bluuebunny/crossref_metadata_2025 huggingface dataset:
Unlocking the functional potential of polyploid yeasts
Authors: Mozzachiodi Simone , Krogerus Kristoffer , Gibson Brian , Nicolas Alain , Liti Gianni
Published: May 2022

Breeding and domestication have generated widely exploited crops, animals and microbes. However, many Saccharomyces cerevisiae industrial strains have complex polyploid genomes and are sterile, preventing genetic improvement strategies based on breeding. Here, we present a strain improvement approach based on the budding yeasts’ property to promote genetic recombination when meiosis is interrupted and cells return-to-mitotic-growth (RTG). We demonstrate that two unrelated sterile industrial strains with complex triploid and tetraploid genomes are RTG-competent and develop a visual screening for easy and high-throughput identification of recombined RTG clones based on colony phenotypes. Sequencing of the evolved clones reveal unprecedented levels of RTG-induced genome-wide recombination. We generate and extensively phenotype a RTG library and identify clones with superior biotechnological traits. Thus, we propose the RTG-framework as a fully non-GMO workflow to rapidly improve industrial yeasts that can be easily brought to the market.
A rare variant analysis framework using public genotype summary counts to prioritize disease-predisposition genes
Authors: Chen Wenan , Wang Shuoguo , Tithi Saima Sultana , Ellison David W. , Schaid Daniel J. , Wu Gang
Published: May 2022

Sequencing cases without matched healthy controls hinders prioritization of germline disease-predisposition genes. To circumvent this problem, genotype summary counts from public data sets can serve as controls. However, systematic inflation and false positives can arise if confounding factors are not controlled. We propose a framework,consistent summarycounts basedrarevariant burden test (CoCoRV), to address these challenges. CoCoRV implements consistent variant quality control and filtering, ethnicity-stratified rare variant association test, accurate estimation of inflation factors, powerful FDR control, and detection of rare variant pairs in high linkage disequilibrium. When we applied CoCoRV to pediatric cancer cohorts, the top genes identified were cancer-predisposition genes. We also applied CoCoRV to identify disease-predisposition genes in adult brain tumors and amyotrophic lateral sclerosis. Given that potential confounding factors were well controlled after applying the framework, CoCoRV provides a cost-effective solution to prioritizing disease-risk genes enriched with rare pathogenic variants.
On-chip nanophotonic topological rainbow
Authors: Lu Cuicui , Sun Yi-Zhi , Wang Chenyang , Zhang Hongyu , Zhao Wen , Hu Xiaoyong , Xiao Meng , Ding Wei , Liu Yong-Chun , Chan C. T.
Published: May 2022

The era of Big Data requires nanophotonic chips to have large information processing capacity. Multiple frequency on-chip nanophotonic devices are highly desirable for density integration, but such devices are more susceptible to structural imperfection because of their nano-scale. Topological photonics provides a robust platform for next-generation nanophotonic chips. Here we give an experimental report of an on-chip nanophotonic topological rainbow realized by employing a translational deformation freedom as a synthetic dimension. The topological rainbow can separate, slow, and trap topological photonic states of different frequencies into different positions. A homemade scattering scanning near-field optical microscope with high resolution is introduced to directly measure the topological rainbow effect of the silicon-based photonic chip. The topological rainbow based on synthetic dimension have no restrictions for optical lattice types, symmetries, materials, wavelength band, and is easy for on-chip integration. This work builds a bridge between silicon chip technologies and topological photonics.
Discovery and characterization of a terpene biosynthetic pathway featuring a norbornene-forming Diels-Alderase
Authors: Sun Zuodong , Jamieson Cooper S. , Ohashi Masao , Houk K. N. , Tang Yi
Published: May 2022

Pericyclases, enzymes that catalyze pericyclic reactions, form an expanding family of enzymes that have biocatalytic utility. Despite the increasing number of pericyclases discovered, the Diels-Alder cyclization between a cyclopentadiene and an olefinic dienophile to form norbornene, which is among the best-studied cycloadditions in synthetic chemistry, has surprisingly no enzymatic counterpart to date. Here we report the discovery of a pathway featuring a norbornene synthase SdnG for the biosynthesis of sordaricin-the terpene precursor of antifungal natural product sordarin. Full reconstitution of sordaricin biosynthesis reveals a concise oxidative strategy used by Nature to transform an entirely hydrocarbon precursor into the highly functionalized substrate of SdnG for intramolecular Diels-Alder cycloaddition. SdnG generates the norbornene core of sordaricin and accelerates this reaction to suppress host-mediated redox modifications of the activated dienophile. Findings from this work expand the scopes of pericyclase-catalyzed reactions and P450-mediated terpene maturation.
Water coordinated on Cu(I)-based catalysts is the oxygen source in CO2 reduction to CO
Authors: Zheng Yajun , Yao Hedan , Di Ruinan , Xiang Zhicheng , Wang Qiang , Lu Fangfang , Li Yu , Yang Guangxing , Ma Qiang , Zhang Zhiping
Published: May 2022

Catalytic reduction of CO2 over Cu-based catalysts can produce various carbon-based products such as the critical intermediate CO, yet significant challenges remain in shedding light on the underlying mechanisms. Here, we develop a modified triple-stage quadrupole mass spectrometer to monitor the reduction of CO2 to CO in the gas phase online. Our experimental observations reveal that the coordinated H2O on Cu(I)-based catalysts promotes CO2 adsorption and reduction to CO, and the resulting efficiencies are two orders of magnitude higher than those without H2O. Isotope-labeling studies render compelling evidence that the O atom in produced CO originates from the coordinated H2O on catalysts, rather than CO2 itself. Combining experimental observations and computational calculations with density functional theory, we propose a detailed reaction mechanism of CO2 reduction to CO over Cu(I)-based catalysts with coordinated H2O. This study offers an effective method to reveal the vital roles of H2O in promoting metal catalysts to CO2 reduction.
3D chromatin remodelling in the germ line modulates genome evolutionary plasticity
Authors: Álvarez-González Lucía , Burden Frances , Doddamani Dadakhalandar , Malinverni Roberto , Leach Emma , Marín-García Cristina , Marín-Gual Laia , Gubern Albert , Vara Covadonga , Paytuví-Gallart Andreu , Buschbeck Marcus , Ellis Peter J. I. , Farré Marta , Ruiz-Herrera Aurora
Published: May 2022

Chromosome folding has profound impacts on gene regulation, whose evolutionary consequences are far from being understood. Here we explore the relationship between 3D chromatin remodelling in mouse germ cells and evolutionary changes in genome structure. Using a comprehensive integrative computational analysis, we (i) reconstruct seven ancestral rodent genomes analysing whole-genome sequences of 14 species representatives of the major phylogroups, (ii) detect lineage-specific chromosome rearrangements and (iii) identify the dynamics of the structural and epigenetic properties of evolutionary breakpoint regions (EBRs) throughout mouse spermatogenesis. Our results show that EBRs are devoid of programmed meiotic DNA double-strand breaks (DSBs) and meiotic cohesins in primary spermatocytes, but are associated in post-meiotic cells with sites of DNA damage and functional long-range interaction regions that recapitulate ancestral chromosomal configurations. Overall, we propose a model that integrates evolutionary genome reshuffling with DNA damage response mechanisms and the dynamic spatial genome organisation of germ cells.
Metabolite trafficking enables membrane-impermeable-terpene secretion by yeast
Authors: Son So-Hee , Kim Jae-Eung , Park Gyuri , Ko Young-Joon , Sung Bong Hyun , Seo Jongcheol , Oh Seung Soo , Lee Ju Young
Published: May 2022

Metabolites are often unable to permeate cell membranes and are thus accumulated inside cells. We investigate whether engineered microbes can exclusively secrete intracellular metabolites because sustainable metabolite secretion holds a great potential for mass-production of high-value chemicals in an efficient and continuous manner. In this study, we demonstrate a synthetic pathway for a metabolite trafficking system that enables lipophilic terpene secretion by yeast cells. When metabolite-binding proteins are tagged with signal peptides, metabolite trafficking is highly achievable; loaded metabolites can be precisely delivered to a desired location within or outside the cell. As a proof of concept, we systematically couple a terpene-binding protein with an export signal peptide and subsequently demonstrate efficient, yet selective terpene secretion by yeast (~225 mg/L for squalene and ~1.6 mg/L for β-carotene). Other carrier proteins can also be readily fused with desired signal peptides, thereby tailoring different metabolite trafficking pathways in different microbes. To the best of our knowledge, this is the most efficient cognate pathway for metabolite secretion by microorganisms.
Atomic overlayer of permeable microporous cuprous oxide on palladium promotes hydrogenation catalysis
Authors: Liu Kunlong , Jiang Lizhi , Huang Wugen , Zhu Guozhen , Zhang Yue-Jiao , Xu Chaofa , Qin Ruixuan , Liu Pengxin , Hu Chengyi , Wang Jingjuan , Li Jian-Feng , Yang Fan , Fu Gang , Zheng Nanfeng
Published: May 2022

The interfacial sites of metal-support interface have been considered to be limited to the atomic region of metal/support perimeter, despite their high importance in catalysis. By using single-crystal surface and nanocrystal as model catalysts, we now demonstrate that the overgrowth of atomic-thick Cu2O on metal readily creates a two-dimensional (2D) microporous interface with Pd to enhance the hydrogenation catalysis. With the hydrogenation confined within the 2D Cu2O/Pd interface, the catalyst exhibits outstanding activity and selectivity in the semi-hydrogenation of alkynes. Alloying Cu(0) with Pd under the overlayer is the major contributor to the enhanced activity due to the electronic modulation to weaken the H adsorption. Moreover, the boundary or defective sites on the Cu2O overlayer can be passivated by terminal alkynes, reinforcing the chemical stability of Cu2O and thus the catalytic stability toward hydrogenation. The deep understanding allows us to extend the interfacial sites far beyond the metal/support perimeter and provide new vectors for catalyst optimization through 2D interface interaction.
Subnanometric Cu clusters on atomically Fe-doped MoO2 for furfural upgrading to aviation biofuels
Authors: Zhao Xin , Wang Fengliang , Kong Xiangpeng , Fang Ruiqi , Li Yingwei
Published: May 2022

Single cluster catalysts (SCCs) are considered as versatile boosters in heterogeneous catalysis due to their modifiable single cluster sites and supports. In this work, we report subnanometric Cu clusters dispersed on Fe-doped MoO2 support for biomass-derived furfural upgrading. Systematical characterizations suggest uniform Cu clusters (composing four Cu atoms in average) are homogeneously immobilized on the atomically Fe-doped ultrafine MoO2 nanocrystals (Cu4/Fe0.3Mo0.7O2@C). The atomic doping of Fe into MoO2 leads to significantly modified electronic structure and consequently charge redistribution inside the supported Cu clusters. The as-prepared Cu4/Fe0.3Mo0.7O2@C shows superior catalytic performance in the oxidative coupling of furfural with C3~C10 primary/secondary alcohols to produce C8~C15 aldehydes/ketones (aviation biofuel intermediates), outperforming the conventionally prepared counterparts. DFT calculations and control experiments are further carried out to interpret the structural and compositional merits of Cu4/Fe0.3Mo0.7O2@C in the oxidative coupling reaction, and elucidate the reaction pathway and related intermediates.
Patatin-like phospholipase CapV in Escherichia coli - morphological and physiological effects of one amino acid substitution
Authors: Li Fengyang , Cao Lianying , Bähre Heike , Kim Soo-Kyoung , Schroeder Kristen , Jonas Kristina , Koonce Kira , Mekonnen Solomon A. , Mohanty Soumitra , Bai Fengwu , Brauner Annelie , Lee Vincent T. , Rohde Manfred , Römling Ute
Published: May 2022

In rod-shaped bacteria, morphological plasticity occurs in response to stress, which blocks cell division to promote filamentation. We demonstrate here that overexpression of the patatin-like phospholipase variant CapVQ329R, but not CapV, causes pronouncedsulA-independent pyridoxine-inhibited cell filamentation in theEscherichia coliK-12-derivative MG1655 associated with restriction of flagella production and swimming motility. Conserved amino acids in canonical patatin-like phospholipase A motifs, but not the nucleophilic serine, are required to mediate CapVQ329Rphenotypes. Furthermore, CapVQ329Rproduction substantially alters the lipidome and colony morphotype including rdar biofilm formation with modulation of the production of the biofilm activator CsgD, and affects additional bacterial traits such as the efficiency of phage infection and antimicrobial susceptibility. Moreover, genetically diverse commensal and pathogenicE. colistrains andSalmonella typhimuriumresponded with cell filamentation and modulation in colony morphotype formation to CapVQ329Rexpression. In conclusion, this work identifies the CapV variant CapVQ329Ras a pleiotropic regulator, emphasizes a scaffold function for patatin-like phospholipases, and highlights the impact of the substitution of a single conserved amino acid for protein functionality and alteration of host physiology.
A prebiotically plausible scenario of an RNA–peptide world
Authors: Müller Felix , Escobar Luis , Xu Felix , Węgrzyn Ewa , Nainytė Milda , Amatov Tynchtyk , Chan Chun‐Yin , Pichler Alexander , Carell Thomas
Published: May 2022

The RNA world concept1 is one of the most fundamental pillars of the origin of life theory2–4. It predicts that life evolved from increasingly complex self-replicating RNA molecules1,2,4. The question of how this RNA world then advanced to the next stage, in which proteins became the catalysts of life and RNA reduced its function predominantly to information storage, is one of the most mysterious chicken-and-egg conundrums in evolution3–5. Here we show that non-canonical RNA bases, which are found today in transfer and ribosomal RNAs6,7, and which are considered to be relics of the RNA world8–12, are able to establish peptide synthesis directly on RNA. The discovered chemistry creates complex peptide-decorated RNA chimeric molecules, which suggests the early existence of an RNA–peptide world13 from which ribosomal peptide synthesis14 may have emerged15,16. The ability to grow peptides on RNA with the help of non-canonical vestige nucleosides offers the possibility of an early co-evolution of covalently connected RNAs and peptides13,17,18, which then could have dissociated at a higher level of sophistication to create the dualistic nucleic acid–protein world that is the hallmark of all life on Earth.
Fundamental immune–oncogenicity trade-offs define driver mutation fitness
Authors: Hoyos David , Zappasodi Roberta , Schulze Isabell , Sethna Zachary , de Andrade Kelvin César , Bajorin Dean F. , Bandlamudi Chaitanya , Callahan Margaret K. , Funt Samuel A. , Hadrup Sine R. , Holm Jeppe S. , Rosenberg Jonathan E. , Shah Sohrab P. , Vázquez-García Ignacio , Weigelt Britta , Wu Michelle , Zamarin Dmitriy , Campitelli Laura F. , Osborne Edward J. , Klinger Mark , Robins Harlan S. , Khincha Payal P. , Savage Sharon A. , Balachandran Vinod P. , Wolchok Jedd D. , Hellmann Matthew D. , Merghoub Taha , Levine Arnold J. , Łuksza Marta , Greenbaum Benjamin D.
Published: May 2022

Missense driver mutations in cancer are concentrated in a few hotspots1. Various mechanisms have been proposed to explain this skew, including biased mutational processes2, phenotypic differences3–6 and immunoediting of neoantigens7,8; however, to our knowledge, no existing model weighs the relative contribution of these features to tumour evolution. We propose a unified theoretical ‘free fitness’ framework that parsimoniously integrates multimodal genomic, epigenetic, transcriptomic and proteomic data into a biophysical model of the rate-limiting processes underlying the fitness advantage conferred on cancer cells by driver gene mutations. Focusing on TP53, the most mutated gene in cancer1, we present an inference of mutant p53 concentration and demonstrate that TP53 hotspot mutations optimally solve an evolutionary trade-off between oncogenic potential and neoantigen immunogenicity. Our model anticipates patient survival in The Cancer Genome Atlas and patients with lung cancer treated with immunotherapy as well as the age of tumour onset in germline carriers of TP53 variants. The predicted differential immunogenicity between hotspot mutations was validated experimentally in patients with cancer and in a unique large dataset of healthy individuals. Our data indicate that immune selective pressure on TP53 mutations has a smaller role in non-cancerous lesions than in tumours, suggesting that targeted immunotherapy may offer an early prophylactic opportunity for the former. Determining the relative contribution of immunogenicity and oncogenic function to the selective advantage of hotspot mutations thus has important implications for both precision immunotherapies and our understanding of tumour evolution.
Extricating human tumour immune alterations from tissue inflammation
Authors: Mair Florian , Erickson Jami R. , Frutoso Marie , Konecny Andrew J. , Greene Evan , Voillet Valentin , Maurice Nicholas J. , Rongvaux Anthony , Dixon Douglas , Barber Brittany , Gottardo Raphael , Prlic Martin
Published: May 2022

Immunotherapies have achieved remarkable successes in the treatment of cancer, but major challenges remain1,2. An inherent weakness of current treatment approaches is that therapeutically targeted pathways are not restricted to tumours, but are also found in other tissue microenvironments, complicating treatment3,4. Despite great efforts to define inflammatory processes in the tumour microenvironment, the understanding of tumour-unique immune alterations is limited by a knowledge gap regarding the immune cell populations in inflamed human tissues. Here, in an effort to identify such tumour-enriched immune alterations, we used complementary single-cell analysis approaches to interrogate the immune infiltrate in human head and neck squamous cell carcinomas and site-matched non-malignant, inflamed tissues. Our analysis revealed a large overlap in the composition and phenotype of immune cells in tumour and inflamed tissues. Computational analysis identified tumour-enriched immune cell interactions, one of which yields a large population of regulatory T (Treg) cells that is highly enriched in the tumour and uniquely identified among all haematopoietically-derived cells in blood and tissue by co-expression of ICOS and IL-1 receptor type 1 (IL1R1). We provide evidence that these intratumoural IL1R1+ Treg cells had responded to antigen recently and demonstrate that they are clonally expanded with superior suppressive function compared with IL1R1− Treg cells. In addition to identifying extensive immunological congruence between inflamed tissues and tumours as well as tumour-specific changes with direct disease relevance, our work also provides a blueprint for extricating disease-specific changes from general inflammation-associated patterns.
Structural basis of sodium-dependent bile salt uptake into the liver
Authors: Goutam Kapil , Ielasi Francesco S. , Pardon Els , Steyaert Jan , Reyes Nicolas
Published: May 2022

The liver takes up bile salts from blood to generate bile, enabling absorption of lipophilic nutrients and excretion of metabolites and drugs1. Human Na+–taurocholate co-transporting polypeptide (NTCP) is the main bile salt uptake system in liver. NTCP is also the cellular entry receptor of human hepatitis B and D viruses2,3 (HBV/HDV), and has emerged as an important target for antiviral drugs4. However, the molecular mechanisms underlying NTCP transport and viral receptor functions remain incompletely understood. Here we present cryo-electron microscopy structures of human NTCP in complexes with nanobodies, revealing key conformations of its transport cycle. NTCP undergoes a conformational transition opening a wide transmembrane pore that serves as the transport pathway for bile salts, and exposes key determinant residues for HBV/HDV binding to the outside of the cell. A nanobody that stabilizes pore closure and inward-facing states impairs recognition of the HBV/HDV receptor-binding domain preS1, demonstrating binding selectivity of the viruses for open-to-outside over inward-facing conformations of the NTCP transport cycle. These results provide molecular insights into NTCP ‘gated-pore’ transport and HBV/HDV receptor recognition mechanisms, and are expected to help with development of liver disease therapies targeting NTCP.
Pivotal Response Treatment (PRT) parent group training for young children with autism spectrum disorder: a pilot study
Authors: de Korte Manon W. P. , van Dongen‑Boomsma Martine , Oosterling Iris J. , Buitelaar Jan. K. , Staal Wouter G.
Published: May 2022

Pivotal Response Treatment (PRT) is a promising intervention addressing core symptoms of autism spectrum disorder (ASD), with parent involvement as key component. Parent group-delivered PRT may be an effective treatment model, but currently the evidence is limited. Also, little attention has been paid to therapeutic involvement of multiple important contexts (e.g. home, school, community) of the young child. The current study explores a 14-week protocol of PRT parent group training (PRT-PG), complemented with individual parent–child sessions and involvement of teachers and other childcare providers. Children aged 2–6 years old with ASD and their parents (n = 20) were included. Preliminary results showed a significant increase in spontaneous initiations during a semi-structured therapist-child interaction together with widespread gains in clinical global functioning. No significant improvement on parent-rated general social-communication skills was observed. These findings justify further research on parent group delivered PRT models.
Quantum pixel representations and compression for N-dimensional images
Authors: Amankwah Mercy G. , Camps Daan , Bethel E. Wes , Van Beeumen Roel , Perciano Talita
Published: May 2022

We introduce a novel and uniform framework for quantum pixel representations that overarches many of the most popular representations proposed in the recent literature, such as (I)FRQI, (I)NEQR, MCRQI, and (I)NCQI. The proposed QPIXL framework results in more efficient circuit implementations and significantly reduces the gate complexity for all considered quantum pixel representations. Our method scales linearly in the number of pixels and does not use ancilla qubits. Furthermore, the circuits only consist of $$R_y$$

R
y

gates and $$\text {CNOT}$$
CNOT
gates making them practical in the NISQ era. Additionally, we propose a circuit and image compression algorithm that is shown to be highly effective, being able to reduce the necessary gates to prepare an FRQI state for example scientific images by up to 90% without sacrificing image quality. Our algorithms are made publicly available as part of , a Quantum Image Pixel Library.
On the net primary productivity over the Arabian Sea due to the reduction in mineral dust deposition
Authors: Tandule Chakradhar Rao , Gogoi Mukunda M. , Kotalo Rama Gopal , Babu S. Suresh
Published: May 2022

The dust plume tracks from the Middle East and Eastern Africa to the Indian subcontinent have an impact on the atmospheric and ocean biogeochemistry of the Arabian Sea (AS). Here, we present the impact of dust on net primary productivity (NPP) over the AS using satellite-based observation and model simulation. Seasonal episodes and long-term trends in dust optical depth (DOD), dust mass flux (DMF) and dust deposition flux (DDF) from 2007 to 2020 are quantified. Nearly 32% of the total dust is advected to the AS during transport (maximum in JJA; DMF ~ 33.1 Tg year−1 ~ 56% of annual and DDF ~ 5.5 Tg year−1 ~ 63% of annual). Over the last one and half decades, there has been a statistically significant decreasing trend in DOD, associated with precipitation, enhanced vegetation index and surface soil moisture over the landmasses in the proximity of the AS. Similarly, the depletion in DDF suppresses the NPP over different regions of the AS, especially over the central AS, where the oceanic supply of nutrients is limited.
First fluvial archive of the 8.2 and 7.6–7.3 ka events in North Africa (Charef River, High Plateaus, NE Morocco)
Authors: Depreux Bruno , Berger Jean-François , Lefèvre David , Wackenheim Quentin , Andrieu-Ponel Valérie , Vinai Sylvia , Degeai Jean-Philippe , El Harradji Abderrahmane , Boudad Larbi , Sanz-Laliberté Séverine , Michel Kristell , Limondin-Lozouet Nicole
Published: May 2022

The Early–Mid Holocene transition is a period of profound changes in climatic mechanisms and hydrological features in Europe and North Africa. The melting of the Laurentide ice sheet led to an oceanic and atmospheric reorganisation in the North Atlantic, while the Mediterranean underwent a major hydrological shift. The impacts on Mediterranean rivers remain unclear, as there are few records documenting responses to the 8.2 ka event (the main Holocene climatic degradation). We present a fluvial record from Eastern Morocco documenting detailed hydrological variations from 8200 to 7500 cal. BP and their climatic forcing. A major hydrogeomorphic evolution of the Charef River occurred at that time, marked by two major incision stages close in time, under hyper-arid conditions at 8200 and ca. 7500 cal. BP. The impacts of these phenomena on the alluvial plains and associated archaeological records during Neolithisation, a major process in human history, currently remain unidentified. This new record sheds light on the fluvial response to the 8.2 ka event in North Africa and why other records are missing. We also bring new insights into the hydrological disruption at the Early–Mid Holocene transition, which was driven by the end of deglaciation combined with insolation and solar forcing. Furthermore, centennial solar variability may have paced river activity in the Moulouya basin and arid regions of North Africa.
The feasibility to use artificial intelligence to aid detecting focal liver lesions in real-time ultrasound: a preliminary study based on videos
Authors: Tiyarattanachai Thodsawit , Apiparakoon Terapap , Marukatat Sanparith , Sukcharoen Sasima , Yimsawad Sirinda , Chaichuen Oracha , Bhumiwat Siwat , Tanpowpong Natthaporn , Pinjaroen Nutcha , Rerknimitr Rungsun , Chaiteerakij Roongruedee
Published: May 2022

Despite the wide availability of ultrasound machines for hepatocellular carcinoma surveillance, an inadequate number of expert radiologists performing ultrasounds in remote areas remains a primary barrier for surveillance. We demonstrated feasibility of artificial intelligence (AI) to aid in the detection of focal liver lesions (FLLs) during ultrasound. An AI system for FLL detection in ultrasound videos was developed. Data in this study were prospectively collected at a university hospital. We applied a two-step training strategy for developing the AI system by using a large collection of ultrasound snapshot images and frames from full-length ultrasound videos. Detection performance of the AI system was evaluated and then compared to detection performance by 25 physicians including 16 non-radiologist physicians and 9 radiologists. Our dataset contained 446 videos (273 videos with 387 FLLs and 173 videos without FLLs) from 334 patients. The videos yielded 172,035 frames with FLLs and 1,427,595 frames without FLLs for training on the AI system. The AI system achieved an overall detection rate of 89.8% (95%CI: 84.5–95.0) which was significantly higher than that achieved by non-radiologist physicians (29.1%, 95%CI: 21.2–37.0,p < 0.001) and radiologists (70.9%, 95%CI: 63.0–78.8,p < 0.001). Median false positive detection rate by the AI system was 0.7% (IQR: 1.3%). AI system operation speed reached 30–34 frames per second, showing real-time feasibility. A further study to demonstrate whether the AI system can assist operators during ultrasound examinations is warranted.
Quantifying firm-level economic systemic risk from nation-wide supply networks
Authors: Diem Christian , Borsos András , Reisch Tobias , Kertész János , Thurner Stefan
Published: May 2022

Crises like COVID-19 exposed the fragility of highly interdependent corporate supply networks and the complex production processes depending on them. However, a quantitative assessment of individual companies’ impact on the networks’ overall production is hitherto non-existent. Based on a unique value added tax dataset, we construct the firm-level production network of an entire country at an unprecedented granularity and present a novel approach for computing the economic systemic risk (ESR) of all firms within the network. We demonstrate that 0.035% of companies have extraordinarily high ESR, impacting about 23% of the national economic production should any of them default. Firm size cannot explain the ESR of individual companies; their position in the production networks matters substantially. A reliable assessment of ESR seems impossible with aggregated data traditionally used in Input-Output Economics. Our findings indicate that ESR of some extremely risky companies can be reduced by introducing supply chain redundancies and changes in the network topology.
Neurophysiological effects of human-derived pathological tau conformers in the APPKM670/671NL.PS1/L166P amyloid mouse model of Alzheimer’s disease
Authors: Tok S. , Maurin H. , Delay C. , Crauwels D. , Manyakov N. V. , Van Der Elst W. , Moechars D. , Drinkenburg W. H. I. M.
Published: May 2022

Alzheimer’s Disease (AD) is a neurodegenerative disease characterized by two main pathological hallmarks: amyloid plaques and intracellular tau neurofibrillary tangles. However, a majority of studies focus on the individual pathologies and seldom on the interaction between the two pathologies. Herein, we present the longitudinal neuropathological and neurophysiological effects of a combined amyloid-tau model by hippocampal seeding of human-derived tau pathology in the APP.PS1/L166P amyloid animal model. We statistically assessed both neurophysiological and pathological changes using linear mixed modelling to determine if factors such as the age at which animals were seeded, genotype, seeding or buffer, brain region where pathology was quantified, and time-post injection differentially affect these outcomes. We report that AT8-positive tau pathology progressively develops and is facilitated by the amount of amyloid pathology present at the time of injection. The amount of AT8-positive tau pathology was influenced by the interaction of age at which the animal was injected, genotype, and time after injection. Baseline pathology-related power spectra and Higuchi Fractal Dimension (HFD) score alterations were noted in APP.PS1/L166P before any manipulations were performed, indicating a baseline difference associated with genotype. We also report immediate localized hippocampal dysfunction in the electroencephalography (EEG) power spectra associated with tau seeding which returned to comparable levels at 1 month-post-injection. Longitudinal effects of seeding indicated that tau-seeded wild-type mice showed an increase in gamma power earlier than buffer control comparisons which was influenced by the age at which the animal was injected. A reduction of hippocampal broadband power spectra was noted in tau-seeded wild-type mice, but absent in APP.PS1 animals. HFD scores appeared to detect subtle effects associated with tau seeding in APP.PS1 animals, which was differentially influenced by genotype. Notably, while tau histopathological changes were present, a lack of overt longitudinal electrophysiological alterations was noted, particularly in APP.PS1 animals that feature both pathologies after seeding, reiterating and underscoring the difficulty and complexity associated with elucidating physiologically relevant and translatable biomarkers of Alzheimer’s Disease at the early stages of the disease.
On the relationship between mind wandering and mindfulness
Authors: Belardi Angelo , Chaieb Leila , Rey-Mermet Alodie , Mormann Florian , Rothen Nicolas , Fell Juergen , Reber Thomas P.
Published: May 2022

Mind wandering (MW) and mindfulness have both been reported to be vital moderators of psychological wellbeing. Here, we aim to examine how closely associated these phenomena are and evaluate the psychometrics of measures often used to quantify them. We investigated two samples, one consisting of German-speaking unpaid participants (GUP, n $$=$$
=
313) and one of English-speaking paid participants (EPP, n $$=$$
=
228) recruited through MTurk.com. In an online experiment, we collected data using the Mindful Attention Awareness Scale (MAAS) and the sustained attention to response task (SART) during which self-reports of MW and meta-awareness of MW were recorded using experience sampling (ES) probes. Internal consistency of the MAAS was high (Cronbachs $$\alpha$$
α
of 0.96 in EPP and 0.88 in GUP). Split-half reliability for SART measures and self-reported MW was overall good with the exception of SART measures focusing on Nogo trials, and those restricted to SART trials preceding ES in a 10 s time window. We found a moderate negative association between trait mindfulness and MW as measured with ES probes in GUP, but not in EPP. Our results suggest that MW and mindfulness are on opposite sides of a spectrum of how attention is focused on the present moment and the task at hand.
Development of a predictive model for luteal phase oocyte retrieval in poor responders undergoing natural cycle IVF
Authors: Simopoulou Mara , Galatis Dionysios , Maziotis Evangelos , Pantou Agni , Giannelou Polina , Grigoriadis Sokratis , Tzonis Panagiotis , Griva Theodora , Zikopoulos Athanasios , Philippou Anastasios , Koutsilieris Michael , Pantos Konstantinos , Sfakianoudis Konstantinos
Published: May 2022

The aim of this study is the development of a prediction model indicating successful application of Oocyte Retrieval performed during the Luteal Phase (LuPOR) in poor responders, as defined by the retrieval of at least one MII oocyte. Recruitment included 1688 poor responders diagnosed as per Bologna Criteria, undergoing natural cycle ICSI between 2012 and 2020. Oocyte collections were performed during the follicular phase and during the luteal phase similarly. Antral Follicle Count (AFC), Estradiol (E2) levels evaluated on both trigger days prior to Follicular Phase Oocyte Retrieval (FoPOR) and LuPOR, and the number of small follicles 8–12 mm that were not aspirated during FoPOR were identified as predictive factors indicative of an efficient LuPOR practice with an Area Under the Curve (AUC) of 0.86, 0.86, 0.89 as well as 0.82 respectively. The combination of the above-mentioned characteristics into a prediction model provided an AUC of 0.88, specificity and a sensitivity of 0.73 and 0.94 respectively and an accuracy of 0.89. The model provided a positive predictive value (PPV) of 93.5% and a negative predictive value (NPV) of 46.8%. The clinical conclusion of the present study aims to be of added value to the clinician, by providing a prediction model defining the POR population benefiting from LuPOR. The high PPV of this model may renders this tool helpful for the practitioner that considers LuPOR.
Expanding the use of ethanol as a feedstock for cell-free synthetic biochemistry by implementing acetyl-CoA and ATP generating pathways
Authors: Liu Hongjiang , Arbing Mark A. , Bowie James U.
Published: May 2022

Ethanol is a widely available carbon compound that can be increasingly produced with a net negative carbon balance. Carbon-negative ethanol might therefore provide a feedstock for building a wider range of sustainable chemicals. Here we show how ethanol can be converted with a cell free system into acetyl-CoA, a central precursor for myriad biochemicals, and how we can use the energy stored in ethanol to generate ATP, another key molecule important for powering biochemical pathways. The ATP generator produces acetone as a value-added side product. Our ATP generator reached titers of 27 ± 6 mM ATP and 59 ± 15 mM acetone with maximum ATP synthesis rate of 2.8 ± 0.6 mM/h and acetone of 7.8 ± 0.8 mM/h. We illustrated how the ATP generating module can power cell-free biochemical pathways by converting mevalonate into isoprenol at a titer of 12.5 ± 0.8 mM and a maximum productivity of 1.0 ± 0.05 mM/h. These proof-of-principle demonstrations may ultimately find their way to the manufacture of diverse chemicals from ethanol and other simple carbon compounds.
Evaluation of protein production in rice seedlings under dark conditions
Authors: Watanabe Akiko , Hatanaka Yoshino , Takeshima Yukino , Sasaki Karin , Takahashi Noa , Ito Yukihiro
Published: May 2022

Although plants have several advantages for foreign protein production, cultivation of transgenic plants in artificial plant growth facilities involves the use of a great amount of electricity for lightning and air conditioning, reducing cost-effectiveness. Protein production in plants grown in darkness can overcome this problem, but the amount of protein produced in the dark is unknown. In this study, the total amount of soluble protein produced in rice seedlings germinated and grown in light or darkness were examined at several time points after germination and under different temperature, nutritional, and seedling density conditions. Our results indicate that rice seedlings grown in darkness produce a comparable amount of total soluble protein to those grown in light. Furthermore, we found that the best conditions for protein production in dark-grown rice seedlings are large seeds germinated and grown for 10–12 days at 28 °C supplemented with Murashige and Skoog medium and 30 g/l sucrose in dense planting. Therefore, our results suggest that foreign proteins can be produced in rice seedlings in the dark, with a reduced electricity use and an increase in cost-effectiveness.
Three-dimensional shape and deformation measurement on complex structure parts
Authors: Wu Zhoujie , Guo Wenbo , Chen Zhengdong , Wang Haoran , Li Xunren , Zhang Qican
Published: May 2022

Stereo digital image correlation technique (stereo-DIC or 3D-DIC) has been widely used in three-dimensional (3D) shape and deformation measurement due to its high accuracy and flexibility. But it is a tough task for it to deal with complex structure components because of the severe perspective distortion in two views. This paper seeks to resolve this issue using a single-camera system based on DIC-assisted fringe projection profilometry (FPP). A pixel-wise and complete 3D geometry of complex structures can be reconstructed using the robust and efficient Gray-coded method based on a FPP system. And then, DIC is just used to perform the temporal matching and complete full-field pixel-to-pixel tracking. The in- and out-of-plane deformation are obtained at the same time by directly comparing the accurate and complete 3D data of each corresponding pixel. Speckle pattern design and fringe denoising methods are carefully compared and chosen to simultaneously guarantee the measuring accuracy of 3D shape and deformation. Experimental results demonstrate the proposed method is an effective means to achieve full-field 3D shape and deformation measurement on complex parts, such as honeycomb structure and braided composite tube, which are challenging and even impossible for the traditional stereo-DIC method.
Microwave treatment of rice bran and its effect on phytochemical content and antioxidant activity
Authors: Pokkanta Piramon , Yuenyong Jitkunya , Mahatheeranont Sugunya , Jiamyangyuen Sudarat , Sookwong Phumon
Published: May 2022

An alternative approach for rice bran stabilization is microwave treatment. However, the effects of the microwave treatment on the contents of bioactive compounds and antioxidant activities of the rice bran have rarely been reported in detail. In this study, microwave pretreatment (130–880 W for 0.5–5.0 min) of rice bran was proposed where the antioxidant activity, total flavonoids, and total phenolic contents were determined using UV–Vis spectrometry. Tocols, γ-oryzanols, squalene, phytosterols and phenolic compounds were quantified using high-performance liquid chromatography. The results showed an increase in the antioxidant activity (0.5 folds), total phenolic contents (1.3 folds), total flavonoid contents (0.9 folds), total tocols (2.6 folds), total γ-oryzanols (1.6 folds), and total phytosterols (1.4 folds). Phytochemicals were enhanced, especially trans-p-coumaric acid (10.3 folds) and kaempferol (8.6 folds). The microwave treatment at 440 W for 2.5 min provided the best contents of the bioactive compounds and antioxidant activity. This work revealed the microwave treatment as a potential tool for stabilizing rice bran and increasing the usability of its phytochemicals, which applies to several industries concerning the use of rice bran as an ingredient.
Temporary cable force monitoring techniques during bridge construction-phase: the Tajo River Viaduct experience
Authors: Gaute-Alonso Alvaro , Garcia-Sanchez David , Alonso-Cobo Carlos , Calderon-Uriszar-Aldaca Iñigo
Published: May 2022

This article deals with the comparative analysis of current cable force monitoring techniques. In addition, the experience of three cable stress monitoring techniques during the construction phase is included: (a) the installation of load cells on the active anchorages of the cables, (b) the installation of unidirectional strain gauges, and (c) the evaluation of stresses in cables applying the vibrating wire technique by means of the installation of accelerometers. The main advantages and disadvantages of each technique analysed are highlighted in the Construction Process context of the Tajo Viaduct, one of the most singular viaducts recently built in Spain.
Simple, fast and reliable CE method for simultaneous determination of ciprofloxacin and ofloxacin in human urine
Authors: Kośka Izabella , Purgat Krystian , Kubalczyk Paweł
Published: May 2022

A simple, fast, and accurate capillary zone electrophoresis method has been developed for the determination of ciprofloxacin and ofloxacin. This method uses liquid–liquid extraction. Therefore, it is characterized by a very simple procedure of sample preparation but at the same time satisfactory precision and accuracy. The extraction process of the same urine sample was repeated three times. The extraction protocol was performed each time for 15 min with 1 mL of dichloromethane and chloroform mixture in a 3:1 volume ratio. A 0.1 mol/L phosphate-borate buffer (pH 8.40) was selected as the background electrolyte. UV detection was performed at 288 nm. The separation was carried out at a voltage of 16 kV, at a temperature of 25 °C. Experimentally evaluated LOQ values for ciprofloxacin and ofloxacin were 0.2 nmol/mL urine and 0.05 nmol/mL urine, respectively. For both analytes the calibration curves exhibited linearity over the entire tested concentration range of 1–6 nmol/mL urine. The precision of the method did not exceed 15%, and the recovery was in the range of 85–115%. The developed and validated procedure was applied to analyze human urine for the content of ciprofloxacin and ofloxacin.
Population distributions of single-cell adhesion parameters during the cell cycle from high-throughput robotic fluidic force microscopy
Authors: Nagy Ágoston G. , Kanyó Nicolett , Vörös Alexandra , Székács Inna , Bonyár Attila , Horvath Robert
Published: May 2022

Single-cell adhesion plays an essential role in biological and biomedical sciences, but its precise measurement for a large number of cells is still a challenging task. At present, typical force measuring techniques usually offer low throughput, a few cells per day, and therefore are unable to uncover phenomena emerging at the population level. In this work, robotic fluidic force microscopy (FluidFM) was utilized to measure the adhesion parameters of cells in a high-throughput manner to study their population distributions in-depth. The investigated cell type was the genetically engineered HeLa Fucci construct with cell cycle-dependent expression of fluorescent proteins. This feature, combined with the high-throughput measurement made it possible for the first time to characterize the single-cell adhesion distributions at various stages of the cell cycle. It was found that parameters such as single-cell adhesion force and energy follow a lognormal population distribution. Therefore, conclusions based on adhesion data of a low number of cells or treating the population as normally distributed can be misleading. Moreover, we found that the cell area was significantly the smallest, and the area normalized maximal adhesion force was significantly the largest for the colorless cells (the mitotic (M) and early G1 phases). Notably, the parameter characterizing the elongation of the cells until the maximum level of force between the cell and its substratum was also dependent on the cell cycle, which quantity was the smallest for the colorless cells. A novel parameter, named the spring coefficient of the cell, was introduced as the fraction of maximal adhesion force and maximal cell elongation during the mechanical detachment, which was found to be significantly the largest for the colorless cells. Cells in the M phase adhere in atypical way, with so-called reticular adhesions, which are different from canonical focal adhesions. We first revealed that reticular adhesion can exert a higher force per unit area than canonical focal adhesions, and cells in this phase are significantly stiffer. The possible biological consequences of these findings were also discussed, together with the practical relevance of the observed population-level adhesion phenomena.
Network topological determinants of pathogen spread
Authors: Pérez-Ortiz María , Manescu Petru , Caccioli Fabio , Fernández-Reyes Delmiro , Nachev Parashkev , Shawe-Taylor John
Published: May 2022

How do we best constrain social interactions to decrease transmission of communicable diseases? Indiscriminate suppression is unsustainable long term and presupposes that all interactions carry equal importance. Instead, transmission within a social network has been shown to be determined by its topology. In this paper, we deploy simulations to understand and quantify the impact on disease transmission of a set of topological network features, building a dataset of 9000 interaction graphs using generators of different types of synthetic social networks. Independently of the topology of the network, we maintain constant the total volume of social interactions in our simulations, to show how even with the same social contact some network structures are more or less resilient to the spread. We find a suitable intervention to be specific suppression of unfamiliar and casual interactions that contribute to the network’s global efficiency. This is, pathogen spread is significantly reduced by limiting specific kinds of contact rather than their global number. Our numerical studies might inspire further investigation in connection to public health, as an integrative framework to craft and evaluate social interventions in communicable diseases with different social graphs or as a highlight of network metrics that should be captured in social studies.