demonstrates that copper is not only the site of oxygen activation, but is also involved in the formation of undesired carbon dioxide. Without detecting the presence of Cu(0) and Pd(I), our results suggest that two one-electron transfers to two Cu(II) ions to reoxidize Pd(0) is at work in this heterogeneous Wacker catalyst.