bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific NOTCH1 antibody targets DLL4-induced proliferation, migration, and angiogenesis in NOTCH1-mutated CLL cells
Authors: López-Guerra Mónica , Xargay-Torrent Sílvia , Fuentes Patricia , Roldán Jocabed , González-Farré Blanca , Rosich Laia , Silkenstedt Elisabeth , García-León María J. , Lee-Vergés Eriong , Giménez Neus , Giró Ariadna , Aymerich Marta , Villamor Neus , Delgado Julio , López-Guillermo Armando , Puente Xose S. , Campo Elias , Toribio María L. , Colomer Dolors 
Published: October 2019

AbstractTargeting Notch signaling has emerged as a promising therapeutic strategy for chronic lymphocytic leukemia (CLL), particularly inNOTCH1-mutated patients. We provide first evidence that the Notch ligand DLL4 is a potent stimulator of Notch signaling inNOTCH1-mutated CLL cells while increases cell proliferation. Importantly, DLL4 is expressed in histiocytes from the lymph node, both inNOTCH1-mutated and -unmutated cases. We also show that the DLL4-induced activation of the Notch signaling pathway can be efficiently blocked with the specific anti-Notch1 antibody OMP-52M51. Accordingly, OMP-52M51 also reverses Notch-inducedMYC, CCND1, andNPM1gene expression as well as cell proliferation inNOTCH1-mutated CLL cells. In addition, DLL4 stimulation triggers the expression of protumor target genes, such asCXCR4,NRARP, andVEGFA, together with an increase in cell migration and angiogenesis. All these events can be antagonized by OMP-52M51. Collectively, our results emphasize the role of DLL4 stimulation inNOTCH1-mutated CLL and confirm the specific therapeutic targeting of Notch1 as a promising approach for this group of poor prognosis CLL patients.
LncRNA HOXA-AS3 confers cisplatin resistance by interacting with HOXA3 in non-small-cell lung carcinoma cells
Authors: Lin Shuang , Zhang Rui , An Xiaoxia , Li Zhoubin , Fang Cheng , Pan Bo , Chen Wei , Xu Guodong , Han Weili 
Published: October 2019

AbstractMany studies have indicated that the aberrant expression of long noncoding RNAs (lncRNAs) is responsible for drug resistance, which represents a substantial obstacle for cancer therapy. In the present study, we aimed to investigate the role of the lncRNA HOXA-AS3 in drug resistance and elucidate its underlying mechanisms in non-small-cell lung carcinoma (NSCLC) cells. The role of HOXA-AS3 in drug resistance was demonstrated by the cell counting kit-8 assay (CCK-8), ethynyldeoxyuridine (EDU) assay, and flow cytometry analysis. Tumor xenografts in nude mice were established to evaluate the antitumor effects of HOXA-AS3 knockdown in vivo. Western blotting and quantitative real-time PCR were used to evaluate protein and RNA expression. RNA pull-down assays, mass spectrometry, and RNA immunoprecipitation were performed to confirm the molecular mechanism of HOXA-AS3 in the cisplatin resistance of NSCLC cells. We found that HOXA-AS3 levels increased with cisplatin treatment and knockdown of HOXA-AS3 enhance the efficacy of cisplatin in vitro and in vivo. Mechanistic investigations showed that HOXA-AS3 conferred cisplatin resistance by down-regulating homeobox A3 (HOXA3) expression. Moreover, HOXA-AS3 was demonstrated to interact with both the mRNA and protein forms of HOXA3. In addition, HOXA3 knockdown increased cisplatin resistance and induced epithelial-mesenchymal transition (EMT). Taken together, our findings suggested that additional research into HOXA-AS3 might provide a better understanding of the mechanisms of drug resistance and promote the development of a novel and efficient strategy to treat NSCLC.
The TLR7/8 agonist R848 remodels tumor and host responses to promote survival in pancreatic cancer
Authors: Michaelis Katherine A. , Norgard Mason A. , Zhu Xinxia , Levasseur Peter R. , Sivagnanam Shamilene , Liudahl Shannon M. , Burfeind Kevin G. , Olson Brennan , Pelz Katherine R. , Angeles Ramos Diana M. , Maurer H. Carlo , Olive Kenneth P. , Coussens Lisa M. , Morgan Terry K. , Marks Daniel L. 
Published: October 2019

AbstractA priority in cancer research is to innovate therapies that are not only effective against tumor progression but also address comorbidities such as cachexia that limit quality and quantity of life. We demonstrate that TLR7/8 agonist R848 induces anti-tumor responses and attenuates cachexia in murine models of pancreatic ductal adenocarcinoma (PDAC). In vivo, tumors from two of three cell lines were R848-sensitive, resulting in smaller tumor mass, increased immune complexity, increased CD8+ T-cell infiltration and activity, and decreased Treg frequency. R848-treated mice demonstrated improvements in behavioral and molecular cachexia manifestations, resulting in a near-doubling of survival duration. Knockout mouse studies revealed that stromal, not neoplastic, TLR7 is requisite for R848-mediated responses. In patient samples, we found Tlr7 is ubiquitously expressed in stroma across all stages of pancreatic neoplasia, but epithelial Tlr7 expression is relatively uncommon. These studies indicate immune-enhancing approaches including R848 may be useful in PDAC and cancer-associated cachexia.
Ba-induced phase segregation and band gap reduction in mixed-halide inorganic perovskite solar cells
Authors: Xiang Wanchun , Wang Zaiwei , Kubicki Dominik J. , Wang Xueting , Tress Wolfgang , Luo Jingshan , Zhang Jiahuan , Hofstetter Albert , Zhang Lijun , Emsley Lyndon , Grätzel Michael , Hagfeldt Anders 
Published: October 2019

AbstractAll-inorganic metal halide perovskites are showing promising development towards efficient long-term stable materials and solar cells. Element doping, especially on the lead site, has been proved to be a useful strategy to obtain the desired film quality and material phase for high efficient and stable inorganic perovskite solar cells. Here we demonstrate a function by adding barium in CsPbI2Br. We find that barium is not incorporated into the perovskite lattice but induces phase segregation, resulting in a change in the iodide/bromide ratio compared with the precursor stoichiometry and consequently a reduction in the band gap energy of the perovskite phase. The device with 20 mol% barium shows a high power conversion efficiency of 14.0% and a great suppression of non-radiative recombination within the inorganic perovskite, yielding a high open-circuit voltage of 1.33 V and an external quantum efficiency of electroluminescence of 10−4.
Statistical learning goes beyond the d-band model providing the thermochemistry of adsorbates on transition metals
Authors: García-Muelas Rodrigo , López Núria 
Published: October 2019

AbstractThe rational design of heterogeneous catalysts relies on the efficient survey of mechanisms by density functional theory (DFT). However, massive reaction networks cannot be sampled effectively as they grow exponentially with the size of reactants. Here we present a statistical principal component analysis and regression applied to the DFT thermochemical data of 71 C$${}_{1}$$

1

–C$${}_{2}$$

2

species on 12 close-packed metal surfaces. Adsorption is controlled by covalent ($$d$$
d
-band center) and ionic terms (reduction potential), modulated by conjugation and conformational contributions. All formation energies can be reproduced from only three key intermediates (predictors) calculated with DFT. The results agree with accurate experimental measurements having error bars comparable to those of DFT. The procedure can be extended to single-atom and near-surface alloys reducing the number of explicit DFT calculation needed by a factor of 20, thus paving the way for a rapid and accurate survey of whole reaction networks on multimetallic surfaces.
Analog Coupled Oscillator Based Weighted Ising Machine
Authors: Chou Jeffrey , Bramhavar Suraj , Ghosh Siddhartha , Herzog William 
Published: October 2019

AbstractWe report on an analog computing system with coupled non-linear oscillators which is capable of solving complex combinatorial optimization problems using the weighted Ising model. The circuit is composed of a fully-connected 4-node LC oscillator network with low-cost electronic components and compatible with traditional integrated circuit technologies. We present the theoretical modeling, experimental characterization, and statistical analysis our system, demonstrating single-run ground state accuracies of 98% on randomized MAX-CUT problem sets with binary weights and 84% with 5-bit weight resolutions. Solutions are obtained within 5 oscillator cycles, and the time-to-solution has been demonstrated to scale directly with oscillator frequency. We present scaling analysis which suggests that large coupled oscillator networks may be used to solve computationally intensive problems faster and more efficiently than conventional algorithms. The proof-of-concept system presented here provides the foundation for realizing such larger scale systems using existing hardware technologies and could pave the way towards an entirely novel computing paradigm.
Low Dose Carbon Monoxide Exposure in Idiopathic Pulmonary Fibrosis Produces a CO Signature Comprised of Oxidative Phosphorylation Genes
Authors: Casanova Nancy , Zhou Tong , Gonzalez-Garay Manuel L. , Rosas Ivan O. , Goldberg Hilary J. , Ryter Stefan W. , Collard Harold R. , El-Chemaly Souheil , Flaherty Kevin R. , Hunninghake Gary M. , Lasky Joseph A. , Lederer David J. , Machado Roberto F. , Martinez Fernando J. , Noth Imre , Raghu Ganesh , Choi Augustine M. K. , Garcia Joe G. N. 
Published: October 2019

AbstractCompelling preclinical studies indicate that low-dose carbon monoxide (CO) abrogates experimental lung fibrosis. We recently reported the results of a multicenter, double-blinded, clinical trial of inhaled CO in patients with idiopathic pulmonary fibrosis (IPF). Identifying no significantly changes in metalloproteinase-7 (MMP7) serum concentration, or secondary endpoints of physiologic measurements, hospitalization, death, or patient-reported outcomes. In the present study, we evaluated the effect of low dose CO exposure (100–200 ppm) for 12 weeks on genome-wide gene expression in peripheral blood mononuclear cells (PBMC) derived from these IPF study subjects. We conducted transcriptome profiling on 38 IPF subjects with time points available at 0, 12, and 24 weeks. Total RNA isolated from PBMCs was hybridized onto the Affymetrix Human Gene 2.0 ST Array. We identified 621 genes significantly upregulated in the 24-week CO exposed group compared with the 12-week. Pathway analysis demonstrated association with Oxidative Phosphorylation (adjusted P < 0.05). We identified a clear CO signature dominated with 23 oxidative phosphorylation-related genes (FDR <10%). We confirmed the expression of nine selected gene products using Nanostring’s nCounter analysis system. These findings suggest this signature may serve as a potential genomic biomarker for CO exposure and for potential titration of dosage to allow precision testing of therapies in future low dose CO therapeutic studies in IPF.
Rich Magnetic Quantization Phenomena in AA Bilayer Silicene
Authors: Shih Po-Hsin , Do Thi-Nga , Gumbs Godfrey , Huang Danhong , Pham Hai Duong , Lin Ming-Fa 
Published: October 2019

AbstractThe rich magneto-electronic properties of AA-bottom-top (bt) bilayer silicene are investigated using a generalized tight-binding model. The electronic structure exhibits two pairs of oscillatory energy bands for which the lowest conduction and highest valence states of the low-lying pair are shifted away from the K point. The quantized Landau levels (LLs) are classified into various separated groups by the localization behaviors of their spatial distributions. The LLs in the vicinity of the Fermi energy do not present simple wave function modes. This behavior is quite different from other two-dimensional systems. The geometry symmetry, intralayer and interlayer atomic interactions, and the effect of a perpendicular magnetic field are responsible for the peculiar LL energy spectra in AA-bt bilayer silicene. This work provides a better understanding of the diverse magnetic quantization phenomena in 2D condensed-matter materials.
Anatomic Factors Predicting Postoperative Strabismus in Orbital Wall Fracture Repair
Authors: Hsu Chih-Kang , Hsieh Meng-Wei , Chang Hsu-Chieh , Tai Ming-Cheng , Chien Ke-Hung 
Published: October 2019

AbstractThis study is aimed to determine the relationship between orbital fracture sites in each CT scan view and postoperative diplopia. Data for 141 patients of orbital wall fracture were analyzed retrospectively. One group of examiners reviewed sagittal, coronal and axial CT scans. Descriptive statistical analysis was used to assess each fracture area and its potential relationship with the occurrence of postoperative diplopia. Among the three anatomical views, sagittal sections were significantly associated with post-operative diplopia (PD) (p = 0.044). For orbital wall fractures in a single location, C1 (p = 0.015), A1 (p = 0.004) and S3 (p = 0.006) fractures were significantly related to PD. Orbital wall fractures found in more than one location resulted in a higher probability of PD in all sections:, C1 + C2 group (p = 0.010), C1 + C2 + C3 group (p = 0.005), A1 + A2 group (p = 0.034), A3 + A1 group (p = 0.005), S1 + S2 group (p < 0.001), S2 + S3 group (p = 0.006) and S1 + S2 + S3 group (p < 0.001). For combinations of two or three sections, we found that only fractures involving both coronal and sagittal sections led to a significantly increased risk of PD (p = 0.031). PD is the main posttreatment complication of orbital bone fracture reduction. In addition to the known myogenic cause (failure to relieve entrapment) of diplopia, both trauma and surgical manipulation can compromise ocular motor nerve function and possibly result in the development of neurogenic causes of diplopia. Careful assessment of patient symptoms (whether preoperative diplopia is present), and the location of orbital fractures (and the influence of related musculature, fat, and nerves) on CT scans are strongly related to surgical success.
Subjective estimates of uncertainty during gambling and impulsivity after subthalamic deep brain stimulation for Parkinson’s disease
Authors: Paliwal Saee , Mosley Philip E. , Breakspear Michael , Coyne Terry , Silburn Peter , Aponte Eduardo , Mathys Christoph , Stephan Klaas E. 
Published: October 2019

AbstractSubthalamic deep brain stimulation (DBS) for Parkinson’s disease (PD) may modulate chronometric and instrumental aspects of choice behaviour, including motor inhibition, decisional slowing, and value sensitivity. However, it is not well known whether subthalamic DBS affects more complex aspects of decision-making, such as the influence of subjective estimates of uncertainty on choices. In this study, 38 participants with PD played a virtual casino prior to subthalamic DBS (whilst ‘on’ medication) and again, 3-months postoperatively (whilst ‘on’ stimulation). At the group level, there was a small but statistically significant decrease in impulsivity postoperatively, as quantified by the Barratt Impulsiveness Scale (BIS). The gambling behaviour of participants (bet increases, slot machine switches and double or nothing gambles) was associated with this self-reported measure of impulsivity. However, there was a large variance in outcome amongst participants, and we were interested in whether individual differences in subjective estimates of uncertainty (specifically, volatility) were related to differences in pre- and postoperative impulsivity. To examine these individual differences, we fit a computational model (the Hierarchical Gaussian Filter, HGF), to choices made during slot machine game play as well as a simpler reinforcement learning model based on the Rescorla-Wagner formalism. The HGF was superior in accounting for the behaviour of our participants, suggesting that participants incorporated beliefs about environmental uncertainty when updating their beliefs about gambling outcome and translating these beliefs into action. A specific aspect of subjective uncertainty, the participant’s estimate of the tendency of the slot machine’s winning probability to change (volatility), increased subsequent to DBS. Additionally, the decision temperature of the response model decreased post-operatively, implying greater stochasticity in the belief-to-choice mapping of participants. Model parameter estimates were significantly associated with impulsivity; specifically, increased uncertainty was related to increased postoperative impulsivity. Moreover, changes in these parameter estimates were significantly associated with the maximum post-operative change in impulsivity over a six month follow up period. Our findings suggest that impulsivity in PD patients may be influenced by subjective estimates of uncertainty (environmental volatility) and implicate a role for the subthalamic nucleus in the modulation of outcome certainty. Furthermore, our work outlines a possible approach to characterising those persons who become more impulsive after subthalamic DBS, an intervention in which non-motor outcomes can be highly variable.
Structure, Dynamics, and Wettability of Water at Metal Interfaces
Authors: Gim Suji , Cho Kang Jin , Lim Hyung-Kyu , Kim Hyungjun 
Published: October 2019

AbstractThe water/metal interface often governs important chemophysical processes in various technologies. Therefore, from scientific and engineering perspectives, the detailed molecular-level elucidation of the water/metal interface is of high priority, but the related research is limited. In experiments, the surface-science techniques, which can provide full structural details of the surface, are not easy to directly apply to the interfacial systems under ambient conditions, and the well-defined facets cannot be entirely free from contamination at the contact with water. To answer long-standing debates regarding the wettability, structure, and dynamics of water at metal interfaces, we here develop reliable first-principles-based multiscale simulations. Using the state-of-the-art simulations, we find that the clean metal surfaces are actually superhydrophilic and yield zero contact angles. Furthermore, we disclose an inadequacy of widespread ice-like bilayer model of the water adlayers on metal surfaces from both averaged structural and dynamic points of view. Our findings on the nature of water on metal surfaces provide new molecular level perspectives on the tuning and design of water/metal interfaces that are at the heart of many energy applications.
The relevant range of scales for multi-scale contextual spatial modelling
Authors: Behrens Thorsten , Viscarra Rossel Raphael A. , Kerry Ruth , MacMillan Robert , Schmidt Karsten , Lee Juhwan , Scholten Thomas , Zhu A-Xing 
Published: October 2019

AbstractSpatial autocorrelation in the residuals of spatial environmental models can be due to missing covariate information. In many cases, this spatial autocorrelation can be accounted for by using covariates from multiple scales. Here, we propose a data-driven, objective and systematic method for deriving the relevant range of scales, with distinct upper and lower scale limits, for spatial modelling with machine learning and evaluated its effect on modelling accuracy. We also tested an approach that uses the variogram to see whether such an effective scale space can be approximated a priori and at smaller computational cost. Results showed that modelling with an effective scale space can improve spatial modelling with machine learning and that there is a strong correlation between properties of the variogram and the relevant range of scales. Hence, the variogram of a soil property can be used for a priori approximations of the effective scale space for contextual spatial modelling and is therefore an important analytical tool not only in geostatistics, but also for analyzing structural dependencies in contextual spatial modelling.
Flow
Authors: Spitzer Manf 
Published: October 2019

Zusammenfassung:
Mit dem Wort „Flow“ wird seit Mitte der 1970er-Jahre eine positiv konnotierte Form des Erlebens körperlicher oder geistiger Arbeit bezeichnet, das sich einstellt, wenn die Arbeit nicht zu einfach und nicht zu schwierig und man ganz bei der Sache (und nicht bei sich selbst) ist. Experimentelle Studien zum Flow-Erleben mittels funktioneller Bildgebung aus der Ulmer Psychiatrie um die Arbeitsgruppe von Georg Grön und Martin Ulrich konnten über die Jahre hinweg zeigen, dass das Flow-Erleben mit einem ganz bestimmten Muster zentralnervöser Aktivierungen und Deaktivierungen einhergeht: Aktiviert sind sensorische Verarbeitung sowie das linke Putamen und der linke inferiore frontale Kortex, wohingegen der mediale präfrontale Kortex (MPFC) beidseits und der Mandelkern deaktiviert sind. Wenn also die Arbeit zum Können „passt“, dann „verliert“ man sich selbst in der Arbeit (deaktiviertes selbstreflektierendes Denken im MPFC), ist angeregt (mittels EDA gemessenes vermehrtes Arousal) und ist zugleich angstfrei (deaktivierte Amygdala). Durch Stimulation (tDCS) des MPFC ließ sich zudem Flow bei Menschen, die diesen Zustand trotz entsprechender Rahmenbedingungen (noch) nicht erreicht haben, fördern. Diese Ergebnisse haben Konsequenzen für eine klarere Einordnung der Symptome (Grübelneigung) und Therapie (Ergotherapie) der Depression und erweitern unser Verständnis von kognitiver Kontrolle, der Rolle von Fehlern beim Lernen, der kulturellen Produktion und Transmission von Wissen sowie der Bedeutung des Informationsbegriffs beim Verständnis von „Leben“.
Genetik der primären arteriellen Hypertonie
Authors: Algharably Engi , Bolbrinker Juliane , Kreutz Reinhold 
Published: October 2019

ZusammenfassungDie Entschlüsselung der molekulargenetischen Grundlage der primären Hypertonie ist Gegenstand intensiver Forschung und hat in der jüngsten Vergangenheit einen rasanten Fortschritt erfahren. Hierbei spielen genomweite Assoziationsstudien (GWAS) und deren Metaanalysen eine maßgebliche Rolle. In aktuellen Untersuchungen wurden genomweit insgesamt über 900 unabhängige blutdruckassoziierte Genloci identifiziert. Neben einem besseren Verständnis der Mechanismen, die an der Pathogenese der Hypertonie beteiligt sind, kann basierend auf den Daten in Zukunft feine Risikoabschätzung für die Entwicklung der Hypertonie erfolgen. Weiterhin können die Ergebnisse die Entwicklung neuer Pharmaka und individualisierter Therapiestrategien (Pharmakogenetik) der Hypertonie ermöglichen. Eine Relevanz für das Management der primären Hypertonie in der klinischen Praxis haben diese Ergebnisse derzeit allerdings noch nicht.
„Wir kennen sehr unterschiedliche Bilder sogenannter Autoimmunerkrankungen“
Authors: Michalsen Andreas 
Published: October 2019

ZusammenfassungPD Dr. Thomas Häupl ist als Internist an der Medizinischen Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Charité Universitätsmedizin Berlin, tätig. Er leitet die AG Bioinformatik in der Rheumatologie und Immunologie. Einer seiner Forschungsschwerpunkte sind die Zusammenhänge von Rheumatoider Arthritis und Darm-Mikrobiom.Im zkm-Gespräch erzählt Thomas Häupl u. a., warum der Begriff der Autoimmunerkrankungen definitorisch ambivalent ist und dass Fasten, Ernährung und bestimmte Kräuter großes therapeutisches Potenzial bezüglich der mikrobiellen Besiedlung des Organismus haben.
Phytotherapie bei Rheuma
Authors: Huber Roman 
Published: October 2019

ZusammenfassungBei entzündlichem Rheuma oder Arthrose hat sich der Einsatz von Phythotherapeutika bewährt. Die pflanzlichen Arzneimittel werden äußerlich, aber auch innerlich oder subkutan angewandt. Brennnessel, Borretschsamen, Teufelskralle oder Weidenrinde gehören zu den effektivsten Wirkstoffen. Erste Studien belegen ihre Wirksamkeit.