bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-reproductive stress in adolescent female rats alters oocyte microRNA expression and offspring phenotypes: pharmacological interventions and putative mechanisms
Authors: Zaidan Hiba , Galiani Dalia , Gaisler-Salomon Inna
Published: February 2021

Pre-reproductive stress (PRS) to adolescent female rats alters anxiogenic behavior in first (F1)- and second-generation (F2) offspring and increases mRNA expression of corticotropin-releasing factor receptor type 1 (Crhr1) in oocytes and in neonate offspring brain. Here, we ask whether the expression of Crhr1 and Crhr1-targeting microRNA is altered in brain, blood, and oocytes of exposed females and in the brain of their neonate and adult F1 and F2 offspring. In addition, we inquire whether maternal post-stress drug treatment reverses PRS-induced abnormalities in offspring. We find that PRS induces a selective increase in Crhr1-targeting mir-34a and mir-34c in blood and oocytes, while non-Crhr1 microRNA molecules remain unaltered. PRS induces similar microRNA changes in prefrontal cortex of F1 and F2 neonates. In adult animals, cortical Crhr1, but not mir-34, expression is affected by both maternal and direct stress exposure. Post-PRS fluoxetine (FLX) treatment increases pup mortality, and both FLX and the Crhr1 antagonist NBI 27914 reverse some of the effects of PRS and also have independent effects on F1 behavior and gene expression. PRS also alters behavior as well as gene and miRNA expression patterns in paternally derived F2 offspring, producing effects that are different from those previously found in maternally derived F2 offspring. These findings extend current knowledge on inter- and trans-generational transfer of stress effects, point to microRNA changes in stress-exposed oocytes as a potential mechanism, and highlight the consequences of post-stress pharmacological interventions in adolescence.
Adenosine A2A receptor inhibition reduces synaptic and cognitive hippocampal alterations in Fmr1 KO mice
Authors: Ferrante Antonella , Boussadia Zaira , Borreca Antonella , Mallozzi Cinzia , Pedini Giorgia , Pacini Laura , Pezzola Antonella , Armida Monica , Vincenzi Fabrizio , Varani Katia , Bagni Claudia , Popoli Patrizia , Martire Alberto
Published: February 2021

In fragile X syndrome (FXS) the lack of the fragile X mental retardation protein (FMRP) leads to exacerbated signaling through the metabotropic glutamate receptors 5 (mGlu5Rs). The adenosine A2Areceptors (A2ARs), modulators of neuronal damage, could play a role in FXS. A synaptic colocalization and a strong permissive interaction between A2Aand mGlu5 receptors in the hippocampus have been previously reported, suggesting that blocking A2ARs might normalize the mGlu5R-mediated effects of FXS. To study the cross-talk between A2Aand mGlu5 receptors in the absence of FMRP, we performed extracellular electrophysiology experiments in hippocampal slices ofFmr1KO mouse. The depression of field excitatory postsynaptic potential (fEPSPs) slope induced by the mGlu5R agonist CHPG was completely blocked by the A2AR antagonist ZM241385 and strongly potentiated by the A2AR agonist CGS21680, suggesting that the functional synergistic coupling between the two receptors could be increased in FXS. To verify if chronic A2AR blockade could reverse the FXS phenotypes, we treated theFmr1KO mice with istradefylline, an A2AR antagonist. We found that hippocampal DHPG-induced long-term depression (LTD), which is abnormally increased in FXS mice, was restored to the WT level. Furthermore, istradefylline corrected aberrant dendritic spine density, specific behavioral alterations, and overactive mTOR, TrkB, and STEP signaling inFmr1KO mice. Finally, we identifiedA2ARmRNA as a target of FMRP. Our results show that the pharmacological blockade of A2ARs partially restores some of the phenotypes ofFmr1KO mice, both by reducing mGlu5R functioning and by acting on other A2AR-related downstream targets.
Sensing soluble uric acid by Naip1-Nlrp3 platform
Authors: Braga Tarcio Teodoro , Davanso Mariana Rodrigues , Mendes Davi , de Souza Tiago Antonio , de Brito Anderson Fernandes , Cruz Mario Costa , Hiyane Meire Ioshie , de Lima Dhemerson Souza , Nunes Vinicius , de Fátima Giarola Juliana , Souto Denio Emanuel Pires , Próchnicki Tomasz , Lauterbach Mario , Biscaia Stellee Marcela Petris , de Freitas Rilton Alves , Curi Rui , Pontillo Alessandra , Latz Eicke , Camara Niels Olsen Saraiva
Published: February 2021

Uric acid (UA), a product of purine nucleotide degradation able to initiate an immune response, represents a breakpoint in the evolutionary history of humans, when uricase, the enzyme required for UA cleavage, was lost. Despite being inert in human cells, UA in its soluble form (sUA) can increase the level of interleukin-1β (IL-1β) in murine macrophages. We, therefore, hypothesized that the recognition of sUA is achieved by the Naip1-Nlrp3 inflammasome platform. Through structural modelling predictions and transcriptome and functional analyses, we found that murine Naip1 expression in human macrophages induces IL-1β expression, fatty acid production and an inflammation-related response upon sUA stimulation, a process reversed by the pharmacological and genetic inhibition of Nlrp3. Moreover, molecular interaction experiments showed that Naip1 directly recognizes sUA. Accordingly, Naip may be the sUA receptor lost through the human evolutionary process, and a better understanding of its recognition may lead to novel anti-hyperuricaemia therapies.
Molecular recognition in the infection, replication, and transmission of COVID-19-causing SARS-CoV-2: an emerging interface of infectious disease, biological chemistry, and nanoscience
Authors: Kumar Prem , Sobhanan Jeladhara , Takano Yuta , Biju Vasudevanpillai
Published: February 2021

A coronavirus (CoV) commonly known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and causing COVID-19 (coronavirus disease of 2019) has become a pandemic following an outbreak in Wuhan. Although mutations in the SARS-CoV-2 spike glycoprotein (SGP) are obvious from comparative genome studies, the novel infectious nature of the virus, its new varients detected in the UK, and outside and recovery–death ratios of COVID-19 inspired us to review the mechanisms of the infection, replication, release, and transmission of progeny virions and the immune response in the host cell. In addition to the specificity of SARS-CoV-2 binding to angiotensin-converting enzyme 2 receptor and transmembrane protease serine 2, the varied symptoms and severity of the infection by the original and mutated forms of the virus suggest the significance of correlating the host innate and adaptive immunity with the binding of the virus to the mannose receptor via lipopolysaccharides (LPSs), toll-like receptors via LPS/proteins/RNA, and sialic acid (Sia) via hemagglutinin, or sugar-acid segments of glycans. HA-to-Sia binding is considered based on the innate Sia N-acetylneuraminic acid and the acquired Sia N-glycolylneuraminic acid in the epithelial cells and the sialidase/neuraminidase- or esterase-hydrolyzed release and transmission of CoVs. Furthermore, the cytokine storms common to aged humans infected with SARS-CoV-2 and aged macaques infected with SARS-CoV encourage us to articulate the mechanism by which the nuclear capsid protein and RNAs bypass the pattern recognition-induced secretion of interferons (IFNs), which stimulate IFN genes through the Janus-activated kinase-signal transducer and activator of a transcription pathway, leading to the secretion of antiviral proteins such as myxovirus resistance protein A/B. By considering the complexities of the structure, and the infectious nature of the virus and the structures and functions of the molecules involved in CoV infection, replication, and immune response, a new interface among virology, immunology, chemistry, imaging technology, drug delivery, and nanoscience is proposed and will be developed. This interface can be an essential platform for researchers, technologists, and physicians to collaborate and develop vaccines and medicines against COVID-19 and other pandemics in the future.
Spectral phase transitions in optical parametric oscillators
Authors: Roy Arkadev , Jahani Saman , Langrock Carsten , Fejer Martin , Marandi Alireza
Published: February 2021

Driven nonlinear resonators provide a fertile ground for phenomena related to phase transitions far from equilibrium, which can open opportunities unattainable in their linear counterparts. Here, we show that optical parametric oscillators (OPOs) can undergo second-order phase transitions in the spectral domain between degenerate and non-degenerate regimes. This abrupt change in the spectral response follows a square-root dependence around the critical point, exhibiting high sensitivity to parameter variation akin to systems around an exceptional point. We experimentally demonstrate such a phase transition in a quadratic OPO. We show that the divergent susceptibility of the critical point is accompanied by spontaneous symmetry breaking and distinct phase noise properties in the two regimes, indicating the importance of a beyond nonlinear bifurcation interpretation. We also predict the occurrence of first-order spectral phase transitions in coupled OPOs. Our results on non-equilibrium spectral behaviors can be utilized for enhanced sensing, advanced computing, and quantum information processing.
Elucidating intrinsic contribution of d-orbital states to oxygen evolution electrocatalysis in oxides
Authors: Yun Tae Gyu , Heo Yoon , Bin Bae Hyung , Chung Sung-Yoon
Published: February 2021

Although numerous studies on oxide catalysts for an efficient oxygen evolution reaction have been carried out to compare their catalytic performance and suggest new compositions, two significant constraints have been overlooked. One is the difference in electronic conduction behavior between catalysts (metallic versus insulating) and the other is the strong crystallographic surface orientation dependence of the catalysis in a crystal. Consequently, unless a comprehensive comparison of the oxygen-evolution catalytic activity between samples is made on a crystallographically identical surface with sufficient electron conduction, misleading interpretations on the catalytic performance and mechanism may be unavoidable. To overcome these limitations, we utilize both metallic (001) LaNiO3 epitaxial thin films together with metal dopants and semiconducting (001) LaCoO3 epitaxial thin films supported with a conductive interlayer. We identify that Fe, Cr, and Al are beneficial to enhance the catalysis in LaNiO3 although their perovskite counterparts, LaFeO3, LaCrO3, and LaAlO3, with a large bandgap are inactive. Furthermore, semiconducting LaCoO3 is found to have more than one order higher activity than metallic LaNiO3, in contrast to previous reports. Showing the importance of facilitating electron conduction, our work highlights the impact of the near-Fermi-level d-orbital states on the oxygen-evolution catalysis performance in perovskite oxides.
Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle
Authors: Biebl Maximilian M. , Lopez Abraham , Rehn Alexandra , Freiburger Lee , Lawatscheck Jannis , Blank Birgit , Sattler Michael , Buchner Johannes
Published: February 2021

The co-chaperone p23 is a central part of the Hsp90 machinery. It stabilizes the closed conformation of Hsp90, inhibits its ATPase and is important for client maturation. Yet, how this is achieved has remained enigmatic. Here, we show that a tryptophan residue in the proximal region of the tail decelerates the ATPase by allosterically switching the conformation of the catalytic loop in Hsp90. We further show by NMR spectroscopy that the tail interacts with the Hsp90 client binding site via a conserved helix. This helical motif in the p23 tail also binds to the client protein glucocorticoid receptor (GR) in the free and Hsp90-bound form. In vivo experiments confirm the physiological importance of ATPase modulation and the role of the evolutionary conserved helical motif for GR activation in the cellular context.
Anomalous thickness dependence of Curie temperature in air-stable two-dimensional ferromagnetic 1T-CrTe2 grown by chemical vapor deposition
Authors: Meng Lingjia , Zhou Zhang , Xu Mingquan , Yang Shiqi , Si Kunpeng , Liu Lixuan , Wang Xingguo , Jiang Huaning , Li Bixuan , Qin Peixin , Zhang Peng , Wang Jinliang , Liu Zhiqi , Tang Peizhe , Ye Yu , Zhou Wu , Bao Lihong , Gao Hong-Jun , Gong Yongji
Published: February 2021

The discovery of ferromagnetic two-dimensional van der Waals materials has opened up opportunities to explore intriguing physics and to develop innovative spintronic devices. However, controllable synthesis of these 2D ferromagnets and enhancing their stability under ambient conditions remain challenging. Here, we report chemical vapor deposition growth of air-stable 2D metallic 1T-CrTe2 ultrathin crystals with controlled thickness. Their long-range ferromagnetic ordering is confirmed by a robust anomalous Hall effect, which has seldom been observed in other layered 2D materials grown by chemical vapor deposition. With reducing the thickness of 1T-CrTe2 from tens of nanometers to several nanometers, the easy axis changes from in-plane to out-of-plane. Monotonic increase of Curie temperature with the thickness decreasing from ~130.0 to ~7.6 nm is observed. Theoretical calculations indicate that the weakening of the Coulomb screening in the two-dimensional limit plays a crucial role in the change of magnetic properties.
Digital navigation of energy–structure–function maps for hydrogen-bonded porous molecular crystals
Authors: Zhao Chengxi , Chen Linjiang , Che Yu , Pang Zhongfu , Wu Xiaofeng , Lu Yunxiang , Liu Honglai , Day Graeme M. , Cooper Andrew I.
Published: February 2021

Energy–structure–function (ESF) maps can aid the targeted discovery of porous molecular crystals by predicting the stable crystalline arrangements along with their functions of interest. Here, we compute ESF maps for a series of rigid molecules that comprise either a triptycene or a spiro-biphenyl core, functionalized with six different hydrogen-bonding moieties. We show that the positioning of the hydrogen-bonding sites, as well as their number, has a profound influence on the shape of the resulting ESF maps, revealing promising structure–function spaces for future experiments. We also demonstrate a simple and general approach to representing and inspecting the high-dimensional data of an ESF map, enabling an efficient navigation of the ESF data to identify ‘landmark’ structures that are energetically favourable or functionally interesting. This is a step toward the automated analysis of ESF maps, an important goal for closed-loop, autonomous searches for molecular crystals with useful functions.
A flexible electromagnetic wave-electricity harvester
Authors: Lv Hualiang , Yang Zhihong , Liu Bo , Wu Guanglei , Lou Zhichao , Fei Ben , Wu Renbing
Published: February 2021

Developing an ultimate electromagnetic (EM)-absorbing material that can not only dissipate EM energy but also convert the generated heat into electricity is highly desired but remains a significant challenge. Here, we report a hybrid Sn@C composite with a biological cell-like splitting ability to address this challenge. The composite consisting of Sn nanoparticles embedded within porous carbon would split under a cycled annealing treatment, leading to more dispersed nanoparticles with an ultrasmall size. Benefiting from an electron-transmitting but a phonon-blocking structure created by the splitting behavior, an EM wave-electricity device constructed by the optimum Sn@C composite could achieve an efficiency of EM to heat at widely used frequency region and a maximum thermoelectric figure of merit of 0.62 at 473 K, as well as a constant output voltage and power under the condition of microwave radiation. This work provides a promising solution for solving EM interference with self-powered EM devices.
Ultra-fast charging in aluminum-ion batteries: electric double layers on active anode
Authors: Shen Xuejing , Sun Tao , Yang Lei , Krasnoslobodtsev Alexey , Sabirianov Renat , Sealy Michael , Mei Wai-Ning , Wu Zhanjun , Tan Li
Published: February 2021

With the rapid iteration of portable electronics and electric vehicles, developing high-capacity batteries with ultra-fast charging capability has become a holy grail. Here we report rechargeable aluminum-ion batteries capable of reaching a high specific capacity of 200 mAh g−1. When liquid metal is further used to lower the energy barrier from the anode, fastest charging rate of 104 C (duration of 0.35 s to reach a full capacity) and 500% more specific capacity under high-rate conditions are achieved. Phase boundaries from the active anode are believed to encourage a high-flux charge transfer through the electric double layers. As a result, cationic layers inside the electric double layers responded with a swift change in molecular conformation, but anionic layers adopted a polymer-like configuration to facilitate the change in composition.
Anoxic chlorophyll maximum enhances local organic matter remineralization and nitrogen loss in Lake Tanganyika
Authors: Callbeck Cameron M. , Ehrenfels Benedikt , Baumann Kathrin B. L. , Wehrli Bernhard , Schubert Carsten J.
Published: February 2021

In marine and freshwater oxygen-deficient zones, the remineralization of sinking organic matter from the photic zone is central to driving nitrogen loss. Deep blooms of photosynthetic bacteria, which form the suboxic/anoxic chlorophyll maximum (ACM), widespread in aquatic ecosystems, may also contribute to the local input of organic matter. Yet, the influence of the ACM on nitrogen and carbon cycling remains poorly understood. Using a suite of stable isotope tracer experiments, we examined the transformation of nitrogen and carbon under an ACM (comprising of Chlorobiaceae and Synechococcales) and a non-ACM scenario in the anoxic zone of Lake Tanganyika. We find that the ACM hosts a tight coupling of photo/litho-autotrophic and heterotrophic processes. In particular, the ACM was a hotspot of organic matter remineralization that controlled an important supply of ammonium driving a nitrification-anammox coupling, and thereby played a key role in regulating nitrogen loss in the oxygen-deficient zone.
The effects of releasing early results from ongoing clinical trials
Authors: Ventz Steffen , Bacallado Sergio , Rahman Rifaquat , Tolaney Sara , Schoenfeld Jonathan D. , Alexander Brian M. , Trippa Lorenzo
Published: February 2021

Most trials do not release interim summaries on efficacy and toxicity of the experimental treatments being tested, with this information only released to the public after the trial has ended. While early release of clinical trial data to physicians and patients can inform enrollment decision making, it may also affect key operating characteristics of the trial, statistical validity and trial duration. We investigate the public release of early efficacy and toxicity results, during ongoing clinical studies, to better inform patients about their enrollment options. We use simulation models of phase II glioblastoma (GBM) clinical trials in which early efficacy and toxicity estimates are periodically released accordingly to a pre-specified protocol. Patients can use the reported interim efficacy and toxicity information, with the support of physicians, to decide which trial to enroll in. We describe potential effects on various operating characteristics, including the study duration, selection bias and power.
Rapid electrochemical detection of coronavirus SARS-CoV-2
Authors: Chaibun Thanyarat , Puenpa Jiratchaya , Ngamdee Tatchanun , Boonapatcharoen Nimaradee , Athamanolap Pornpat , O’Mullane Anthony Peter , Vongpunsawad Sompong , Poovorawan Yong , Lee Su Yin , Lertanantawong Benchaporn
Published: February 2021

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnosis of COVID-19 depends on quantitative reverse transcription PCR (qRT-PCR), which is time-consuming and requires expensive instrumentation. Here, we report an ultrasensitive electrochemical biosensor based on isothermal rolling circle amplification (RCA) for rapid detection of SARS-CoV-2. The assay involves the hybridization of the RCA amplicons with probes that were functionalized with redox active labels that are detectable by an electrochemical biosensor. The one-step sandwich hybridization assay could detect as low as 1 copy/μL of N and S genes, in less than 2 h. Sensor evaluation with 106 clinical samples, including 41 SARS-CoV-2 positive and 9 samples positive for other respiratory viruses, gave a 100% concordance result with qRT-PCR, with complete correlation between the biosensor current signals and quantitation cycle (Cq) values. In summary, this biosensor could be used as an on-site, real-time diagnostic test for COVID-19.
Pathological conformations of disease mutant Ryanodine Receptors revealed by cryo-EM
Authors: Woll Kellie A. , Haji-Ghassemi Omid , Van Petegem Filip
Published: February 2021

Ryanodine Receptors (RyRs) are massive channels that release Ca2+ from the endoplasmic and sarcoplasmic reticulum. Hundreds of mutations are linked to malignant hyperthermia (MH), myopathies, and arrhythmias. Here, we explore the first MH mutation identified in humans by providing cryo-EM snapshots of the pig homolog, R615C, showing that it affects an interface between three solenoid regions. We also show the impact of apo-calmodulin (apoCaM) and how it can induce opening by bending of the bridging solenoid, mediated by its N-terminal lobe. For R615C RyR1, apoCaM binding abolishes a pathological ‘intermediate’ conformation, distributing the population to a mixture of open and closed channels, both different from the structure without apoCaM. Comparisons show that the mutation primarily affects the closed state, inducing partial movements linked to channel activation. This shows that disease mutations can cause distinct pathological conformations of the RyR and facilitate channel opening by disrupting interactions between different solenoid regions.
Lung microbiota associations with clinical features of COPD in the SPIROMICS cohort
Authors: Opron Kristopher , Begley Lesa A. , Erb-Downward John R. , Freeman Christine , Madapoosi Siddharth , Alexis Neil E. , Barjaktarevic Igor , Graham Barr R. , Bleecker Eugene R. , Bowler Russell P. , Christenson Stephanie A. , Comellas Alejandro P. , Cooper Christopher B. , Couper David J. , Doerschuk Claire M. , Dransfield Mark T. , Han MeiLan K. , Hansel Nadia N. , Hastie Annette T. , Hoffman Eric A. , Kaner Robert J. , Krishnan Jerry , O’Neal Wanda K. , Ortega Victor E. , Paine Robert , Peters Stephen P. , Michael Wells J. , Woodruff Prescott G. , Martinez Fernando J. , Curtis Jeffrey L. , Huffnagle Gary B. , Huang Yvonne J.
Published: February 2021

Chronic obstructive pulmonary disease (COPD) is heterogeneous in development, progression, and phenotypes. Little is known about the lung microbiome, sampled by bronchoscopy, in milder COPD and its relationships to clinical features that reflect disease heterogeneity (lung function, symptom burden, and functional impairment). Using bronchoalveolar lavage fluid collected from 181 never-smokers and ever-smokers with or without COPD (GOLD 0-2) enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we find that lung bacterial composition associates with several clinical features, in particular bronchodilator responsiveness, peak expiratory flow rate, and forced expiratory flow rate between 25 and 75% of FVC (FEF25–75). Measures of symptom burden (COPD Assessment Test) and functional impairment (six-minute walk distance) also associate with disparate lung microbiota composition. Drivers of these relationships include members of theStreptococcus, Prevotella, Veillonella, Staphylococcus, andPseudomonasgenera. Thus, lung microbiota differences may contribute to airway dysfunction and airway disease in milder COPD.
Biogeographical patterns and mechanisms of microbial community assembly that underlie successional biocrusts across northern China
Authors: Li Yuanlong , Hu Chunxiang
Published: February 2021

Biocrusts play critical eco-functions in many drylands, however it is challenging to explore their community assembly, particularly within patched successional types and across climate zones. Here, different successional biocrusts (alga, lichen, and moss-dominated biocrusts) were collected across the northern China, and assembly of biocrust microbial communities was investigated by high-throughput sequencing combined with measurements of soil properties and microclimate environments. Bacterial and eukaryotic communities showed that the maximum and minimum community variation occurred across longitude and latitude, respectively. In the regions where all three stages of biocrusts were involved, the highest community difference existed between successional stages, and decreased with distance. The community assembly was generally driven by dispersal limitation, although neutral processes have controlled the eukaryotic community assembly in hyperarid areas. Along the succession, bacterial community had no obvious patterns, but eukaryotic community showed increasing homogeneity, with increased species sorting and decreased dispersal limitation for community assembly. Compared to early successional biocrusts, there were higher microbial mutual exclusions and more complex networks at later stages, with distinct topological features. Correlation analysis further indicated that the balance between deterministic and stochastic processes might be mediated by aridity, salinity, and total phosphorus, although the mediations were opposite for bacteria and eukaryotes.
Topological representations of crystalline compounds for the machine-learning prediction of materials properties
Authors: Jiang Yi , Chen Dong , Chen Xin , Li Tangyi , Wei Guo-Wei , Pan Feng
Published: February 2021

Accurate theoretical predictions of desired properties of materials play an important role in materials research and development. Machine learning (ML) can accelerate the materials design by building a model from input data. For complex datasets, such as those of crystalline compounds, a vital issue is how to construct low-dimensional representations for input crystal structures with chemical insights. In this work, we introduce an algebraic topology-based method, called atom-specific persistent homology (ASPH), as a unique representation of crystal structures. The ASPH can capture both pairwise and many-body interactions and reveal the topology-property relationship of a group of atoms at various scales. Combined with composition-based attributes, ASPH-based ML model provides a highly accurate prediction of the formation energy calculated by density functional theory (DFT). After training with more than 30,000 different structure types and compositions, our model achieves a mean absolute error of 61 meV/atom in cross-validation, which outperforms previous work such as Voronoi tessellations and Coulomb matrix method using the same ML algorithm and datasets. Our results indicate that the proposed topology-based method provides a powerful computational tool for predicting materials properties compared to previous works.
Efficient and noise resilient measurements for quantum chemistry on near-term quantum computers
Authors: Huggins William J. , McClean Jarrod R. , Rubin Nicholas C. , Jiang Zhang , Wiebe Nathan , Whaley K. Birgitta , Babbush Ryan
Published: February 2021

Variational algorithms are a promising paradigm for utilizing near-term quantum devices for modeling electronic states of molecular systems. However, previous bounds on the measurement time required have suggested that the application of these techniques to larger molecules might be infeasible. We present a measurement strategy based on a low-rank factorization of the two-electron integral tensor. Our approach provides a cubic reduction in term groupings over prior state-of-the-art and enables measurement times three orders of magnitude smaller than those suggested by commonly referenced bounds for the largest systems we consider. Although our technique requires execution of a linear-depth circuit prior to measurement, this is compensated for by eliminating challenges associated with sampling nonlocal Jordan–Wigner transformed operators in the presence of measurement error, while enabling a powerful form of error mitigation based on efficient postselection. We numerically characterize these benefits with noisy quantum circuit simulations for ground-state energies of strongly correlated electronic systems.
Tight finite-key security for twin-field quantum key distribution
Authors: Currás-Lorenzo Guillermo , Navarrete Álvaro , Azuma Koji , Kato Go , Curty Marcos , Razavi Mohsen
Published: February 2021

Quantum key distribution (QKD) offers a reliable solution to communication problems that require long-term data security. For its widespread use, however, the rate and reach of QKD systems must be improved. Twin-field (TF) QKD is a step forward toward this direction, with early demonstrations suggesting it can beat the current rate-versus-distance records. A recently introduced variant of TF-QKD is particularly suited for experimental implementation, and has been shown to offer a higher key rate than other variants in the asymptotic regime, where users exchange an infinite number of signals. Here, we extend the security of this protocol to the finite-key regime, showing that it can overcome the fundamental bounds on point-to-point QKD with ~1010 transmitted signals. In many practical regimes of interest, our analysis offers higher key rates than those of alternative variants. Moreover, some of the techniques we develop are applicable to the finite-key analysis of other QKD protocols.
Creation of Greenberger-Horne-Zeilinger states with thousands of atoms by entanglement amplification
Authors: Zhao Yajuan , Zhang Rui , Chen Wenlan , Wang Xiang-Bin , Hu Jiazhong
Published: February 2021

We propose an entanglement-creation scheme in a multi-atom ensemble trapped in an optical cavity, named entanglement amplification, converting unentangled states into entangled states and amplifying less-entangled ones to maximally entangled Greenberger-Horne-Zeilinger (GHZ) states whose fidelity is logarithmically dependent on the atom number and robust against common experimental noises. The scheme starts with a multi-atom ensemble initialized in a coherent spin state. By shifting the energy of a particular Dicke state, we break the Hilbert space of the ensemble into two isolated subspaces to tear the coherent spin state into two components so that entanglement is introduced. After that, we utilize the isolated subspaces to further enhance the entanglement by coherently separating the two components. By single-particle Rabi drivings on atoms in a high-finesse optical cavity illuminated by a single-frequency light, 2000-atom GHZ states can be created with a fidelity above 80% in an experimentally achievable system, making resources of ensembles at Heisenberg limit practically available for quantum metrology.
Extracellular DNA, cell surface proteins and c-di-GMP promote biofilm formation in Clostridioides difficile
Authors: Dawson Lisa F. , Peltier Johann , Hall Catherine L. , Harrison Mark A. , Derakhshan Maria , Shaw Helen A. , Fairweather Neil F. , Wren Brendan W.
Published: February 2021

Clostridioides difficile is the leading cause of nosocomial antibiotic-associated diarrhoea worldwide, yet there is little insight into intestinal tract colonisation and relapse. In many bacterial species, the secondary messenger cyclic-di-GMP mediates switching between planktonic phase, sessile growth and biofilm formation. We demonstrate that c-di-GMP promotes early biofilm formation in C. difficile and that four cell surface proteins contribute to biofilm formation, including two c-di-GMP regulated; CD2831 and CD3246, and two c-di-GMP-independent; CD3392 and CD0183. We demonstrate that C. difficile biofilms are composed of extracellular DNA (eDNA), cell surface and intracellular proteins, which form a protective matrix around C. difficile vegetative cells and spores, as shown by a protective effect against the antibiotic vancomycin. We demonstrate a positive correlation between biofilm biomass, sporulation frequency and eDNA abundance in all five C. difficile lineages. Strains 630 (RT012), CD305 (RT023) and M120 (RT078) contain significantly more eDNA in their biofilm matrix than strains R20291 (RT027) and M68 (RT017). DNase has a profound effect on biofilm integrity, resulting in complete disassembly of the biofilm matrix, inhibition of biofilm formation and reduced spore germination. The addition of exogenous DNase could be exploited in treatment of C. difficile infection and relapse, to improve antibiotic efficacy.
Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment
Authors: Oluwayiose Oladele A. , Wu Haotian , Saddiki Hachem , Whitcomb Brian W. , Balzer Laura B. , Brandon Nicole , Suvorov Alexander , Tayyab Rahil , Sites Cynthia K. , Hill Lisa , Marcho Chelsea , Pilsner J. Richard
Published: February 2021

Parental age at time of offspring conception is increasing in developed countries. Advanced male age is associated with decreased reproductive success and increased risk of adverse neurodevelopmental outcomes in offspring. Mechanisms for these male age effects remain unclear, but changes in sperm DNA methylation over time is one potential explanation. We assessed genome-wide methylation of sperm DNA from 47 semen samples collected from male participants of couples seeking infertility treatment. We report that higher male age was associated with lower likelihood of fertilization and live birth, and poor embryo development (p < 0.05). Furthermore, our multivariable linear models showed male age was associated with alterations in sperm methylation at 1698 CpGs and 1146 regions (q < 0.05), which were associated with > 750 genes enriched in embryonic development, behavior and neurodevelopment among others. High dimensional mediation analyses identified four genes (DEFB126, TPI1P3, PLCH2 and DLGAP2) with age-related sperm differential methylation that accounted for 64% (95% CI 0.42–0.86%; p < 0.05) of the effect of male age on lower fertilization rate. Our findings from this modest IVF population provide evidence for sperm methylation as a mechanism of age-induced poor reproductive outcomes and identifies possible candidate genes for mediating these effects.
Photoneutron spectrometry by novel multi-directional spherical neutron spectrometry system
Authors: Sohrabi Mehdi , Hakimi Amir
Published: February 2021

Neutron spectrometry in science and technology applications in general and accurate exotic photoneutron (PN) dosimetry of cancer patients undergoing high-dose high-energy X-rays therapy in medical accelerators in particular is of vital need. In this study, a novel passive multi-directional multi-detector neutron spectrometry system was developed and home-made using 6 polycarbonate/10B detectors on 6 sides of polyethylene (PE) cubes used bare and also embedded at center of PE spheres of 8 different diameters. The system provided well-resolved unfolded directional PN spectra showing thermal and fast PN peaks of 6 sides and mean spectrum in 5 field sizes at isocenter and other locations in 18 MV Siemens ONCOR medical linear accelerator bunker. The neutron spectrometry system developed has unique characteristics such as being simple, efficient, low cost, practical, and insensitive to low-LET radiation with well-resolved directional and mean spectra easily applicable in medicine, health, environment, science and technology in developing and developed laboratories.
Developing and validating COVID-19 adverse outcome risk prediction models from a bi-national European cohort of 5594 patients
Authors: Jimenez-Solem Espen , Petersen Tonny S. , Hansen Casper , Hansen Christian , Lioma Christina , Igel Christian , Boomsma Wouter , Krause Oswin , Lorenzen Stephan , Selvan Raghavendra , Petersen Janne , Nyeland Martin Erik , Ankarfeldt Mikkel Zöllner , Virenfeldt Gert Mehl , Winther-Jensen Matilde , Linneberg Allan , Ghazi Mostafa Mehdipour , Detlefsen Nicki , Lauritzen Andreas David , Smith Abraham George , de Bruijne Marleen , Ibragimov Bulat , Petersen Jens , Lillholm Martin , Middleton Jon , Mogensen Stine Hasling , Thorsen-Meyer Hans-Christian , Perner Anders , Helleberg Marie , Kaas-Hansen Benjamin Skov , Bonde Mikkel , Bonde Alexander , Pai Akshay , Nielsen Mads , Sillesen Martin
Published: February 2021

Patients with severe COVID-19 have overwhelmed healthcare systems worldwide. We hypothesized that machine learning (ML) models could be used to predict risks at different stages of management and thereby provide insights into drivers and prognostic markers of disease progression and death. From a cohort of approx. 2.6 million citizens in Denmark, SARS-CoV-2 PCR tests were performed on subjects suspected for COVID-19 disease; 3944 cases had at least one positive test and were subjected to further analysis. SARS-CoV-2 positive cases from the United Kingdom Biobank was used for external validation. The ML models predicted the risk of death (Receiver Operation Characteristics—Area Under the Curve, ROC-AUC) of 0.906 at diagnosis, 0.818, at hospital admission and 0.721 at Intensive Care Unit (ICU) admission. Similar metrics were achieved for predicted risks of hospital and ICU admission and use of mechanical ventilation. Common risk factors, included age, body mass index and hypertension, although the top risk features shifted towards markers of shock and organ dysfunction in ICU patients. The external validation indicated fair predictive performance for mortality prediction, but suboptimal performance for predicting ICU admission. ML may be used to identify drivers of progression to more severe disease and for prognostication patients in patients with COVID-19. We provide access to an online risk calculator based on these findings.
Reduction of visual stimulus artifacts using a spherical tank for small, aquatic animals
Authors: Wang Kun , Arrenberg Burkhard , Hinz Julian , Arrenberg Aristides B.
Published: February 2021

Delivering appropriate stimuli remains a challenge in vision research, particularly for aquatic animals such as zebrafish. Due to the shape of the water tank and the associated optical paths of light rays, the stimulus can be subject to unwanted refraction or reflection artifacts, which may spoil the experiment and result in wrong conclusions. Here, we employ computer graphics simulations and calcium imaging in the zebrafish optic tectum to show, how a spherical glass container optically outperforms many previously used water containers, including Petri dish lids. We demonstrate that aquatic vision experiments suffering from total internal reflection artifacts at the water surface or at the flat container bottom may result in the erroneous detection of visual neurons with bipartite receptive fields and in the apparent absence of neurons selective for vertical motion. Our results and demonstrations will help aquatic vision neuroscientists on optimizing their stimulation setups.
A two dimensional semi-continuum model to explain wetting front instability in porous media
Authors: Kmec Jakub , Fürst Tomáš , Vodák Rostislav , Šír Miloslav
Published: February 2021

Modelling fluid flow in an unsaturated porous medium is a complex problem with many practical applications. There is enough experimental and theoretical evidence that the standard continuum mechanics based modelling approach is unable to capture many important features of porous media flow. In this paper, a two-dimensional semi-continuum model is presented that combines ideas from continuum mechanics with invasion percolation models. The medium is divided into blocks of finite size that retain the nature of a porous medium. Each block is characterized by its porosity, permeability, and a retention curve. The saturation and pressure of the fluids are assumed to be uniform throughout each block. It is demonstrated that the resulting semi-continuum model is able to reproduce (1) gravity induced preferential flow with a spatially rich system of rivulets (fingers) characterized by saturation overshoot, (2) diffusion-like flow with a monotonic saturation profile, (3) the transition between the two. The model helps to explain the formation of the preferential pathways and their persistence and structure (the core and fringe of the fingers), the effect of the initial saturation of the matrix, and the saturation overshoot phenomenon.
Ab initio predictions of structure and physical properties of the Zr2GaC and Hf2GaC MAX phases under pressure
Authors: Qureshi Muhammad Waqas , Ma Xinxin , Tang Guangze , Paudel Ramesh
Published: February 2021

The electronic structure, structural stability, mechanical, phonon, and optical properties of Zr2GaC and Hf2GaC MAX phases have been investigated under high pressure using first-principles calculations. Formation enthalpy of competing phases, elastic constants, and phonon calculations revealed that both compounds are thermodynamically, mechanically, and dynamically stable under pressure. The compressibility of Zr2GaC is higher than that of Hf2GaC along the c-axis, and pressure enhanced the resistance to deformation. The electronic structure calculations reveal that M2GaC is metallic in nature, and the metallicity of Zr2GaC increased more than that of Hf2GaC at higher pressure. The mechanical properties, including elastic constants, elastic moduli, Vickers hardness, Poisson’s ratio anisotropy index, and Debye temperature, are reported with fundamental insights. The elastic constants C11 and C33 increase rapidly compared with other elastic constants with an increase in pressure, and the elastic anisotropy of Hf2GaC is higher than that of the Zr2GaC. The optical properties revealed that Zr2GaC and Hf2GaC MAX phases are suitable for optoelectronic devices in the visible and UV regions and can also be used as a coating material for reducing solar heating at higher pressure up to 50 GPa.
Novel semi-analytical optoelectronic modeling based on homogenization theory for realistic plasmonic polymer solar cells
Authors: Arefinia Zahra , Samajdar Dip Prakash
Published: February 2021

Numerical-based simulations of plasmonic polymer solar cells (PSCs) incorporating a disordered array of non-uniform sized plasmonic nanoparticles (NPs) impose a prohibitively long-time and complex computational demand. To surmount this limitation, we present a novel semi-analytical modeling, which dramatically reduces computational time and resource consumption and yet is acceptably accurate. For this purpose, the optical modeling of active layer-incorporated plasmonic metal NPs, which is described by a homogenization theory based on a modified Maxwell–Garnett-Mie theory, is inputted in the electrical modeling based on the coupled equations of Poisson, continuity, and drift–diffusion. Besides, our modeling considers the effects of absorption in the non-active layers, interference induced by electrodes, and scattered light escaping from the PSC. The modeling results satisfactorily reproduce a series of experimental data for photovoltaic parameters of plasmonic PSCs, demonstrating the validity of our modeling approach. According to this, we implement the semi-analytical modeling to propose a new high-efficiency plasmonic PSC based on the PM6:Y6 PSC, having the highest reported power conversion efficiency (PCE) to date. The results show that the incorporation of plasmonic NPs into PM6:Y6 active layer leads to the PCE over 18%.
GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells
Authors: Stavniichuk Roman , DeLaForest Ann , Thompson Cayla A. , Miller James , Souza Rhonda F. , Battle Michele A.
Published: February 2021

GATA4 promotes columnar epithelial cell fate during gastric development. When ectopically expressed in the developing mouse forestomach, the tissue emerges as columnar-like rather than stratified squamous with gene expression changes that parallel those observed in the pre-malignant squamous to columnar metaplasia known as Barrett’s esophagus (BE). GATA4 mRNA up-regulation and gene amplification occur in BE and its associated cancer, esophageal adenocarcinoma (EAC), and GATA4 gene amplification correlates with poor patient outcomes. Here, we explored the effect of ectopic expression of GATA4 in mature human esophageal squamous epithelial cells. We found that GATA4 expression in esophageal squamous epithelial cells compromised squamous cell marker gene expression and up-regulated expression of the canonical columnar cell cytokeratin KRT8. We observed GATA4 occupancy in the p63, KRT5, and KRT15 promoters, suggesting that GATA4 directly represses expression of squamous epithelial cell marker genes. Finally, we verified GATA4 protein expression in BE and EAC and found that exposure of esophageal squamous epithelial cells to acid and bile, known BE risk factors, induced GATA4 mRNA expression. We conclude that GATA4 suppresses expression of genes marking the stratified squamous epithelial cell lineage and that this repressive action by GATA4 may have implications in BE and EAC.
Hybridisation capture allows DNA damage analysis of ancient marine eukaryotes
Authors: Armbrecht L. , Hallegraeff G. , Bolch C. J. S. , Woodward C. , Cooper A.
Published: February 2021

Marine sedimentary ancient DNA (sedaDNA) is increasingly used to study past ocean ecosystems, however, studies have been severely limited by the very low amounts of DNA preserved in the subseafloor, and the lack of bioinformatic tools to authenticatesedaDNA in metagenomic data. We applied a hybridisation capture ‘baits’ technique to target marine eukaryotesedaDNA (specifically, phyto- and zooplankton, ‘Planktonbaits1’; and harmful algal bloom taxa, ‘HABbaits1’), which resulted in up to 4- and 9-fold increases, respectively, in the relative abundance of eukaryotes compared to shotgun sequencing. We further used the bioinformatic tool ‘HOPS’ to authenticate thesedaDNA component, establishing a new proxy to assesssedaDNA authenticity, “% eukaryotesedaDNA damage”, that is positively correlated with subseafloor depth. We used this proxy to report the first-ever DNA damage profiles from a marine phytoplankton species, the ubiquitous coccolithophoreEmiliania huxleyi. Our approach opens new avenues for the detailed investigation of long-term change and evolution of marine eukaryotes over geological timescales.
Homeostatic plasticity and burst activity are mediated by hyperpolarization-activated cation currents and T-type calcium channels in neuronal cultures
Authors: Rátkai Anikó , Tárnok Krisztián , Aouad Hajar El , Micska Brigitta , Schlett Katalin , Szücs Attila
Published: February 2021

Homeostatic plasticity stabilizes neuronal networks by adjusting the responsiveness of neurons according to their global activity and the intensity of the synaptic inputs. We investigated the homeostatic regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) and T-type calcium (CaV3) channels in dissociated and organotypic slice cultures. After 48 h blocking of neuronal activity by tetrodotoxin (TTX), our patch-clamp experiments revealed an increase in the depolarizing voltage sag and post-inhibitory rebound mediated by HCN and CaV3 channels, respectively. All HCN subunits (HCN1 to 4) and T-type Ca-channel subunits (CaV3.1, 3.2 and 3.3) were expressed in both control and activity-deprived hippocampal cultures. Elevated expression levels of CaV3.1 mRNA and a selective increase in the expression of TRIP8b exon 4 isoforms, known to regulate HCN channel localization, were also detected in TTX-treated cultured hippocampal neurons. Immunohistochemical staining in TTX-treated organotypic slices verified a more proximal translocation of HCN1 channels in CA1 pyramidal neurons. Computational modeling also implied that HCN and T-type calcium channels have important role in the regulation of synchronized bursting evoked by previous activity-deprivation. Thus, our findings indicate that HCN and T-type Ca-channels contribute to the homeostatic regulation of excitability and integrative properties of hippocampal neurons.