bluuebunny/crossref_metadata_2025_split huggingface dataset:
A versatile photodetector assisted by photovoltaic and bolometric effects
Authors: Jiang Wei , Zheng Tan , Wu Binmin , Jiao Hanxue , Wang Xudong , Chen Yan , Zhang Xiaoyu , Peng Meng , Wang Hailu , Lin Tie , Shen Hong , Ge Jun , Hu Weida , Xu Xiaofeng , Meng Xiangjian , Chu Junhao , Wang Jianlu 
Published: September 2020

AbstractThe advent of low-dimensional materials with peculiar structure and superb band properties provides a new canonical form for the development of photodetectors. However, the limited exploitation of basic properties makes it difficult for devices to stand out. Here, we demonstrate a hybrid heterostructure with ultrathin vanadium dioxide film and molybdenum ditelluride nanoflake. Vanadium dioxide is a classical semiconductor with a narrow bandgap, a high temperature coefficient of resistance, and phase transformation. Molybdenum ditelluride, a typical two-dimensional material, is often used to construct optoelectronic devices. The heterostructure can realize three different functional modes: (i) the p–n junction exhibits ultrasensitive detection (450 nm–2 μm) with a dark current down to 0.2 pA and a response time of 17 μs, (ii) the Schottky junction works stably under extreme conditions such as a high temperature of 400 K, and (iii) the bolometer shows ultrabroad spectrum detection exceeding 10 μm. The flexible switching between the three modes makes the heterostructure a potential candidate for next-generation photodetectors from visible to longwave infrared radiation (LWIR). This type of photodetector combines versatile detection modes, shedding light on the hybrid application of novel and traditional materials, and is a prototype of advanced optoelectronic devices.
Defining the susceptibility of colorectal cancers to BH3-mimetic compounds
Authors: Luo Ming-Jie , Palmieri Michelle , Riffkin Chris D. , Sakthianandeswaren Anuratha , Djajawi Tirta Mario , Hirokawa Yumiko , Shuttleworth Victoria , Segal David H. , White Christine A. , Nhu Duong , Lessene Guillaume , Lee Margaret , Gibbs Peter , Huang David C. S. , Sieber Oliver M. , Gong Jia-nan 
Published: September 2020

AbstractNovel targets are required to improve the outcomes for patients with colorectal cancers. In this regard, the selective inhibitor of the pro-survival protein BCL2, venetoclax, has proven highly effective in several hematological malignancies. In addition to BCL2, potent and highly selective small molecule inhibitors of its relatives, BCLxL and MCL1, are now available, prompting us to investigate the susceptibility of colorectal cancers to the inhibition of one or more of these pro-survival proteins. While targeting BCLxL, but not BCL2 or MCL1, on its own had some impact, most (15/17) of the immortalized colorectal cancer cell lines studied were efficiently killed by the combined targeting of BCLxL and MCL1. Importantly, these in vitro findings were confirmed in a xenograft model and, interestingly, in all (5/5) patient derived tumor organoids evaluated. Our results lend strong support to the notion that BCLxL and MCL1 are highly promising targets for further evaluation in efforts to improve the treatment of colorectal cancers.
Rac1 conditional deletion attenuates retinal ganglion cell apoptosis by accelerating autophagic flux in a mouse model of chronic ocular hypertension
Authors: Zhang Meng-Lu , Zhao Guo-Li , Hou Yu , Zhong Shu-Min , Xu Lin-Jie , Li Fang , Niu Wei-Ran , Yuan Fei , Yang Xiong-Li , Wang Zhongfeng , Miao Yanying 
Published: September 2020

AbstractAutophagy has a fundamental role in maintaining cell homeostasis. Although autophagy has been implicated in glaucomatous pathology, how it regulates retinal ganglion cell (RGC) injury is largely unknown. In the present work, we found that biphasic autophagy in RGCs occurred in a mouse model of chronic ocular hypertension (COH), accompanied by activation of Rac1, a member of the Rho family. Rac1 conditional knockout (Rac1 cKO) in RGCs attenuated RGC apoptosis, in addition to blocking the increase in the number of autophagosomes and the expression of autophagy-related proteins (Beclin1, LC3-II/I, and p62) in COH retinas. Electron micrograph and double immunostaining of LAMP1 and LC3B showed that Rac1 cKO accelerated autolysosome fusion in RGC axons of COH mice. Inhibiting the first autophagic peak with 3-methyladenine or Atg13 siRNA reduced RGC apoptosis, whereas inhibiting the second autophagic peak with 3-MA or blocking autophagic flux by chloroquine increased RGC apoptosis. Furthermore, Rac1 cKO reduced the number of autophagosomes and apoptotic RGCs induced by rapamycin injected intravitreally, which suggests that Rac1 negatively regulates mTOR activity. Moreover, Rac1 deletion decreased Bak expression and did not interfere with the interaction of Beclin1 and Bcl-2 or Bak in COH retinas. In conclusion, autophagy promotes RGC apoptosis in the early stages of glaucoma and results in autophagic cell death in later stages. Rac1 deletion alleviates RGC damage by regulating the cross talk between autophagy and apoptosis through mTOR/Beclin1-Bak. Interfering with the Rac1/mTOR signaling pathway may provide a new strategy for treating glaucoma.
Intratumoral generation of photothermal gold nanoparticles through a vectorized biomineralization of ionic gold
Authors: Schwartz-Duval Aaron S. , Konopka Christian J. , Moitra Parikshit , Daza Enrique A. , Srivastava Indrajit , Johnson Elyse V. , Kampert Taylor L. , Fayn Stanley , Haran Anand , Dobrucki Lawrence W. , Pan Dipanjan 
Published: September 2020

AbstractVarious cancer cells have been demonstrated to have the capacity to form plasmonic gold nanoparticles when chloroauric acid is introduced to their cellular microenvironment. But their biomedical applications are limited, particularly considering the millimolar concentrations and longer incubation period of ionic gold. Here, we describe a simplistic method of intracellular biomineralization to produce plasmonic gold nanoparticles at micromolar concentrations within 30 min of application utilizing polyethylene glycol as delivery vector for ionic gold. We have characterized this process for intracellular gold nanoparticle formation, which progressively accumulates proteins as the ionic gold clusters migrate to the nucleus. This nano-vectorized application of ionic gold emphasizes its potential biomedical opportunities while reducing the quantity of ionic gold and required incubation time. To demonstrate its biomedical potential, we further induce in-situ biosynthesis of gold nanoparticles within MCF7 tumor mouse xenografts which is followed by its photothermal remediation.
Exciton g-factors in monolayer and bilayer WSe2 from experiment and theory
Authors: Förste Jonathan , Tepliakov Nikita V. , Kruchinin Stanislav Yu. , Lindlau Jessica , Funk Victor , Förg Michael , Watanabe Kenji , Taniguchi Takashi , Baimuratov Anvar S. , Högele Alexander 
Published: September 2020

AbstractThe optical properties of monolayer and bilayer transition metal dichalcogenide semiconductors are governed by excitons in different spin and valley configurations, providing versatile aspects for van der Waals heterostructures and devices. Here, we present experimental and theoretical studies of exciton energy splittings in external magnetic field in neutral and charged WSe2 monolayer and bilayer crystals embedded in a field effect device for active doping control. We develop theoretical methods to calculate the exciton g-factors from first principles for all possible spin-valley configurations of excitons in monolayer and bilayer WSe2 including valley-indirect excitons. Our theoretical and experimental findings shed light on some of the characteristic photoluminescence peaks observed for monolayer and bilayer WSe2. In more general terms, the theoretical aspects of our work provide additional means for the characterization of single and few-layer transition metal dichalcogenides, as well as their heterostructures, in the presence of external magnetic fields.
Local heating of radiation belt electrons to ultra-relativistic energies
Authors: Allison Hayley J. , Shprits Yuri Y. 
Published: September 2020

AbstractElectrically charged particles are trapped by the Earth’s magnetic field, forming the Van Allen radiation belts. Observations show that electrons in this region can have energies in excess of 7 MeV. However, whether electrons at these ultra-relativistic energies are locally accelerated, arise from betatron and Fermi acceleration due to transport across the magnetic field, or if a combination of both mechanisms is required, has remained an unanswered question in radiation belt physics. Here, we present a unique way of analyzing satellite observations which demonstrates that local acceleration is capable of heating electrons up to 7 MeV. By considering the evolution of phase space density peaks in magnetic coordinate space, we observe distinct signatures of local acceleration and the subsequent outward radial diffusion of ultra-relativistic electron populations. The results have important implications for understanding the origin of ultra-relativistic electrons in Earth’s radiation belts, as well as in magnetized plasmas throughout the solar system.
Area law of noncritical ground states in 1D long-range interacting systems
Authors: Kuwahara Tomotaka , Saito Keiji 
Published: September 2020

AbstractThe area law for entanglement provides one of the most important connections between information theory and quantum many-body physics. It is not only related to the universality of quantum phases, but also to efficient numerical simulations in the ground state. Various numerical observations have led to a strong belief that the area law is true for every non-critical phase in short-range interacting systems. However, the area law for long-range interacting systems is still elusive, as the long-range interaction results in correlation patterns similar to those in critical phases. Here, we show that for generic non-critical one-dimensional ground states with locally bounded Hamiltonians, the area law robustly holds without any corrections, even under long-range interactions. Our result guarantees an efficient description of ground states by the matrix-product state in experimentally relevant long-range systems, which justifies the density-matrix renormalization algorithm.
A molecular sensor to quantify the localization of proteins, DNA and nanoparticles in cells
Authors: FitzGerald Laura I. , Aurelio Luigi , Chen Moore , Yuen Daniel , Rennick Joshua J. , Graham Bim , Johnston Angus P. R. 
Published: September 2020

AbstractIntracellular trafficking governs receptor signaling, pathogenesis, immune responses and fate of nanomedicines. These processes are typically tracked by observing colocalization of fluorescent markers using confocal microscopy. However, this method is low throughput, limited by the resolution of microscopy, and can miss fleeting interactions. To address this, we developed a localization sensor composed of a quenched SNAP-tag substrate (SNAPSwitch) that can be conjugated to biomolecules using click chemistry. SNAPSwitch enables quantitative detection of trafficking to locations of interest within live cells using flow cytometry. Using SNAPSwitch, we followed the trafficking of DNA complexes from endosomes into the cytosol and nucleus. We show that antibodies against the transferrin or hyaluronan receptor are initially sorted into different compartments following endocytosis. In addition, we can resolve which side of the cellular membrane material was located. These results demonstrate SNAPSwitch is a high-throughput and broadly applicable tool to quantitatively track localization of materials in cells.
A role for Biofoundries in rapid development and validation of automated SARS-CoV-2 clinical diagnostics
Authors: Crone Michael A. , Priestman Miles , Ciechonska Marta , Jensen Kirsten , Sharp David J. , Anand Arthi , Randell Paul , Storch Marko , Freemont Paul S. 
Published: September 2020

AbstractThe SARS-CoV-2 pandemic has shown how a rapid rise in demand for patient and community sample testing can quickly overwhelm testing capability globally. With most diagnostic infrastructure dependent on specialized instruments, their exclusive reagent supplies quickly become bottlenecks, creating an urgent need for approaches to boost testing capacity. We address this challenge by refocusing the London Biofoundry onto the development of alternative testing pipelines. Here, we present a reagent-agnostic automated SARS-CoV-2 testing platform that can be quickly deployed and scaled. Using an in-house-generated, open-source, MS2-virus-like particle (VLP) SARS-CoV-2 standard, we validate RNA extraction and RT-qPCR workflows as well as two detection assays based on CRISPR-Cas13a and RT-loop-mediated isothermal amplification (RT-LAMP). In collaboration with an NHS diagnostic testing lab, we report the performance of the overall workflow and detection of SARS-CoV-2 in patient samples using RT-qPCR, CRISPR-Cas13a, and RT-LAMP. The validated RNA extraction and RT-qPCR platform has been installed in NHS diagnostic labs, increasing testing capacity by 1000 samples per day.
Maintenance of sarcomeric integrity in adult muscle cells crucially depends on Z-disc anchored titin
Authors: Swist Sandra , Unger Andreas , Li Yong , Vöge Anja , von Frieling-Salewsky Marion , Skärlén Åsa , Cacciani Nicola , Braun Thomas , Larsson Lars , Linke Wolfgang A. 
Published: September 2020

AbstractThe giant protein titin is thought to be required for sarcomeric integrity in mature myocytes, but direct evidence for this hypothesis is limited. Here, we describe a mouse model in which Z-disc-anchored TTN is depleted in adult skeletal muscles. Inactivation of TTN causes sarcomere disassembly and Z-disc deformations, force impairment, myocyte de-stiffening, upregulation of TTN-binding mechanosensitive proteins and activation of protein quality-control pathways, concomitant with preferential loss of thick-filament proteins. Interestingly, expression of the myosin-bound Cronos-isoform of TTN, generated from an alternative promoter not affected by the targeting strategy, does not prevent deterioration of sarcomere formation and maintenance. Finally, we demonstrate that loss of Z-disc-anchored TTN recapitulates muscle remodeling in critical illness ‘myosinopathy’ patients, characterized by TTN-depletion and loss of thick filaments. We conclude that full-length TTN is required to integrate Z-disc and A-band proteins into the mature sarcomere, a function that is lost when TTN expression is pathologically lowered.
The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia
Authors: Ham Daniel J. , Börsch Anastasiya , Lin Shuo , Thürkauf Marco , Weihrauch Martin , Reinhard Judith R. , Delezie Julien , Battilana Fabienne , Wang Xueyong , Kaiser Marco S. , Guridi Maitea , Sinnreich Michael , Rich Mark M. , Mittal Nitish , Tintignac Lionel A. , Handschin Christoph , Zavolan Mihaela , Rüegg Markus A. 
Published: September 2020

AbstractWith human median lifespan extending into the 80s in many developed countries, the societal burden of age-related muscle loss (sarcopenia) is increasing. mTORC1 promotes skeletal muscle hypertrophy, but also drives organismal aging. Here, we address the question of whether mTORC1 activation or suppression is beneficial for skeletal muscle aging. We demonstrate that chronic mTORC1 inhibition with rapamycin is overwhelmingly, but not entirely, positive for aging mouse skeletal muscle, while genetic, muscle fiber-specific activation of mTORC1 is sufficient to induce molecular signatures of sarcopenia. Through integration of comprehensive physiological and extensive gene expression profiling in young and old mice, and following genetic activation or pharmacological inhibition of mTORC1, we establish the phenotypically-backed, mTORC1-focused, multi-muscle gene expression atlas, SarcoAtlas (https://sarcoatlas.scicore.unibas.ch/), as a user-friendly gene discovery tool. We uncover inter-muscle divergence in the primary drivers of sarcopenia and identify the neuromuscular junction as a focal point of mTORC1-driven muscle aging.
Enhanced carbon dioxide conversion at ambient conditions via a pore enrichment effect
Authors: Zhou Wei , Deng Qi-Wen , Ren Guo-Qing , Sun Lei , Yang Li , Li Yi-Meng , Zhai Dong , Zhou Yi-Hong , Deng Wei-Qiao 
Published: September 2020

AbstractChemical fixation of carbon dioxide (CO2) may be a pathway to retard the current trend of rapid global warming. However, the current economic cost of chemical fixation remains high because the chemical fixation of CO2 usually requires high temperature or high pressure. The rational design of an efficient catalyst that works at ambient conditions might substantially reduce the economic cost of fixation. Here, we report the rational design of covalent organic frameworks (COFs) as efficient CO2 fixation catalysts under ambient conditions based on the finding of “pore enrichment”, which is concluded by a detailed investigation of the 10994 COFs. The best predicted COF, Zn-Salen-COF-SDU113, is synthesized, and its efficient catalytic performance for CO2 cycloaddition to terminal epoxide is confirmed with a yield of 98.2% and turnover number (TON) of 3068.9 under ambient conditions, which is comparable to the reported leading catalysts. Moreover, this COF achieves the cycloaddition of CO2 to 2,3-epoxybutane under ambient conditions among all porous materials. This work provides a strategy for designing porous catalysts in the economic fixation of carbon dioxide.
FastClone is a probabilistic tool for deconvoluting tumor heterogeneity in bulk-sequencing samples
Authors: Xiao Yao , Wang Xueqing , Zhang Hongjiu , Ulintz Peter J. , Li Hongyang , Guan Yuanfang 
Published: September 2020

AbstractDissecting tumor heterogeneity is a key to understanding the complex mechanisms underlying drug resistance in cancers. The rich literature of pioneering studies on tumor heterogeneity analysis spurred a recent community-wide benchmark study that compares diverse modeling algorithms. Here we present FastClone, a top-performing algorithm in accuracy in this benchmark. FastClone improves over existing methods by allowing the deconvolution of subclones that have independent copy number variation events within the same chromosome regions. We characterize the behavior of FastClone in identifying subclones using stage III colon cancer primary tumor samples as well as simulated data. It achieves approximately 100-fold acceleration in computation for both simulated and patient data. The efficacy of FastClone will allow its application to large-scale data and clinical data, and facilitate personalized medicine in cancers.
ER-mitochondria contacts promote mtDNA nucleoids active transportation via mitochondrial dynamic tubulation
Authors: Qin Jinshan , Guo Yuting , Xue Boxin , Shi Peng , Chen Yang , Su Qian Peter , Hao Huiwen , Zhao Shujuan , Wu Congying , Yu Li , Li Dong , Sun Yujie 
Published: September 2020

AbstractA human cell contains hundreds to thousands of mitochondrial DNA (mtDNA) packaged into nucleoids. Currently, the segregation and allocation of nucleoids are thought to be passively determined by mitochondrial fusion and division. Here we provide evidence, using live-cell super-resolution imaging, that nucleoids can be actively transported via KIF5B-driven mitochondrial dynamic tubulation (MDT) activities that predominantly occur at the ER-mitochondria contact sites (EMCS). We further demonstrate that a mitochondrial inner membrane protein complex MICOS links nucleoids to Miro1, a KIF5B receptor on mitochondria, at the EMCS. We show that such active transportation is a mechanism essential for the proper distribution of nucleoids in the peripheral zone of the cell. Together, our work identifies an active transportation mechanism of nucleoids, with EMCS serving as a key platform for the interplay of nucleoids, MICOS, Miro1, and KIF5B to coordinate nucleoids segregation and transportation.
A moonlighting role for enzymes of glycolysis in the co-localization of mitochondria and chloroplasts
Authors: Zhang Youjun , Sampathkumar Arun , Kerber Sandra Mae-Lin , Swart Corné , Hille Carsten , Seerangan Kumar , Graf Alexander , Sweetlove Lee , Fernie Alisdair R. 
Published: September 2020

AbstractGlycolysis is one of the primordial pathways of metabolism, playing a pivotal role in energy metabolism and biosynthesis. Glycolytic enzymes are known to form transient multi-enzyme assemblies. Here we examine the wider protein-protein interactions of plant glycolytic enzymes and reveal a moonlighting role for specific glycolytic enzymes in mediating the co-localization of mitochondria and chloroplasts. Knockout mutation of phosphoglycerate mutase or enolase resulted in a significantly reduced association of the two organelles. We provide evidence that phosphoglycerate mutase and enolase form a substrate-channelling metabolon which is part of a larger complex of proteins including pyruvate kinase. These results alongside a range of genetic complementation experiments are discussed in the context of our current understanding of chloroplast-mitochondrial interactions within photosynthetic eukaryotes.
Synthesis of chiral anti-1,2-diamine derivatives through copper(I)-catalyzed asymmetric α-addition of ketimines to aldimines
Authors: Gan Xu-Cheng , Zhang Cheng-Yuan , Zhong Feng , Tian Ping , Yin Liang 
Published: September 2020

AbstractChiral 1,2-diamines serve as not only common structure units in bioactive molecules but also useful ligands for a range of catalytic asymmetric reactions. Here, we report a method to access anti-1,2-diamine derivatives. By means of the electron-withdrawing nature of 2- or 4-nitro-phenyl group, a copper(I)-catalyzed asymmetric α-addition of ketimines derived from trifluoroacetophenone and 2- or 4-NO2-benzylamines to aldimines is achieved, which affords a series of chiral anti-1,2-diamine derivatives in moderate to high yields with moderate to high diastereoselectivity and high to excellent enantioselectivity. Aromatic aldimines, heteroaromatic aldimines, and aliphatic aldimines serve as suitable substrates. The nitro group is demonstrated as a synthetical handle by several transformations, including a particularly interesting Fe(acac)3-catalyzed radical hydroamination with a trisubstituted olefin. Moreover, the aryl amine moiety obtained by the reduction of the nitro group serves as a synthetically versatile group, which leads to the generation of several functional groups by the powerful Sandmeyer reaction, such as -OH, -Br, -CF3, and -BPin.
Mapping and identification of soft corona proteins at nanoparticles and their impact on cellular association
Authors: Mohammad-Beigi Hossein , Hayashi Yuya , Zeuthen Christina Moeslund , Eskandari Hoda , Scavenius Carsten , Juul-Madsen Kristian , Vorup-Jensen Thomas , Enghild Jan J. , Sutherland Duncan S. 
Published: September 2020

AbstractThe current understanding of the biological identity that nanoparticles may acquire in a given biological milieu is mostly inferred from the hard component of the protein corona (HC). The composition of soft corona (SC) proteins and their biological relevance have remained elusive due to the lack of analytical separation methods. Here, we identify a set of specific corona proteins with weak interactions at silica and polystyrene nanoparticles by using an in situ click-chemistry reaction. We show that these SC proteins are present also in the HC, but are specifically enriched after the capture, suggesting that the main distinction between HC and SC is the differential binding strength of the same proteins. Interestingly, the weakly interacting proteins are revealed as modulators of nanoparticle-cell association mainly through their dynamic nature. We therefore highlight that weak interactions of proteins at nanoparticles should be considered when evaluating nano-bio interfaces.