bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rewiring of endogenous signaling pathways to genomic targets for therapeutic cell reprogramming
Authors: Krawczyk Krzysztof , Scheller Leo , Kim Hyojin , Fussenegger Martin 
Published: January 2020

AbstractRewiring cellular sensors to trigger non-natural responses is fundamental for therapeutic cell engineering. Current designs rely on engineered receptors that are limited to single inputs, and often suffer from high leakiness and low fold induction. Here, we present Generalized Engineered Activation Regulators (GEARs) that overcome these limitations by being pathway-specific rather than input-specific. GEARs consist of the MS2 bacteriophage coat protein fused to regulatory or transactivation domains, and work by rerouting activation of the NFAT, NFκB, MAPK or SMAD pathways to dCas9-directed gene expression from genomic loci. This system enables membrane depolarization-induced activation of insulin expression in β-mimetic cells and IL-12 expression in activated Jurkat cells, as well as IL-12 production in response to the immunomodulatory cytokines TGFβ and TNFα in HEK293T cells. Engineered cells with the ability to reinterpret the extracellular milieu have potential for applications in immunotherapy and in the treatment of metabolic diseases.
Structure of the prefusion-locking broadly neutralizing antibody RVC20 bound to the rabies virus glycoprotein
Authors: Hellert Jan , Buchrieser Julian , Larrous Florence , Minola Andrea , de Melo Guilherme Dias , Soriaga Leah , England Patrick , Haouz Ahmed , Telenti Amalio , Schwartz Olivier , Corti Davide , Bourhy Hervé , Rey Félix A. 
Published: January 2020

AbstractRabies virus (RABV) causes fatal encephalitis in more than 59,000 people yearly. Upon the bite of an infected animal, the development of clinical disease can be prevented with post-exposure prophylaxis (PEP), which includes the administration of Rabies immunoglobulin (RIG). However, the high cost and limited availability of serum-derived RIG severely hamper its wide use in resource-limited countries. A safe low-cost alternative is provided by using broadly neutralizing monoclonal antibodies (bnAbs). Here we report the X-ray structure of one of the most potent and most broadly reactive human bnAbs, RVC20, in complex with its target domain III of the RABV glycoprotein (G). The structure reveals that the RVC20 binding determinants reside in a highly conserved surface of G, rationalizing its broad reactivity. We further show that RVC20 blocks the acid-induced conformational change required for membrane fusion. Our results may guide the future development of direct antiviral small molecules for Rabies treatment.
The role of photon recycling in perovskite light-emitting diodes
Authors: Cho Changsoon , Zhao Baodan , Tainter Gregory D. , Lee Jung-Yong , Friend Richard H. , Di Dawei , Deschler Felix , Greenham Neil C. 
Published: January 2020

AbstractPerovskite light-emitting diodes have recently broken the 20% barrier for external quantum efficiency. These values cannot be explained with classical models for optical outcoupling. Here, we analyse the role of photon recycling (PR) in assisting light extraction from perovskite light-emitting diodes. Spatially-resolved photoluminescence and electroluminescence measurements combined with optical modelling show that repetitive re-absorption and re-emission of photons trapped in substrate and waveguide modes significantly enhance light extraction when the radiation efficiency is sufficiently high. In this manner, PR can contribute more than 70% to the overall emission, in agreement with recently-reported high efficiencies. While an outcoupling efficiency of 100% is theoretically possible with PR, parasitic absorption losses due to absorption from the electrodes are shown to limit practical efficiencies in current device architectures. To overcome the present limits, we propose a future configuration with a reduced injection electrode area to drive the efficiency toward 100%.
Network-induced multistability through lossy coupling and exotic solitary states
Authors: Hellmann Frank , Schultz Paul , Jaros Patrycja , Levchenko Roman , Kapitaniak Tomasz , Kurths Jürgen , Maistrenko Yuri 
Published: January 2020

AbstractThe stability of synchronised networked systems is a multi-faceted challenge for many natural and technological fields, from cardiac and neuronal tissue pacemakers to power grids. For these, the ongoing transition to distributed renewable energy sources leads to a proliferation of dynamical actors. The desynchronisation of a few or even one of those would likely result in a substantial blackout. Thus the dynamical stability of the synchronous state has become a leading topic in power grid research. Here we uncover that, when taking into account physical losses in the network, the back-reaction of the network induces new exotic solitary states in the individual actors and the stability characteristics of the synchronous state are dramatically altered. These effects will have to be explicitly taken into account in the design of future power grids. We expect the results presented here to transfer to other systems of coupled heterogeneous Newtonian oscillators.
Optogenetic regulation of endogenous proteins
Authors: Redchuk Taras A. , Karasev Maksim M. , Verkhusha Polina V. , Donnelly Sara K. , Hülsemann Maren , Virtanen Jori , Moore Henna M. , Vartiainen Maria K. , Hodgson Louis , Verkhusha Vladislav V. 
Published: January 2020

AbstractTechniques of protein regulation, such as conditional gene expression, RNA interference, knock-in and knock-out, lack sufficient spatiotemporal accuracy, while optogenetic tools suffer from non-physiological response due to overexpression artifacts. Here we present a near-infrared light-activatable optogenetic system, which combines the specificity and orthogonality of intrabodies with the spatiotemporal precision of optogenetics. We engineer optically-controlled intrabodies to regulate genomically expressed protein targets and validate the possibility to further multiplex protein regulation via dual-wavelength optogenetic control. We apply this system to regulate cytoskeletal and enzymatic functions of two non-tagged endogenous proteins, actin and RAS GTPase, involved in complex functional networks sensitive to perturbations. The optogenetically-enhanced intrabodies allow fast and reversible regulation of both proteins, as well as simultaneous monitoring of RAS signaling with visible-light biosensors, enabling all-optical approach. Growing number of intrabodies should make their incorporation into optogenetic tools the versatile technology to regulate endogenous targets.
Carbon doping switching on the hydrogen adsorption activity of NiO for hydrogen evolution reaction
Authors: Kou Tianyi , Chen Mingpeng , Wu Feng , Smart Tyler J. , Wang Shanwen , Wu Yishang , Zhang Ying , Li Shengtong , Lall Supriya , Zhang Zhonghua , Liu Yi-Sheng , Guo Jinghua , Wang Gongming , Ping Yuan , Li Yat 
Published: January 2020

AbstractHydrogen evolution reaction (HER) is more sluggish in alkaline than in acidic media because of the additional energy required for water dissociation. Numerous catalysts, including NiO, that offer active sites for water dissociation have been extensively investigated. Yet, the overall HER performance of NiO is still limited by lacking favorable H adsorption sites. Here we show a strategy to activate NiO through carbon doping, which creates under-coordinated Ni sites favorable for H adsorption. DFT calculations reveal that carbon dopant decreases the energy barrier of Heyrovsky step from 1.17 eV to 0.81 eV, suggesting the carbon also serves as a hot-spot for the dissociation of water molecules in water-alkali HER. As a result, the carbon doped NiO catalyst achieves an ultralow overpotential of 27 mV at 10 mA cm−2, and a low Tafel slope of 36 mV dec−1, representing the best performance among the state-of-the-art NiO catalysts.
Valley phonons and exciton complexes in a monolayer semiconductor
Authors: He Minhao , Rivera Pasqual , Van Tuan Dinh , Wilson Nathan P. , Yang Min , Taniguchi Takashi , Watanabe Kenji , Yan Jiaqiang , Mandrus David G. , Yu Hongyi , Dery Hanan , Yao Wang , Xu Xiaodong 
Published: January 2020

AbstractThe coupling between spin, charge, and lattice degrees of freedom plays an important role in a wide range of fundamental phenomena. Monolayer semiconducting transitional metal dichalcogenides have emerged as an outstanding platform for studying these coupling effects. Here, we report the observation of multiple valley phonons – phonons with momentum vectors pointing to the corners of the hexagonal Brillouin zone – and the resulting exciton complexes in the monolayer semiconductor WSe2. We find that these valley phonons lead to efficient intervalley scattering of quasi particles in both exciton formation and relaxation. This leads to a series of photoluminescence peaks as valley phonon replicas of dark trions. Using identified valley phonons, we also uncover an intervalley exciton near charge neutrality. Our work not only identifies a number of previously unknown 2D excitonic species, but also shows that monolayer WSe2 is a prime candidate for studying interactions between spin, pseudospin, and zone-edge phonons.
Vibronic coherence contributes to photocurrent generation in organic semiconductor heterojunction diodes
Authors: Bian Qingzhen , Ma Fei , Chen Shula , Wei Qi , Su Xiaojun , Buyanova Irina A. , Chen Weimin M. , Ponseca Carlito S. , Linares Mathieu , Karki Khadga J. , Yartsev Arkady , Inganäs Olle 
Published: January 2020

AbstractCharge separation dynamics after the absorption of a photon is a fundamental process relevant both for photosynthetic reaction centers and artificial solar conversion devices. It has been proposed that quantum coherence plays a role in the formation of charge carriers in organic photovoltaics, but experimental proofs have been lacking. Here we report experimental evidence of coherence in the charge separation process in organic donor/acceptor heterojunctions, in the form of low frequency oscillatory signature in the kinetics of the transient absorption and nonlinear two-dimensional photocurrent spectroscopy. The coherence plays a decisive role in the initial ~200 femtoseconds as we observe distinct experimental signatures of coherent photocurrent generation. This coherent process breaks the energy barrier limitation for charge formation, thus competing with excitation energy transfer. The physics may inspire the design of new photovoltaic materials with high device performance, which explore the quantum effects in the next-generation optoelectronic applications.
Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy
Authors: Kumpel Belinda M. , Saldova Radka , Koeleman Carolien A. M. , Abrahams Jodie L. , Ederveen Agnes Hipgrave , Armour Kathryn L. , Olovnikova Natalia I. , Vidarsson Gestur , Kapur Rick , Rudd Pauline M. , Wuhrer Manfred 
Published: January 2020

AbstractAnti-D immunoglobulin (Anti-D Ig) prophylaxis prevents haemolytic disease of the fetus and newborn. Monoclonal IgG anti-Ds (mAb-Ds) would enable unlimited supplies but have differed in efficacy in FcγRIIIa-mediated ADCC assays and clinical trials. Structural variations of the oligosaccharide chains of mAb-Ds are hypothesised to be responsible. Quantitative data on 12 Fc-glycosylation features of 23 mAb-Ds (12 clones, 5 produced from multiple cell lines) and one blood donor-derived anti-D Ig were obtained by HPLC and mass spectrometry using 3 methods. Glycosylation of mAb-Ds from human B-lymphoblastoid cell lines (B) was similar to anti-D Ig although fucosylation varied, affecting ADCC activity.In vivo, two B mAb-Ds with 77–81% fucosylation cleared red cells and prevented D-immunisation but less effectively than anti-D Ig. High fucosylation (>89%) of mouse-human heterohybridoma (HH) and Chinese hamster ovary (CHO) mAb-Ds blocked ADCC and clearance. Rat YB2/0 mAb-Ds with <50% fucosylation mediated more efficient ADCC and clearance than anti-D Ig. Galactosylation of B mAb-Ds was 57–83% but 15–58% for rodent mAb-Ds. HH mAb-Ds had non-human sugars. These data reveal high galactosylation like anti-D Ig (>60%) together with lower fucosylation (<60%) as safe features of mAb-Ds for mediating rapid red cell clearance at low doses, to enable effective, inexpensive prophylaxis.
Iodinated Polyesters with Enhanced X-ray Contrast Properties for Biomedical Imaging
Authors: Lex Timothy R. , Brummel Beau R. , Attia Mohamed F. , Giambalvo Lauren N. , Lee Kinsey G. , Van Horn Brooke A. , Whitehead Daniel. C. , Alexis Frank 
Published: January 2020

AbstractSynthetic materials exhibiting contrast imaging properties have become vital to the field of biomedical imaging. However, polymeric biomaterials are lacking imaging contrast properties for deep tissue imaging. This report details the synthesis and characterization of a suite of aryl-iodo monomers, which were used to prepare iodinated polyesters using a pre-functionalization approach. Commercially available 4-iodo-phenylalanine or 4-iodobenzyl bromide served as the starting materials for the synthesis of three iodinated monomeric moieties (a modified lactide, morpholine-2,5-dione, and caprolactone), which under a tin-mediated ring-opening polymerization (ROP), generated their respective polyesters (PE) or poly(ester amides) (PEA). An increase in X-ray intensity of all synthesized iodine-containing polymers, in comparison to non-iodinated poly(lactic acid) (PLA), validated their functionality as radio-opaque materials. The iodinated-poly(lactic acid) (iPLA) material was visualized through varying thicknesses of chicken tissue, thus demonstrating its potenial as a radio-opaque biomaterial.
Computer simulation study of the penetration of pulsed 30, 60 and 90 GHz radiation into the human ear
Authors: Vilagosh Zoltan , Lajevardipour Alireza , Wood Andrew 
Published: January 2020

AbstractThere is increasing interest in applications which use the 30 to 90 GHz frequency range, including automotive radar, 5 G cellular networks and wireless local area links. This study investigated pulsed 30–90 GHz radiation penetration into the human ear canal and tympanic membrane using computational phantoms. Modelling involved 100 ps and 20 ps pulsed excitation at three angles: direct (orthogonal), 30° anterior, and 45° superior to the ear canal. The incident power flux density (PD) estimation was normalised to the International Commission on Non-Ionizing Radiation Protection (1998) standard for general population exposure of 10 Wm−2 and occupational exposure of 50 Wm−2. The PD, specific absorption rate (SAR) and temperature rise within the tympanic membrane was highly dependent on the incident angle of the radiation and frequency. Using a 30 GHz pulse directed orthogonally into the ear canal, the PD in the tympanic membrane was 0.2% of the original maximal signal intensity. The corresponding PD at 90 GHz was 13.8%. A temperature rise of 0.032° C (+20%, −50%) was noted within the tympanic membrane using the equivalent of an occupational standard exposure at 90 GHz. The central area of the tympanic membrane is exposed in a preferential way and local effects on small regions cannot be excluded. The authors strongly advocate further research into the effects of radiation above 60 GHz on the structures of the ear to assist the process of setting standards.
Automatic vocal tract landmark localization from midsagittal MRI data
Authors: Eslami Mohammad , Neuschaefer-Rube Christiane , Serrurier Antoine 
Published: January 2020

AbstractThe various speech sounds of a language are obtained by varying the shape and position of the articulators surrounding the vocal tract. Analyzing their variations is crucial for understanding speech production, diagnosing speech disorders and planning therapy. Identifying key anatomical landmarks of these structures on medical images is a pre-requisite for any quantitative analysis and the rising amount of data generated in the field calls for an automatic solution. The challenge lies in the high inter- and intra-speaker variability, the mutual interaction between the articulators and the moderate quality of the images. This study addresses this issue for the first time and tackles it by means of Deep Learning. It proposes a dedicated network architecture named Flat-net and its performance are evaluated and compared with eleven state-of-the-art methods from the literature. The dataset contains midsagittal anatomical Magnetic Resonance Images for 9 speakers sustaining 62 articulations with 21 annotated anatomical landmarks per image. Results show that the Flat-net approach outperforms the former methods, leading to an overall Root Mean Square Error of 3.6 pixels/0.36 cm obtained in a leave-one-out procedure over the speakers. The implementation codes are also shared publicly on GitHub.
The critical role of glucose deprivation in epithelial-mesenchymal transition in hepatocellular carcinoma under hypoxia
Authors: Jo Hanhee , Lee Jongsook , Jeon Jeongyong , Kim Seon yoo , Chung Jee-in , Ko Hae yong , Lee Misu , Yun Mijin 
Published: January 2020

AbstractImaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is used to determine sites of abnormal glucose metabolism to predict high tumor grade, metastasis, and poor patient survival. However, not all tumors with increased 18F-FDG uptake show aggressive tumor biology, as evident from the moderate correlation between metastasis and high FDG uptake. We hypothesized that metastasis is likely attributable to the complexity and heterogeneity of the cancer microenvironment. To identify the cancer microenvironment that induces the epithelial-mesenchymal transition (EMT) process, tumor areas of patients with HCC were analyzed by immunostaining. Our data demonstrated the induction of EMT process in HCC cells with low proliferation under hypoxic conditions. To validate our finding, among HCC cell lines, HepG2 cells with highly increased expression of HIF1α under hypoxia were employed in vitro and in vivo. Major changes in EMT-associated protein expression, such as the up-regulation of N-cadherin and snail/slug are associated with decreased proliferation-related protein (PCNA) caused by glucose deprivation under hypoxia. Indeed, PCNA knockdown-HepG2 cells under hypoxia showed the induction of more EMT process compare to the control. Thus, HCC cells with low proliferative potential under glucose-deprived and hypoxic conditions show high probability for induced EMT process and promote cell invasion. This study investigates reasons as to why an EMT process cannot fully be predicted. Our observations indicate that rather than analyzing a single factor, an integrated analysis of hypoxia with low glucose metabolism and low cell proliferation might be helpful to predict the potential impact on induction of EMT process and promotion of cell invasion.
Superconducting phase transitions in disordered NbTiN films
Authors: Burdastyh M. V. , Postolova S. V. , Proslier T. , Ustavshikov S. S. , Antonov A. V. , Vinokur V. M. , Mironov A. Yu. 
Published: January 2020

AbstractSuppression of superconductivity in disordered systems is a fundamental problem of condensed matter physics. Here we investigate superconducting niobium-titanium-nitride (Nb1−xTixN) thin films grown by the atomic layer deposition (ALD) with slightly different growth process parameters. We observe a smooth crossover from the disorder-driven superconductor-normal metal transition (SMT) to the superconductor-insulator transition (SIT) via the intermediate Bose metal state detected by the low-temperature saturation of the temperature dependence of the sheet resistance. We demonstrate that the SIT via the intervening Bose metal state occurs if the sheet resistance of the film in the maximum, Rmax prior to the superconducting drop of R(T), exceeds Rq = h/4e2.
RNA Profiling Analysis of the Serum Exosomes Derived from Patients with Chronic Hepatitis and Acute-on-chronic Liver Failure Caused By HBV
Authors: Chen Jiajia , Xu Qingsheng , Zhang Yan , Zhang Huafen 
Published: January 2020

AbstractHepatitis B virus (HBV) is the main causative viral agent for liver diseases in China. In liver injury, exosomes may impede the interaction with chromatin in the target cell and transmit inflammatory, apoptosis, or regeneration signals through RNAs. Therefore, we attempted to determine the potential functions of exosomal RNAs using bioinformatics technology. We performed RNA sequencing analysis in exosomes derived from clinical specimens of healthy control (HC) individuals and patients with chronic hepatitis B (CHB) and acute-on-chronic liver failure caused by HBV (HBV-ACLF). This analysis resulted in the identification of different types and proportions of RNAs in exosomes from the HC individuals and patients. Exosomes from the CHB and HBV-ACLF patients showed distinct upregulation and downregulation patterns of differentially expressed genes compared with those from the HC subjects. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway analysis further confirmed different patterns of biological functions and signalling pathways in CHB and HBV-ACLF. Then we chose two upregulated RNAs both in CHB and HBV-ACLF for further qPCR validation. It confirmed the significantly different expression levels in CHB and HBV-ACLF compared with HC. Our findings indicate selective packaging of the RNA cargo into exosomes under different HBV attacks; these may represent potential targets for the diagnosis and treatment of HBV-caused liver injury.
Genome-scale data reveal the role of hybridization in lichen-forming fungi
Authors: Keuler Rachel , Garretson Alexis , Saunders Theresa , Erickson Robert J. , St. Andre Nathan , Grewe Felix , Smith Hayden , Lumbsch H. Thorsten , Huang Jen-Pan , St. Clair Larry L. , Leavitt Steven D. 
Published: January 2020

AbstractAdvancements in molecular genetics have revealed that hybridization may be common among plants, animals, and fungi, playing a role in evolutionary dynamics and speciation. While hybridization has been well-documented in pathogenic fungi, the effects of these processes on speciation in fungal lineages with different life histories and ecological niches are largely unexplored. Here we investigated the potential influence of hybridization on the emergence of morphologically and reproductively distinct asexual lichens. We focused on vagrant forms (growing obligately unattached to substrates) within a clade of rock-dwelling, sexually reproducing species in the Rhizoplaca melanophthalma (Lecanoraceae, Ascomycota) species complex. We used phylogenomic data from both mitochondrial and nuclear genomes to infer evolutionary relationships and potential patterns of introgression. We observed multiple instances of discordance between the mitochondrial and nuclear trees, including the clade comprising the asexual vagrant species R. arbuscula, R. haydenii, R. idahoensis, and a closely related rock-dwelling lineage. Despite well-supported phylogenies, we recovered strong evidence of a reticulated evolutionary history using a network approach that incorporates both incomplete lineage sorting and hybridization. These data suggest that the rock-dwelling western North American subalpine endemic R. shushanii is potentially the result of a hybrid speciation event, and introgression may have also played a role in other taxa, including vagrant species R. arbuscula, R. haydenii and R. idahoensis. We discuss the potential roles of hybridization in terms of generating asexuality and novel morphological traits in lichens. Furthermore, our results highlight the need for additional study of reticulate phylogenies when investigating species boundaries and evolutionary history, even in cases with well-supported topologies inferred from genome-scale data.