bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern
Authors: Skelly Donal T. , Harding Adam C. , Gilbert-Jaramillo Javier , Knight Michael L. , Longet Stephanie , Brown Anthony , Adele Sandra , Adland Emily , Brown Helen ,   Medawar Laboratory Team, Chinnakannan Senthil , Donnison Timothy , Ali Mohammad , Rongkard Patpong , Pace Matthew , Zacharopoulou Peny , Robinson Nicola , Csala Anna , De Lara Cathy , Hutchings Claire L. , Mehta Hema , Lee Lian Ni , Edmans Matthew , Hackstein Carl-Philipp , Phalora Prabhjeet , Li Wenqin , Phillips Eloise , Malone Tom , Ogbe Ane , Jay Cecilia , Tipoe Timothy , Tipton Tom , Stafford Lizzie , Mentzer Alexander J. , Johnson Síle A. , Amini Ali ,   OPTIC (Oxford Protective T cell Immunology for COVID-19) Clinical Group, Marjot Thomas , Dimitriadis Stavros , Simmons Beatrice , Deeks Alexandra , Kerneis Sven , Abuelgasim Hibatullah , Wilson Robert , Thomas Sarah R. , Watson Adam , Alhussni Ahmed , Cutteridge Joseph , Weeks Esme , Denly Lucy , Lillie Katy , Holmes Jennifer , Matthews Philppa C. , O’Donnell Denise , Tan Tiong Kit , Schimanski Lisa , Huang Kuan-Ying A. , Rijal Pramila ,   PITCH (Protective Immunity T cells in Health Care Worker) Study Group, Turtle Lance , de Silva Thushan , Richter Alex , Duncan Christopher J. A. , Payne Rebecca P. , Moore Shona C. ,   C-MORE/PHOSP-C Group, Knight Julian C. , Cassar Mark Philip , Raman Betty , Neubauer Stefan , Fries Anastasia , Talbot Nick P. , Petousi Nayia , Ho Ling-Pei , Peng Yanchun , Dong Tao , Camara Susana , Marinou Spyridoula , Linder Aline , Adlou Syed , Kasanyinga Mwila , Bridges-Webb Alice , Hill Jennifer , Silva-Reyes Laura , Blackwell Luke , Frater John , Goulder Philip , Conlon Christopher P. , Jeffery Katie , Dold Christina , Pollard Andrew J. , Sigal Alex , de Oliveira Tulio , Townsend Alain R. , Klenerman Paul , Dunachie Susanna J. , Barnes Eleanor , Carroll Miles W. , James William S. 
Published: August 2021

AbstractThe extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.
High COVID-19 transmission potential associated with re-opening universities can be mitigated with layered interventions
Authors: Brooks-Pollock Ellen , Christensen Hannah , Trickey Adam , Hemani Gibran , Nixon Emily , Thomas Amy C. , Turner Katy , Finn Adam , Hickman Matt , Relton Caroline , Danon Leon 
Published: August 2021

AbstractControlling COVID-19 transmission in universities poses challenges due to the complex social networks and potential for asymptomatic spread. We developed a stochastic transmission model based on realistic mixing patterns and evaluated alternative mitigation strategies. We predict, for plausible model parameters, that if asymptomatic cases are half as infectious as symptomatic cases, then 15% (98% Prediction Interval: 6–35%) of students could be infected during the first term without additional control measures. First year students are the main drivers of transmission with the highest infection rates, largely due to communal residences. In isolation, reducing face-to-face teaching is the most effective intervention considered, however layering multiple interventions could reduce infection rates by 75%. Fortnightly or more frequent mass testing is required to impact transmission and was not the most effective option considered. Our findings suggest that additional outbreak control measures should be considered for university settings.
High-harmonic generation in metallic titanium nitride
Authors: Korobenko A. , Saha S. , Godfrey A. T. K. , Gertsvolf M. , Naumov A. Yu. , Villeneuve D. M. , Boltasseva A. , Shalaev V. M. , Corkum P. B. 
Published: August 2021

AbstractHigh-harmonic generation is a cornerstone of nonlinear optics. It has been demonstrated in dielectrics, semiconductors, semi-metals, plasmas, and gases, but, until now, not in metals. Here we report high harmonics of 800-nm-wavelength light irradiating metallic titanium nitride film. Titanium nitride is a refractory metal known for its high melting temperature and large laser damage threshold. We show that it can withstand few-cycle light pulses with peak intensities as high as 13 TW/cm2, enabling high-harmonics generation up to photon energies of 11 eV. We measure the emitted vacuum ultraviolet radiation as a function of the crystal orientation with respect to the laser polarization and show that it is consistent with the anisotropic conduction band structure of titanium nitride. The generation of high harmonics from metals opens a link between solid and plasma harmonics. In addition, titanium nitride is a promising material for refractory plasmonic devices and could enable compact vacuum ultraviolet frequency combs.
Dual metal nanoparticles within multicompartmentalized mesoporous organosilicas for efficient sequential hydrogenation
Authors: Zou Houbing , Dai Jinyu , Suo Jinquan , Ettelaie Rammile , Li Yuan , Xue Nan , Wang Runwei , Yang Hengquan 
Published: August 2021

AbstractControlling localization of multiple metal nanoparticles on a single support is at the cutting edge of designing cascade catalysts, but is still a scientific and technological challenge because of the lack of nanostructured materials that can not only host metal nanoparticles in different sub-compartments but also enable efficient molecular transport between different metals. Herein we report a multicompartmentalized mesoporous organosilica with spatially separated sub-compartments that are connected by short nanochannels. Such a unique structure allows co-localization of Ru and Pd nanoparticles in a nanoscale proximal fashion. The so designed cascade catalyst exhibits an order of magnitude activity enhancement in the sequential hydrogenation of nitroarenes to cyclohexylamines compared with its mono/bi-metallic counterparts. Crucially, an interesting phenomenon of neighboring metal-assisted hydrogenation via hydrogen spillover is observed, contributing to the significant enhancement in catalytic efficiency. The multicompartmentalized architectures along with the revealed mechanism of accelerated hydrogenation provide vast opportunity for designing efficient cascade catalysts.
Direct deoxygenative borylation of carboxylic acids
Authors: Li Jianbin , Huang Chia-Yu , Ataya Mohamad , Khaliullin Rustam Z. , Li Chao-Jun 
Published: August 2021

AbstractCarboxylic acids are readily available, structurally diverse and shelf-stable; therefore, converting them to the isoelectronic boronic acids, which play pivotal roles in different settings, would be highly enabling. In contrast to the well-recognised decarboxylative borylation, the chemical space of carboxylic-to-boronic acid transformation via deoxygenation remains underexplored due to the thermodynamic and kinetic inertness of carboxylic C-O bonds. Herein, we report a deoxygenative borylation reaction of free carboxylic acids or their sodium salts to synthesise alkylboronates under metal-free conditions. Promoted by a uniquely Lewis acidic and strongly reducing diboron reagent, bis(catecholato)diboron (B2cat2), a library of aromatic carboxylic acids are converted to the benzylboronates. By leveraging the same borylative manifold, a facile triboration process with aliphatic carboxylic acids is also realised, diversifying the pool of available 1,1,2-alkyl(trisboronates) that were otherwise difficult to access. Detailed mechanistic studies reveal a stepwise C-O cleavage profile, which could inspire and encourage future endeavours on more appealing reductive functionalisation of oxygenated feedstocks.
Genome-scale target identification in Escherichia coli for high-titer production of free fatty acids
Authors: Fang Lixia , Fan Jie , Luo Shulei , Chen Yaru , Wang Congya , Cao Yingxiu , Song Hao 
Published: August 2021

AbstractTo construct a superior microbial cell factory for chemical synthesis, a major challenge is to fully exploit cellular potential by identifying and engineering beneficial gene targets in sophisticated metabolic networks. Here, we take advantage of CRISPR interference (CRISPRi) and omics analyses to systematically identify beneficial genes that can be engineered to promote free fatty acids (FFAs) production in Escherichia coli. CRISPRi-mediated genetic perturbation enables the identification of 30 beneficial genes from 108 targets related to FFA metabolism. Then, omics analyses of the FFAs-overproducing strains and a control strain enable the identification of another 26 beneficial genes that are seemingly irrelevant to FFA metabolism. Combinatorial perturbation of four beneficial genes involving cellular stress responses results in a recombinant strain ihfAL−-aidB+-ryfAM−-gadAH−, producing 30.0 g L−1 FFAs in fed-batch fermentation, the maximum titer in E. coli reported to date. Our findings are of help in rewiring cellular metabolism and interwoven intracellular processes to facilitate high-titer production of biochemicals.
Revealing the chirality origin and homochirality crystallization of Ag14 nanocluster at the molecular level
Authors: Liang Xiao-Qian , Li Ying-Zhou , Wang Zhi , Zhang Shan-Shan , Liu Yi-Cheng , Cao Zhao-Zhen , Feng Lei , Gao Zhi-Yong , Xue Qing-Wang , Tung Chen-Ho , Sun Di 
Published: August 2021

AbstractAlthough chirality is an ever-present characteristic in biology and some artificial molecules, controlling the chirality and demystifying the chirality origin of complex assemblies remain challenging. Herein, we report two homochiral Ag14 nanoclusters with inherent chirality originated from identical rotation of six square faces on a Ag8 cube driven by intra-cluster π···π stacking interaction between pntp− (Hpntp = p-nitrothiophenol) ligands. The spontaneous resolution of the racemic (SD/rac-Ag14a) to homochiral nanoclusters (SD/L-Ag14 and SD/R-Ag14) can be realized by re-crystallizing SD/rac-Ag14a in acetonitrile, which promotes the homochiral crystallization in solid state by forming C–H···O/N hydrogen bonds with nitro oxygen atoms in pntp− or aromatic hydrogen atoms in dpph (dpph = 1,6-bis(diphenylphosphino)hexane) on Ag14 nanocluster. This work not only provides strategic guidance for the syntheses of chiral silver nanoclusters in an all-achiral environment, but also deciphers the origin of chirality at molecular level by identifying the special effects of intra- and inter-cluster supramolecular interactions.
Structural basis for the inhibition of HTLV-1 integration inferred from cryo-EM deltaretroviral intasome structures
Authors: Barski Michal S. , Vanzo Teresa , Zhao Xue Zhi , Smith Steven J. , Ballandras-Colas Allison , Cronin Nora B. , Pye Valerie E. , Hughes Stephen H. , Burke Terrence R. , Cherepanov Peter , Maertens Goedele N. 
Published: August 2021

AbstractBetween 10 and 20 million people worldwide are infected with the human T-cell lymphotropic virus type 1 (HTLV-1). Despite causing life-threatening pathologies there is no therapeutic regimen for this deltaretrovirus. Here, we screened a library of integrase strand transfer inhibitor (INSTI) candidates built around several chemical scaffolds to determine their effectiveness in limiting HTLV-1 infection. Naphthyridines with substituents in position 6 emerged as the most potent compounds against HTLV-1, with XZ450 having highest efficacy in vitro. Using single-particle cryo-electron microscopy we visualised XZ450 as well as the clinical HIV-1 INSTIs raltegravir and bictegravir bound to the active site of the deltaretroviral intasome. The structures reveal subtle differences in the coordination environment of the Mg2+ ion pair involved in the interaction with the INSTIs. Our results elucidate the binding of INSTIs to the HTLV-1 intasome and support their use for pre-exposure prophylaxis and possibly future treatment of HTLV-1 infection.
Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines
Authors: Su Jianke , Hu Xinyuan , Huang Hua , Guo Yu , Song Qiuling 
Published: August 2021

Abstract2-Fluoroindoles as an important structural scaffold are widely existing in many bioactive or therapeutic agents. Despite their potential usefulness, efficient constructions of 2-fluoroindole derivatives are very sparce. The development of straightforward synthetic approaches to access 2-fluoroindoles is highly desirable for studying their fundamental properties and applications. Herein, we report an efficient and general strategy for the construction of 2-fluoroindoles in which a wide variety of 2-fluoroindoles were accessed with high efficiency and chemoselectivity. Instead of starting from indole skeletons, our strategy constructs indole scaffolds alongside the incorporation of fluorine atom on C2 position in a formal [4+1] cyclization from readily accessible ortho-vinylanilines and difluorocarbene. In our protocol, commercially accessible halodifluoroalkylative reagents provide one carbon and one fluorine atom by cleaving one C-N tertiary bond and forming one C-N bond and one C-C double bond with ortho-vinylanilines. Downstream transformations on 2-fluoroindoles lead to various valuable bioactive molecules which demonstrated significant synthetic advantages over previous reports. And mechanistic studies suggest that the reaction undergoes a cascade difluorocarbene-trapping and intramolecular Michael addition reaction followed by Csp3-F bond cleavage.
Circulating cell-free DNA-based methylation patterns for breast cancer diagnosis
Authors: Zhang Xianyu , Zhao Dezhi , Yin Yanling , Yang Ting , You Zilong , Li Dalin , Chen Yanbo , Jiang Yongdong , Xu Shouping , Geng Jingshu , Zhao Yashuang , Wang Jun , Li Hui , Tao Jinsheng , Lei Shan , Jiang Zeyu , Chen Zhiwei , Yu Shihui , Fan Jian-Bing , Pang Da 
Published: August 2021

AbstractMammography is used to detect breast cancer (BC), but its sensitivity is limited, especially for dense breasts. Circulating cell-free DNA (cfDNA) methylation tests is expected to compensate for the deficiency of mammography. We derived a specific panel of markers based on computational analysis of the DNA methylation profiles from The Cancer Genome Atlas (TCGA). Through training (n = 160) and validation set (n = 69), we developed a diagnostic prediction model with 26 markers, which yielded a sensitivity of 89.37% and a specificity of 100% for differentiating malignant disease from normal lesions [AUROC = 0.9816 (95% CI: 96.09-100%), and AUPRC = 0.9704 (95% CI: 94.54–99.46%)]. A simplified 4-marker model including cg23035715, cg16304215, cg20072171, and cg21501525 had a similar diagnostic power [AUROC = 0.9796 (95% CI: 95.56–100%), and AUPRC = 0.9220 (95% CI: 91.02–94.37%)]. We found that a single cfDNA methylation marker, cg23035715, has a high diagnostic power [AUROC = 0.9395 (95% CI: 89.72–99.27%), and AUPRC = 0.9111 (95% CI: 88.45–93.76%)], with a sensitivity of 84.90% and a specificity of 93.88%. In an independent testing dataset (n = 104), the obtained diagnostic prediction model discriminated BC patients from normal controls with high accuracy [AUROC = 0.9449 (95% CI: 90.07–98.91%), and AUPRC = 0.8640 (95% CI: 82.82–89.98%)]. We compared the diagnostic power of cfDNA methylation and mammography. Our model yielded a sensitivity of 94.79% (95% CI: 78.72–97.87%) and a specificity of 98.70% (95% CI: 86.36–100%) for differentiating malignant disease from normal lesions [AUROC = 0.9815 (95% CI: 96.75–99.55%), and AUPRC = 0.9800 (95% CI: 96.6–99.4%)], with better diagnostic power and had better diagnostic power than that of using mammography [AUROC = 0.9315 (95% CI: 89.95–96.34%), and AUPRC = 0.9490 (95% CI: 91.7–98.1%)]. In addition, hypermethylation profiling provided insights into lymph node metastasis stratifications (p < 0.05). In conclusion, we developed and tested a cfDNA methylation model for BC diagnosis with better performance than mammography.
Emergent properties at oxide interfaces controlled by ferroelectric polarization
Authors: Ye Fan , Zhang Yi , Addiego Christopher , Xu Mingjie , Huyan Huaixun , Ren Xiaobing , Pan Xiaoqing 
Published: August 2021

AbstractFerroelectric materials are characterized by the spontaneous polarization switchable by the applied fields, which can act as a “gate” to control various properties of ferroelectric/insulator interfaces. Here we review the recent studies on the modulation of oxide hetero-/homo-interfaces by ferroelectric polarization. We discuss the potential applications of recently developed four-dimensional scanning transmission electron microscopy and how it can provide insights into the fundamental understanding of ferroelectric polarization-induced phenomena and stimulate future computational studies. Finally, we give the outlook for the potentials, the challenges, and the opportunities for the contribution of materials computation to future progress in the area.
Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice
Authors: Bravard Amélie , Gérard Céline , Defois Clémence , Benoit Bérengère , Makki Kassem , Meugnier Emmanuelle , Rainteau Dominique , Rieusset Jennifer , Godet Murielle , Vidal Hubert 
Published: August 2021

AbstractAlthough the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, it is well accepted that the gut plays an important role. To gain more insights into the mechanisms occurring in the different regions of the intestine, adult male mice were fed a high-fat-high sucrose (HFS) diet for 8 days and treated with metformin by gavage (300 mg/day/kg body weight) during the HFS diet. Metformin counteracted HFS diet-induced overexpression of a network of genes involved in the transport of glucose and fatty acids in the different regions of the small intestine. It also induced beneficial modification of secondary bile acid profile in the caecum, with a reduction of deoxycholic acid and lithocholic acid levels and increased abundance of ursodeoxycholic acid and tauroursodeoxycholic acid, potentially leading to FRX inhibition. In parallel, metformin treatment was associated with specific changes of the microbiota composition in the lumen of the different regions of the intestine. Metformin induced a marked increase in the abundance of Akkermansia muciniphila in the lumen all along the gut and counteracted the effects of HFS diet on the abundances of some bacterial groups generally associated with metabolic disturbances (f-Lachnospiraceae, f-Petostreptococcaceae, g-Clostidium). Therefore, the present work clearly emphasises the role of all the regions of the intestinal tract in the beneficial action of the antidiabetic drug metformin in a prediabetic mouse model.
The development of L-type Ca2+ current mediated alternans does not depend on the restitution slope in canine ventricular myocardium
Authors: Tóth Noémi , Szlovák Jozefina , Kohajda Zsófia , Bitay Gergő , Veress Roland , Horváth Balázs , Papp Julius Gy. , Varró András , Nagy Norbert 
Published: August 2021

AbstractCardiac alternans have crucial importance in the onset of ventricular fibrillation. The early explanation for alternans development was the voltage-driven mechanism, where the action potential (AP) restitution steepness was considered as crucial determining factor. Recent results suggest that restitution slope is an inadequate predictor for alternans development, but several studies still claim the role of membrane potential as underlying mechanism of alternans. These controversial data indicate that the relationship of restitution and alternans development is not completely understood. APs were measured by conventional microelectrode technique from canine right ventricular papillary muscles. Ionic currents combined with fluorescent measurements were recorded by patch-clamp technique. APs combined with fluorescent measurements were monitored by sharp microelectrodes. Rapid pacing evoked restitution-independent AP duration (APD) alternans. When non-alternating AP voltage command was used, Ca2+i-transient (CaT) alternans were not observed. When alternating rectangular voltage pulses were applied, CaT alternans were proportional to ICaL amplitude alternans. Selective ICaL inhibition did not influence the fast phase of APD restitution. In this study we found that ICaL has minor contribution in shaping the fast phase of restitution curve suggesting that ICaL—if it plays important role in the alternans mechanism—could be an additional factor that attenuates the reliability of APD restitution slope to predict alternans.
Successful artificial reefs depend on getting the context right due to complex socio-bio-economic interactions
Authors: Brochier Timothée , Brehmer Patrice , Mbaye Adama , Diop Mamadou , Watanuki Naohiko , Terashima Hiroaki , Kaplan David , Auger Pierre 
Published: August 2021

AbstractArtificial reefs (ARs) are one of the most popular means of supporting marine ecosystem conservation and coastal fisheries, particularly in developing countries. However, ARs generate complex socio-bio-economic interactions that require careful evaluation. This is particularly the case for ARs outside no-take zones, where fish might be subject to enhanced exploitation due to easier catchability. Here, we conducted an interdisciplinary study on how ARs impact fish and fishing yields, combining mathematical and sociological approaches. Both approaches converge to confirm that fishery yields decline when ARs are exploited as if they were open access areas. This situation typically occurs in areas with weak governance and/or high levels of illegal fishing activity, both of which are common in many developing countries. To avoid these adverse effects and their associated ecological consequences, we recommend prioritizing the onset of a long-term surveillance system against illegal fishing activities, and adapting design and location of the ARs based on both and local and academic knowledge, before the deployment of ARs.