bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and mechanical properties of biodegradable poly(lactic acid) and pectin composites: using bionucleating agent to improve crystallization behavior
Authors: Satsum Apiwat , Busayaporn Wutthikrai , Rungswang Wonchalerm , Soontaranon Siriwat , Thumanu Kanjana , Wanapu Chokchai
Published: April 2022

Biocomposites of poly(lactic acid) (PLA) and pectin, which are low-cost organic materials, were prepared using an internal mixing machine in various pectin contents, i.e., 2, 4, 6 and 8% w/w. When pectin was added as a nucleating agent, the mechanical properties of the biocomposites, such as tensile and impact testing, were considerably improved, particularly following the annealing process. In addition, the PLA–pectin annealed at 4% w/w showed the highest strength and thermal stability. This can be explained by the fact that PLA containing 4% pectin by weight had the best dispersion, as indicated by scanning electron microscopy (SEM) and synchrotron-based 2D chemical mapping FT-IR. Moreover, pectin not only serves as a reinforcing material to improve mechanical characteristics but also aids in the crystallization of PLA, which was confirmed by in situ synchrotron-based wide-angle X-ray scattering (SR-WAXS). The crystallization rate and crystallinity were maximum at 8% w/w pectin addition according to the SR-WAXS results. This shows that pectin dispersion is the most important factor in determining the mechanical and thermal properties of biocomposites.
Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers
Authors: Molinos-Albert Luis M. , Lorin Valérie , Monceaux Valérie , Orr Sylvie , Essat Asma , Dufloo Jérémy , Schwartz Olivier , Rouzioux Christine , Meyer Laurence , Hocqueloux Laurent , Sáez-Cirión Asier , Mouquet Hugo ,   ANRS VISCONTI Study Group, Prazuck Thierry , Dieuleveult Barbara De , Bani-Sadr Firouzé , Hentzien Maxime , Berger Jean-Luc , Kmiec Isabelle , Pichancourt Gilles , Nasri Safa , Hittinger Gilles , Lambry Véronique , Beauey Anne-Cécile , Pialoux Gilles , Palacios Christia , Siguier Martin , Adda Anne , Foucoin Jane , Weiss Laurence , Karmochkine Marina , Meghadecha Mohamed , Ptak Magali , Salmon-Ceron Dominique , Blanche Philippe , Piétri Marie-Pierre , Molina Jean-Michel , Taulera Olivier , Lascoux-Combe Caroline , Ponscarme Diane , Bertaut Jeannine Delgado , Makhloufi Djamila , Godinot Matthieu , Artizzu Valérie , Yazdanpanah Yazdan , Matheron Sophie , Godard Cindy , Julia Zélie , Bernard Louis , Bastides Frédéric , Bourgault Olivier , Jacomet Christine , Goncalves Emilie , Meybeck Agnès , Huleux Thomas , Cornavin Pauline , Debab Yasmine , Théron David , Miailhes Patrick , Cotte Laurent , Pailhes Sophie , Ogoudjobi Stanislas , Viard Jean Paul , Dulucq Marie-Josée , Bodard Loïc , Churaqui Francoise , Guimard Thomas , Laine Laetitia
Published: April 2022

HIV-1 post-treatment controllers are rare individuals controlling HIV-1 infection for years after antiretroviral therapy interruption. Identification of immune correlates of control in post-treatment controllers could aid in designing effective HIV-1 vaccine and remission strategies. Here, we perform comprehensive immunoprofiling of the humoral response to HIV-1 in long-term post-treatment controllers. Global multivariate analyses combining clinico-virological and humoral immune data reveal distinct profiles in post-treatment controllers experiencing transient viremic episodes off therapy compared to those stably aviremic. Virally-exposed post-treatment controllers display stronger HIV-1 humoral responses, and develop more frequently Env-specific memory B cells and cross-neutralizing antibodies. Both are linked to short viremic exposures, which are also accompanied by an increase in blood atypical memory B cells and activated subsets of circulating follicular helper T cells. Still, most humoral immune variables only correlate with Th2-like circulating follicular helper T cells. Thus, post-treatment controllers form a heterogeneous group with two distinct viral behaviours and associated immune signatures. Post-treatment controllers stably aviremic present “silent” humoral profiles, while those virally-exposed develop functionally robust HIV-specific B-cell and antibody responses, which may participate in controlling infection.
Multidimensional chromatin profiling of zebrafish pancreas to uncover and investigate disease-relevant enhancers
Authors: Bordeira-Carriço Renata , Teixeira Joana , Duque Marta , Galhardo Mafalda , Ribeiro Diogo , Acemel Rafael D. , Firbas Panos. N. , Tena Juan J. , Eufrásio Ana , Marques Joana , Ferreira Fábio J. , Freitas Telmo , Carneiro Fátima , Goméz-Skarmeta José Luís , Bessa José
Published: April 2022

The pancreas is a central organ for human diseases. Most alleles uncovered by genome-wide association studies of pancreatic dysfunction traits overlap with non-coding sequences of DNA. Many contain epigenetic marks of cis-regulatory elements active in pancreatic cells, suggesting that alterations in these sequences contribute to pancreatic diseases. Animal models greatly help to understand the role of non-coding alterations in disease. However, interspecies identification of equivalent cis-regulatory elements faces fundamental challenges, including lack of sequence conservation. Here we combine epigenetic assays with reporter assays in zebrafish and human pancreatic cells to identify interspecies functionally equivalent cis-regulatory elements, regardless of sequence conservation. Among other potential disease-relevant enhancers, we identify a zebrafish ptf1a distal-enhancer whose deletion causes pancreatic agenesis, a phenotype previously found to be induced by mutations in a distal-enhancer of PTF1A in humans, further supporting the causality of this condition in vivo. This approach helps to uncover interspecies functionally equivalent cis-regulatory elements and their potential role in human disease.
Insights into the inhibition of type I-F CRISPR-Cas system by a multifunctional anti-CRISPR protein AcrIF24
Authors: Yang Lingguang , Zhang Laixing , Yin Peipei , Ding Hao , Xiao Yu , Zeng Jianwei , Wang Wenhe , Zhou Huan , Wang Qisheng , Zhang Yi , Chen Zeliang , Yang Maojun , Feng Yue
Published: April 2022

CRISPR-Cas systems are prokaryotic adaptive immune systems and phages use anti-CRISPR proteins (Acrs) to counteract these systems. Here, we report the structures of AcrIF24 and its complex with the crRNA-guided surveillance (Csy) complex. The HTH motif of AcrIF24 can bind the Acr promoter region and repress its transcription, suggesting its role as an Aca gene in self-regulation. AcrIF24 forms a homodimer and further induces dimerization of the Csy complex. Apart from blocking the hybridization of target DNA to the crRNA, AcrIF24 also induces the binding of non-sequence-specific dsDNA to the Csy complex, similar to AcrIF9, although this binding seems to play a minor role in AcrIF24 inhibitory capacity. Further structural and biochemical studies of the Csy-AcrIF24-dsDNA complexes and of AcrIF24 mutants reveal that the HTH motif of AcrIF24 and the PAM recognition loop of the Csy complex are structural elements essential for this non-specific dsDNA binding. Moreover, AcrIF24 and AcrIF9 display distinct characteristics in inducing non-specific DNA binding. Together, our findings highlight a multifunctional Acr and suggest potential wide distribution of Acr-induced non-specific DNA binding.
Narrowband microwave-photonic notch filters using Brillouin-based signal transduction in silicon
Authors: Gertler Shai , Otterstrom Nils T. , Gehl Michael , Starbuck Andrew L. , Dallo Christina M. , Pomerene Andrew T. , Trotter Douglas C. , Lentine Anthony L. , Rakich Peter T.
Published: April 2022

The growing demand for bandwidth makes photonic systems a leading candidate for future telecommunication and radar technologies. Integrated photonic systems offer ultra-wideband performance within a small footprint, which can naturally interface with fiber-optic networks for signal transmission. However, it remains challenging to realize narrowband (∼MHz) filters needed for high-performance communications systems using integrated photonics. In this paper, we demonstrate all-silicon microwave-photonic notch filters with 50× higher spectral resolution than previously realized in silicon photonics. This enhanced performance is achieved by utilizing optomechanical interactions to access long-lived phonons, greatly extending available coherence times in silicon. We use a multi-port Brillouin-based optomechanical system to demonstrate ultra-narrowband (2.7 MHz) notch filters with high rejection (57 dB) and frequency tunability over a wide spectral band (6 GHz) within a microwave-photonic link. We accomplish this with an all-silicon waveguide system, using CMOS-compatible fabrication techniques.
Impact of horizontal gene transfer on emergence and stability of cooperative virulence in Salmonella Typhimurium
Authors: Bakkeren Erik , Gül Ersin , Huisman Jana S. , Steiger Yves , Rocker Andrea , Hardt Wolf-Dietrich , Diard Médéric
Published: April 2022

Intestinal inflammation fuels the transmission of Salmonella Typhimurium (S.Tm). However, a substantial fitness cost is associated with virulence expression. Mutations inactivating transcriptional virulence regulators generate attenuated variants profiting from inflammation without enduring virulence cost. Such variants interfere with the transmission of fully virulent clones. Horizontal transfer of functional regulatory genes (HGT) into attenuated variants could nevertheless favor virulence evolution. To address this hypothesis, we cloned hilD, coding for the master regulator of virulence, into a conjugative plasmid that is highly transferrable during intestinal colonization. The resulting mobile hilD allele allows virulence to emerge from avirulent populations, and to be restored in attenuated mutants competing against virulent clones within-host. However, mutations inactivating the mobile hilD allele quickly arise. The stability of virulence mediated by HGT is strongly limited by its cost, which depends on the hilD expression level, and by the timing of transmission. We conclude that robust evolution of costly virulence expression requires additional selective forces such as narrow population bottlenecks during transmission.
Sucrose addition directionally enhances bacterial community convergence and network stability of the shrimp culture system
Authors: Guo Haipeng , Dong Pengsheng , Gao Fan , Huang Lei , Wang Sipeng , Wang Ruoyu , Yan Mengchen , Zhang Demin
Published: April 2022

Sucrose is an effective carbon source for creating more reliable and environmentally friendly conditions for shrimp growth by regulating bacteria in biofloc-based culture systems. However, the influence of sucrose addition on the interaction, co-occurrence networks, and assembly mechanisms of bacterial communities in biofloc-based culture systems remains largely unknown. Here, we comprehensively investigated the effects of sucrose addition on bacterial communities in three habitats (water, bioflocs, and gut). The bacterial community structures and compositions of these three habitats became more similar in groups with sucrose addition, compared with those in controls. More than 50% gut bacterial communities were mainly derived from water and biofloc communities in the sucrose addition groups, but only about 33% bacterial communities migrated from water and biofloc to the gut in the control culture system. Sucrose addition accordantly enriched core taxa belonging to the phylum Actinobacteria and the families Rhodobacteraceae and Flavobacteriaceae in water, biofloc, and gut habitats. These core taxa were important for maintaining bacterial network stability in the sucrose addition culture systems and some were identified as keystone taxa for improving shrimp growth. Furthermore, after sucrose addition, gut bacterial community assembly from water and biofloc was dominated by the heterogeneous select with the ratios of 55–91% and 67–83%, respectively, indicating that sucrose addition can directionally shape the bacterial assembly of the shrimp culture system. These results provide a basis for selectively regulating certain beneficial taxa to improve shrimp growth in culture systems.
Niche differentiation drives microbial community assembly and succession in full-scale activated sludge bioreactors
Authors: de Celis Miguel , Duque Javier , Marquina Domingo , Salvadó Humbert , Serrano Susana , Arregui Lucía , Santos Antonio , Belda Ignacio
Published: April 2022

Network models and community phylogenetic analyses are applied to assess the composition, structure, and ecological assembly mechanisms of microbial communities. Here we combine both approaches to investigate the temporal dynamics of network properties in individual samples of two activated sludge systems at different adaptation stages. At initial assembly stages, we observed microbial communities adapting to activated sludge, with an increase in network modularity and co-exclusion proportion, and a decrease in network clustering, here interpreted as a consequence of niche specialization. The selective pressure of deterministic factors at wastewater treatment plants produces this trend and maintains the structure of highly functional and specialized communities responding to seasonal environmental changes.
MaterialsAtlas.org: a materials informatics web app platform for materials discovery and survey of state-of-the-art
Authors: Hu Jianjun , Stefanov Stanislav , Song Yuqi , Omee Sadman Sadeed , Louis Steph-Yves , Siriwardane Edirisuriya M. D. , Zhao Yong , Wei Lai
Published: April 2022

The availability and easy access of large-scale experimental and computational materials data have enabled the emergence of accelerated development of algorithms and models for materials property prediction, structure prediction, and generative design of materials. However, the lack of user-friendly materials informatics web servers has severely constrained the wide adoption of such tools in the daily practice of materials screening, tinkering, and design space exploration by materials scientists. Herein we first survey current materials informatics web apps and then propose and develop MaterialsAtlas.org, a web-based materials informatics toolbox for materials discovery, which includes a variety of routinely needed tools for exploratory materials discovery, including material’s composition and structure validity check (e.g. charge neutrality, electronegativity balance, dynamic stability, Pauling rules), materials property prediction (e.g. band gap, elastic moduli, hardness, and thermal conductivity), search for hypothetical materials, and utility tools. These user-friendly tools can be freely accessed at http://www.materialsatlas.org. We argue that such materials informatics apps should be widely developed by the community to speed up materials discovery processes.
Optimization of cognitive assessment in Parkinsonisms by applying artificial intelligence to a comprehensive screening test
Authors: Ortelli Paola , Ferrazzoli Davide , Versace Viviana , Cian Veronica , Zarucchi Marianna , Gusmeroli Anna , Canesi Margherita , Frazzitta Giuseppe , Volpe Daniele , Ricciardi Lucia , Nardone Raffaele , Ruffini Ingrid , Saltuari Leopold , Sebastianelli Luca , Baranzini Daniele , Maestri Roberto
Published: April 2022

The assessment of cognitive deficits is pivotal for diagnosis and management in patients with parkinsonisms. Low levels of correspondence are observed between evaluations assessed with screening cognitive tests in comparison with those assessed with in-depth neuropsychological batteries. A new tool, we named CoMDA (Cognition in Movement Disorders Assessment), was composed by merging Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Frontal Assessment Battery (FAB). In total, 500 patients (400 with Parkinson’s disease, 41 with vascular parkinsonism, 31 with progressive supranuclear palsy, and 28 with multiple system atrophy) underwent CoMDA (level 1–L1) and in-depth neuropsychological battery (level 2–L2). Machine learning was developed to classify the CoMDA score and obtain an accurate prediction of the cognitive profile along three different classes: normal cognition (NC), mild cognitive impairment (MCI), and impaired cognition (IC). The classification accuracy of CoMDA, assessed by ROC analysis, was compared with MMSE, MoCA, and FAB. The area under the curve (AUC) of CoMDA was significantly higher than that of MMSE, MoCA and FAB (p < 0.0001,p = 0.028 andp = 0.0007, respectively). Among 15 different algorithmic methods, the Quadratic Discriminant Analysis algorithm (CoMDA-ML) showed higher overall-metrics performance levels in predictive performance. Considering L2 as a 3-level continuous feature, CoMDA-ML produces accurate and generalizable classifications: micro-average ROC curve, AUC = 0.81; and AUC = 0.85 for NC, 0.67 for MCI, and 0.83 for IC. CoMDA and COMDA-ML are reliable and time-sparing tools, accurate in classifying cognitive profile in parkinsonisms.

This study has been registered on ClinicalTrials.gov (NCT04858893).
Sound disrupts sleep-associated brain oscillations in rodents in a meaning-dependent manner
Authors: van Kronenberg Philipp , Milinski Linus , Kruschke Zoë , de Hoz Livia
Published: April 2022

Sleep is essential but places animals at risk. Filtering acoustic information according to its relevance, a process generally known as sensory gating, is crucial during sleep to ensure a balance between rest and danger detection. The mechanisms of this sensory gating and its specificity are not understood. Here, we tested the effect that sounds of different meaning have on sleep-associated ongoing oscillations. We recorded EEG and EMG from mice during REM and NREM sleep while presenting sounds with or without behavioural relevance. We found that sound presentation per se, in the form of a neutral sound, elicited a weak or no change in the power of sleep-state-dependent EEG during REM and NREM sleep. In contrast, the presentation of a sound previously conditioned in an aversive task, elicited a clear and fast decrease in the EEG power during both sleep phases, suggesting a transition to lighter sleep without awakening. The observed changes generally weakened over training days and were not present in animals that failed to learn. Interestingly, the effect could be generalized to unfamiliar neutral sounds if presented following conditioned training, an effect that depended on sleep phase and sound type. The data demonstrate that sounds are differentially gated during sleep depending on their meaning and that this process is reflected in disruption of sleep-associated brain oscillations without behavioural arousal.
Hydrocoel morphogenesis forming the pentaradial body plan in a sea cucumber, Apostichopus japonicus
Authors: Udagawa Sumio , Ikeda Takafumi , Oguchi Kohei , Kohtsuka Hisanori , Miura Toru
Published: April 2022

Echinoderms constitute an animal phylum characterized by the pentaradial body plan. During the development from bilateral larvae to pentaradial adults, the formation of the multiple of five hydrocoel lobes, i.e., the buddings from the mesodermal coelom, is the firstly emerging pentameral character. The developmental mechanism underlying the hydrocoel-lobe formation should be revealed to understand the evolutionary process of this unique and highly derived body plan of echinoderms, although the morphogenetic mechanisms of hydrocoel lobes are largely uninvestigated. In this study, using the sea cucumberApostichopus japonicus,in which hydrocoel is easily observable, the developmental process of hydrocoel lobes was described in detail, focusing on cell proliferation and rearrangement. Cell proliferation was not specifically distributed in the growing tips of the hydrocoel lobes, and inhibition of cell proliferation did not affect lobe formation. During lobe formation, the epithelium of the hydrocoel lobes was firstly thickened and then transformed into a simple epithelium, suggesting that tissue expansion via tissue remodeling contributes to the hydrocoel-lobe formation.
PACE4-altCT isoform of proprotein convertase PACE4 as tissue and plasmatic biomarker for prostate cancer
Authors: Couture Frédéric , Wang Luojun , Dufour Frédérik , Chabot-Maheux Keena , Ekindi Ndongo Nadia , Sabbagh Robert , Day Robert
Published: April 2022

The proprotein convertase PACE4 has demonstrated value as a viable therapeutic target in prostate cancer (PCa). A novel isoform named PACE4-altCT, which arises in neoplastic lesions, plays an important role in tumor progression and has been validated as a pharmacological target. With the discovery of its overexpression in PCa and the alternative splicing of its pre-RNA to generate an oncogenic C-terminally modified isoform named PACE4-altCT, understanding and validating its value as a potential biomarker is of great interest either from prognostic or targeted therapy intervention. Expression of ERG in LNCaP cells was used to investigate the relationship between ERG expression occurring in PCa cells and PACE4-altCT expression by Western blot and qPCR. Using immunohistochemistry, the expression levels of PACE4 isoforms in patient tissues were investigated and correlated with ERG tumor status and Gleason score. An ELISA method was developed using affinity purified recombinant protein and used for quantitative analysis of plasma concentrations of PACE4-altCT and used for correlation. In contrast with the consensual isoform, PACE4-altCT was only strongly overexpressed in prostate cancer patients, correlated with ERG expression levels. Despite its intracellular retention PACE4-altCT could be detected in the plasma of most patients with prostate cancer, whereas it was only found at low levels in normal patients whereas total plasmatic PACE4 levels did not vary significantly between groups. Our study demonstrates that PACE4-altCT is strongly overexpressed in prostate cancer using both immunohistochemical and ELISA techniques and may have some interesting potential as a biomarker.
rs-fMRI and machine learning for ASD diagnosis: a systematic review and meta-analysis
Authors: Santana Caio Pinheiro , de Carvalho Emerson Assis , Rodrigues Igor Duarte , Bastos Guilherme Sousa , de Souza Adler Diniz , de Brito Lucelmo Lacerda
Published: April 2022

Autism Spectrum Disorder (ASD) diagnosis is still based on behavioral criteria through a lengthy and time-consuming process. Much effort is being made to identify brain imaging biomarkers and develop tools that could facilitate its diagnosis. In particular, using Machine Learning classifiers based on resting-state fMRI (rs-fMRI) data is promising, but there is an ongoing need for further research on their accuracy and reliability. Therefore, we conducted a systematic review and meta-analysis to summarize the available evidence in the literature so far. A bivariate random-effects meta-analytic model was implemented to investigate the sensitivity and specificity across the 55 studies that offered sufficient information for quantitative analysis. Our results indicated overall summary sensitivity and specificity estimates of 73.8% and 74.8%, respectively. SVM stood out as the most used classifier, presenting summary estimates above 76%. Studies with bigger samples tended to obtain worse accuracies, except in the subgroup analysis for ANN classifiers. The use of other brain imaging or phenotypic data to complement rs-fMRI information seems promising, achieving higher sensitivities when compared to rs-fMRI data alone (84.7% versus 72.8%). Finally, our analysis showed AUC values between acceptable and excellent. Still, given the many limitations indicated in our study, further well-designed studies are warranted to extend the potential use of those classification algorithms to clinical settings.
Optimized assay for transposase-accessible chromatin by sequencing (ATAC-seq) library preparation from adult Drosophila melanogaster neurons
Authors: Merrill Collin B. , Pabon Miguel A. , Montgomery Austin B. , Rodan Aylin R. , Rothenfluh Adrian
Published: April 2022

Assay for transposase-accessible chromatin by sequencing (ATAC-seq) is rapidly becoming the assay of choice to investigate chromatin-mediated gene regulation, largely because of low input requirements, a fast workflow, and the ability to interrogate the entire genome in an untargeted manner. Many studies using ATAC-seq use mammalian or human-derived tissues, and established protocols work well in these systems. However, ATAC-seq is not yet widely used in Drosophila. Vinegar flies present several advantages over mammalian systems that make them an excellent model for ATAC-seq studies, including abundant genetic tools that allow straightforward targeting, transgene expression, and genetic manipulation that are not available in mammalian models. Because current ATAC-seq protocols are not optimized to use flies, we developed an optimized workflow that accounts for several complicating factors present in Drosophila. We examined parameters affecting nuclei isolation, including input size, freezing time, washing, and possible confounds from retinal pigments. Then, we optimized the enzymatic steps of library construction to account for the smaller Drosophila genome size. Finally, we used our optimized protocol to generate ATAC-seq libraries that meet ENCODE quality metrics. Our optimized protocol enables extensive ATAC-seq experiments in Drosophila, thereby leveraging the advantages of this powerful model system to understand chromatin-mediated gene regulation.
Engineering and validation of a dual luciferase reporter system for quantitative and systematic assessment of regulatory sequences in Chinese hamster ovary cells
Authors: Toktay Yagmur , Dayanc Bengisu , Senturk Serif
Published: April 2022

Ongoing research efforts to identify potent regulatory sequences that deliver robust and sustained transgene expression are critical for Chinese hamster ovary (CHO) cell line development technologies to meet the growing demand for recombinant proteins. Here we report the engineering and validation of a highly customizable single vector toolkit that comprises an all-in-one dual luciferase reporter system for quantitative and systematic interrogation of transcriptional regulatory sequences in transient and stable transfectants of CHO cells. To model the execution of the reporter system, we implemented a battery of known constitutive promoters including human CMV-mIE, SV40, HSV-TK, mouse PGK, human EF1α, EF1α short (EFS), human UBC, synthetic CAG, and Chinese hamster EF1α (CHEF1α). Of the nine promoters, CMV-mIE yielded the highest transcriptional activity in transient transfection settings, while CHEF1α was the strongest among a select subset of promoters in stable transfectants of CHO-DG44 pools. Remodeling the vector toolkit to build a dual fluorescent reporter system featured an alternative to bioluminescence based reporters. We infer that the findings of this study may serve as a basis to establish new vectors with weak or strong constitutive promoters. Furthermore, the modular all-in-one architecture of the reporter system proved to be a viable tool for discovering novel regulatory sequences that ensure high levels of transient and stable transgene expression in CHO and perhaps other mammalian cell lines.
The application and limitations of exposure multiplication factors in sublethal effect modelling
Authors: Sherborne Neil , Jager Tjalling , Goussen Benoit , Trijau Marie , Ashauer Roman
Published: April 2022

Thanks to growing interest and research in the field, toxicokinetic–toxicodynamic (TKTD) models are close to realising their potential in environmental risk assessment (ERA) of chemicals such as plant protection products. A fundamental application is to find a multiplicative scale factor which—when applied to an exposure profile—results in some specified effect relative to a control. The approach is similar to applying assessment factors to experimental results, common in regulatory frameworks. It also relies on the same core assumption: that increasing the scaling always produces more extreme effects. Unlike experimental approaches, TKTD models offer an opportunity to interrogate this assumption in a mathematically rigorous manner. For four well-known TKTD models we seek to prove that the approach guarantees a unique scale factor for any percentage effect. Somewhat surprisingly, certain model configurations may have multiple scale factors which result in the same percentage effect. These cases require a more cautious regulatory approach and generate open biological and mathematical questions. We provide examples of the violations and suggest how to deal with them. Mathematical proofs provide the strongest possible backing for TKTD modelling approaches in ERA, since the applicability of the models can be determined exactly.
An in vivo model for overloading-induced soft tissue injury
Authors: Chatzistergos Panagiotis E. , Chockalingam Nachiappan
Published: April 2022

This proof-of-concept study demonstrates that repetitive loading to the pain threshold can safely recreate overloading-induced soft tissue damage and that localised tissue stiffening can be a potential marker for injury. This concept was demonstrated here for the soft tissue of the sole of the foot where it was found that repeated loading to the pain threshold led to long-lasting statistically significant stiffening in the overloaded areas. Loading at lower magnitudes did not have the same effect. This method can shed new light on the aetiology of overloading injury in the foot to improve the management of conditions such as diabetic foot ulceration and heel pain syndrome. Moreover, the link between overloading and tissue stiffening, which was demonstrated here for the first time for the plantar soft tissue, opens the way for an assessment of overloading thresholds that is not based on the subjective measurement of pain thresholds.
Prognostics of unsupported railway sleepers and their severity diagnostics using machine learning
Authors: Sresakoolchai Jessada , Kaewunruen Sakdirat
Published: April 2022

Railway sleepers are safety–critical components of a railway structure. They support ballasted track superstructure and are a critical factor in track geometry and track components’ deterioration. Unsupported sleepers are a common issue incurred after tracks have been utilized. When unsupported sleepers are present, they cause differential settlements of track superstructures, additional dynamic loading, and excessive train-track vibrations which affect passenger comfort, safety, and maintenance cost. This study is the world's first to develop new machine learning models to prognose and better diagnose defect severities of unsupported sleepers aligned with practical track inspection guidelines. Data used to develop machine learning models are based on a verified finite element model with actual field measurements, enabling unbiased full data ranges that govern all defect conditions. Different conditions of unsupported sleepers can be explored by varying locations of unsupported sleepers and the number of unsupported sleepers. Also, other operational parameters can be addressed such as speeds of rolling stock, the roughness of rail surface, and vertical stiffness of wheel-rail contact. In total, 2016 data sets have been obtained. Axle box accelerations are adopted as key indicators for machine learning models. Machine learning techniques used in the study are the convolutional neural network, recurrent neural network, ResNet, and fully convolutional neural network. Data fusion and assimilation have been conducted since the data points are dependent on the train speeds. Our new results reveal a breakthrough essential for real-world applications that the convolutional neural network model provides the best accuracy in both unsupported sleeper prognostics and severity identification. The accuracies of detection and severity identification are 99.34% and 97.02% respectively.
The influence of EEG oscillations, heart rate variability changes, and personality on self-pain and empathy for pain under placebo analgesia
Authors: De Pascalis Vilfredo , Vecchio Arianna
Published: April 2022

We induced placebo analgesia (PA), a phenomenon explicitly attenuating the self-pain feeling, to assess whether this resulted in reduced empathy pain when witnessing a confederate undergoing such pain experience. We recorded EEG and electrocardiogram during a painful Control and PA treatment in healthy adults who rated their experienced pain and empathy for pain. We derived HRV changes and, using wavelet analysis of non-phase-locked event-related EEG oscillations, EEG spectral power differences for self-pain and other-pain conditions. First-hand PA reduced self-pain and self-unpleasantness, whereas we observed only a slight decrease in other unpleasantness. We derived linear combinations of HRV and EEG band power changes significantly associated with self-pain and empathy for pain changes using PCAs. Lower Behavioral Inhibition System scores predicted self-pain reduction through the mediating effect of a relative HR-slowing and a decreased midline ϑ-band (4–8 Hz) power factor moderated by lower Fight-Flight-Freeze System trait scores. In the other-pain condition, we detected a direct positive influence of Total Empathic Ability on the other-pain decline with a mediating role of the midline β2-band (22–30 Hz) power reduction. These findings suggest that PA modulation of first-hand versus other pain relies on functionally different physiological processes involving different personality traits.
A review on I–III–VI ternary quantum dots for fluorescence detection of heavy metals ions in water: optical properties, synthesis and application
Authors: May Bambesiwe M. , Bambo Mokae F. , Hosseini Seyed Saeid , Sidwaba Unathi , Nxumalo Edward N. , Mishra Ajay K.
Published: April 2022

Ternary I–III–VI quantum dots used in the fluorescence detection of heavy metals ions in water.
Nucleation and growth mechanism in the early stages of nickel coating in jet electrodeposition: a coarse-grained molecular simulation and experimental study
Authors: Zhang Fan , Liu Shenggui , Wang Fei
Published: April 2022

A coarse-grained molecular dynamics model and the vertical three-electrode device with flow-injection function are established to reveal the influences of different growth conditions on the microscopic nucleation growth of coating.
Non-invasive radionuclide imaging of trace metal trafficking in health and disease: “PET metallomics”
Authors: Firth George , Blower Julia E. , Bartnicka Joanna J. , Mishra Aishwarya , Michaels Aidan M. , Rigby Alex , Darwesh Afnan , Al-Salemee Fahad , Blower Philip J.
Published: April 2022

Radioactive isotopes of elements from across the periodic table allow for non-invasive imaging of essential metals in health and disease.
Fundamental understanding of the synthesis of well-defined supported non-noble metal intermetallic compound nanoparticles
Authors: Song Yuanjun , He Yang , Laursen Siris
Published: April 2022

Fundamental insights into the synthesis of model-like, supported, non-noble metal intermetallic compound nanoparticle catalysts with phase pure bulk and bulk-like 1st-atomic-layer particle surface composition.
Multifunctional platinum(iv) complex bearing HDAC inhibitor and biotin moiety exhibits prominent cytotoxicity and tumor-targeting ability
Authors: Han Weinan , He Weiyu , Song Yutong , Zhao Jian , Song Zhiheng , Shan Yi , Hua Wuyang , Sun Yanyan
Published: April 2022

A multifunctional platinum(iv) compound conjugated with phenylbutyric acid and biotin was prepared. Biological evaluations demonstrated the prominent antitumor activity and tumor targeting ability as well as the mitochondrial apoptotic pathway.
A multifunctional basic pH indicator probe for distinguishable detection of Co2+, Cu2+and Zn2+with its utility in mitotracking and monitoring cytoplasmic viscosity in apoptotic cells
Authors: Yadav Pranjalee , Gond Sarita , Shekher Anusmita , Gupta Subash Chandra , Singh Udai P. , Singh Vinod P.
Published: April 2022

A single multifunctional probe for discriminating sensing and bioimaging applications has been synthesized and characterizedviaa single crystal XRD technique.
Thermally encapsulated phenothiazine@MWCNT cathode for aqueous zinc ion battery
Authors: Chola Noufal Merukan , Nagarale Rajaram K.
Published: April 2022

Phenothiazine is a p-type cathode that follows the anion pairing mechanism, where the electrode undergoes extensive expansion and contraction during cycling, which deleteriously affects the battery performance.
Rare earth nanoparticles for sprayed and intravenous NIR II imaging and photodynamic therapy of tongue cancer
Authors: Cai Lingling , Wang Zhan , Lin Bi , Liu Kaikai , Wang Yanxing , Yuan Ying , Tao Xiaofeng , Lv Ruichan
Published: April 2022

In this research, rare earth nanoparticles coupled with dihydroartemisinin (DHA) and a targeted antibody (RENP-DHA-Cap) for sprayed NIR II imaging and photodynamic therapy (PDT) of tongue cancer were designed.
Nature of the 1/f noise in graphene—direct evidence for the mobility fluctuation mechanism
Authors: Rehman Adil , Delgado Notario Juan Antonio , Salvador Sanchez Juan , Meziani Yahya Moubarak , Cywiński Grzegorz , Knap Wojciech , Balandin Alexander A. , Levinshtein Michael , Rumyantsev Sergey
Published: April 2022

Measurements under conditions of geometrical magnetoresistance prove that 1/f noise in graphene is dominated by mobility fluctuations.
Copper(ii)-catalyzed direct dehydrative alkynylation of 2H-chromene hemiketals with terminal alkynes to 2,2-disubstituted 2-alkynylated 2H-chromenes
Authors: Zheng Shi-Lu , Wen Zhong , Yang Kai-Cheng , Zeng Yao , Chen Long , Deng Jun-Feng
Published: April 2022

The first copper-catalyzed dehydrative alkynylation of 2H-chromene hemiketals with aryl and alkyl terminal alkynes is reported, which provides 2,2-disubstituted 2-alkynylated 2H-chromenes with rich diversity in up to 83% yield.
3-Ketoquinolones as new photoinitiators for free radical photopolymerization under LED
Authors: Morone Marika , Postle Stephen , Razzano Vincenzo , Deguines Charles , Allonas X.
Published: April 2022

3-Ketoquinolones are efficient Type II photoinitiators for free radical photopolymerization.
Facile fabrication of a phosphonium-based ionic liquid impregnated chitosan adsorbent for the recovery of hexavalent chromium
Authors: Firmansyah Mochamad Lutfi , Ilmi Thalabul , Mukti Rino Rakhmata , Patmawati  , Goto Masahiro
Published: April 2022

Trioctyldodecyl phosphonium chloride was impregnated onto chitosan and able to efficiently remove Cr(vi) in batch and continuous adsorption. The Cr(vi) was chemically adsorbed onto the adsorbent through anionic exchange with the ionic liquid moieties.
Liposome-based nanocapsules for the controlled release of dietary curcumin: PDDA and silica nanoparticle-coated DMPC liposomes enhance the fluorescence efficiency and anticancer activity of curcumin
Authors: Othman Alaa K. , El Kurdi Riham , Badran Adnan , Mesmar Joelle , Baydoun Elias , Patra Digambara
Published: April 2022

Nanosystems with various compositions and biological properties are being extensively investigated for drug and gene delivery applications.
The role of particulate matter in reduced visibility and anionic composition of winter fog: a case study for Amritsar city
Authors: Yadav Rekha , Sugha Aditi , Bhatti Manpreet S. , Kansal Sushil K. , Sharma Sudhir K. , Mandal Tuhin K.
Published: April 2022

Severe fog events during winter months in India are a serious concern due to the higher incidence of road accidents, flight delays and increased occurrence of respiratory diseases.
Single-channel digital LAMP multiplexing using amplification curve analysis
Authors: Malpartida-Cardenas Kenny , Miglietta Luca , Peng Tianyi , Moniri Ahmad , Holmes Alison , Georgiou Pantelis , Rodriguez-Manzano Jesus
Published: April 2022

We demonstrate LAMP multiplexing (5-plex) in a single reaction with a single fluorescent channel using the machine learning-based method amplification curve analysis, showing a classification accuracy of 91.33% for detection of respiratory pathogens.
Li+-assisted treatment of graphene oxide for ultrahigh volumetric performance supercapacitors
Authors: Liu Zhaoyuan , Yang Yue , Yuan Yinan , Wang Lidong , Sheng Jie , Fei Weidong
Published: April 2022

Compact reduced graphene oxide powder was prepared via Li+-assisted treatment of graphene oxide and exhibited a high specific volume capacitance.
Radical doped hole transporting material for high-efficiency and thermostable perovskite solar cells
Authors: Zhang Yuxi , Huang Bo , Hu Min , Tan Boer , Huang Fuzhi , Cheng Yi-Bing , Simonov Alexandr N. , Lu Jianfeng
Published: April 2022

We report a new p-doping strategy for organic semiconductors with free radicals that enable reproducible enhancement in the conductivity and tuning of the work function. High efficiency and thermo-stability perovskite solar cells were achieved.
High energy density of polyimide films employing an imidization reaction kinetics strategy at elevated temperature
Authors: Liu Xue-Jie , Zheng Ming-Sheng , Wang Gang , Zhang Yi-Yi , Dang Zhi-Min , Chen George , Zha Jun-Wei
Published: April 2022

By employing imidization reaction kinetics, the molecular structure optimization of polyimide was realized, resulting in significant improvement of high temperature energy storage performance.
Selective assembly of magnetic nano-antenna for electromagnetic dissipation
Authors: Fang Jiefeng , Lv Hualiang , Zhao Biao , Liu Zhengwang , Li Xiaohui , Xu Chunyang , Zhang Ruixuan , Zhang Huibin , Liu Xianhu , Zhang Xuefeng , Wang Min , Che Renchao
Published: April 2022

A 3D anisotropic magnetic nanostructure is prepared using a selective assembly approach. Ultrabroad effective absorption bandwidth is achieved by the multi-scale magnetic coupling system we constructed.
A TiO2-based bioprobe enabling excellent SERS activity in the detection of diverse circulating tumor cells
Authors: Xu Yanping , Lin Jie , Wu Xiaoxia , Xu Xiawei , Zhang Dinghu , Xie Yujiao , Pan Ting , He Yiwei , Wu Aiguo , Shao Guoliang
Published: April 2022

The designed TiO2-based SERS bioprobe can be effectively utilized in detecting 4 diverse types of cancer cells in rabbit blood, which shows good sensitivity of the SERS detection technology.
Molecular clustering behaviour in the cybotactic nematic phase of a spin-labelled liquid crystal
Authors: Uchida Yoshiaki , Akita Takuya , Hanada Kazuki , Kiyohara Daichi , Nishiyama Norikazu
Published: April 2022

A newly synthesised liquid crystalline nitroxide radical with a terminal trifluoromethyl group exhibits a cybotactic nematic phase. EPR spectroscopy of the spin-labelled LC implies that molecules move into and out of the cybotactic clusters.
An Al-doped TiO2 interfacial layer for effective hole injection characteristics of quantum-dot light-emitting diodes
Authors: Kim Min Gye , Shin Jae Seung , Ma Jin Hyun , Jeong Jun Hyung , Han Dong Hee , Kim Beom-Su , Jeon Woojin , Park Yongsup , Kang Seong Jun
Published: April 2022

Al-doped TiO2 (ATO) interfacial layer improves the charge balance and the performance of quantum-dot light-emitting diodes (QLEDs).
3-Cyanocarbazole/phosphine oxide hybrid host with increased molecular polarity towards universally enhanced efficiency for TADF OLEDs
Authors: Zhu Mengyuan , Hu Weiyang , Shi Wei , Yuan Wenbo , Shi Changsheng , Sun Ning , Tao Youtian
Published: April 2022

Introducing cyano units to improve the molecular polarity of the host material greatly enhances the device efficiency for TADF OLEDs.
A solution-fabricated tellurium/silicon mixed-dimensional van der Waals heterojunction for self-powered photodetectors
Authors: Zheng Tao , Yang Mengmeng , Sun Yiming , Han Lixiang , Pan Yuan , Zhao Qixiao , Zheng Zhaoqiang , Huo Nengjie , Gao Wei , Li Jingbo
Published: April 2022

A solution-fabricated Te/Si mixed-dimensional vdWH can function well as a high-performance broadband self-powered photodetector, achieving an ultrahigh responsivity of 6.49 A W−1 at 0 V.
Carbon nanomaterial-based aerogels for improved removal of copper(ii), zinc(ii), and lead(ii) ions from water
Authors: Smith Darren M. , Hamwi Badri , Rogers Reginald E.
Published: April 2022

Carbon-based aerogels have the capability of high adsorption removal of copper, lead, and zinc metal ions from water systems.
Effective modelling of sinkhole detection algorithm for edge‐based Internet of Things (IoT) sensing devices
Authors: Bilal Ahmad , Hasany Syed Muhammad Noman , Pitafi Abdul Hameed
Published: April 2022

The sinkhole attacks for Internet of Things (IoT) situations can overcome the network and interrupt communication. Sinkhole attacker nodes can advertise the best possible shortest path towards the destination, and once the normal node starts transferring the packets by the given path, the attacker node starts troublemaking the flow of the network. In this environment, the destination is unable to receive proper information or may not receive complete information. Sinkhole attacked network keeps the problems like the enhanced end‐to‐end delay, less throughput, and reduced packet delivery. Furthermore, it can affect other network constraints. So, it has become important to design an effective model to prevent the IoT environment from sinkhole attacks. In this article, an intrusion detection model is proposed to protect the IoT environment from sinkhole attacks. A model proposed by using rich resourced edge nodes to detect various kinds of sinkhole attacker nodes by exchanging messages. A well‐known NS2 simulator is used for the practical implementation of the model. The proposed model attains more than 95% detection rate with a near about 1.4% false‐positive rate, which seems better than previously given schemes. Finally, the proposed scheme is the appropriate match for a sensitive platform like a monitoring and security system.
Parameter estimation of multiple frequency‐hopping signals based on Bayesian compressive sensing and atomic norm soft thresholding with missing observations
Authors: Wang Hongbin , Zhang Bangning , Wang Heng , Wu Binbin , Guo Daoxing
Published: April 2022

In this study, the problem of estimating multiple frequency‐hopping (FH) signal parameters in situations in which random observations are missing is addressed. A uniform linear array (ULA) is utilized to receive FH signals, and the missing observations are considered to be equivalent to randomly missing elements in the space‐time matrix obtained from the ULA. Bayesian compressed sensing (BCS) estimates the hopping time of received FH signals by the spatial information from the space‐time matrix and restores the missing observations. The estimated hopping time is implemented as the boundary to divide the signals such that each segment contains a superposition of time‐invariant multiple components. Then, the instantaneous frequency (IF) of multiple components can be estimated precisely by atomic norm soft thresholding (AST) within each segment. After estimating the hopping time and IF, the direction of arrival (DOA) of multiple signals is directly calculated using these two parameters. The simulation results show that the proposed method is superior to existing approaches. Provided that sufficient array elements are available, multi‐FH signal parameters can be estimated with satisfactory accuracy even when a large portion of observations is missing.