bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic signature of the pathogenic 22q11.2 deletion identifies carriers and provides insight into systemic dysregulation
Authors: Courraud Julie , Russo Francesco , Themudo Gonçalo Espregueira , Laursen Susan Svane , Ingason Andrés , Hougaard David M. , Cohen Arieh S. , Werge Thomas , Ernst Madeleine
Published: December 2023

Large deletions at chromosome 22q11.2 are known to cause severe clinical conditions collectively known as 22q11.2 deletion syndrome. Notwithstanding the pathogenicity of these deletions, affected individuals are typically diagnosed in late childhood or early adolescence, and little is known of the molecular signaling cascades and biological consequences immediately downstream of the deleted genes. Here, we used targeted metabolomics to compare neonatal dried blood spot samples from 203 individuals clinically identified as carriers of a deletion at chromosome 22q11.2 with 203 unaffected individuals. A total of 173 metabolites were successfully identified and used to inform on systemic dysregulation caused by the genomic lesion and to discriminate carriers from non-carriers. We found 84 metabolites to be differentially abundant between carriers and non-carriers of the 22q11.2 deletion. A predictive model based on all 173 metabolites achieved high Accuracy (89%), Area Under the Curve (93%), F1 (88%), Positive Predictive Value (94%), and Negative Predictive Value (84%) with tyrosine and proline having the highest individual contributions to the model as well as the highest interaction strength. Targeted metabolomics provides insight into the molecular consequences possibly contributing to the pathology underlying the clinical manifestations of the 22q11 deletion and is an easily applicable approach to first-pass screening for carrier status of the 22q11 to prompt subsequent verification of the genomic diagnosis.
Breaking solvation dominance of ethylene carbonate via molecular charge engineering enables lower temperature battery
Authors: Chen Yuqing , He Qiu , Zhao Yun , Zhou Wang , Xiao Peitao , Gao Peng , Tavajohi Naser , Tu Jian , Li Baohua , He Xiangming , Xing Lidan , Fan Xiulin , Liu Jilei
Published: December 2023

Low temperatures severely impair the performance of lithium-ion batteries, which demand powerful electrolytes with wide liquidity ranges, facilitated ion diffusion, and lower desolvation energy. The keys lie in establishing mild interactions between Li+ and solvent molecules internally, which are hard to achieve in commercial ethylene-carbonate based electrolytes. Herein, we tailor the solvation structure with low-ε solvent-dominated coordination, and unlock ethylene-carbonate via electronegativity regulation of carbonyl oxygen. The modified electrolyte exhibits high ion conductivity (1.46 mS·cm−1) at −90 °C, and remains liquid at −110 °C. Consequently, 4.5 V graphite-based pouch cells achieve ~98% capacity over 200 cycles at −10 °C without lithium dendrite. These cells also retain ~60% of their room-temperature discharge capacity at −70 °C, and miraculously retain discharge functionality even at ~−100 °C after being fully charged at 25 °C. This strategy of disrupting solvation dominance of ethylene-carbonate through molecular charge engineering, opens new avenues for advanced electrolyte design.
Identification of inulin-responsive bacteria in the gut microbiota via multi-modal activity-based sorting
Authors: Riva Alessandra , Rasoulimehrabani Hamid , Cruz-Rubio José Manuel , Schnorr Stephanie L. , von Baeckmann Cornelia , Inan Deniz , Nikolov Georgi , Herbold Craig W. , Hausmann Bela , Pjevac Petra , Schintlmeister Arno , Spittler Andreas , Palatinszky Márton , Kadunic Aida , Hieger Norbert , Del Favero Giorgia , von Bergen Martin , Jehmlich Nico , Watzka Margarete , Lee Kang Soo , Wiesenbauer Julia , Khadem Sanaz , Viernstein Helmut , Stocker Roman , Wagner Michael , Kaiser Christina , Richter Andreas , Kleitz Freddy , Berry David
Published: December 2023

Prebiotics are defined as non-digestible dietary components that promote the growth of beneficial gut microorganisms. In many cases, however, this capability is not systematically evaluated. Here, we develop a methodology for determining prebiotic-responsive bacteria using the popular dietary supplement inulin. We first identify microbes with a capacity to bind inulin using mesoporous silica nanoparticles functionalized with inulin. 16S rRNA gene amplicon sequencing of sorted cells revealed that the ability to bind inulin was widespread in the microbiota. We further evaluate which taxa are metabolically stimulated by inulin and find that diverse taxa from the phyla Firmicutes and Actinobacteria respond to inulin, and several isolates of these taxa can degrade inulin. Incubation with another prebiotic, xylooligosaccharides (XOS), in contrast, shows a more robust bifidogenic effect. Interestingly, the Coriobacteriia Eggerthella lenta and Gordonibacter urolithinfaciens are indirectly stimulated by the inulin degradation process, expanding our knowledge of inulin-responsive bacteria.
Static and dynamic coding in distinct cell types during associative learning in the prefrontal cortex
Authors: Ceccarelli Francesco , Ferrucci Lorenzo , Londei Fabrizio , Ramawat Surabhi , Brunamonti Emiliano , Genovesio Aldo
Published: December 2023

The prefrontal cortex maintains information in memory through static or dynamic population codes depending on task demands, but whether the population coding schemes used are learning-dependent and differ between cell types is currently unknown. We investigate the population coding properties and temporal stability of neurons recorded from male macaques in two mapping tasks during and after stimulus-response associative learning, and then we use a Strategy task with the same stimuli and responses as control. We identify a heterogeneous population coding for stimuli, responses, and novel associations: static for putative pyramidal cells and dynamic for putative interneurons that show the strongest selectivity for all the variables. The population coding of learned associations shows overall the highest stability driven by cell types, with interneurons changing from dynamic to static coding after successful learning. The results support that prefrontal microcircuitry expresses mixed population coding governed by cell types and changes its stability during associative learning.
Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma
Authors: Calderaro Julien , Ghaffari Laleh Narmin , Zeng Qinghe , Maille Pascale , Favre Loetitia , Pujals Anaïs , Klein Christophe , Bazille Céline , Heij Lara R. , Uguen Arnaud , Luedde Tom , Di Tommaso Luca , Beaufrère Aurélie , Chatain Augustin , Gastineau Delphine , Nguyen Cong Trung , Nguyen-Canh Hiep , Thi Khuyen Nguyen , Gnemmi Viviane , Graham Rondell P. , Charlotte Frédéric , Wendum Dominique , Vij Mukul , Allende Daniela S. , Aucejo Federico , Diaz Alba , Rivière Benjamin , Herrero Astrid , Evert Katja , Calvisi Diego Francesco , Augustin Jérémy , Leow Wei Qiang , Leung Howard Ho Wai , Boleslawski Emmanuel , Rela Mohamed , François Arnaud , Cha Anthony Wing-Hung , Forner Alejandro , Reig Maria , Allaire Manon , Scatton Olivier , Chatelain Denis , Boulagnon-Rombi Camille , Sturm Nathalie , Menahem Benjamin , Frouin Eric , Tougeron David , Tournigand Christophe , Kempf Emmanuelle , Kim Haeryoung , Ningarhari Massih , Michalak-Provost Sophie , Gopal Purva , Brustia Raffaele , Vibert Eric , Schulze Kornelius , Rüther Darius F. , Weidemann Sören A. , Rhaiem Rami , Pawlotsky Jean-Michel , Zhang Xuchen , Luciani Alain , Mulé Sébastien , Laurent Alexis , Amaddeo Giuliana , Regnault Hélène , De Martin Eleonora , Sempoux Christine , Navale Pooja , Westerhoff Maria , Lo Regina Cheuk-Lam , Bednarsch Jan , Gouw Annette , Guettier Catherine , Lequoy Marie , Harada Kenichi , Sripongpun Pimsiri , Wetwittayaklang Poowadon , Loménie Nicolas , Tantipisit Jarukit , Kaewdech Apichat , Shen Jeanne , Paradis Valérie , Caruso Stefano , Kather Jakob Nikolas
Published: December 2023

Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.
Hydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis
Authors: Wei Zhao , Lei Meng , Wang Yaohui , Xie Yizhou , Xie Xueyong , Lan Dongwei , Jia Yuanbo , Liu Jingyi , Ma Yufei , Cheng Bo , Gerecht Sharon , Xu Feng
Published: December 2023

The endothelial cell (EC) outgrowth in both vasculogenesis and angiogenesis starts with remodeling surrounding matrix and proceeds with the crosstalk between cells for the multicellular vasculature formation. The mechanical plasticity of matrix, defined as the ability to permanently deform by external traction, is pivotal in modulating cell behaviors. Nevertheless, the implications of matrix plasticity on cell-to-cell interactions during EC outgrowth, along with the molecular pathways involved, remain elusive. Here we develop a collagen-hyaluronic acid based hydrogel platform with tunable plasticity by using compositing strategy of dynamic and covalent networks. We show that although the increasing plasticity of the hydrogel facilitates the matrix remodeling by ECs, the largest tubular lumens and the longest invading distance unexpectedly appear in hydrogels with medium plasticity instead of the highest ones. We unravel that the high plasticity of the hydrogels promotes stable integrin cluster of ECs and recruitment of focal adhesion kinase with an overenhanced contractility which downregulates the vascular endothelial cadherin expression and destabilizes the adherens junctions between individual ECs. Our results, further validated with mathematical simulations and in vivo angiogenic tests, demonstrate that a balance of matrix plasticity facilitates both cell-matrix binding and cell-to-cell adherens, for promoting vascular assembly and invasion.
Evolutionary modelling indicates that mosquito metabolism shapes the life-history strategies of Plasmodium parasites
Authors: Carrillo-Bustamante Paola , Costa Giulia , Lampe Lena , Levashina Elena A.
Published: December 2023

Within-host survival and between-host transmission are key life-history traits of single-celled malaria parasites. Understanding the evolutionary forces that shape these traits is crucial to predict malaria epidemiology, drug resistance, and virulence. However, very little is known about how Plasmodium parasites adapt to their mosquito vectors. Here, we examine the evolution of the time Plasmodium parasites require to develop within the vector (extrinsic incubation period) with an individual-based model of malaria transmission that includes mosquito metabolism. Specifically, we model the metabolic cascade of resource allocation induced by blood-feeding, as well as the influence of multiple blood meals on parasite development. Our model predicts that successful vector-to-human transmission events are rare, and are caused by long-lived mosquitoes. Importantly, our results show that the life-history strategies of malaria parasites depend on the mosquito’s metabolic status. In our model, additional resources provided by multiple blood meals lead to selection for parasites with slow or intermediate developmental time. These results challenge the current assumption that evolution favors fast developing parasites to maximize their chances to complete their within-mosquito life cycle. We propose that the long sporogonic cycle observed for Plasmodium is not a constraint but rather an adaptation to increase transmission potential.
Edge effects on tree architecture exacerbate biomass loss of fragmented Amazonian forests
Authors: Nunes Matheus Henrique , Vaz Marcel Caritá , Camargo José Luís Campana , Laurance William F. , de Andrade Ana , Vicentini Alberto , Laurance Susan , Raumonen Pasi , Jackson Toby , Zuquim Gabriela , Wu Jin , Peñuelas Josep , Chave Jérôme , Maeda Eduardo Eiji
Published: December 2023

Habitat fragmentation could potentially affect tree architecture and allometry. Here, we use ground surveys of terrestrial LiDAR in Central Amazonia to explore the influence of forest edge effects on tree architecture and allometry, as well as forest biomass, 40 years after fragmentation. We find that young trees colonising the forest fragments have thicker branches and architectural traits that optimise for light capture, which result in 50% more woody volume than their counterparts of similar stem size and height in the forest interior. However, we observe a disproportionately lower height in some large trees, leading to a 30% decline in their woody volume. Despite the substantial wood production of colonising trees, the lower height of some large trees has resulted in a net loss of 6.0 Mg ha−1 of aboveground biomass – representing 2.3% of the aboveground biomass of edge forests. Our findings indicate a strong influence of edge effects on tree architecture and allometry, and uncover an overlooked factor that likely exacerbates carbon losses in fragmented forests.
PolyMOF nanoparticles constructed from intrinsically microporous polymer ligand towards scalable composite membranes for CO2 separation
Authors: Lee Tae Hoon , Lee Byung Kwan , Yoo Seung Yeon , Lee Hyunhee , Wu Wan-Ni , Smith Zachary P. , Park Ho Bum
Published: December 2023

Integrating different modification strategies into a single step to achieve the desired properties of metal–organic frameworks (MOFs) has been very synthetically challenging, especially in developing advanced MOF/polymer mixed matrix membranes (MMMs). Herein, we report a polymer–MOF (polyMOF) system constructed from a carboxylated polymer with intrinsic microporosity (cPIM-1) ligand. This intrinsically microporous ligand could coordinate with metals, leading to ~100 nm-sized polyMOF nanoparticles. Compared to control MOFs, these polyMOFs exhibit enhanced ultramicroporosity for efficient molecular sieving, and they have better dispersion properties in casting solutions to prepare MMMs. Ultimately, integrating coordination chemistries through the cPIM-1 and polymer-based functionality into porous materials results in polyMOF/PIM-1 MMMs that display excellent CO2 separation performance (surpassing the CO2/N2 and CO2/CH4 upper bounds). In addition to exploring the physicochemical and transport properties of this polyMOF system, scalability has been demonstrated by converting the developed MMM material into large-area (400 cm2) thin-film nanocomposite (TFN) membranes.
Prediction and stratification of longitudinal risk for chronic obstructive pulmonary disease across smoking behaviors
Authors: He Yixuan , Qian David C. , Diao James A. , Cho Michael H. , Silverman Edwin K. , Gusev Alexander , Manrai Arjun K. , Martin Alicia R. , Patel Chirag J.
Published: December 2023

Smoking is the leading risk factor for chronic obstructive pulmonary disease (COPD) worldwide, yet many people who never smoke develop COPD. We perform a longitudinal analysis of COPD in the UK Biobank to derive and validate the Socioeconomic and Environmental Risk Score which captures additive and cumulative environmental, behavioral, and socioeconomic exposure risks beyond tobacco smoking. The Socioeconomic and Environmental Risk Score is more predictive of COPD than smoking status and pack-years. Individuals in the highest decile of the risk score have a greater risk for incident COPD compared to the remaining population. Never smokers in the highest decile of exposure risk are more likely to develop COPD than previous and current smokers in the lowest decile. In general, the prediction accuracy of the Social and Environmental Risk Score is lower in non-European populations. While smoking status is often considered in screening COPD, our finding highlights the importance of other non-smoking environmental and socioeconomic variables.
Structures revealing mechanisms of resistance and collateral sensitivity of Plasmodium falciparum to proteasome inhibitors
Authors: Hsu Hao-Chi , Li Daqiang , Zhan Wenhu , Ye Jianxiang , Liu Yi Jing , Leung Annie , Qin Junling , Crespo Benigno , Gamo Francisco-Javier , Zhang Hao , Cui Liwang , Roth Alison , Kirkman Laura A. , Li Huilin , Lin Gang
Published: December 2023

The proteasome of the malaria parasite Plasmodium falciparum (Pf20S) is an advantageous drug target because its inhibition kills P. falciparum in multiple stages of its life cycle and synergizes with artemisinins. We recently developed a macrocyclic peptide, TDI-8304, that is highly selective for Pf20S over human proteasomes and is potent in vitro and in vivo against P. falciparum. A mutation in the Pf20S β6 subunit, A117D, confers resistance to TDI-8304, yet enhances both enzyme inhibition and anti-parasite activity of a tripeptide vinyl sulfone β2 inhibitor, WLW-vs. Here we present the high-resolution cryo-EM structures of Pf20S with TDI-8304, of human constitutive proteasome with TDI-8304, and of Pf20Sβ6A117D with WLW-vs that give insights into the species selectivity of TDI-8304, resistance to it, and the collateral sensitivity associated with resistance, including that TDI-8304 binds β2 and β5 in wild type Pf20S as well as WLW-vs binds β2 and β5 in Pf20Sβ6A117D. We further show that TDI-8304 kills P. falciparum as quickly as chloroquine and artemisinin and is active against P. cynomolgi at the liver stage. This increases interest in using these structures to facilitate the development of Pf20S inhibitors that target multiple proteasome subunits and limit the emergence of resistance.
How frictional slip evolves
Authors: Shi Songlin , Wang Meng , Poles Yonatan , Fineberg Jay
Published: December 2023

Earthquake-like ruptures break the contacts that form the frictional interface separating contacting bodies and mediate the onset of frictional motion (stick-slip). The slip (motion) of the interface immediately resulting from the rupture that initiates each stick-slip event is generally much smaller than the total slip logged over the duration of the event. Slip after the onset of friction is generally attributed to continuous motion globally attributed to ‘dynamic friction’. Here we show, by means of direct measurements of real contact area and slip at the frictional interface, that sequences of myriad hitherto invisible, secondary ruptures are triggered immediately in the wake of each initial rupture. Each secondary rupture generates incremental slip that, when not resolved, may appear as steady sliding of the interface. Each slip increment is linked, via fracture mechanics, to corresponding variations of contact area and local strain. Only by accounting for the contributions of these secondary ruptures can the accumulated interface slip be described. These results have important ramifications both to our fundamental understanding of frictional motion as well as to the essential role of aftershocks within natural faults in generating earthquake-mediated slip.
Site-selective chemical reactions by on-water surface sequential assembly
Authors: Prasoon Anupam , Yu Xiaoqing , Hambsch Mike , Bodesheim David , Liu Kejun , Zacarias Angelica , Nguyen Nguyen Ngan , Seki Takakazu , Dianat Aerzoo , Croy Alexander , Cuniberti Gianaurelio , Fontaine Philippe , Nagata Yuki , Mannsfeld Stefan C. B. , Dong Renhao , Bonn Mischa , Feng Xinliang
Published: December 2023

Controlling site-selectivity and reactivity in chemical reactions continues to be a key challenge in modern synthetic chemistry. Here, we demonstrate the discovery of site-selective chemical reactions on the water surface via a sequential assembly approach. A negatively charged surfactant monolayer on the water surface guides the electrostatically driven, epitaxial, and aligned assembly of reagent amino-substituted porphyrin molecules, resulting in a well-defined J-aggregated structure. This constrained geometry of the porphyrin molecules prompts the subsequent directional alignment of the perylenetetracarboxylic dianhydride reagent, enabling the selective formation of a one-sided imide bond between porphyrin and reagent. Surface-specific in-situ spectroscopies reveal the underlying mechanism of the dynamic interface that promotes multilayer growth of the site-selective imide product. The site-selective reaction on the water surface is further demonstrated by three reversible and irreversible chemical reactions, such as imide-, imine-, and 1, 3-diazole (imidazole)- bonds involving porphyrin molecules. This unique sequential assembly approach enables site-selective chemical reactions that can bring on-water surface synthesis to the forefront of modern organic chemistry.
Pyrotinib plus docetaxel as first-line treatment for HER2-positive metastatic breast cancer: the PANDORA phase II trial
Authors: Zheng Yabing , Cao Wen-Ming , Shao Xiying , Shi Yanxia , Cai Li , Chen Wenyan , Liu Jian , Shen Peng , Chen Yiding , Wang Xian , Li Huiping , Li Man , Chen Zhanhong , Wang Xiaojia
Published: December 2023

The role of pyrotinib in the treatment of HER2-positive metastatic breast cancer (MBC) has been well-established. This multicenter, single-arm phase II trial (NCT03876587) aimed to assess the benefit of pyrotinib plus docetaxel as a first-line treatment for HER2-positive MBC. Women with HER2-positive MBC who had not undergone HER2 blockade or chemotherapy for metastatic disease were enrolled in the study and received daily oral pyrotinib 400 mg plus intravenous docetaxel 75 mg/m2 every 3 weeks. The primary endpoint was the objective response rate (ORR), secondary endpoints included progression-free survival (PFS), duration of response (DoR), clinical benefit rate (CBR), overall survival (OS) and safety. From June 2019 to June 2021, 79 patients were enrolled. The confirmed ORR was 79.7% (95% confidence interval [CI], 70.8-88.6), and the CBR was 87.3% (95%CI, 80.0-94.6) in the intention-to-treat population. The pre-specified primary endpoint was met. The median DoR was 15.9 months (interquartile range, 8.3-19.5); the median PFS was 16.0 months (95% CI, 11.2-20.8), and the median OS was not reached. The most common grade ≥3 treatment-related adverse events observed were leukopenia (29.1%), neutropenia (27.8%), and diarrhea (21.5%). This study demonstrates that pyrotinib plus docetaxel show an acceptable safety profile and promising antitumor activity as a first-line treatment option for patients with HER2-positive MBC.
Elemental partitioning and corrosion resistance of Ni–Cr alloys revealed by accurate ab-initio thermodynamic and electrochemical calculations
Authors: Huang Liang-Feng , Xie Yusi , Sieradzki Karl , Rondinelli James M.
Published: December 2023

Elemental partitioning during thermal processing can significantly affect the corrosion resistance of bulk alloys operating in aggressive electrochemical environments, for which, despite decades of experimental and theoretical studies, the thermodynamic and electrochemical mechanisms still lack accurate quantitative descriptions. Here, we formulate an ab initio thermodynamic model to obtain the composition- and temperature-dependent free energies of formation (ΔfG) for Ni–Cr alloys, a prototypical group of corrosion-resistant metals, and discover two equilibrium states that produce the driving forces for the elemental partitioning in Ni–Cr. The results are in quantitative agreement with the experimental studies on the thermodynamic stability of Ni–Cr. We further construct electrochemical (potential–pH) diagrams by obtaining the required ΔfG values of native oxides and (oxy)hydroxides using high-fidelity ab-initio calculations that include exact electronic exchange and phononic contributions. We then analyze the passivation and electrochemical trends of Ni–Cr alloys, which closely explain various oxide-film growth and corrosion behaviors observed on alloy surfaces. We finally determine the optimal Cr content range of 14–34 at%, which provides the Ni–Cr alloys with both the preferred heat-treatment stability and superior corrosion resistance. We conclude by discussing the consequences of these findings on other Ni–Cr alloys with more complex additives, which can guide the further optimization of industrial Ni–Cr-based alloys.
Temporal patterns of fucoxanthin in four species of European marine brown macroalgae
Authors: Cunningham Eoghan M. , O’Kane Aaron P. , Ford Lauren , Sheldrake Gary N. , Cuthbert Ross N. , Dick Jaimie T. A. , Maggs Christine A. , Walsh Pamela J.
Published: December 2023

Brown seaweeds are a rich source of carotenoids, particularly fucoxanthin, which has a wide range of potential health applications. Fucoxanthin fluctuates within and among seaweeds over time, frustrating efforts to utilise this resource. Thus, we require comprehensive analyses of long- and short-term concentrations across species in field conditions. Here, we used High Performance Liquid Chromatography to compare fucoxanthin content in four brown macroalgae, Ascophyllum nodosum, Fucus serratus, Fucus vesiculosus and Saccharina latissima, monthly for 1 year. F. serratus and F. vesiculosus had significantly higher fucoxanthin content (mg/g), which was highest in Spring (0.39 ± 0.04) and Autumn (0.45 ± 0.04) [mean (± SE)]. Two species, A. nodosum and F. serratus, were collected monthly at the same location for a further two non-consecutive years. For both A. nodosum and F. serratus, a significant interaction effect of seasons and years was identified, highlighting that there is variation in fucoxanthin content among and within species over time. We also show that fucoxanthin content differs significantly among months even within seasons. Therefore, it is not sufficient to assess fucoxanthin in single months to represent seasonality. We discuss how weather, nutrients and reproduction may have driven the seasonal variation, and reveal patterns of fucoxanthin concentration that can provide information concerning its availability for many important medical functions.
Altitude measurement method of VHF radar based on spatial smoothing of correlation matrix
Authors: Wang Xianchao , Wei Yanping , Li Shaoyi , Hou Changhui , Zhang Guoming
Published: December 2023

For very high frequency (VHF) phased array radar, the key problem to be solved in altitude measurement is the super-resolution spatial spectrum estimation under the condition of coherent sources. The spatial smoothing algorithm is a kind of decorrelation algorithm with excellent properties, but the decorrelation process is at the expense of the effective array aperture. Because it only uses the autocorrelation information of the subspace, its performance is significantly reduced, when the positions of the coherent sources are very close. In order to solve the above problems, this paper proposes an altitude measurement method of VHF radar based on the space smoothing of autocorrelation and cross-correlation matrix, which is used to realize the correlation and super-resolution processing of echo signals and multipath signals. The proposed method does not need to construct a weighting matrix, and can make full use of the received data, enhance the signal components in the equivalent spatial smoothing matrix, reduce the impact of noise, and improve the resolution of coherent sources. The simulation results show that the weighted spatial smoothing method proposed in this paper is correct and effective.
First discovery of charcoal-based prehistoric cave art in Dordogne
Authors: Reiche Ina , Coquinot Yvan , Trosseau Antoine , Maigret Anne
Published: December 2023

Archaeologists have long been puzzled by the exact age of Paleolithic cave art in Europe especially in the Franco-Cantabrian region with hundreds of decorated caves because the creation of this parietal art (paintings, drawings and engravings) is closely tied to the appearance of first modern humans in Europe and their ways of life. The Dordogne region, one of the richest regions in terms of Paleolithic cave art in the world with more than 200 cave sites, is currently known to provide figures of cave art solely made with mineral coloring matters that cannot be dated directly. Using in-situ non-invasive Raman spectroscopy combined with portable X-ray fluorescence analysis as well as visible and infrared imaging of the decor of the Font-de-Gaume cave, we show the presence of a large number of charcoal-based Paleolithic figures besides others made of iron and manganese oxides in the main galleries for the first time. The creation periods of the cave art at Font-de-Gaume are mainly attributed to the Magdalenian period and probably more complicated constituted of at least two creation phases than commonly established as shown by the direct or partial superimposition of carbon-based and iron- and/or manganese-based figures. Our new results contribute to a better understanding of the organisation of the ornamentation and thus of the imaginary language of our Prehistoric ancestors. The discovery opens new research possibilities for re-reading of the complex panels and absolute radiocarbon dating.
An efficient instance segmentation approach for studying fission gas bubbles in irradiated metallic nuclear fuel
Authors: Sun Shoukun , Xu Fei , Cai Lu , Salvato Daniele , Dilemma Fidelma , Capriotti Luca , Xian Min , Yao Tiankai
Published: December 2023

Gaseous fission products from nuclear fission reactions tend to form fission gas bubbles of various shapes and sizes inside nuclear fuel. The behavior of fission gas bubbles dictates nuclear fuel performances, such as fission gas release, grain growth, swelling, and fuel cladding mechanical interaction. Although mechanical understanding of the overall evolution behavior of fission gas bubbles is well known, lacking the quantitative data and high-level correlation between burnup/temperature and microstructure evolution blocks the development of predictive models and reduces the possibility of accelerating the qualification for new fuel forms. Historical characterization of fission gas bubbles in irradiated nuclear fuel relied on a simple threshold method working on low-resolution optical microscopy images. Advanced characterization of fission gas bubbles using scanning electron microscopic images reveals unprecedented details and extensive morphological data, which strains the effectiveness of conventional methods. This paper proposes a hybrid framework, based on digital image processing and deep learning models, to efficiently detect and classify fission gas bubbles from scanning electron microscopic images. The developed bubble annotation tool used a multitask deep learning network that integrates U-Net and ResNet to accomplish instance-level bubble segmentation. With limited annotated data, the model achieves a recall ratio of more than 90%, a leap forward compared to the threshold method. The model has the capability to identify fission gas bubbles with and without lanthanides to better understand the movement of lanthanide fission products and fuel cladding chemical interaction. Lastly, the deep learning model is versatile and applicable to the micro-structure segmentation of similar materials.
Self-reported energy use behaviour changed significantly during the cost-of-living crisis in winter 2022/23: insights from cross-sectional and longitudinal surveys in Great Britain
Authors: Huebner Gesche M. , Hanmer Clare , Zapata-Webborn Ellen , Pullinger Martin , McKenna Eoghan James , Few Jessica , Elam Simon , Oreszczyn Tadj
Published: December 2023

The winter of 2022/23 has seen large increases in energy prices and in the cost of living in many countries around the world, including Great Britain. Here, we report the results of two surveys, combining cross-sectional and longitudinal analysis, in a sample of about 5400 British households. One survey was conducted early in 2023, the other when participants had signed up to an ongoing research study in the past five years. Thermostat settings were about 1°C lower during the cost-of-living crisis than before, and householders were more likely to turn the heating off when the home was unoccupied. The effort to save energy increased compared to pre-cost-of-living-crisis levels. Using the in-home display more in the cost-of-living crisis than before correlated with greater effort to save energy, supporting the notion that displaying energy data can be a useful tool for energy reductions. Finding it difficult to keep comfortably warm in the home and struggling with meeting heating costs were linked to lower wellbeing, strengthening evidence links between cold, damp, and hard-to-heat homes and negative mental health outcomes. About 40% of respondents lowered the flow temperature of the boiler which might imply that highly tailored information campaigns can be effective in changing behaviour.
Reservoir impoundment-triggered seismicity in Brazil: the case of M4.0 Nova Ponte earthquake
Authors: Raza Haris , Kivi Iman Rahimzadeh , França George Sand , Vilarrasa Victor
Published: December 2023

Reservoir-triggered seismicity commonly occurs as a result of reservoir impoundment. In particular, the Nova Ponte reservoir triggered a series of earthquakes, including the 1998 M4.0 earthquake, which represents the second-largest earthquake triggered by reservoir impoundment in Brazil. The earthquake occurred after prolonged seismic activity following reservoir impoundment starting in 1993. After more than two decades, the mechanisms governing these earthquakes and their relation with the spatiotemporal evolution of the seismic events are still poorly understood. Here, we explain the causal mechanisms of the two largest earthquakes: an initial response M3.5 in 1995 and the delayed M4.0 in 1998. To this end, we numerically simulate the poromechanical subsurface response to reservoir impoundment using a 3D model that includes three geological layers down to 10 km depth. From the proposed potential nodal planes of the 1995 M3.5 earthquake, we show that the earthquake has most likely occurred on a vertical, E–W-oriented strike-slip fault with a reverse-displacement component. Deviatoric stresses generated by the water column loading on the surface, superimposed by undrained pore pressure enhancement in deep low-permeability layers can explain the fault reactivation. We find that for the 1998 M4.0 earthquake to occur, conductive flow pathways with permeability as high as 6.6·10−15 m2 should exist to transmit pore pressure to a deep critically oriented fault. Our analysis raises the importance of accounting for coupled poromechanical mechanisms controlling fault stability, hydromechanical properties of different rock layers, and realistic shape of the reservoir to accurately assess the potential for reservoir-triggered seismicity. We conclude that reliable forecasting models require accurate subsurface characterization before reservoir filling to enable managing the associated reservoir-triggered seismicity.
An ensemble-based deep learning model for detection of mutation causing cutaneous melanoma
Authors: Ali Shah Asghar , Shaker Ayesha Sher Ali , Jabbar Sohail , Abbas Qaisar , Al-Balawi Talal Saad , Celebi M. Emre
Published: December 2023

When the mutation affects the melanocytes of the body, a condition called melanoma results which is one of the deadliest skin cancers. Early detection of cutaneous melanoma is vital for raising the chances of survival. Melanoma can be due to inherited defective genes or due to environmental factors such as excessive sun exposure. The accuracy of the state-of-the-art computer-aided diagnosis systems is unsatisfactory. Moreover, the major drawback of medical imaging is the shortage of labeled data. Generalized classifiers are required to diagnose melanoma to avoid overfitting the dataset. To address these issues, blending ensemble-based deep learning (BEDLM-CMS) model is proposed to detect mutation of cutaneous melanoma by integrating long short-term memory (LSTM), Bi-directional LSTM (BLSTM) and gated recurrent unit (GRU) architectures. The dataset used in the proposed study contains 2608 human samples and 6778 mutations in total along with 75 types of genes. The most prominent genes that function as biomarkers for early diagnosis and prognosis are utilized. Multiple extraction techniques are used in this study to extract the most-prominent features. Afterwards, we applied different DL models optimized through grid search technique to diagnose melanoma. The validity of the results is confirmed using several techniques, including tenfold cross validation (10-FCVT), independent set (IST), and self-consistency (SCT). For validation of the results multiple metrics are used which include accuracy, specificity, sensitivity, and Matthews’s correlation coefficient. BEDLM gives the highest accuracy of 97% in the independent set test whereas in self-consistency test and tenfold cross validation test it gives 94% and 93% accuracy, respectively. Accuracy of in self-consistency test, independent set test, and tenfold cross validation test is LSTM (96%, 94%, 92%), GRU (93%, 94%, 91%), and BLSTM (99%, 98%, 93%), respectively. The findings demonstrate that the proposed BEDLM-CMS can be used effectively applied for early diagnosis and treatment efficacy evaluation of cutaneous melanoma.
Proposing new path-planning metrics for operating rovers on Mars
Authors: Muñoz Pablo , Bellutta Paolo , R-Moreno Maria D.
Published: December 2023

The on-ground operation of Mars rovers is a complex task that requires comprehensive planning in which path planning plays a fundamental role. The selection of paths has to be carefully chosen considering the scientific objectives, terrain, energy, and safety. In this regard, operators are assisted by path-planning algorithms that generate candidate paths based on cost functions. Distance traveled has always been considered one of the primary criteria when comparing paths. Other metrics such as the run-time to generate the solution or the number of expanded nodes are common measures considered in the literature. However, we want to analyze if those metrics provide useful information in challenging and partially known terrain. In this paper, we will review those metrics using two-path planning algorithms on real Mars maps. Based on our experience operating Mars rovers, we propose new metrics for assessing paths in real-world applications.
Deployment and assessment of a deep learning model for real-time detection of anal precancer with high frame rate high-resolution microendoscopy
Authors: Brenes David , Kortum Alex , Coole Jackson , Carns Jennifer , Schwarz Richard , Vohra Imran , Richards-Kortum Rebecca , Liu Yuxin , Cai Zhenjian , Sigel Keith , Anandasabapathy Sharmila , Gaisa Michael , Chiao Elizabeth
Published: December 2023

Anal cancer incidence is significantly higher in people living with HIV as HIV increases the oncogenic potential of human papillomavirus. The incidence of anal cancer in the United States has recently increased, with diagnosis and treatment hampered by high loss-to-follow-up rates. Novel methods for the automated, real-time diagnosis of AIN 2+ could enable "see and treat" strategies, reducing loss-to-follow-up rates. A previous retrospective study demonstrated that the accuracy of a high-resolution microendoscope (HRME) coupled with a deep learning model was comparable to expert clinical impression for diagnosis of AIN 2+ (sensitivity 0.92 [P = 0.68] and specificity 0.60 [P = 0.48]). However, motion artifacts and noise led to many images failing quality control (17%). Here, we present a high frame rate HRME (HF-HRME) with improved image quality, deployed in the clinic alongside a deep learning model and evaluated prospectively for detection of AIN 2+ in real-time. The HF-HRME reduced the fraction of images failing quality control to 4.6% by employing a high frame rate camera that enhances contrast and limits motion artifacts. The HF-HRME outperformed the previous HRME (P < 0.001) and clinical impression (P < 0.0001) in the detection of histopathologically confirmed AIN 2+ with a sensitivity of 0.91 and specificity of 0.87.
Development of a quantum dot-based lateral flow immunoassay strip for rapid and sensitive detection of SARS-CoV-2 neutralizing antibodies
Authors: Wang Xirong , Shao Shulin , Ye Huan , Li Sen , Gu Bing , Tang Bo
Published: December 2023

To a certain extent, the development and vaccination of COVID-19 vaccine have reduced the alarming rate of transmission speed and mortality rate. At present, vaccine coverage is quite high in countries around the world. Since individual differences are unavoidable, it is necessary to assess the efficacy of the vaccine in each vaccinated person in order to reflect the protective effect of the vaccine in different populations. In this study, we developed a novel COVID-19 neutralizing antibody detection kit combining lateral flow immunochromatography and novel quantum dot technology with 85.23% sensitivity, 92.50% specificity. The novel QD-ICA could achieve an accurate detection of SARS-CoV-2 neutralizing antibodies with 10 minutes, two steps, small equipment size, and broad testing application, suggesting its capability to assess vaccine effectiveness on a large scale in areas of world that currently affected by the pandemic.
Downregulation of osteoprotegerin in colorectal cancer cells promotes liver metastasis via activating tumor-associated macrophage
Authors: Hirata Wataru , Itatani Yoshiro , Masui Hideyuki , Kawada Kenji , Mizuno Rei , Yamamoto Takamasa , Okamoto Takuya , Ogawa Ryotaro , Inamoto Susumu , Maekawa Hisatsugu , Okamura Ryosuke , Kiyasu Yoshiyuki , Hanada Keita , Okamoto Michio , Nishikawa Yasuyo , Sugimoto Naoko , Tamura Takuya , Hatano Etsuro , Sakai Yoshiharu , Obama Kazutaka
Published: December 2023

Osteoprotegerin (OPG) is a secreted cytokine that functions as a decoy receptor for receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL). Anti-RANKL treatment for bone metastasis has been widely accepted for solid tumors. However, the mechanism of OPG-RANKL-RANK signaling in systemic colorectal cancer (CRC) metastasis remains unclear. In this study, we investigated the relevance and function of OPG expression in CRC liver metastasis. First, we performed in silico analysis using The Cancer Genome Atlas public database and found that lower OPG expression in CRC was associated with poor overall survival. Immunohistochemistry analyses using resected specimen from patients with CRC in our institute confirmed the result. Patient-matched primary CRC and liver metastases showed a significant downregulation of OPG expression in metastatic lesions. In CRC cell lines, OPG expression did not suppress cell proliferation and migration. However, OPG expression inhibited macrophage migration by suppressing the RANKL-RANK pathway. Moreover, in vivo mouse liver metastasis models showed that OPG expression in CRC cells suppressed liver metastases. In addition, treatment with an anti-RANKL neutralizing antibody also suppressed liver metastases. These results showed that downregulation of OPG expression in CRC cells promotes liver metastasis by activating tumor-associated macrophage, which can become a candidate for targeted therapy with anti-RANKL neutralizing antibody for CRC liver metastasis.
In silico investigation on sensing of tyramine by boron and silicon doped C60 fullerenes
Authors: Pattanaik S. , Vishwkarma A. K. , Yadav T. , Shakerzadeh E. , Sahu D. , Chakroborty S. , Tripathi P. K. , Zereffa E. A. , Malviya J. , Barik A. , Sarankar S. K. , Sharma P. , Upadhye V. J. , Wagadre S.
Published: December 2023

The present communication deals with the adsorption of tyramine neurotransmitter over the surface of pristine, Boron (B) and Silicon (Si) doped fullerenes. Density functional theory (DFT) calculations have been used to investigate tyramine adsorption on the surface of fullerenes in terms of stability, shape, work function, electronic characteristics, and density of state spectra. The most favourable adsorption configurations for tyramine have been computed to have adsorption energies of − 1.486, − 30.889, and − 31.166 kcal/mol, respectively whereas for the rest three configurations, it has been computed to be − 0.991, − 6.999, and − 8.796 kcal/mol, respectively. The band gaps for all six configurations are computed to be 2.68, 2.67, 2.06, 2.17, 2.07, and 2.14 eV, respectively. The band gap of pristine, B and Si doped fullerenes shows changes in their band gaps after adsorption of tyramine neurotransmitters. However, the change in band gaps reveals more in B doped fullerene rather than pristine and Si doped fullerenes. The change in band gaps of B and Si doped fullerenes leads a change in the electrical conductivity which helps to detect tyramine. Furthermore, natural bond orbital (NBO) computations demonstrated a net charge transfer of 0.006, 0.394, and 0.257efrom tynamine to pristine, B and Si doped fullerenes.
Immune response to zinc oxide inhalation in metal fume fever, and the possible role of IL-17f
Authors: Szűcs-Somlyó Éva , Lehel József , Májlinger Kornél , Tóth Fruzsina , Jerzsele Ákos , Kővágó Csaba
Published: December 2023

Metal fume fever (MFF) is a work-related disease caused by the inhalation of metal particles, including zinc oxide. Chronic asthma may develop as a long-term consequence of exposure, particularly for welders and metal workers who are most at risk. In this study, we investigated the effects of ZnO fume inhalation on multiple inflammation-related cytokine- and cytokine receptor genes in mice from lung and lymph node samples, to explore the role of these in the pathogenesis of MFF. In our experiments, the animals were treated with a sub-toxic amount of ZnO fume for 4 h a day for 3 consecutive days. Sampling occurred 3 and 12 h post-treatment. We are the first to demonstrate that ZnO inhalation causes extremely increased levels of IL-17f gene expression at both sampling time points, in addition to increased gene expression rates of several other interleukins and cytokines, such as IL-4, IL-13, CXCL5, CSF-3, and IFN-γ. Our animal experiment provides new insights into the immunological processes of early metal fume fever development. IL-17f plays a crucial role in connecting immunological and oxidative stress events. The increased levels of IL-4 and IL-13 cytokines may explain the development of long-term allergic asthma after exposure to ZnO nanoparticles, which is well-known among welders, smelters, and metal workers.