bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatially dispersing Yu-Shiba-Rusinov states in the unconventional superconductor FeTe0.55Se0.45
Authors: Chatzopoulos Damianos , Cho Doohee , Bastiaans Koen M. , Steffensen Gorm O. , Bouwmeester Damian , Akbari Alireza , Gu Genda , Paaske Jens , Andersen Brian M. , Allan Milan P. 
Published: January 2021

AbstractBy using scanning tunneling microscopy (STM) we find and characterize dispersive, energy-symmetric in-gap states in the iron-based superconductor FeTe0.55Se0.45, a material that exhibits signatures of topological superconductivity, and Majorana bound states at vortex cores or at impurity locations. We use a superconducting STM tip for enhanced energy resolution, which enables us to show that impurity states can be tuned through the Fermi level with varying tip-sample distance. We find that the impurity state is of the Yu-Shiba-Rusinov (YSR) type, and argue that the energy shift is caused by the low superfluid density in FeTe0.55Se0.45, which allows the electric field of the tip to slightly penetrate the sample. We model the newly introduced tip-gating scenario within the single-impurity Anderson model and find good agreement to the experimental data.
Tailoring of a visible-light-absorbing biaxial ferroelectric towards broadband self-driven photodetection
Authors: Han Shiguo , Li Maofan , Liu Yi , Guo Wuqian , Hong Mao-Chun , Sun Zhihua , Luo Junhua 
Published: January 2021

AbstractIn terms of strong light-polarization coupling, ferroelectric materials with bulk photovoltaic effects afford a promising avenue for optoelectronic devices. However, due to severe polarization deterioration caused by leakage current of photoexcited carriers, most of ferroelectrics are merely capable of absorbing 8–20% of visible-light spectra. Ferroelectrics with the narrow bandgap (<2.0 eV) are still scarce, hindering their practical applications. Here, we present a lead-iodide hybrid biaxial ferroelectric, (isopentylammonium)2(ethylammonium)2Pb3I10, which shows large spontaneous polarization (~5.2 μC/cm2) and a narrow direct bandgap (~1.80 eV). Particularly, the symmetry breaking of 4/mmmFmm2 species results in its biaxial attributes, which has four equivalent polar directions. Accordingly, exceptional in-plane photovoltaic effects are exploited along the crystallographic [001] and [010] axes directions inside the crystallographic bc-plane. The coupling between ferroelectricity and photovoltaic effects endows great possibility toward self-driven photodetection. This study sheds light on future optoelectronic device applications.
Engineering and elucidation of the lipoinitiation process in nonribosomal peptide biosynthesis
Authors: Zhong Lin , Diao Xiaotong , Zhang Na , Li Fengwei , Zhou Haibo , Chen Hanna , Bai Xianping , Ren Xintong , Zhang Youming , Wu Dalei , Bian Xiaoying 
Published: January 2021

AbstractNonribosomal peptide synthetases containing starter condensation domains direct the biosynthesis of nonribosomal lipopeptides, which generally exhibit wide bioactivities. The acyl chain has strong impacts on bioactivity and toxicity, but the lack of an in-depth understanding of starter condensation domain-mediated lipoinitiation limits the bioengineering of NRPSs to obtain novel derivatives with desired acyl chains. Here, we show that the acyl chains of the lipopeptides rhizomide, holrhizin, and glidobactin were modified by engineering the starter condensation domain, suggesting a workable approach to change the acyl chain. Based on the structure of the mutated starter condensation domain of rhizomide biosynthetic enzyme RzmA in complex with octanoyl-CoA and related point mutation experiments, we identify a set of residues responsible for the selectivity of substrate acyl chains and extend the acyl chains from acetyl to palmitoyl. Furthermore, we illustrate three possible conformational states of starter condensation domains during the reaction cycle of the lipoinitiation process. Our studies provide further insights into the mechanism of lipoinitiation and the engineering of nonribosomal peptide synthetases.
Millennial scale persistence of organic carbon bound to iron in Arctic marine sediments
Authors: Faust Johan C. , Tessin Allyson , Fisher Ben J. , Zindorf Mark , Papadaki Sonia , Hendry Katharine R. , Doyle Katherine A. , März Christian 
Published: January 2021

AbstractBurial of organic material in marine sediments represents a dominant natural mechanism of long-term carbon sequestration globally, but critical aspects of this carbon sink remain unresolved. Investigation of surface sediments led to the proposition that on average 10-20% of sedimentary organic carbon is stabilised and physically protected against microbial degradation through binding to reactive metal (e.g. iron and manganese) oxides. Here we examine the long-term efficiency of this rusty carbon sink by analysing the chemical composition of sediments and pore waters from four locations in the Barents Sea. Our findings show that the carbon-iron coupling persists below the uppermost, oxygenated sediment layer over thousands of years. We further propose that authigenic coprecipitation is not the dominant factor of the carbon-iron bounding in these Arctic shelf sediments and that a substantial fraction of the organic carbon is already bound to reactive iron prior deposition on the seafloor.
A random-walk benchmark for single-electron circuits
Authors: Reifert David , Kokainis Martins , Ambainis Andris , Kashcheyevs Vyacheslavs , Ubbelohde Niels 
Published: January 2021

AbstractMesoscopic integrated circuits aim for precise control over elementary quantum systems. However, as fidelities improve, the increasingly rare errors and component crosstalk pose a challenge for validating error models and quantifying accuracy of circuit performance. Here we propose and implement a circuit-level benchmark that models fidelity as a random walk of an error syndrome, detected by an accumulating probe. Additionally, contributions of correlated noise, induced environmentally or by memory, are revealed as limits of achievable fidelity by statistical consistency analysis of the full distribution of error counts. Applying this methodology to a high-fidelity implementation of on-demand transfer of electrons in quantum dots we are able to utilize the high precision of charge counting to robustly estimate the error rate of the full circuit and its variability due to noise in the environment. As the clock frequency of the circuit is increased, the random walk reveals a memory effect. This benchmark contributes towards a rigorous metrology of quantum circuits.
Giant isotropic magneto-thermal conductivity of metallic spin liquid candidate Pr2Ir2O7 with quantum criticality
Authors: Ni J. M. , Huang Y. Y. , Cheng E. J. , Yu Y. J. , Pan B. L. , Li Q. , Xu L. M. , Tian Z. M. , Li S. Y. 
Published: January 2021

AbstractSpin liquids are exotic states with no spontaneous symmetry breaking down to zero-temperature because of the highly entangled and fluctuating spins in frustrated systems. Exotic excitations like magnetic monopoles, visons, and photons may emerge from quantum spin ice states, a special kind of spin liquids in pyrochlore lattices. These materials usually are insulators, with an exception of the pyrochlore iridate Pr2Ir2O7, which was proposed as a metallic spin liquid located at a zero-field quantum critical point. Here we report the ultralow-temperature thermal conductivity measurements on Pr2Ir2O7. The Wiedemann–Franz law is verified at high fields and inferred at zero field, suggesting no breakdown of Landau quasiparticles at the quantum critical point, and the absence of mobile fermionic excitations. This result puts strong constraints on the description of the quantum criticality in Pr2Ir2O7. Unexpectedly, although the specific heats are anisotropic with respect to magnetic field directions, the thermal conductivities display the giant but isotropic response. This indicates that quadrupolar interactions and quantum fluctuations are important, which will help determine the true ground state of this material.
Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis
Authors: Gao Teng , Ptashkin Ryan , Bolton Kelly L. , Sirenko Maria , Fong Christopher , Spitzer Barbara , Menghrajani Kamal , Ossa Juan E. Arango , Zhou Yangyu , Bernard Elsa , Levine Max , Martinez Juan S. Medina , Zhang Yanming , Franch-Expósito Sebastià , Patel Minal , Braunstein Lior Z. , Kelly Daniel , Yabe Mariko , Benayed Ryma , Caltabellotta Nicole M. , Philip John , Paraiso Ederlinda , Mantha Simon , Solit David B. , Diaz Luis A. , Berger Michael F. , Klimek Virginia , Levine Ross L. , Zehir Ahmet , Devlin Sean M. , Papaemmanuil Elli 
Published: January 2021

AbstractStably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n = 14,789) and mCAs (n = 383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7–22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR = 14, 95% CI: 6–33, P < 0.001). Our results suggest that mCA should be considered in conjunction with gene mutations in the surveillance of patients at risk of hematologic neoplasms.
SCISSOR: a framework for identifying structural changes in RNA transcripts
Authors: Choi Hyo Young , Jo Heejoon , Zhao Xiaobei , Hoadley Katherine A. , Newman Scott , Holt Jeremiah , Hayward Michele C. , Love Michael I. , Marron J. S. , Hayes D. Neil 
Published: January 2021

AbstractHigh-throughput sequencing protocols such as RNA-seq have made it possible to interrogate the sequence, structure and abundance of RNA transcripts at higher resolution than previous microarray and other molecular techniques. While many computational tools have been proposed for identifying mRNA variation through differential splicing/alternative exon usage, challenges in its analysis remain. Here, we propose a framework for unbiased and robust discovery of aberrant RNA transcript structures using short read sequencing data based on shape changes in an RNA-seq coverage profile. Shape changes in selecting sample outliers in RNA-seq, SCISSOR, is a series of procedures for transforming and normalizing base-level RNA sequencing coverage data in a transcript independent manner, followed by a statistical framework for its analysis (https://github.com/hyochoi/SCISSOR). The resulting high dimensional object is amenable to unsupervised screening of structural alterations across RNA-seq cohorts with nearly no assumption on the mutational mechanisms underlying abnormalities. This enables SCISSOR to independently recapture known variants such as splice site mutations in tumor suppressor genes as well as novel variants that are previously unrecognized or difficult to identify by any existing methods including recurrent alternate transcription start sites and recurrent complex deletions in 3′ UTRs.
Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy
Authors: Somasundaram Rajasekharan , Connelly Thomas , Choi Robin , Choi Hyeree , Samarkina Anastasia , Li Ling , Gregorio Elizabeth , Chen Yeqing , Thakur Rohit , Abdel-Mohsen Mohamed , Beqiri Marilda , Kiernan Meaghan , Perego Michela , Wang Fang , Xiao Min , Brafford Patricia , Yang Xue , Xu Xiaowei , Secreto Anthony , Danet-Desnoyers Gwenn , Traum Daniel , Kaestner Klaus H. , Huang Alexander C. , Hristova Denitsa , Wang Joshua , Fukunaga-Kalabis Mizuho , Krepler Clemens , Ping-Chen Fang , Zhou Xiangyang , Gutierrez Alexis , Rebecca Vito W. , Vonteddu Prashanthi , Dotiwala Farokh , Bala Shashi , Majumdar Sonali , Dweep Harsh , Wickramasinghe Jayamanna , Kossenkov Andrew V. , Reyes-Arbujas Jorge , Santiago Kenisha , Nguyen Tran , Griss Johannes , Keeney Frederick , Hayden James , Gavin Brian J. , Weiner David , Montaner Luis J. , Liu Qin , Peiffer Lukas , Becker Jürgen , Burton Elizabeth M. , Davies Michael A. , Tetzlaff Michael T. , Muthumani Kar , Wargo Jennifer A. , Gabrilovich Dmitry , Herlyn Meenhard 
Published: January 2021

AbstractAnti-PD-1 therapy is used as a front-line treatment for many cancers, but mechanistic insight into this therapy resistance is still lacking. Here we generate a humanized (Hu)-mouse melanoma model by injecting fetal liver-derived CD34+ cells and implanting autologous thymus in immune-deficient NOD-scid IL2Rγnull (NSG) mice. Reconstituted Hu-mice are challenged with HLA-matched melanomas and treated with anti-PD-1, which results in restricted tumor growth but not complete regression. Tumor RNA-seq, multiplexed imaging and immunohistology staining show high expression of chemokines, as well as recruitment of FOXP3+ Treg and mast cells, in selective tumor regions. Reduced HLA-class I expression and CD8+/Granz B+ T cells homeostasis are observed in tumor regions where FOXP3+ Treg and mast cells co-localize, with such features associated with resistance to anti-PD-1 treatment. Combining anti-PD-1 with sunitinib or imatinib results in the depletion of mast cells and complete regression of tumors. Our results thus implicate mast cell depletion for improving the efficacy of anti-PD-1 therapy.
A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein
Authors: Kim Cheolmin , Ryu Dong-Kyun , Lee Jihun , Kim Young-Il , Seo Ji-Min , Kim Yeon-Gil , Jeong Jae-Hee , Kim Minsoo , Kim Jong-In , Kim Pankyeom , Bae Jin Soo , Shim Eun Yeong , Lee Min Seob , Kim Man Su , Noh Hanmi , Park Geun-Soo , Park Jae Sang , Son Dain , An Yongjin , Lee Jeong No , Kwon Ki-Sung , Lee Joo-Yeon , Lee Hansaem , Yang Jeong-Sun , Kim Kyung-Chang , Kim Sung Soon , Woo Hye-Min , Kim Jun-Won , Park Man-Seong , Yu Kwang-Min , Kim Se-Mi , Kim Eun-Ha , Park Su-Jin , Jeong Seong Tae , Yu Chi Ho , Song Youngjo , Gu Se Hun , Oh Hanseul , Koo Bon-Sang , Hong Jung Joo , Ryu Choong-Min , Park Wan Beom , Oh Myoung-don , Choi Young Ki , Lee Soo-Young 
Published: January 2021

AbstractVaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.
Granzyme B inhibition reduces disease severity in autoimmune blistering diseases
Authors: Hiroyasu Sho , Zeglinski Matthew R. , Zhao Hongyan , Pawluk Megan A. , Turner Christopher T. , Kasprick Anika , Tateishi Chiharu , Nishie Wataru , Burleigh Angela , Lennox Peter A. , Van Laeken Nancy , Carr Nick J. , Petersen Frank , Crawford Richard I. , Shimizu Hiroshi , Tsuruta Daisuke , Ludwig Ralf J. , Granville David J. 
Published: January 2021

AbstractPemphigoid diseases refer to a group of severe autoimmune skin blistering diseases characterized by subepidermal blistering and loss of dermal-epidermal adhesion induced by autoantibody and immune cell infiltrate at the dermal-epidermal junction and upper dermis. Here, we explore the role of the immune cell-secreted serine protease, granzyme B, in pemphigoid disease pathogenesis using three independent murine models. In all models, granzyme B knockout or topical pharmacological inhibition significantly reduces total blistering area compared to controls. In vivo and in vitro studies show that granzyme B contributes to blistering by degrading key anchoring proteins in the dermal-epidermal junction that are necessary for dermal-epidermal adhesion. Further, granzyme B mediates IL-8/macrophage inflammatory protein-2 secretion, lesional neutrophil infiltration, and lesional neutrophil elastase activity. Clinically, granzyme B is elevated and abundant in human pemphigoid disease blister fluids and lesional skin. Collectively, granzyme B is a potential therapeutic target in pemphigoid diseases.
H2AK121ub in Arabidopsis associates with a less accessible chromatin state at transcriptional regulation hotspots
Authors: Yin Xiaochang , Romero-Campero Francisco J. , de Los Reyes Pedro , Yan Peng , Yang Jing , Tian Guangmei , Yang XiaoZeng , Mo Xiaorong , Zhao Shuangshuang , Calonje Myriam , Zhou Yue 
Published: January 2021

AbstractAlthough it is well established that the Polycomb Group (PcG) complexes maintain gene repression through the incorporation of H2AK121ub and H3K27me3, little is known about the effect of these modifications on chromatin accessibility, which is fundamental to understand PcG function. Here, by integrating chromatin accessibility, histone marks and expression analyses in different Arabidopsis PcG mutants, we show that PcG function regulates chromatin accessibility. We find that H2AK121ub is associated with a less accessible but still permissive chromatin at transcriptional regulation hotspots. Accessibility is further reduced by EMF1 acting in collaboration with PRC2 activity. Consequently, H2AK121ub/H3K27me3 marks are linked to inaccessible although responsive chromatin. In contrast, only-H3K27me3-marked chromatin is less responsive, indicating that H2AK121ub-marked hotspots are required for transcriptional responses. Nevertheless, despite the loss of PcG activities leads to increased chromatin accessibility, this is not necessarily accompanied by transcriptional activation, indicating that accessible chromatin is not always predictive of gene expression.
Collective synthesis of acetylenic pharmaceuticals via enantioselective Nickel/Lewis acid-catalyzed propargylic alkylation
Authors: Chang Xihao , Zhang Jiayin , Peng Lingzi , Guo Chang 
Published: January 2021

AbstractChiral acetylenic derivatives are found in many bioactive compounds and are versatile functional groups in organic chemistry. Here, we describe an enantioselective nickel/Lewis acid-catalyzed asymmetric propargylic substitution reaction from simple achiral materials under mild condition. The introduction of a Lewis acid cocatalyst is crucial to the efficiency of the transformation. Notably, we investigate this asymmetric propargylic substitution reaction for the development of a range of structurally diverse natural products. The power of this strategy is highlighted by the collective synthesis of seven biologically active compounds: (−)-Thiohexital, (+)-Thiopental, (+)-Pentobarbital, (−)-AMG 837, (+)-Phenoxanol, (+)-Citralis, and (−)-Citralis Nitrile.
Experimental determination of the effects of pretreatment on selected Nigerian lignocellulosic biomass in bioethanol production
Authors: Awoyale Adeolu A. , Lokhat David 
Published: January 2021

AbstractIn the present study, five lignocellulosic biomass namely, corn cobs (Zea mays), rice husks (Oryza sativa), cassava peels (Manihot esculenta), sugar cane bagasse (Saccharum officinarum), and white yam peels (Dioscorea rotundata) of two mesh sizes of 300 and 425 microns and a combination of some and all of the biomass were pretreated using combined hydrothermal and acid-based, combined hydrothermal and alkali-based and hydrothermal only processes. The raw and pretreated biomass were also characterized by Fourier transform infrared spectroscopy (FT-IR), Brunauer–Emmett–Teller (BET), X-Ray diffraction (XRD), and Scanning electron microscopy (SEM) to determine the effects of the various pretreatments on the biomass being studied. The cellulose values of the raw biomass range from 25.8 wt% for cassava peels biomass to 40.0 wt% for sugar cane bagasse. The values of the cellulose content increased slightly with the pretreatment, ranging from 33.2 to 43.8 wt%. The results of the analysis indicate that the hydrothermal and alkaline-based pretreatment shows more severity on the different biomass being studied as seen from the pore characteristics results of corn cobs + rice husks biomass, which also shows that the combination of feedstocks can effectively improve the properties of the biomass in the bioethanol production process. The FTIR analysis also showed that the crystalline cellulose present in all the biomass was converted to the amorphous form after the pretreatment processes. The pore characteristics for mixed corn cobs and rice husks biomass have the highest specific surface area and pore volume of 1837 m2/g and 0.5570 cc/g respectively.
Integrative microRNA and gene expression analysis identifies new epigenetically regulated microRNAs mediating taxane resistance in ovarian cancer
Authors: Hassan Mohamed K. , Waly Amr A. , Elsayed Waheba , Keshk Sarah , Allam Walaa Ramadan , El-khamisy Sherif F. 
Published: January 2021

AbstractTaxane is a family of front-line chemotherapeutic agents against ovarian cancer (OC). The therapeutic efficacy is frequently counteracted by the development of chemoresistance, leading to high rates of relapse in OC patients. The role(s) of microRNAs (miRNAs) in cancer chemoresistance had been supported by many evidences Epigenetic regulation by miRNAs has been reported to influence cancer development and response to therapeutics, however, their role in OC resistance to paclitaxel (PTX) is unclear. Here, we conducted miRNA profiling in the responsive and PTX-resistant OC cell lines before and after treatment with epigenetic modulators. We reveal 157 miRNAs to be downregulated in the PTX-resistant cells compared to parental controls. The expression of five miRNAs (miRNA-7-5p, -204-3p, -501-5p, -3652 and -4286) was restored after epigenetic modulation, which was further confirmed by qPCR. In silico analysis of the signaling pathways targeted by the selected miRNAs identified the PI3K-AKT pathway as the primary target. Subsequent cDNA array analysis confirmed multiple PI3K-AKT pathway members such as AKT2, PIK3R3, CDKN1A, CCND2 and FGF2 to be upregulated in PTX-resistant cells. STRING analysis showed the deregulated genes in PTX-resistant cells to be primarily involved in cell cycle progression and survival. Thus, high throughput miRNA and cDNA profiling coupled with pathway analysis and data mining provide evidence for epigenetically regulated miRNAs-induced modulation of signaling pathways in PTX resistant OC cells. It paves the way to more in-depth mechanistic studies and new therapeutic strategies to combat chemoresistance.