bluuebunny/crossref_metadata_2025 huggingface dataset:
Tensions between technology integration practices of teachers and ICT in education policy expectations: implications for change in teacher knowledge, beliefs and teaching practices
Authors: Abedi Emmanuel Ayisi
Published: September 2023

In line with ICT in education policies and curricula in Ghana and many other countries, teachers are expected to integrate digital technologies into instruction to facilitate meaningful and engaging student learning experiences. More research is however needed to investigate teachers’ actual classroom practices with technology to determine whether these align with national ICT in education policies and curricula expectations. This qualitative study conducted phone interviews with twenty teachers from twelve schools and used a synthesised ICT pedagogy classification framework as a lens to investigate teachers’ technology integration practices in relation to Ghana's ICT policies and curricula requirements. Following a thematic analysis procedure, the article finds that teachers mainly use technology conveniently for lesson preparation and direct instruction delivery, treating technology primarily as a productivity tool to support traditional teacher-centred teaching tasks. The use of technology for constructivist practices and fostering student-centred learning appears to be limited, which contradicts the priorities outlined in ICT in education policies and curricula in Ghana. The findings highlight a discrepancy between the requirements of ICT policies and the actual classroom practices of teachers. The implications of the findings are discussed, emphasising the need to action change in teachers’ knowledge, beliefs, and teaching practices in order to bridge the gap and effectively translate ICT curricula and policy plans into actual teaching practices.
Precise Detection, Control and Synthesis of Chiral Compounds at Single-Molecule Resolution
Authors: Yang Chen , Hu Weilin , Guo Xuefeng
Published: September 2023

Chirality, as the symmetric breaking of molecules, plays an essential role in physical, chemical and especially biological processes, which highlights the accurate distinction among heterochiralities as well as the precise preparation for homochirality. To this end, the well-designed structure-specific recognizer and catalysis reactor are necessitated, respectively. However, each kind of target molecules requires a custom-made chiral partner and the dynamic disorder of spatial-orientation distribution of molecules at the ensemble level leads to an inefficient protocol. In this perspective article, we developed a universal strategy capable of realizing the chirality detection and control by the external symmetry breaking based on the alignment of the molecular frame to external stimuli. Specifically, in combination with the discussion about the relationship among the chirality (molecule), spin (electron) and polarization (photon), i.e., the three natural symmetry breaking, single-molecule junctions were proposed to achieve a single-molecule/event-resolved detection and synthesis. The fixation of the molecular orientation and the CMOS-compatibility provide an efficient interface to achieve the external input of symmetry breaking. This perspective is believed to offer more efficient applications in accurate chirality detection and precise asymmetric synthesis via the close collaboration of chemists, physicists, materials scientists, and engineers.
Through the looking glass: evaluating post hoc explanations using transparent models
Authors: Velmurugan Mythreyi , Ouyang Chun , Sindhgatta Renuka , Moreira Catarina
Published: September 2023

Modern machine learning methods allow for complex and in-depth analytics, but the predictive models generated by these methods are often highly complex and lack transparency. Explainable Artificial Intelligence (XAI) methods are used to improve the interpretability of these complex “black box” models, thereby increasing transparency and enabling informed decision-making. However, the inherent fitness of these explainable methods, particularly the faithfulness of explanations to the decision-making processes of the model, can be hard to evaluate. In this work, we examine and evaluate the explanations provided by four XAI methods, using fully transparent “glass box” models trained on tabular data. Our results suggest that the fidelity of explanations is determined by the types of variables used, as well as the linearity of the relationship between variables and model prediction. We find that each XAI method evaluated has its own strengths and weaknesses, determined by the assumptions inherent in the explanation mechanism. Thus, though such methods are model-agnostic, we find significant differences in explanation quality across different technical setups. Given the numerous factors that determine the quality of explanations, including the specific explanation-generation procedures implemented by XAI methods, we suggest that model-agnostic XAI methods may still require expert guidance for implementation.
Nudging cooperation among agents in an experimental social network
Authors: Jensen Gorm Gruner , Busch Martin Benedikt , Piovesan Marco , Haerter Jan O.
Published: September 2023

We investigate the development of cooperative behavior in networks over time. In our controlled laboratory experiment, subjects can cooperate by sending costly messages that contain valuable information for the receiver or other subjects in the network. Any message sent can increase the chance that subjects find the information they are looking for and consequently their profit. We find that cooperation emerges spontaneously and remains stable over time. In an additional treatment, we provide a non-binding suggestion about who to contact at the beginning of the experiment. We find that subjects partially follow our recommendation, and this increases their own and others’ profit. Despite the removal of suggestions, subjects build long-lasting relationships with the suggested contacts.
Acceptance and hesitancy of COVID-19 vaccine among university community members of Otukpo, Nigeria: a cross-sectional study
Authors: Zakari Suleiman , Ogbu Celestine O. , Zakari Hajara , Chioma Eze Sabina , Ijimbili Samuel Bawa , Idoko Jennifer Ene , Emmanuel Andrew Oche , Nnenna Amuji Doris , Agwara Bright Chiaka , Adokiye Efere Sarah , Idowu Ayodeji Oluwafemi , Edegbene Ovie Augustine , Anejo-Okopi Joseph
Published: September 2023

Coronavirus disease (COVID-19) is a global public health problem that has had a detrimental influence on the economy of countries of the world, including Nigeria: (1) Background: The study aimed to assess COVID-19 vaccine acceptance and hesitancy among staff and students at Federal University of Health Sciences Otukpo, Benue State, Nigeria, while exploring the factors influencing these attitudes; (2) Methods: A web-based cross-sectional survey was conducted between November 2021 and April 2022, with data analyzed using descriptive and inferential statistics; (3) Results: Of the hundred and fifty (150) completed and analysed questionnaires the mean age of the respondents was 34.8 ± 8.64 years, of which majority of them 80.0% (122) ranging between 16 and 45 years. The majority of the respondents 77.3% (116) have been tested for the virus to know their status. In total, 51.2% of trial participants indicated hesitancy to get the COVID-19 vaccine. The two most frequent reasons for hesitation were scepticism about the vaccination due to fast production and rollout (32.2%) and fear of vaccine side effects due to social media movements (23.3%). The most often cited reasons for not receiving the COVID-19 vaccination included uncertainty about its efficacy, a lack of knowledge about the vaccine, a preference for another kind of protection, and unreliability of the vaccine (due to its rapid development). Staff category (Academics, non-academics, students, and health workers), age, and religion were the significant associated factors influencing vaccine acceptance and hesitancy (P < 0.05); (4) Conclusions: The university community has a high level of awareness of COVID-19 pandemic but vaccine acceptance is low resulting high levels of vaccine hesitancy. These findings suggest that there is a need for further information and education on the COVID-19 vaccine, particularly in communities where vaccine hesitancy is prevalent. This can be achieved through targeted outreach programs, community engagement initiatives, and effective communication strategies that address the concerns and questions of individuals who are hesitant about receiving the vaccine.
Żuk’s criterion for Banach spaces and random groups
Authors: Oppenheim Izhar
Published: September 2023

We prove a Banach version of Żuk’s criterion for groups acting on partite (i.e., colorable) simplicial complexes. Using this new criterion, we derive a new fixed point theorem for random groups in the Gromov density model with respect to several classes of Banach spaces (

$L^p$

spaces, Hilbertian spaces, uniformly curved spaces). In particular, we show that for every p, a group in the Gromov density model has asymptotically almost surely property

$(F L^p)$

and give a sharp lower bound for the growth of the conformal dimension of the boundary of such group as a function of the parameters of the density model.
Advances in the molecular neurobiology of posttraumatic stress disorder from global contexts: A systematic review of longitudinal studies
Authors: Womersley Jacqueline S. , du Plessis Morne , Greene M. Claire , van den Heuwel Leigh L. , Kinyanda Eugene , Seedat Soraya
Published: September 2023

Trauma exposure is prevalent globally and is a defining event for the development of posttraumatic stress disorder (PTSD), characterised by intrusive thoughts, avoidance behaviours, hypervigilance and negative alterations in cognition and mood. Exposure to trauma elicits a range of physiological responses which can interact with environmental factors to confer relative risk or resilience for PTSD. This systematic review summarises the findings of longitudinal studies examining biological correlates predictive of PTSD symptomology. Databases (Pubmed, Scopus and Web of Science) were systematically searched using relevant keywords for studies published between 1 January 2021 and 31 December 2022. English language studies were included if they were original research manuscripts or meta-analyses of cohort investigations that assessed longitudinal relationships between one or more molecular-level measures and either PTSD status or symptoms. Eighteen of the 1,042 records identified were included. Studies primarily included military veterans/personnel, individuals admitted to hospitals after acute traumatic injury, and women exposed to interpersonal violence or rape. Genomic, inflammation and endocrine measures were the most commonly assessed molecular markers and highlighted processes related to inflammation, stress responding, and learning and memory. Quality assessments were done using the Systematic Appraisal of Quality in Observational Research, and the majority of studies were rated as being of high quality, with the remainder of moderate quality. Studies were predominantly conducted in upper-income countries. Those performed in low- and middle-income countries were not broadly representative in terms of demographic, trauma type and geographic profiles, with three out of the four studies conducted assessing only female participants, rape exposure and South Africa, respectively. They also did not generate multimodal data or use machine learning or multilevel modelling, potentially reflecting greater resource limitations in LMICs. Research examining molecular contributions to PTSD does not adequately reflect the global burden of the disorder.
Structure of the Assynt window, Moine Thrust Zone and relationship of thrusts to alkaline igneous complexes, Caledonian orogeny, NW Scotland
Authors: Searle Michael P.
Published: September 2023

The Moine Thrust Zone forms the Caledonian orogenic thrust front where the Moine Supergroup metamorphic rocks have been thrust westward across the Laurentia plate stable foreland, comprising Archean-Proterozoic granulite and amphibolite facies rocks (Lewisian gneisses), with unconformably overlying Mesoproterozoic and Neoproterozoic Torridonian clastic sediments and Cambrian-Ordovician passive margin sedimentary rocks. Four major thrusts beneath the Moine thrust in the Assynt window include the (i) Ben More Thrust, which places the Loch Ailsh syenite intruded into Lewisian basement and Cambrian-Ordovician sedimentary rocks over the Sole thrust sheet, (ii) Glencoul thrust, which places Lewisian basement and folded cover rocks over Cambrian-Ordovician sedimentary rocks, (iii) Borralan thrust, which carries a large alkaline syenite intrusion beneath the Ben More roof thrust and (iv) the Sole thrust sheet, which carries imbricated Cambrian-Ordovician sedimentary rocks and lamprophyre sills over the stable foreland. Three further thrust sheets within the Lewisian basement gneisses are now recognised through restoration of balanced cross-sections, which were responsible for doming of the Assynt window. Although the Moine thrust is mapped as a single line on the map it encompasses, (a) deep ductile shear zone formed of mylonites derived from hangingwall Moine schists, footwall Cambrian quartzites and Ordovician limestones, and basement Lewisian gneisses, (b) roof thrust of the Glencoul and Ben More Thrust sheets and (c) brittle out-of-sequence motion where the Moine schists have been thrust over mylonites, which directly overlie the stable foreland (Knockan Crag).
CURIOSITAS AND PSYCHE'S GROWTH IN APULEIUS' METAMORPHOSES
Authors: He Pei
Published: September 2023

In the tale-within-tale ‘Cupid and Psyche’ narrated in Apuleius’ Metamorphoses, the female heroine Psyche goes through a series of wanderings and tasks as punishments for seeing her husband Cupid's real form out of curiosity. Psyche's curiosity connects this internal tale with the external narratives in Metamorphoses, the protagonist of which, Lucius, shares a similar curiosity that leads to his downfall. While scholars attribute favourable qualities to Lucius’ curiosity despite its negative consequences, they deny the same value to Psyche's curiosity. In this paper, I argue against the condemnation of Psyche's curiosity due to the stereotype of transgressive females. Instead, I propose to view her curiosity as the drive for her awakening, empowerment, and growth, which transforms her into a fully powered agent and leads to her final reunion with Cupid in immortality.
Roman history
Authors: Corke-Webster James
Published: September 2023

The figure of the Roman emperor – ubiquitous yet ever-elusive – remains the flame to which Roman historians are ever drawn. And Fergus Millar's The Emperor in the Roman World remains the yardstick against which all subsequent efforts are judged, and with which they are all inevitably in dialogue. That is true too of Caesar Rules, the major new offering from Olivier Hekster, a one-time doctoral student of Millar's, and now one of the leading contenders for his crown. Hekster's core interest is what the emperor was; in particular, how this institution could survive and adapt to changing circumstances despite the fact that formally it did not exist, certainly was not defined, and practically existed in a society antithetical on principle to both monarchy and change. Hekster finds the key for this long-worried lock in ‘the presentation and perception of power’ (10), and in particular the expectations – from all sides, and at all times – that both consolidated and constrained emperors’ authority. To demonstrate this he conceives a largely unprecedented ambition in this context: to consider source material in all media from the late Republic to the reign of Justinian.
Word segmentation from transcriptions of child-directed speech using lexical and sub-lexical cues
Authors: GORIELY Zébulon , CAINES Andrew , BUTTERY Paula
Published: September 2023

We compare two frameworks for the segmentation of words in child-directed speech, PHOCUS and MULTICUE. PHOCUS is driven by lexical recognition, whereas MULTICUE combines sub-lexical properties to make boundary decisions, representing differing views of speech processing. We replicate these frameworks, perform novel benchmarking and confirm that both achieve competitive results. We develop a new framework for segmentation, the DYnamic Programming MULTIple-cue framework (DYMULTI), which combines the strengths of PHOCUS and MULTICUE by considering both sub-lexical and lexical cues when making boundary decisions. DYMULTI achieves state-of-the-art results and outperforms PHOCUS and MULTICUE on 15 of 26 languages in a cross-lingual experiment. As a model built on psycholinguistic principles, this validates DYMULTI as a robust model for speech segmentation and a contribution to the understanding of language acquisition.
MF, ZF, and MMSE filters for automotive OFDM radar
Authors: Benmeziane Bochra , Baudais Jean-Yves , Méric Stéphane , Cinglant Kevin
Published: September 2023

The delay estimation for orthogonal frequency division multiplexing automotive radars can be achieved through the use of different filters. This paper compares two of these filters, namely the matched filter and the zero forcing filter through two metrics, which are the peak to side lobe ratio and the integrated side lobe ratio estimated on their range profiles. The analysis is then extended to the minimum mean squared error filter.
Palmitic Acid Is Not a Proper Salinity Proxy in Baffin Bay and the Labrador Sea but Reflects the Variability in Organic Matter Sources Modulated by Sea Ice Coverage
Authors: Allan Estelle , Douglas Peter M. J. , de Vernal Anne , Gélinas Yves , Mucci Alfonso O.
Published: September 2023

Palmitic acid (PA) is ubiquitous in the biosphere and its hydrogen isotopic composition (δ2HPA) was proposed as a potential paleoenvironmental proxy for salinity, with δ2HPA values increasing with salinity. In this study, we analyzed 40 surface sediment samples from Baffin Bay and the Labrador Sea to examine the isotopic composition of PA in relation to local environmental variables, including salinity. In contrast to expectations, our results show a negative relationship between the δ2HPA and sea‐surface salinity, raising questions about its pertinence and usefulness as a salinity proxy. Instead, our results suggest that the relative abundance of distinct organisms that employ different metabolisms is the key in determining the hydrogen isotopic fractionations in PA. While we show that PA is mostly produced through photoautotrophic metabolisms by diatoms and dinoflagellates, varying contributions from heterotrophic metabolisms may obscure the stable isotope composition of PA. Surprisingly, we found no correlation between the stable carbon isotopic composition of the sedimentary organic matter (δ13Corg) and PA (δ13CPA), implying major differences in either the dominant organisms producing sedimentary PA or in carbon isotope fractionation during lipid biosynthesis. We also found that the presence of extended sea‐ice cover leads to enriched carbon and hydrogen isotopic compositions in PA. These enriched values suggest heterotrophic biodegradation in the water column and/or in the sediment as well as an increase in grazing activities. We propose that sea‐ice cover and surface water oxygenation modulate the relative impact of phototrophic and heterotrophic metabolisms, and therefore the isotopic composition of marine sedimentary PA.
Westward‐Propagating Disturbances Shape Diverse MJO Propagation
Authors: Wei Yuntao , Ren Hong‐Li , Duan Wansuo , Sun Guodong
Published: September 2023

Understanding eastward‐propagating mechanisms of the Madden–Julian Oscillation (MJO) is of great importance for the subseasonal prediction of extreme weather and climate worldwide. Using global satellite observations and reanalysis data, this study unravels that dual combinations of strong/weak westward‐ (ISOw) and eastward‐propagating intraseasonal oscillation (ISOe) can shape diverse MJO propagations documented previously using clustering analysis. The dry ISOw signals from the Central Pacific strengthen the leading suppressed convection over the Western Pacific (WP) and, on the contrary, weaken the moist ISOe convection over the Maritime Continent. Thus, when ISOe is weak over the WP, the strong (weak) dryness of ISOw likely causes a jump‐like (stand‐like) MJO mode. In contrast, a propagating MJO is supported when ISOe becomes strong over the WP, and a further strengthening of the ISOw dryness will presumably accelerate MJO; moreover, a weakening of ISOw might slow down the MJO speed.
CBX4 deletion promotes tumorigenesis under KrasG12D background by inducing genomic instability
Authors: Chen Fangzhen , Hou Wulei , Yu Xiangtian , Wu Jing , Li Zhengda , Xu Jietian , Deng Zimu , Chen Gaobin , Liu Bo , Yin Xiaoxing , Yu Wei , Zhang Lei , Xu Guoliang , Ji Hongbin , Liang Chunmin , Wang Zuoyun
Published: September 2023

Chromobox protein homolog 4 (CBX4) is a component of the Polycomb group (PcG) multiprotein Polycomb repressive complexes 1 (PRC1), which is participated in several processes including growth, senescence, immunity, and tissue repair. CBX4 has been shown to have diverse, even opposite functions in different types of tissue and malignancy in previous studies. In this study, we found that CBX4 deletion promoted lung adenocarcinoma (LUAD) proliferation and progression in KrasG12D mutated background. In vitro, over 50% Cbx4L/L, KrasG12D mouse embryonic fibroblasts (MEFs) underwent apoptosis in the initial period after Adeno-Cre virus treatment, while a small portion of survival cells got increased proliferation and transformation abilities, which we called selected Cbx4−/−, KrasG12D cells. Karyotype analysis and RNA-seq data revealed chromosome instability and genome changes in selected Cbx4−/−, KrasG12D cells compared with KrasG12D cells. Further study showed that P15, P16 and other apoptosis-related genes were upregulated in the primary Cbx4−/−, KrasG12D cells due to chromosome instability, which led to the large population of cell apoptosis. In addition, multiple pathways including Hippo pathway and basal cell cancer-related signatures were altered in selected Cbx4−/−, KrasG12D cells, ultimately leading to cancer. We also found that low expression of CBX4 in LUAD was associated with poorer prognosis under Kras mutation background from the human clinical data. To sum up, CBX4 deletion causes genomic instability to induce tumorigenesis under KrasG12D background. Our study demonstrates that CBX4 plays an emerging role in tumorigenesis, which is of great importance in guiding the clinical treatment of lung adenocarcinoma.
Oxytetracycline and heavy metals promote the migration of resistance genes in the intestinal microbiome by plasmid transfer
Authors: Lin Xiaojun , Zhang Chaonan , Han Ruiqi , Li Shoupeng , Peng Huishi , Zhou Xiao , Huang Lu , Xu Yanbin
Published: September 2023

Horizontal gene transfer (HGT) has been considered the most important pathway to introduce antibiotic resistance genes (ARGs), which seriously threatens human health and biological security. The presence of ARGs in the aquatic environment and their effect on the intestinal micro-ecosystem of aquatic animals can occur easily. To investigate the HGT potential and rule of exogenous ARGs in the intestinal flora, a visual conjugative model was developed, including the donor of dual-fluorescent bacterium and the recipient of Xenopus tropicalis intestinal microbiome. Some common pollutants of oxytetracycline (OTC) and three heavy metals (Zn, Cu and Pb) were selected as the stressor. The multi-techniques of flow cytometry (FCM), scanning electron microscopy (SEM), atomic force microscopy (AFM), single-cell Raman spectroscopy with sorting (SCRSS) and indicator analysis were used in this study. The results showed that ARG transfer could occur more easily under stressors. Moreover, the conjugation efficiency mainly depended on the viability of the intestinal bacteria. The mechanisms of OTC and heavy metal stressing conjugation included the upregulation of ompC, traJ, traG and the downregulation of korA gene. Moreover, the enzymatic activities of SOD, CAT, GSH-PX increased and the bacterial surface appearance also changed. The predominant recipient was identified as Citrobacter freundi by SCRSS, in which the abundance and quantity of ARG after conjugation were higher than those before. Therefore, since the diversity of potential recipients in the intestine are very high, the migration of invasive ARGs in the microbiome should be given more attention to prevent its potential risks to public health.
Cross-cultural translation and modification of the revised oral assessment guide for oral health assessment by non-dentists
Authors: Limpuangthip Nareudee , Komin Orapin , Chaichaowarat Jumphitta , Phumkor Patthamaporn
Published: September 2023

Objectives

This study aimed to conduct a cross-cultural translation of the revised oral assessment guide (ROAG) into Thai language and to modify the tool to increase its validity and reliability.

Materials and methods

The present study was a cross-sectional design conducted in dental and hospitalized patients, and community-dwelling people. The original English-version of the ROAG was translated into Thai, which was evaluated for validity and reliability. The tool was then revised to develop the modified ROAG for non-dentist (ndROAG) comprising 9 oral assessment categories with a three-level response; healthy, mild, and severe alteration. The criterion validity of the ndROAG was tested in 82 adult and older participants, and 46 non-dentists comprising dental assistants, dental hygienists, community health volunteers, and nurses, using a calibrated dentist as the reference standard. The ndROAG was translated back into an English version. The criterion validity was evaluated using weighted Kappa (Kw) and intraclass correlation coefficient (ICC). Internal consistency was determined using Cronbach alpha. The three-level response was dichotomized into healthy and changed to determine the sensitivity and specificity.

Results

The Kw values, ICC, and Cronbach alpha values of the ndROAG were higher than those of the pre-test ROAG. The sensitivity of the ndROAG in identifying the healthy and changed state ranged from 57.1 to 100.0% with the lowest value in the saliva category, whereas the specificity ranged from 90.9–100.0%.

Conclusion

The original ROAG was translated and revised into the ndROAG with improved validity and reliability. The ndROAG can be used by non-dentists to assess the oral health of adult and older individuals to detect oral changes, which includes self-care instructions and patient referral guidance.
CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety
Authors: Zhu Xiangjia , Meng Jiaqi , Han Chaofeng , Wu Qingfeng , Du Yu , Qi Jiao , Wei Ling , Li Hao , He Wenwen , Zhang Keke , Lu Yi
Published: September 2023

High myopia is a leading cause of blindness worldwide. It may lead to emotional defects that rely closely on the link between visual sensation and the central nervous system. However, the extent of the defects and its underlying mechanism remain unknown. Here, we report that highly myopic patients exhibit greater anxiety, accompanied by higher CC chemokine ligand 2 (CCL2) and monocyte levels in the blood. Similar findings are found in the mouse model of high myopia. Mechanistic evaluations using GFP-positive bone marrow chimeric mice, parabiotic mouse model, enhanced magnetic resonance imaging, etc., show that highly myopic visual stimulation increases CCL2 expression in eyes, aggravates monocyte/macrophage infiltration into eyes and brains, and disrupts blood–ocular barrier and blood–brain barrier of mice. Conversely, Ccl2-deficient highly myopic mice exhibit attenuated ocular and brain infiltration of monocytes/macrophages, reduced disruption of the blood–ocular barrier and blood–brain barrier, and less anxiety. Substantial alleviation of high myopia-related anxiety can also be achieved with the administration of CCL2-neutralizing antibodies. Our results establish the association between high myopia and anxiety, and implicate the CCL2-mediated inflammatory pathogenesis as an underlying mechanism.
The H163A mutation unravels an oxidized conformation of the SARS-CoV-2 main protease
Authors: Tran Norman , Dasari Sathish , Barwell Sarah A. E. , McLeod Matthew J. , Kalyaanamoorthy Subha , Holyoak Todd , Ganesan Aravindhan
Published: September 2023

The main protease of SARS-CoV-2 (Mpro) is an important target for developing COVID-19 therapeutics. Recent work has highlighted Mpro’s susceptibility to undergo redox-associated conformational changes in response to cellular and immune-system-induced oxidation. Despite structural evidence indicating large-scale rearrangements upon oxidation, the mechanisms of conformational change and its functional consequences are poorly understood. Here, we present the crystal structure of an Mpro point mutant (H163A) that shows an oxidized conformation with the catalytic cysteine in a disulfide bond. We hypothesize that Mpro adopts this conformation under oxidative stress to protect against over-oxidation. Our metadynamics simulations illustrate a potential mechanism by which H163 modulates this transition and suggest that this equilibrium exists in the wild type enzyme. We show that other point mutations also significantly shift the equilibrium towards this state by altering conformational free energies. Unique avenues of SARS-CoV-2 research can be explored by understanding how H163 modulates this equilibrium.
The genomic footprint of whaling and isolation in fin whale populations
Authors: Nigenda-Morales Sergio F. , Lin Meixi , Nuñez-Valencia Paulina G. , Kyriazis Christopher C. , Beichman Annabel C. , Robinson Jacqueline A. , Ragsdale Aaron P. , Urbán R. Jorge , Archer Frederick I. , Viloria-Gómora Lorena , Pérez-Álvarez María José , Poulin Elie , Lohmueller Kirk E. , Moreno-Estrada Andrés , Wayne Robert K.
Published: September 2023

Twentieth century industrial whaling pushed several species to the brink of extinction, with fin whales being the most impacted. However, a small, resident population in the Gulf of California was not targeted by whaling. Here, we analyzed 50 whole-genomes from the Eastern North Pacific (ENP) and Gulf of California (GOC) fin whale populations to investigate their demographic history and the genomic effects of natural and human-induced bottlenecks. We show that the two populations diverged ~16,000 years ago, after which the ENP population expanded and then suffered a 99% reduction in effective size during the whaling period. In contrast, the GOC population remained small and isolated, receiving less than one migrant per generation. However, this low level of migration has been crucial for maintaining its viability. Our study exposes the severity of whaling, emphasizes the importance of migration, and demonstrates the use of genome-based analyses and simulations to inform conservation strategies.
Feeding climate and biodiversity goals with novel plant-based meat and milk alternatives
Authors: Kozicka Marta , Havlík Petr , Valin Hugo , Wollenberg Eva , Deppermann Andre , Leclère David , Lauri Pekka , Moses Rebekah , Boere Esther , Frank Stefan , Davis Chris , Park Esther , Gurwick Noel
Published: September 2023

Plant-based animal product alternatives are increasingly promoted to achieve more sustainable diets. Here, we use a global economic land use model to assess the food system-wide impacts of a global dietary shift towards these alternatives. We find a substantial reduction in the global environmental impacts by 2050 if globally 50% of the main animal products (pork, chicken, beef and milk) are substituted—net reduction of forest and natural land is almost fully halted and agriculture and land use GHG emissions decline by 31% in 2050 compared to 2020. If spared agricultural land within forest ecosystems is restored to forest, climate benefits could double, reaching 92% of the previously estimated land sector mitigation potential. Furthermore, the restored area could contribute to 13-25% of the estimated global land restoration needs under target 2 from the Kunming Montreal Global Biodiversity Framework by 2030, and future declines in ecosystem integrity by 2050 would be more than halved. The distribution of these impacts varies across regions—the main impacts on agricultural input use are in China and on environmental outcomes in Sub-Saharan Africa and South America. While beef replacement provides the largest impacts, substituting multiple products is synergistic.
Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis
Authors: Tharmasothirajan Apilaasha , Melcr Josef , Linney John , Gensch Thomas , Krumbach Karin , Ernst Karla Marlen , Brasnett Christopher , Poggi Paola , Pitt Andrew R. , Goddard Alan D. , Chatgilialoglu Alexandros , Marrink Siewert J. , Marienhagen Jan
Published: September 2023

Microbial synthesis of nutraceutically and pharmaceutically interesting plant polyphenols represents a more environmentally friendly alternative to chemical synthesis or plant extraction. However, most polyphenols are cytotoxic for microorganisms as they are believed to negatively affect cell integrity and transport processes. To increase the production performance of engineered cell factories, strategies have to be developed to mitigate these detrimental effects. Here, we examine the accumulation of the stilbenoid resveratrol in the cell membrane and cell wall during its production using Corynebacterium glutamicum and uncover the membrane rigidifying effect of this stilbenoid experimentally and with molecular dynamics simulations. A screen of free fatty acid supplements identifies palmitelaidic acid and linoleic acid as suitable additives to attenuate resveratrol’s cytotoxic effects resulting in a three-fold higher product titer. This cost-effective approach to counteract membrane-damaging effects of product accumulation is transferable to the microbial production of other polyphenols and may represent an engineering target for other membrane-active bioproducts.
Non-invasive assessment of normal and impaired iron homeostasis in the brain
Authors: Filo Shir , Shaharabani Rona , Bar Hanin Daniel , Adam Miriam , Ben-David Eliel , Schoffman Hanan , Margalit Nevo , Habib Naomi , Shahar Tal , Mezer Aviv A.
Published: September 2023

Strict iron regulation is essential for normal brain function. The iron homeostasis, determined by the milieu of available iron compounds, is impaired in aging, neurodegenerative diseases and cancer. However, non-invasive assessment of different molecular iron environments implicating brain tissue’s iron homeostasis remains a challenge. We present a magnetic resonance imaging (MRI) technology sensitive to the iron homeostasis of the living brain (the r1-r2* relaxivity). In vitro, our MRI approach reveals the distinct paramagnetic properties of ferritin, transferrin and ferrous iron ions. In the in vivo human brain, we validate our approach against ex vivo iron compounds quantification and gene expression. Our approach varies with the iron mobilization capacity across brain regions and in aging. It reveals brain tumors’ iron homeostasis, and enhances the distinction between tumor tissue and non-pathological tissue without contrast agents. Therefore, our approach may allow for non-invasive research and diagnosis of iron homeostasis in living human brains.
Directed exciton transport highways in organic semiconductors
Authors: Müller Kai , Schellhammer Karl S. , Gräßler Nico , Debnath Bipasha , Liu Fupin , Krupskaya Yulia , Leo Karl , Knupfer Martin , Ortmann Frank
Published: September 2023

Exciton bandwidths and exciton transport are difficult to control by material design. We showcase the intriguing excitonic properties in an organic semiconductor material with specifically tailored functional groups, in which extremely broad exciton bands in the near-infrared-visible part of the electromagnetic spectrum are observed by electron energy loss spectroscopy and theoretically explained by a close contact between tightly packing molecules and by their strong interactions. This is induced by the donor–acceptor type molecular structure and its resulting crystal packing, which induces a remarkable anisotropy that should lead to a strongly directed transport of excitons. The observations and detailed understanding of the results yield blueprints for the design of molecular structures in which similar molecular features might be used to further explore the tunability of excitonic bands and pave a way for organic materials with strongly enhanced transport and built-in control of the propagation direction.
A nanoscale MOF-based heterogeneous catalytic system for the polymerization of N-carboxyanhydrides enables direct routes toward both polypeptides and related hybrid materials
Authors: Liu Ying , Ren Zhongwu , Zhang Nannan , Yang Xiaoxin , Wu Qihua , Cheng Zehong , Xing Hang , Bai Yugang
Published: September 2023

Synthetic polypeptides have emerged as versatile tools in both materials science and biomedical engineering due to their tunable properties and biodegradability. While the advancements of N-carboxyanhydride (NCA) ring-opening polymerization (ROP) techniques have aimed to expedite polymerization and reduce environment sensitivity, the broader implications of such methods remain underexplored, and the integration of ROP products with other materials remains a challenge. Here, we show an approach inspired by the success of many heterogeneous catalysts, using nanoscale metal-organic frameworks (MOFs) as co-catalysts for NCA-ROP accelerated also by peptide helices in proximity. This heterogeneous approach offers multiple advantages, including fast kinetics, low environment sensitivity, catalyst recyclability, and seamless integration with hybrid materials preparation. The catalytic system not only streamlines the preparation of polypeptides and polypeptide-coated MOF complexes (MOF@polypeptide hybrids) but also preserves and enhances their homogeneity, processibility, and overall functionalities inherited from the constituting MOFs and polypeptides.
Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome: a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety
Authors: Wortelboer Koen , de Jonge Patrick A. , Scheithauer Torsten P. M. , Attaye Ilias , Kemper E. Marleen , Nieuwdorp Max , Herrema Hilde
Published: September 2023

Bacteriophages (phages) are bacterial viruses that have been shown to shape microbial communities. Previous studies have shown that faecal virome transplantation can decrease weight gain and normalize blood glucose tolerance in diet-induced obese mice. Therefore, we performed a double-blind, randomised, placebo-controlled pilot study in which 24 individuals with metabolic syndrome were randomised to a faecal filtrate transplantation (FFT) from a lean healthy donor (n = 12) or placebo (n = 12). The primary outcome, change in glucose metabolism, and secondary outcomes, safety and longitudinal changes within the intestinal bacteriome and phageome, were assessed from baseline up to 28 days. All 24 included subjects completed the study and are included in the analyses. While the overall changes in glucose metabolism are not significantly different between both groups, the FFT is well-tolerated and without any serious adverse events. The phage virion composition is significantly altered two days after FFT as compared to placebo, which coincides with more virulent phage-microbe interactions. In conclusion, we provide evidence that gut phages can be safely administered to transiently alter the gut microbiota of recipients.
Langerhans cells shape postnatal oral homeostasis in a mechanical-force-dependent but microbiota and IL17-independent manner
Authors: Jaber Yasmin , Netanely Yasmine , Naamneh Reem , Saar Or , Zubeidat Khaled , Saba Yasmin , Georgiev Olga , Kles Paz , Barel Or , Horev Yael , Yosef Omri , Eli-Berchoer Luba , Nadler Chen , Betser-Cohen Gili , Shapiro Hagit , Elinav Eran , Wilensky Asaf , Hovav Avi-Hai
Published: September 2023

The postnatal interaction between microbiota and the immune system establishes lifelong homeostasis at mucosal epithelial barriers, however, the barrier-specific physiological activities that drive the equilibrium are hardly known. During weaning, the oral epithelium, which is monitored by Langerhans cells (LC), is challenged by the development of a microbial plaque and the initiation of masticatory forces capable of damaging the epithelium. Here we show that microbial colonization following birth facilitates the differentiation of oral LCs, setting the stage for the weaning period, in which adaptive immunity develops. Despite the presence of the challenging microbial plaque, LCs mainly respond to masticatory mechanical forces, inducing adaptive immunity, to maintain epithelial integrity that is also associated with naturally occurring alveolar bone loss. Mechanistically, masticatory forces induce the migration of LCs to the lymph nodes, and in return, LCs support the development of immunity to maintain epithelial integrity in a microbiota-independent manner. Unlike in adult life, this bone loss is IL-17-independent, suggesting that the establishment of oral mucosal homeostasis after birth and its maintenance in adult life involve distinct mechanisms.
SHIELD: a platform for high-throughput screening of barrier-type DNA elements in human cells
Authors: Zhang Meng , Ehmann Mary Elisabeth , Matukumalli Srija , Boob Aashutosh Girish , Gilbert David M. , Zhao Huimin
Published: September 2023

Chromatin boundary elements contribute to the partitioning of mammalian genomes into topological domains to regulate gene expression. Certain boundary elements are adopted as DNA insulators for safe and stable transgene expression in mammalian cells. These elements, however, are ill-defined and less characterized in the non-coding genome, partially due to the lack of a platform to readily evaluate boundary-associated activities of putative DNA sequences. Here we report SHIELD (Site-specific Heterochromatin Insertion of Elements at Lamina-associated Domains), a platform tailored for the high-throughput screening of barrier-type DNA elements in human cells. SHIELD takes advantage of the high specificity of serine integrase at heterochromatin, and exploits the natural heterochromatin spreading inside lamina-associated domains (LADs) for the discovery of potent barrier elements. We adopt SHIELD to evaluate the barrier activity of 1000 DNA elements in a high-throughput manner and identify 8 candidates with barrier activities comparable to the core region of cHS4 element in human HCT116 cells. We anticipate SHIELD could facilitate the discovery of novel barrier DNA elements from the non-coding genome in human cells.
Quantum computation of reactions on surfaces using local embedding
Authors: Gujarati Tanvi P. , Motta Mario , Friedhoff Triet Nguyen , Rice Julia E. , Nguyen Nam , Barkoutsos Panagiotis Kl. , Thompson Richard J. , Smith Tyler , Kagele Marna , Brei Mark , Jones Barbara A. , Williams Kristen
Published: September 2023

Modeling electronic systems is an important application for quantum computers. In the context of materials science, an important open problem is the computational description of chemical reactions on surfaces. In this work, we outline a workflow to model the adsorption and reaction of molecules on surfaces using quantum computing algorithms. We develop and compare two local embedding methods for the systematic determination of active spaces. These methods are automated and based on the physics of molecule-surface interactions and yield systematically improvable active spaces. Furthermore, to reduce the quantum resources required for the simulation of the selected active spaces using quantum algorithms, we introduce a technique for exact and automated circuit simplification. This technique is applicable to a broad class of quantum circuits and critical to enable demonstration on near-term quantum devices. We apply the proposed combination of active-space selection and circuit simplification to the dissociation of water on a magnesium surface using classical simulators and quantum hardware. Our study identifies reactions of molecules on surfaces, in conjunction with the proposed algorithmic workflow, as a promising research direction in the field of quantum computing applied to materials science.
Counterfactual communication without a trace in the transmission channel
Authors: Pan Wei-Wei , Liu Xiao , Xu Xiao-Ye , Wang Qin-Qin , Cheng Ze-Di , Wang Jian , Liu Zhao-Di , Chen Geng , Zhou Zong-Quan , Li Chuan-Feng , Guo Guang-Can , Dressel Justin , Vaidman Lev
Published: September 2023

We report an experimental realization of a modified counterfactual communication protocol that eliminates the dominant environmental trace left by photons passing through the transmission channel. Compared to Wheeler’s criterion for inferring past particle paths, as used in prior protocols, our trace criterion provides stronger support for the claim of the counterfactuality of the communication. We verify the lack of trace left by transmitted photons via tagging the propagation arms of an interferometric device by distinct frequency-shifts and finding that the collected photons have no frequency shift which corresponds to the transmission channel. As a proof of principle, we counterfactually transfer a quick response code image with sufficient fidelity to be scanned with a cell phone.
Open access dataset integrating EEG and fNIRS during Stroop tasks
Authors: Chen Zemeng , Gao Chenyang , Li Ting , Ji Xiang , Liu Shuyu , Xiao Ming
Published: September 2023

Conflict monitoring and processing are crucial components of the human cognitive system, with significant implications for daily life and the diagnosis of cognitive disorders. The Stroop task, combined with brain function detection technology, has been widely employed as a classical paradigm for investigating conflict processing. However, there remains a lack of public datasets that integrate Electroencephalogram (EEG) and functional Near-infrared Spectroscopy (fNIRS) to simultaneously record brain activity during a Stroop task. We introduce a dual-modality Stroop task dataset incorporating 34-channel EEG (sampling frequency is 1000 Hz) and 20-channel high temporal resolution fNIRS (sampling frequency is 100 Hz) measurements covering the whole frontal cerebral cortex from 21 participants (9 females/12 males, aged 23.0 ± 2.3 years). Event-related potential analysis of EEG recordings and activation analysis of fNIRS recordings were performed to show the significant Stroop effect. We expected that the data provided would be utilized to investigate multimodal data processing algorithms during cognitive processing.
Exploring the dynamics of viscoelastic adhesion in rough line contacts
Authors: Afferrante Luciano , Violano Guido , Carbone Giuseppe
Published: September 2023

Modeling the adhesion of viscoelastic rough surfaces is a recent challenge in contact mechanics. Existing models have primarily focused on simple systems with smooth topography or single roughness scale due to the co-action of roughness and viscoelasticity leading to elastic instabilities and rate-dependent behavior, resulting in complex adhesion dynamics. In this study, we propose a numerical model based on a finite element methodology to investigate the adhesion between a randomly rough profile and a viscoelastic half-plane. Approach-retraction simulations are performed under controlled displacement conditions of the rough indenter. The results demonstrate that viscous effects dampen the roughness-induced instabilities in both the approach and retraction phases. Interestingly, even when viscous effects are negligible, the pull-off stress, i.e., the maximum tensile stress required to detach the surfaces, is found to depend on the stiffness modulus and maximum load reached during the approach. Furthermore, when unloading is performed from a relaxed state of the viscoelastic half-plane, both adhesion hysteresis and pull-off stress are monotonic increasing functions of the speed. Conversely, when retraction begins from an unrelaxed state of the material, the maximum pull-off stress and hysteretic loss are obtained at intermediate velocities.