bluuebunny/crossref_metadata_2025 huggingface dataset:
AI Pontryagin or how artificial neural networks learn to control dynamical systems
Authors: Böttcher Lucas , Antulov-Fantulin Nino , Asikis Thomas
Published: January 2022

The efficient control of complex dynamical systems has many applications in the natural and applied sciences. In most real-world control problems, both control energy and cost constraints play a significant role. Although such optimal control problems can be formulated within the framework of variational calculus, their solution for complex systems is often analytically and computationally intractable. To overcome this outstanding challenge, we present AI Pontryagin, a versatile control framework based on neural ordinary differential equations that automatically learns control signals that steer high-dimensional dynamical systems towards a desired target state within a specified time interval. We demonstrate the ability of AI Pontryagin to learn control signals that closely resemble those found by corresponding optimal control frameworks in terms of control energy and deviation from the desired target state. Our results suggest that AI Pontryagin is capable of solving a wide range of control and optimization problems, including those that are analytically intractable.
Premature commitment to uncertain decisions during human NMDA receptor hypofunction
Authors: Salvador Alexandre , Arnal Luc H. , Vinckier Fabien , Domenech Philippe , Gaillard Raphaël , Wyart Valentin
Published: January 2022

Making accurate decisions based on unreliable sensory evidence requires cognitive inference. Dysfunction of n-methyl-d-aspartate (NMDA) receptors impairs the integration of noisy input in theoretical models of neural circuits, but whether and how this synaptic alteration impairs human inference and confidence during uncertain decisions remains unknown. Here we use placebo-controlled infusions of ketamine to characterize the causal effect of human NMDA receptor hypofunction on cognitive inference and its neural correlates. At the behavioral level, ketamine triggers inference errors and elevated decision uncertainty. At the neural level, ketamine is associated with imbalanced coding of evidence and premature response preparation in electroencephalographic (EEG) activity. Through computational modeling of inference and confidence, we propose that this specific pattern of behavioral and neural impairments reflects an early commitment to inaccurate decisions, which aims at resolving the abnormal uncertainty generated by NMDA receptor hypofunction.
The three-dimensional structure of Epstein-Barr virus genome varies by latency type and is regulated by PARP1 enzymatic activity
Authors: Morgan Sarah M. , Tanizawa Hideki , Caruso Lisa Beatrice , Hulse Michael , Kossenkov Andrew , Madzo Jozef , Keith Kelsey , Tan Yinfei , Boyle Sarah , Lieberman Paul M. , Tempera Italo
Published: January 2022

Epstein-Barr virus (EBV) persists in human B-cells by maintaining its chromatinized episomes within the nucleus. We have previously shown that cellular factor Poly [ADP-ribose] polymerase 1 (PARP1) binds the EBV genome, stabilizes CTCF binding at specific loci, and that PARP1 enzymatic activity correlates with maintaining a transcriptionally active latency program. To better understand PARP1’s role in regulating EBV latency, here we functionally characterize the effect of PARP enzymatic inhibition on episomal structure through in situ HiC mapping, generating a complete 3D structure of the EBV genome. We also map intragenomic contact changes after PARP inhibition to global binding of chromatin looping factors CTCF and cohesin across the EBV genome. We find that PARP inhibition leads to fewer total unique intragenomic interactions within the EBV episome, yet new chromatin loops distinct from the untreated episome are also formed. This study also illustrates that PARP inhibition alters gene expression at the regions where chromatin looping is most effected. We observe that PARP1 inhibition does not alter cohesin binding sites but does increase its frequency of binding at those sites. Taken together, these findings demonstrate that PARP has an essential role in regulating global EBV chromatin structure and latent gene expression.
Interfacial compatibility critically controls Ru/TiO2 metal-support interaction modes in CO2 hydrogenation
Authors: Zhou Jun , Gao Zhe , Xiang Guolei , Zhai Tianyu , Liu Zikai , Zhao Weixin , Liang Xin , Wang Leyu
Published: January 2022

Supports can widely affect or even dominate the catalytic activity, selectivity, and stability of metal nanoparticles through various metal-support interactions (MSIs). However, underlying principles have not been fully understood yet, because MSIs are influenced by the composition, size, and facet of both metals and supports. Using Ru/TiO2 supported on rutile and anatase as model catalysts, we demonstrate that metal-support interfacial compatibility can critically control MSI modes and catalytic performances in CO2 hydrogenation. Annealing Ru/rutile-TiO2 in air can enhance CO2 conversion to methane resulting from enhanced interfacial coupling driven by matched lattices of RuOx with rutile-TiO2; annealing Ru/anatase-TiO2 in air decreases CO2 conversion and converts the product into CO owing to strong metal-support interaction (SMSI). Although rutile and anatase share the same chemical composition, we show that interfacial compatibility can basically modify metal-support coupling strength, catalyst morphology, surface atomic configuration, MSI mode, and catalytic performances of Ru/TiO2 in heterogeneous catalysis.
Land transpiration-evaporation partitioning errors responsible for modeled summertime warm bias in the central United States
Authors: Dong Jianzhi , Lei Fangni , Crow Wade T.
Published: January 2022

Earth system models (ESMs) from the Coupled Model Intercomparison Project Phase 6 (CMIP6) experiment exhibit a well-known summertime warm bias in mid-latitude land regions – most notably in the central contiguous United States (CUS). The dominant source of this bias is still under debate. Using validated datasets and both coupled and off-line modeling, we find that the CUS summertime warm bias is driven by the incorrect partitioning of evapotranspiration (ET) into its canopy transpiration and soil evaporation components. Specifically, CMIP6 ESMs do not effectively use available rootzone soil moisture for summertime transpiration and instead rely excessively on shallow soil and canopy-intercepted water storage to supply ET. As such, expected summertime precipitation deficits in CUS induce a negative ET bias into CMIP6 ESMs and a corresponding positive temperature bias via local land-atmosphere coupling. This tendency potentially biases CMIP6 projections of regional water stress and summertime air temperature variability under elevated CO2 conditions.
Unprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction
Authors: Islam Md Shafiqul , Junod Samuel L. , Zhang Si , Buuh Zakey Yusuf , Guan Yifu , Zhao Mi , Kaneria Kishan H. , Kafley Parmila , Cohen Carson , Maloney Robert , Lyu Zhigang , Voelz Vincent A. , Yang Weidong , Wang Rongsheng E.
Published: January 2022

We report the discovery of a facile peptide macrocyclization and stapling strategy based on a fluorine thiol displacement reaction (FTDR), which renders a class of peptide analogues with enhanced stability, affinity, cellular uptake, and inhibition of cancer cells. This approach enabled selective modification of the orthogonal fluoroacetamide side chains in unprotected peptides in the presence of intrinsic cysteines. The identified benzenedimethanethiol linker greatly promoted the alpha helicity of a variety of peptide substrates, as corroborated by molecular dynamics simulations. The cellular uptake of benzenedimethanethiol stapled peptides appeared to be universally enhanced compared to the classic ring-closing metathesis (RCM) stapled peptides. Pilot mechanism studies suggested that the uptake of FTDR-stapled peptides may involve multiple endocytosis pathways in a distinct pattern in comparison to peptides stapled by RCM. Consistent with the improved cell permeability, the FTDR-stapled lead Axin and p53 peptide analogues demonstrated enhanced inhibition of cancer cells over the RCM-stapled analogues and the unstapled peptides.
Single-molecule analysis of specificity and multivalency in binding of short linear substrate motifs to the APC/C
Authors: Hartooni Nairi , Sung Jongmin , Jain Ankur , Morgan David O.
Published: January 2022

Robust regulatory signals in the cell often depend on interactions between short linear motifs (SLiMs) and globular proteins. Many of these interactions are poorly characterized because the binding proteins cannot be produced in the amounts needed for traditional methods. To address this problem, we developed a single-molecule off-rate (SMOR) assay based on microscopy of fluorescent ligand binding to immobilized protein partners. We used it to characterize substrate binding to the Anaphase-Promoting Complex/Cyclosome (APC/C), a ubiquitin ligase that triggers chromosome segregation. We find that SLiMs in APC/C substrates (the D box and KEN box) display distinct affinities and specificities for the substrate-binding subunits of the APC/C, and we show that multiple SLiMs in a substrate generate a high-affinity multivalent interaction. The remarkably adaptable substrate-binding mechanisms of the APC/C have the potential to govern the order of substrate destruction in mitosis.
Visualizing the evolution from Mott insulator to Anderson insulator in Ti-doped 1T-TaS2
Authors: Zhang Wenhao , Gao Jingjing , Cheng Li , Bu Kunliang , Wu Zongxiu , Fei Ying , Zheng Yuan , Wang Li , Li Fangsen , Luo Xuan , Liu Zheng , Sun Yuping , Yin Yi
Published: January 2022

The electronic evolution of doped Mott insulators has been extensively studied for decades in search of exotic physical phases. The proposed Mott insulator 1T-TaS2 provides an intriguing platform to study the electronic evolution via doping. Here we apply scanning tunneling microscopy (STM) to study the evolution in Ti-doped 1T-TaS2 at different doping levels. The doping Ti atom locally perturbs the electronic and spin state inside the doped star of David and induces a clover-shaped orbital texture at low-doping levels (x < 0.01). The insulator to metal transition occurs around a critical point x = 0.01, in which small metallic and large insulating domains coexist. The clover-shaped orbital texture emerges at a broader energy range, revealing a competition with the electron correlation. It transforms to a disorder-induced Anderson insulating behavior as doping increases. We directly visualize the trapped electrons in dI/dV conductance maps. The comprehensive study of the series of Ti-doped 1T-TaS2 deepens our understanding of the electronic state evolution in a doped strong-correlated system.
Epicardial slices: an innovative 3D organotypic model to study epicardial cell physiology and activation
Authors: Maselli D. , Matos R. S. , Johnson R. D. , Chiappini C. , Camelliti P. , Campagnolo P.
Published: January 2022

The epicardium constitutes an untapped reservoir for cardiac regeneration. Upon heart injury, the adult epicardium re-activates, leading to epithelial-to-mesenchymal transition (EMT), migration, and differentiation. While interesting mechanistic and therapeutic findings arose from lower vertebrates and rodent models, the introduction of an experimental system representative of large mammals would undoubtedly facilitate translational advancements. Here, we apply innovative protocols to obtain living 3D organotypic epicardial slices from porcine hearts, encompassing the epicardial/myocardial interface. In culture, our slices preserve the in vivo architecture and functionality, presenting a continuous epicardium overlaying a healthy and connected myocardium. Upon thymosin β4 treatment of the slices, the epicardial cells become activated, upregulating epicardial and EMT genes, resulting in epicardial cell mobilization and differentiation into epicardial-derived mesenchymal cells. Our 3D organotypic model enables to investigate the reparative potential of the adult epicardium, offering an advanced tool to explore ex vivo the complex 3D interactions occurring within the native heart environment.
S-PRG-based composites erosive wear resistance and the effect on surrounding enamel
Authors: Bergantin Bianca Tozi Portaluppe , Di Leone Camilla Cristina Lira , Cruvinel Thiago , Wang Linda , Buzalaf Marília Afonso Rabelo , Borges Alessandra Buhler , Honório Heitor Marques , Rios Daniela
Published: January 2022

This study evaluated Surface Pre-Reacted Glass-ionomer (S-PRG)-based-composites’ surface resistance against erosive wear and their protective effect on surrounding enamel. Bovine enamel was randomized into 12 groups (n = 10/group) [erosion (e) or erosion + abrasion (a)]: nanohybrid-S-PRG-based composite (SPRGe/SPRGa), nanohybrid-S-PRG-based bulk-fill (SPRGBFe/SPRGBFa), nanoparticle-composite (RCe/RCa), nanohybrid-bulk-fill (BFe/BFa), Glass Hybrid Restorative System (GHRSe/GHRSa), and resin-modified glass-ionomer-cement (RMGICe/RMGICa). Cavities were prepared and restored. Initial profile assessment was performed on material and on adjacent enamel at distances of 100, 200, 300, 600, and 700 μm from margin. Specimens were immersed in citric acid (2 min; 6×/day for 5 days) for erosion. Erosion + abrasion groups were brushed for 1 min after erosion. Final profile assessment was performed. Two-way ANOVA and Tukey-test showed: for erosion, the GHRSe and RMGICe presented greater material wear compared to the other groups (p = 0.001); up to 300 μm away from restoration, GHRSe and SPRGBFe were able to prevent enamel loss compared to RMGICe and other composite groups (p = 0.001). For erosion + abrasion, none of the materials exhibited a significant protective effect and S-PRG-based groups showed lower wear than RMGICa and GHRSa, and higher wear than composites (p = 0.001). S-PRG-based-composites can diminish surrounding enamel loss only against erosion alone, similarly to GIC, with advantage of being a more resistant material.
The impairment of speech perception in noise following pure tone hearing recovery in patients with sudden sensorineural hearing loss
Authors: Diao Tongxiang , Duan Maoli , Ma Xin , Liu Jinjun , Yu Lisheng , Jing Yuanyuan , Wang Mengyuan
Published: January 2022

To explore whether patients with unilateral idiopathic sudden sensorineural hearing loss (uISSNHL) have normal speech in noise (SIN) perception under different masking conditions after complete recovery of pure tone audiometry. Eight completely recovered uISSNHL patients were enrolled in ISSNHL group, while 8 normal-hearing adults matched with age, gender, and education experience were selected as the control group. Each group was tested SIN under four masking conditions, including noise and speech maskings with and without spatial separation cues. For both ISSNHL and control groups a two-way ANOVA showed a statistically significant effect of masking type (p = 0.007 vs p = 0.012). A significant effect of perceived spatial separation (p < 0.001 vs p < 0.001). A significant interaction between masking type and perceived spatial separation was found (p < 0.001 vs p < 0.001). A paired sample T-test showed that the SIN perception of the control group was statistically significant lower than that of ISSNHL patients only under speech masking without spatial separation cues (p = 0.011). There were still abnormalities in the auditory center shortly after complete recovery in the ISSNHL group (within 2 weeks). However, the auditory periphery and higher-level ability to use spatial cues was normal.
A machine learning application for raising WASH awareness in the times of COVID-19 pandemic
Authors: Pandey Rohan , Gautam Vaibhav , Pal Ridam , Bandhey Harsh , Dhingra Lovedeep Singh , Misra Vihaan , Sharma Himanshu , Jain Chirag , Bhagat Kanav , Arushi  , Patel Lajjaben , Agarwal Mudit , Agrawal Samprati , Jalan Rishabh , Wadhwa Akshat , Garg Ayush , Agrawal Yashwin , Rana Bhavika , Kumaraguru Ponnurangam , Sethi Tavpritesh
Published: January 2022

The COVID-19 pandemic has revealed the power of internet disinformation in influencing global health. The deluge of information travels faster than the epidemic itself and is a threat to the health of millions across the globe. Health apps need to leverage machine learning for delivering the right information while constantly learning misinformation trends and deliver these effectively in vernacular languages in order to combat the infodemic at the grassroot levels in the general public. Our application, WashKaro, is a multi-pronged intervention that uses conversational Artificial Intelligence (AI), machine translation, and natural language processing to combat misinformation (NLP). WashKaro uses AI to provide accurate information matched against WHO recommendations and delivered in an understandable format in local languages. The primary aim of this study was to assess the use of neural models for text summarization and machine learning for delivering WHO matched COVID-19 information to mitigate the misinfodemic. The secondary aim of this study was to develop a symptom assessment tool and segmentation insights for improving the delivery of information. A total of 5026 people downloaded the app during the study window; among those, 1545 were actively engaged users. Our study shows that 3.4 times more females engaged with the App in Hindi as compared to males, the relevance of AI-filtered news content doubled within 45 days of continuous machine learning, and the prudence of integrated AI chatbot “Satya” increased thus proving the usefulness of a mHealth platform to mitigate health misinformation. We conclude that a machine learning application delivering bite-sized vernacular audios and conversational AI is a practical approach to mitigate health misinformation.
Comparative transcriptome analysis of two contrasting resistant and susceptible Aegilops tauschii accessions to wheat leaf rust (Puccinia triticina) using RNA-sequencing
Authors: Dorostkar Saeideh , Dadkhodaie Ali , Ebrahimie Esmaeil , Heidari Bahram , Ahmadi-Kordshooli Mahmood
Published: January 2022

Leaf rust, caused by Puccinia triticina Eriks., is the most common rust disease of wheat (Triticum aestivum L.) worldwide. Owing to the rapid evolution of virulent pathotypes, new and effective leaf rust resistance sources must be found. Aegilops tauschii, an excellent source of resistance genes to a wide range of diseases and pests, may provide novel routes for resistance to this disease. In this study, we aimed to elucidate the transcriptome of leaf rust resistance in two contrasting resistant and susceptible Ae. tauschii accessions using RNA-sequencing. Gene ontology, analysis of pathway enrichment and transcription factors provided an apprehensible review of differentially expressed genes and highlighted biological mechanisms behind the Aegilops–P. triticina interaction. The results showed the resistant accession could uniquely recognize pathogen invasion and respond precisely via reducing galactosyltransferase and overexpressing chromatin remodeling, signaling pathways, cellular homeostasis regulation, alkaloid biosynthesis pathway and alpha-linolenic acid metabolism. However, the suppression of photosynthetic pathway and external stimulus responses were observed upon rust infection in the susceptible genotype. In particular, this first report of comparative transcriptome analysis offers an insight into the strength and weakness of Aegilops against leaf rust and exhibits a pipeline for future wheat breeding programs.
Automated segmentation of multiparametric magnetic resonance images for cerebral AVM radiosurgery planning: a deep learning approach
Authors: Simon Aaron B. , Hurt Brian , Karunamuni Roshan , Kim Gwe-Ya , Moiseenko Vitali , Olson Scott , Farid Nikdokht , Hsiao Albert , Hattangadi-Gluth Jona A.
Published: January 2022

Stereotactic radiosurgery planning for cerebral arteriovenous malformations (AVM) is complicated by the variability in appearance of an AVM nidus across different imaging modalities. We developed a deep learning approach to automatically segment cerebrovascular-anatomical maps from multiple high-resolution magnetic resonance imaging/angiography (MRI/MRA) sequences in AVM patients, with the goal of facilitating target delineation. Twenty-three AVM patients who were evaluated for radiosurgery and underwent multi-parametric MRI/MRA were included. A hybrid semi-automated and manual approach was used to label MRI/MRAs with arteries, veins, brain parenchyma, cerebral spinal fluid (CSF), and embolized vessels. Next, these labels were used to train a convolutional neural network to perform this task. Imaging from 17 patients (6362 image slices) was used for training, and 6 patients (1224 slices) for validation. Performance was evaluated by Dice Similarity Coefficient (DSC). Classification performance was good for arteries, veins, brain parenchyma, and CSF, with DSCs of 0.86, 0.91, 0.98, and 0.91, respectively in the validation image set. Performance was lower for embolized vessels, with a DSC of 0.75. This demonstrates the proof of principle that accurate, high-resolution cerebrovascular-anatomical maps can be generated from multiparametric MRI/MRA. Clinical validation of their utility in radiosurgery planning is warranted.
Proximity ligation strategy for the genomic reconstruction of microbial communities associated with the ectoparasite Caligus rogercresseyi
Authors: Valenzuela-Miranda Diego , Gonçalves Ana Teresa , Valenzuela-Muñoz Valentina , Nuñez-Acuña Gustavo , Liachko Ivan , Nelson Bradley , Gallardo-Escarate Cristian
Published: January 2022

The sea louse Caligus rogercresseyi has become one of the main constraints for the sustainable development of salmon aquaculture in Chile. Although this parasite's negative impacts are well recognized by the industry, some novel potential threats remain unnoticed. The recent sequencing of the C. rogercresseyi genome revealed a large bacterial community associated with the sea louse, however, it is unknown if these microorganisms should become a new focus of sanitary concern. Herein, chromosome proximity ligation (Hi-C) coupled with long-read sequencing were used for the genomic reconstruction of the C. rogercresseyi microbiota. Through deconvolution analysis, we were able to assemble and characterize 413 bacterial genome clusters, including six bacterial genomes with more than 80% of completeness. The most represented bacterial genome belonged to the fish pathogen Tenacibacullum ovolyticum (97.87% completeness), followed by Dokdonia sp. (96.71% completeness). This completeness allowed identifying 21 virulence factors (VF) within the T. ovolyticum genome and four antibiotic resistance genes (ARG). Notably, genomic pathway reconstruction analysis suggests putative metabolic complementation mechanisms between C. rogercresseyi and its associated microbiota. Taken together, our data highlight the relevance of Hi-C techniques to discover pathogenic bacteria, VF, and ARGs and also suggest novel host-microbiota mutualism in sea lice biology.
Potentials of straw return and potassium supply on maize (Zea mays L.) photosynthesis, dry matter accumulation and yield
Authors: Fan Ya-fang , Gao Ju-lin , Sun Ji-ying , Liu Jian , Su Zhi-jun , Hu Shu-ping , Wang Zhi-gang , Yu Xiao-fang
Published: January 2022

Maize (Zea mays L.) is considered one of the most important grains in the world. Straw return has the effect of reducing soil bulk density and increasing soil porosity. Straw returning and potassium fertilizer can supplement soil potassium content. The improvement of soil structure and the optimization of soil nutrient levels provide a good environment for high yield and high efficiency of maize. Therefore, three field experiments were carried out over a three-year period (2018–2020) to study the effects of straw returning on photosynthesis, dry matter accumulation and yield of maize 'Xianyu 335' under two different fertilization methods and four potassium application levels. The results showed that straw returning and potassium application had significant effects on the above indicators. The above indicators were significantly improved by deep tillage straw returning compared with no tillage straw returning. Increasing potassium supply can promote the effect of straw returning. The photosynthesis, dry matter accumulation and yield parameters of maize treated with straw returning and deep tillage combined with 60 kg/hm2 potassium fertilizer (SFK60) reached the highest in the three harvest seasons. The corn planting profit of SFK45 treatment is the highest, which is $1868.92 per ha. Therefore, SFK45 is an effective way to ensure stable and high yield of corn and maximize farmers' income.
Ecological niche divergence between extant and glacial land snail populations explained
Authors: Horsák Michal , Horsáková Veronika , Divíšek Jan , Nekola Jeffrey C.
Published: January 2022

The presence of Last Glacial Maximum (LGM) biotic communities without modern counterparts is well known. It is particularly evident in central European fossil LGM land snails whose assemblages represent an odd mix of species that are currently limited to either xeric or wetland habitats. Here we document a genetically verified discovery of the modern calcareous wetland species Pupilla alpicola on Iceland, where it is limited to dry grasslands. This species also represents a common European LGM fossil, and its new records from Iceland help explain puzzling shifts of some glacial land snails of xeric grassland habitats to open wetlands today. Similarities between the climates of modern Iceland and LGM Eurasia suggest that this species did not become limited to wetlands in continental Europe until after the Late Pleistocene–Holocene climate transition. These results are a strong reminder that assumptions of ecological uniformity must be questioned and that the quality and robustness of palaeoecological reconstructions is dependent upon adequate knowledge of the full autecological range of species over time.
A randomized controlled trial of stem cell injection for tendon tear
Authors: Chun Se-Woong , Kim Won , Lee Sang Yoon , Lim Chai-Young , Kim Keewon , Kim Jeong-Gil , Park Chul-Hyun , Hong Sung Hwan , Yoo Hye Jin , Chung Sun G.
Published: January 2022

Tendons have limited reparative ability and perform a relatively simple mechanical function via the extracellular matrix. Thus, the injured tendon might be treated successfully by stem cell transplantation. We performed a randomized, controlled study to investigate the effects of mesenchymal stem cell injection for treating partial tears in the supraspinatus tendon. We enrolled 24 patients with shoulder pain lasting more than 3 months and partial tears in the supraspinatus tendon. Participants were assigned to three groups: stem cells in fibrin glue, normal saline/fibrin glue mixture, and normal saline only, with which intra-lesional injection was performed. Pain at activity and rest, shoulder function and tear size were evaluated. For safety measures, laboratory tests were taken and adverse events were recorded at every visit. Participants were followed up at 6, 12 weeks, 6, 12 months and 2 years after injection. The primary outcome measure was the improvement in pain at activity at 3 months after injection. Twenty-three patients were included in the final analysis. Primary outcome did not differ among groups (p = 0.35). A mixed effect model revealed no statistically significant interactions. Only time significantly predicted the outcome measure. All participants reported transient pain at the injection site. There were no differences in post-injection pain duration or severity. Safety measures did not differ between groups, and there were no persistent adverse events. Stem cell injection into supraspinatus partial tears in patients with shoulder pain lasting more than 3 months was not more effective than control injections.

ClinicalTrials.gov Identifier: NCT02298023
Binding behavior of spike protein and receptor binding domain of the SARS-CoV-2 virus at different environmental conditions
Authors: Zhang Meiyi , Wang Haoqi , Foster Emma R. , Nikolov Zivko L. , Fernando Sandun D. , King Maria D.
Published: January 2022

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of the COVID-19 pandemic that originated in China in December 2019. Although extensive research has been performed on SARS-CoV-2, the binding behavior of spike (S) protein and receptor binding domain (RBD) of SARS-CoV-2 at different environmental conditions have yet to be studied. The objective of this study is to investigate the effect of temperature, fatty acids, ions, and protein concentration on the binding behavior and rates of association and dissociation between the S protein and RBD of SARS-CoV-2 and the hydrophobic aminopropylsilane (APS) biosensors using biolayer interferometry (BLI) validated with molecular dynamics simulation. Our results suggest three conditions—high ionic concentration, presence of hydrophobic fatty acids, and low temperature—favor the attachment of S protein and RBD to hydrophobic surfaces. Increasing the temperature within an hour from 0 to 25 °C results in S protein detachment, suggesting that freezing can cause structural changes in the S protein, affecting its binding kinetics at higher temperature. At all the conditions, RBD exhibits lower dissociation capabilities than the full-length S trimer protein, indicating that the separated RBD formed stronger attachment to hydrophobic surfaces compared to when it was included in the S protein.
Visualizing the unusual spectral weight transfer in DyBa2Cu3O7–δ thin film
Authors: Li Hui , Du Zengyi , Wu Ze-Bin , Putzky Daniel , Joo Sang Hyun , Kundu Asish K. , Xu Xiaotao , Shi Xiaoyan , Lee Jinho , Pasupathy Abhay N. , Logvenov Gennady , Keimer Bernhard , Valla Tonica , Božović Ivan , Drozdov Ilya K. , Fujita Kazuhiro
Published: January 2022

We report a Spectroscopic Imaging Scanning Tunneling Microscopy (SI-STM) study of a DyBa2Cu3O7-δ (DBCO) thin film (Tc ~ 79 K) synthesized by the molecular beam epitaxy (MBE). We observed an unusual transfer of spectral weight in the local density of states (LDOS) spectra occurring only within the superconducting gap. By a systematic control of the tip-sample distance and the junction resistance, we demonstrate that the spectral weight transfer can be switched at a nano-meter length scale. These results suggest that an interaction between the STM tip and the sample alters the electronic configurations in the film. This probably originates from a combination of an intrinsic band bending at the interface between the surface and the bulk, and a tip-induced band bending. These results may open a new avenue for band engineering and applications of thin films of high-Tc cuprates.
Mutated RAS-associating proteins and ERK activation in relapse/refractory diffuse large B cell lymphoma
Authors: Benoit Alexandre , Bou-Petit Elisabeth , Chou Hsiang , Lu Melissa , Guilbert Cynthia , Luo Vincent Mingyi , Assouline Sarit , Morin Ryan D. , Dmitrienko Svetlana , Estrada-Tejedor Roger , Johnson Nathalie A. , Mann Koren K.
Published: January 2022

Diffuse large B cell lymphoma (DLBCL) is successfully treated with combination immuno-chemotherapy, but relapse with resistant disease occurs in ~ 40% of patients. However, little is known regarding relapsed/refractory DLBCL (rrDLBCL) genetics and alternative therapies. Based on findings from other tumors, we hypothesized that RAS-MEK-ERK signaling would be upregulated in resistant tumors, potentially correlating with mutations in RAS, RAF, or associated proteins. We analyzed mutations and phospho-ERK levels in tumor samples from rrDLBCL patients. Unlike other tumor types, rrDLBCL is not mutated in any Ras or Raf family members, despite having increased expression of p-ERK. In paired biopsies comparing diagnostic and relapsed specimens, 33% of tumors gained p-ERK expression, suggesting a role in promoting survival. We did find mutations in several Ras-associating proteins, including GEFs, GAPs, and downstream effectors that could account for increased ERK activation. We further investigated mutations in one such protein, RASGRP4. In silico modeling indicated an increased interaction between H-Ras and mutant RASGRP4. In cell lines, mutant RASGRP4 increased basal p-ERK expression and lead to a growth advantage in colony forming assays when challenged with doxorubicin. Relapsed/refractory DLBCL is often associated with increased survival signals downstream of ERK, potentially corresponding with mutations in protein controlling RAS/MEK/ERK signaling.
Neuropsychopharmacological profiling of scoparone in mice
Authors: Kowalczyk Joanna , Budzyńska Barbara , Kurach Łukasz , Pellegata Daniele , El Sayed Nesrine S. , Gertsch Jürg , Skalicka-Woźniak Krystyna
Published: January 2022

Scoparone (6,7-dimethoxycoumarin) is a simple coumarin from botanical drugs of Artemisia species used in Traditional Chinese Medicine and Génépi liquor. However, its bioavailability to the brain and potential central effects remain unexplored. We profiled the neuropharmacological effects of scoparone upon acute and subchronic intraperitoneal administration (2.5–25 mg/kg) in Swiss mice and determined its brain concentrations and its effects on the endocannabinoid system (ECS) and related lipids using LC–ESI–MS/MS. Scoparone showed no effect in the forced swimming test (FST) but, administered acutely, led to a bell-shaped anxiogenic-like behavior in the elevated plus-maze test and bell-shaped procognitive effects in the passive avoidance test when given subchronically and acutely. Scoparone rapidly but moderately accumulated in the brain (Cmax < 15 min) with an apparent first-order elimination (95% eliminated at 1 h). Acute scoparone administration (5 mg/kg) significantly increased brain arachidonic acid, prostaglandins, and N-acylethanolamines (NAEs) in the FST. Conversely, subchronic scoparone treatment (2.5 mg/kg) decreased NAEs and increased 2-arachidonoylglycerol. Scoparone differentially impacted ECS lipid remodeling in the brain independent of serine hydrolase modulation. Overall, the unexpectedly potent central effects of scoparone observed in mice could have toxicopharmacological implications for humans.
Modeling risk of Sclerotinia sclerotiorum-induced disease development on canola and dry bean using machine learning algorithms
Authors: Shahoveisi F. , Riahi Manesh M. , del Río Mendoza L. E.
Published: January 2022

Diseases caused by the fungus Sclerotinia sclerotiorum are managed mainly through fungicide applications in canola and dry bean. Accurate estimation of the risk of disease development on these crops could help farmers make spraying decisions. Five machine learning (ML) models were evaluated in classification and regression modes for predicting disease establishment under different air temperatures and leaf wetness duration conditions. Model algorithms were trained and tested using 20-fold cross validation. Correspondence between predicted and observed values were measured using Cohen’s Kappa (classification) and Lin’s concordance coefficients (regression). The artificial neural network (ANN) algorithms had average accuracies ≥ 89% (classification) and R2 ≥ 88% (regression) on canola and dry bean and their correspondence agreements were ≥ 0.83, which is considered substantial to almost perfect. In contrast, logistic regression algorithms had accuracies of 88% for dry bean and 78% for canola; other models were similarly inconsistent. Implementation of ANN models in disease warning systems could help farmers with spraying decisions. At the same time, these models provide insights on temperature and leaf wetness requirements for development of S. sclerotiorum diseases in these crops. Results of this study show the potential of ML models as tools for epidemiological studies on other pathosystems.
Speech air flow with and without face masks
Authors: Derrick Donald , Kabaliuk Natalia , Longworth Luke , Pishyar-Dehkordi Peiman , Jermy Mark
Published: January 2022

Face masks slow exhaled air flow and sequester exhaled particles. There are many types of face masks on the market today, each having widely varying fits, filtering, and air redirection characteristics. While particle filtration and flow resistance from masks has been well studied, their effects on speech air flow has not. We built a schlieren system and recorded speech air flow with 14 different face masks, comparing it to mask-less speech. All of the face masks reduced air flow from speech, but some allowed air flow features to reach further than 40 cm from a speaker’s lips and nose within a few seconds, and all the face masks allowed some air to escape above the nose. Evidence from available literature shows that distancing and ventilation in higher-risk indoor environment provide more benefit than wearing a face mask. Our own research shows all the masks we tested provide some additional benefit of restricting air flow from a speaker. However, well-fitted mask specifically designed for the purpose of preventing the spread of disease reduce air flow the most. Future research will study the effects of face masks on speech communication in order to facilitate cost/benefit analysis of mask usage in various environments.
Bioinspired antifouling Fe-based amorphous coating via killing-resisting dual surface modifications
Authors: Li Yu , Zhang Ling-Yu , Zhang Cheng , Zhang Zhan-Rong , Liu Lin
Published: January 2022

Fe-based amorphous coatings with outstanding corrosion resistance are promise for marine applications. However, these coatings encounter a great challenge of biofouling in marine environments. Inspired by the unique micro-nano hierarchical structure of shark skin with excellent antifouling properties, in this paper, we construct a bioinspired Fe-based amorphous coating with killing-resisting dual-effect via proper surface modifications, i.e., the modification with micro-patterned nanostructured Cu2O fibers (killing effect), followed by the modification with superhydrophobic surface (resisting effect). As a result, the modified amorphous coating exhibits impressive antifouling properties, achieving 98.6% resistance toNitzschia closterium f. minutissima,87% resistance toBovine serum albuminprotein and 99.8% resistance toPseudomonas aeruginosa, respectively. The remarkable antifouling performance is attributed to a synergistic antifouling mechanism from both resisting effect and killing effect, wherein the superhydrophobic surface provides a barrier to resist protein adsorption, while the patterned nanostructured Cu2O fibers supply Cu+ions to kill bacterial cells. In addition, the modified amorphous coating also exhibits excellent mechanical robustness, which ensures the durability of the Fe-based amorphous coating in practical services. This work may promote the development of new durable metal-based coatings integrated with anti-fouling and anti-corrosion properties.
Transvenous lead extraction using the TightRail mechanical rotating dilator sheath for Asian patients
Authors: Choi Ji-Hoon , Park Seung-Jung , Kim Hye Ree , Kwon Hee-Jin , Park Kyoung-Min , On Young Keun , Kim June Soo , Kim Ju Youn , Jung Won Young
Published: January 2022

The need for transvenous lead extraction (TLE) is increasing worldwide including in Asia–Pacific regions. However, supporting evidence for TightRail, a relatively new rotating mechanical dilator sheath, is still lacking in Asian patients. The efficacy and safety of TLE using TightRail performed between March 2018 and June 2021 were evaluated in 86 consecutive patients with 131 leads. The mean lead age was 11.7 ± 7.3 (range, 1.0–41.4) years. Clinical and complete procedural success using TightRail were achieved in 93.0% and 89.5% of 86 patients, respectively, with 6 min of median fluoroscopic time and 9.3% of major complication rate: death (1.2%), cardiac tamponade (3.5%), severe tricuspid regurgitation (3.5%), and stroke (1.2%). However, in 46 patients with longest lead age ≤ 10 years, clinical/complete success and major cardiac complication rates turned out better as 97.8%, 95.7%, and 2.2%, respectively. Additionally, when patients were divided into 3 groups: the first 28, second 29, and the last 29 patients, there was a clear trend toward better efficacy and safety outcomes with more experience with TightRail (Ptrend < 0.05). Longest lead age > 10 years was closely associated with TLE-related major cardiac complication (P = 0.046) with 85.7% sensitivity, 57.0% specificity, 15.0% positive predictive value, and 97.8% negative predictive values. In conclusion, TLE using TightRail may be effectively and safely performed by experienced operators for Asian patients with the longest lead age ≤ 10 years. However, as TightRail is a potentially aggressive tool, special attention should be paid to patients with longer lead dwelling times (e.g., > 10 years).
Diagnosing challenges and setting priorities for sustainable water resource management under climate change
Authors: Mohammed Ibrahim Nourein , Bolten John D. , Souter Nicholas J. , Shaad Kashif , Vollmer Derek
Published: January 2022

Managing transboundary river basins requires balancing tradeoffs of sustainable water use and coping with climate uncertainty. We demonstrate an integrated approach to exploring these issues through the lens of a social-ecological system, combining remote and in-situ earth observations, hydrologic and climate models, and social surveys. Specifically, we examine how climate change and dam development could impact the Se Kong, Se San and Sre Pok rivers in the Mekong region. We find that climate change will lead to increased precipitation, necessitating a shift in dam operations, from maintaining low flows to reducing flood hazards. We also find that existing water governance systems in Laos, Vietnam, and Cambodia are ill-prepared to address the problem. We conclude that the solution space for addressing these complex issues will be highly constrained unless major deficiencies in transboundary water governance, strategic planning, financial capacity, information sharing, and law enforcement are remedied in the next decades.
Multimodal deep learning applied to classify healthy and disease states of human microbiome
Authors: Lee Seung Jae , Rho Mina
Published: January 2022

Metagenomic sequencing methods provide considerable genomic information regarding human microbiomes, enabling us to discover and understand microbial diseases. Compositional differences have been reported between patients and healthy people, which could be used in the diagnosis of patients. Despite significant progress in this regard, the accuracy of these tools needs to be improved for applications in diagnostics and therapeutics. MDL4Microbiome, the method developed herein, demonstrated high accuracy in predicting disease status by using various features from metagenome sequences and a multimodal deep learning model. We propose combining three different features, i.e., conventional taxonomic profiles, genome-level relative abundance, and metabolic functional characteristics, to enhance classification accuracy. This deep learning model enabled the construction of a classifier that combines these various modalities encoded in the human microbiome. We achieved accuracies of 0.98, 0.76, 0.84, and 0.97 for predicting patients with inflammatory bowel disease, type 2 diabetes, liver cirrhosis, and colorectal cancer, respectively; these are comparable or higher than classical machine learning methods. A deeper analysis was also performed on the resulting sets of selected features to understand the contribution of their different characteristics. MDL4Microbiome is a classifier with higher or comparable accuracy compared with other machine learning methods, which offers perspectives on feature generation with metagenome sequences in deep learning models and their advantages in the classification of host disease status.
Phylogenetic relations and range history of jerboas of the Allactaginae subfamily (Dipodidae, Rodentia)
Authors: Lebedev Vladimir S. , Shenbrot Georgy I. , Krystufek Boris , Mahmoudi Ahmad , Melnikova Marina N. , Solovyeva Evgeniya N. , Lisenkova Alexandra A. , Undrakhbayar Enkhbat , Rogovin Konstantin A. , Surov Alexey V. , Bannikova Anna A.
Published: January 2022

Five-toed jerboas of the subfamily Allactaginae comprise several complex taxa occurring over a wide distribution range covering a large part of the Eurasian arid belt. In this study, we employed current methods of molecular phylogenetics based on 15 nuclear genes and the mitochondrial genecytbto revise relations and systematics within Allactaginae. We also applied species distribution modelling projected on paleo-environmental data to reconstruct the geographic patterns of speciation in Allactaginae. We elucidated the intergeneric relationships within this subfamily and clarified interspecies relations within the genusScarturus. Moreover, our results demonstrate the species status ofS. caprimulga; outline the currently understudied diversity withinOrientallactaga,Allactaga, andPygeretmus; and improve the divergence estimates of these taxa. Based on our results from modelling of geographic range fragmentation in allactagines, we suggest the dating and location of speciation events and present hypotheses regarding general habitat niche conservatism in small mammals.
A colonoscopy quality improvement intervention in an endoscopy unit
Authors: Palmier Rémi , Degand Thibault , Aho Serge , Lepage Côme , Facy Olivier , Michiels Christophe , Manfredi Sylvain
Published: January 2022

Many studies identified colonoscopy quality indicators in order to improve performance and safety. We conducted a colonoscopy improvement study. Our study was designed according to a Plan-Do-Study-Act cycle: first recording of our quality indicators and identification of shortcomings, second identification of improvement targets and implementation of new procedures, third second recording of quality indicators, fourth validation of procedures and identification of new goals. Quality indicators derived from European and French guidelines were recorded before and after our improvement actions. We were mainly interested in the quality indicators of the colonic preparation, the description of the diagnosed lesions and on the examination reports. The data of 134 patients prospectively included in January–February 2017 were compared to 133 patients included in May–June 2019, after implementation of improvement procedures, in the digestive endoscopy unit of the university hospital of Dijon, France. Our intervention, and in particular the implementation of new standardized forms, improved preparation quality: Boston Bowel Preparation Scale scores increased significantly from 7.8 to 8.2. Cecal intubation rate increased by 6%, and more adenomas were diagnosed and removed (+3.3%). Adenoma detection rate increased significantly from 26 to 42%. The completion of withdrawal time measure improved from 6.7 to 100%. Our study led to the rapid implementation of corrective actions and improved quality in our unit and in our personal practice. This quality improvement strategy could be easily implemented in every digestive endoscopy unit.