bluuebunny/crossref_metadata_2025 huggingface dataset:
From Automation to Symmation: Ethnographic Perspectives on What Happens in Front of the Screen
Authors: Wagener-Böck Nadine , Macgilchrist Felicitas , Rabenstein Kerstin , Bock Annekatrin
Published: October 2022

The work of automation in education is not automatic but needs to be ‘done’. Grounded in an ethnographic study which followed a Grade 9/10 class through their daily activities in a ‘regular’ high school for a year, this paper asks how automation is enacted by students and teachers, and what these practices imply for forms of knowledge and relationality. Inspired by feminist technoscience, and drawing on recent work on everyday automation, the paper suggests that the ‘auto-’ of automation in practice is very often more of a ‘sym-’, a ‘with’, in which students and machines co-produce something that looks like automation. Rather than ‘automation’, observing practices in classrooms shows practices of ‘symmation’. The paper elaborates on symmation scenes of realigning, revising and reworking relations. Automation is, in these scenes, deeply embedded in social relations, involving the processing of ability, difference and hierarchy. Rather than the industry hype of automation, these sets of socio-technical practices alert us to the messy, non-linear, contested, warm realities of education (and not just learning) in schools today. The paper identifies specific aspects of how these socio-technical realities impact knowledge and teacher-student relations.
Dynamic analysis of shallow embedded jacket offshore structures under wave forces
Authors: Yuan Yanzhao , Wang Xiancheng
Published: October 2022

In this paper, the stress of temporary structures during the construction of offshore structures is analysed through the study of the temporary buried drilling platform. Firstly, The fluid flow is controlled by the modified RANS equation (the Reynolds-average equation) and Forchheimer saturation resistance model, the free surface is tracked by volume of fluid (VOF) method, and the κ–ε closed equation is solved. The finite element numerical simulation software is used to establish a multi-factor coupling calculation model of the stress of temporary buried offshore structures. The maximum wave force of temporary structures under different buried depths, different structural sizes, different load periods and amplitudes is simulated, and the stability of Long Yuan wind turbine pile foundation drilling platform under the maximum wave force is analyzed. The research results of this paper can be used for dynamic design and analysis of wave load conditions, structural design dimensions and load periods in the engineering design of embedded offshore structures in shallow water under wave loads, so as to calculate the wave load values of structures reasonably and provide concrete theoretical basis for the establishment of offshore systems.
Feeling old on Facebook: an autoethnographic analysis of ageism among younger people towards their peers
Authors: sm-Rahman Atiqur
Published: October 2022

Population aging and the proliferation of numerous social networking sites such as Facebook (FB) have necessitated different approaches to investigating age-based discrimination called ageism. Although the current evidence provided information on younger adults’ attitudes towards older adults, little is known about the younger individuals’ attitudes towards their peers in a digital sphere. This autoethnographic study, conducted in November 2020, aimed at understanding younger FB user’s (n = 37) attitudes towards their peers, and the manifestation of plausible digital facets of ageism. I posted a public status using a specific FB feature calledfeeling oldon my FB Wall and analyzed the comments (both emoticons and textual) by others in relation to the post/status. The study is guided by the theoretical lens of symbolic and interpretive anthropology. Results showed (a) younger FB users have age stereotyped negative attitudes towards their peers considering the FB status, and (b) emoticons used in comments expressed more negative attitudes towards old age compared to the textual comments. Both findings indicated potential connection to an internalized sense of ‘young’ and ‘old’ that embedded in socially grounded age stereotypes. Future and more research on digital platforms can be carried out targeting younger adults’ attitudes towards their own age group in order to understand the risk of emergence of ‘digital ageism’.
An Improved Sea Lion Optimization for Workload Elasticity Prediction with Neural Networks
Authors: Nguyen Binh Minh , Tran Trung , Nguyen Thieu , Nguyen Giang
Published: October 2022

The work in this paper presents a study into nature-inspired optimization applied to workload elasticity prediction using neural networks. Currently, the trend is for proactive decision support in increasing or decreasing the available resource in cloud computing. The aim is to avoid overprovision leading to resource waste and to avoid resource under-provisioning. The combination of optimization and neural networks has potential for the performance, accuracy, and stability of the prediction solution. In this context, we initially proposed an improved variant of sea lion optimization (ISLO) to boost the efficiency of the original in solving optimization problems. The designed optimization results are validated against eight well-known metaheuristic algorithms on 20 benchmark functions of CEC’2014 and CEC’2015. After that, improved sea lion optimization (ISLO) is used to train a hybrid neural network. Finally, the trained neural model is used for resource auto-scaling based on workload prediction with 4 real and public datasets. The experiments show that our neural network model provides improved results in comparison with other models, especially in comparison with neural networks trained using the original sea lion optimization. The proposed ISLO proved efficiency and improvement in solving problems ranging from global optimization with swarm intelligence to the prediction of workload elasticity.
Effects of immune cells and cytokines on the endometrial immune microenvironment in polycystic ovary syndrome
Authors: Ye Zhenhong , Zhao Jie , Li Rong
Published: October 2022

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of reproductive age, and its pathogenesis is still unclear. More and more studies have shown that PCOS patients were often accompanied by obesity, insulin resistance and chronic, low-grade inflammation, which were closely related to the endometrial dysfunction. Besides, obesity and insulin resistance also exacerbate inflammatory responses. Therefore, this review provides a summary of the effects of immune cells and inflammatory cytokines on the immune microenvironment of PCOS endometrium, and the impacts of obesity and insulin resistance on endometrial inflammatory homeostasis and possible drug interventions.
Characterization of Clasts in the Glen Torridon Region of Gale Crater Observed by the Mars Science Laboratory Curiosity Rover
Authors: Khan Sabrina Y. , Stack Kathryn M. , Yingst R. Aileen , Bergmann Kristin
Published: October 2022

The morphology and composition of clasts have the potential to reveal the nature and extent of erosional processes acting in a region. Dense accumulations of granule‐ to pebble‐sized clasts covering the ground throughout the Glen Torridon region of Gale crater on Mars were studied using data acquired by the Mars Science Laboratory Curiosity rover between sols 2300 and 2593. In this study, measurements of shape, size, texture, and elemental abundance of unconsolidated granules and pebbles within northern Glen Torridon were compiled. Nine primary clast types were identified through stepwise hierarchical clustering, all of which are sedimentary and can be compositionally linked to local bedrock, suggesting relatively short transport distances. Several clast types display features associated with fragmentation along bedding planes and existing cracks in bedrock. These results indicate that Glen Torridon clasts are primarily the product of in‐situ physical weathering of local bedrock.
A Close Look at Melting Below Antarctica’s Largest Ice Shelf
Authors: Fritts Rachel
Published: October 2022

Radar data reveal where, when, and how fast the base of the Filchner-Ronne Ice Shelf has been losing mass in recent years.
Influence of Fault Architecture on Induced Earthquake Sequence Evolution Revealed by High‐Resolution Focal Mechanism Solutions
Authors: Qin Yan , Chen Xiaowei , Chen Ting , Abercrombie Rachel E.
Published: October 2022

The increasing seismicity and improved seismic observation network in recent years provide an opportunity to explore factors that influence the triggering processes, spatiotemporal evolution, and maximum magnitude of induced sequences. We map the fault architecture and stress state of four induced sequences in Oklahoma to determine their influence on the seismicity. We systematically relocate the earthquakes and compute hundreds of focal mechanisms of small to medium events (1.0 < M < 5.1) using various techniques, including machine learning, for the Guthrie, Woodward, Cushing, and Fairview sequences. The detailed fault geometry and spatiotemporal evolution of seismicity and stress states reveal different dominant driving forces for each sequence. In Cushing and Fairview (largest event ≥M5.0), the main fault structures are near‐vertical narrow strike‐slip faults, with most of the small earthquake fault planes optimally oriented. The two sequences exhibit discontinuous temporal migration but strong earthquake self‐driven rupture growth. In Guthrie and Woodward (largest event <M5.0), the two sequences show more complex diffuse fault structures with varying dipping angles along depth. The inverted focal mechanisms show a mix of strike‐slip faulting and normal faulting in both sequences, and the normal faulting events are less optimally oriented than strike‐slip events. The two sequences are dominated by continuous diffusive migration in time driven by pore pressure propagation. The above results suggest that fault architecture and stress state influence sequence evolution, major driving forces, and possibly maximum magnitude.
The Influence of Synoptic Weather Patterns on Spatiotemporal Characteristics of Ozone Pollution Across Pearl River Delta of Southern China
Authors: Chen Xi , Wang Nan , Wang Gang , Wang Zaihua , Chen Hui , Cheng Chunlei , Li Mei , Zheng Lianming , Wu Liqing , Zhang Qianhua , Tang Mei , Huang Bo , Wang Xuemei , Zhou Zhen
Published: October 2022

Tropospheric ozone (O3) pollution is becoming the primary obstacle to the improvement of air quality in China, especially in the Pearl River Delta (PRD) region. Because O3 pollution episodes are closely related to synoptic weather patterns (SWPs), historical episodes (from 2006 to 2019) were classified according to SWPs using the Lamb‐Jenkinson method. Monitoring network and weather reanalysis data, emission inventories, and satellite retrievals were used to investigate the spatiotemporal characteristics and influences of O3 pollution. It was found that easterly (P_E), anticyclone (P_A), and typhoon‐related (P_NE) SWPs accounted for 75% of all O3 pollution episodes. In the PRD, the O3 formation mechanism showed clear differences under different SWPs, which were affected by local emissions under P_A, whereas regional transmission dominated under P_E and P_NE. The O3 peak concentration was strongly associated with temperature, solar radiation, and shifting of the sea‐land breeze. A delayed shift of land to sea breeze caused by SWPs often caused the O3 peak to appear in the late afternoon. Finally, stepwise regression was used to explain individual meteorological parameters contributing to O3 formation. It was found that the formation of O3 pollution under P_E and P_NE was associated with increases in temperature and radiation, while P_A was mainly affected by the increase of the overnight accumulation of O3. This study advances our knowledge of the formation mechanism of O3 pollution and provides scientific support for effective O3 pollution control.
The Impact of Gravity‐Driven Sedimentation on Reshaping the Huanghe (Yellow River) Delta Front
Authors: Liu Shihao , Goff John A. , Gao Shu , Feng Aiping , Wang Ya Ping , Jia Jianjun , Hu Weifen , Feng Wei , Yu Yonggui
Published: October 2022

Many of the world's mega‐river deltas are currently degrading due to a shortage of sediment supply feeding their construction. Here, using bathymetric and seismic data, the geomorphological/sedimentary evolution on and near a recently abandoned (1976 CE) Huanghe delta lobe is investigated. The delta front (DF) exhibits a lobe switching‐controlled pattern of progradation followed by mass wasting on the upper front, and redeposition at the seaward toe of the front; the latter process appears to be associated with sediment failure and contributes to delta degradation. During degradation, mass wasting‐driven deepening of the upper DF was initially up to ∼0.86 m/yr from 1978 to 1985 CE, slowed to ∼0.12 m/yr from 1985 to 2000 CE, and has been negligible since. In either prograding or degrading, gravity‐driven sedimentation results in a downlapping seismic unit superimposed on the bottomset of an earlier converging clinoform, with numerous buried/exposed submarine channels at its seaward terminus. These units exhibit a shore‐parallel elongated and continuous geometry, suggesting lateral spreading, which we attribute to alongshore hydrodynamic (especially tidal) remolding. Our findings underscore the significance of sediment gravity flows in the evolution of a degrading delta front, particularly as a principal mechanism of downslope mass transport that gentled (halving the gradient) and reshaped the DF over time. Gravity‐driven accumulations sourced from upper DF collapse can account for ∼1/3 of the previous DF and laterally extend over an unexpectedly large area (∼60‐km long) through hydrodynamic redistribution. Both processes should be considered for modeling other subaqueous deltas.
Polygenic heterogeneity in antidepressant treatment and placebo response
Authors: Nøhr Anne Krogh , Forsingdal Annika , Moltke Ida , Howes Oliver D. , Vitezic Morana , Albrechtsen Anders , Dalby Maria
Published: October 2022

The genetic architecture of antidepressant response is poorly understood. Polygenic risk scores (PRS), exploration of placebo response and the use of sub-scales might provide insights. Here, we investigate the association between PRSs for relevant complex traits and response to vortioxetine treatment and placebo using clinical scales, including sub-scales and self-reported assessments. We collected a clinical test sample of Major Depressive Disorder (MDD) patients treated with vortioxetine (N = 907) or placebo (N = 455) from seven randomized, double-blind, clinical trials. In parallel, we obtained data from an observational web-based study of vortioxetine-treated patients (N = 642) with self-reported response. PRSs for antidepressant response, psychiatric disorders, and symptom traits were derived using summary statistics from well-powered genome-wide association studies (GWAS). Association tests were performed between the PRSs and treatment response in each of the two test samples and empirical p-values were evaluated. In the clinical test sample, no PRSs were significantly associated with response to vortioxetine treatment or placebo following Bonferroni correction. However, clinically assessed treatment response PRS was nominally associated with vortioxetine treatment and placebo response given by several secondary outcome scales (improvement on HAM-A, HAM-A Psychic Anxiety sub-scale, CPFQ & PDQ), (P ≤ 0.026). Further, higher subjective well-being PRS (P ≤ 0.033) and lower depression PRS (P = 0.01) were nominally associated with higher placebo response. In the self-reported test sample, higher schizophrenia PRS was significantly associated with poorer self-reported response (P = 0.0001). The identified PRSs explain a low proportion of the variance (1.2–5.3%) in placebo and treatment response. Although the results were limited, we believe that PRS associations bear unredeemed potential as a predictor for treatment response, as more well-powered and phenotypically similar GWAS bases become available.
Desmoglein-2 is important for islet function and β-cell survival
Authors: Myo Min Kay K. , Rojas-Canales Darling , Penko Daniella , DeNichilo Mark , Cockshell Michaelia P. , Ffrench Charlie B. , Thompson Emma J. , Asplund Olof , Drogemuller Christopher J. , Prasad Rashmi B. , Groop Leif , Grey Shane T. , Thomas Helen E. , Loudovaris Thomas , Kay Thomas W. , Mahoney My G. , Jessup Claire F. , Coates P. Toby , Bonder Claudine S.
Published: October 2022

Type 1 diabetes is a complex disease characterized by the lack of endogenous insulin secreted from the pancreatic β-cells. Although β-cell targeted autoimmune processes and β-cell dysfunction are known to occur in type 1 diabetes, a complete understanding of the cell-to-cell interactions that support pancreatic function is still lacking. To characterize the pancreatic endocrine compartment, we studied pancreata from healthy adult donors and investigated a single cell surface adhesion molecule, desmoglein-2 (DSG2). Genetically-modified mice lackingDsg2were examined for islet cell mass, insulin production, responses to glucose, susceptibility to a streptozotocin-induced mouse model of hyperglycaemia, and ability to cure diabetes in a syngeneic transplantation model. Herein, we have identified DSG2 as a previously unrecognized adhesion molecule that supports β-cells. Furthermore, we reveal thatDSG2is within the top 10 percent of all genes expressed by human pancreatic islets and is expressed by the insulin-producing β-cells but not the somatostatin-producing δ-cells. In aDsg2loss-of-function mice (Dsg2lo/lo), we observed a significant reduction in the number of pancreatic islets and islet size, and consequently, there was less total insulin content per islet cluster.Dsg2lo/lomice also exhibited a reduction in blood vessel barrier integrity, an increased incidence of streptozotocin-induced diabetes, and islets isolated fromDsg2lo/lomice were more susceptible to cytokine-induced β-cell apoptosis. Following transplantation into diabetic mice, islets isolated fromDsg2lo/lomice were less effective than their wildtype counterparts at curing diabetes. In vitro assays using the Beta-TC-6 murine β-cell line suggest that DSG2 supports the actin cytoskeleton as well as the release of cytokines and chemokines. Taken together, our study suggests that DSG2 is an under-appreciated regulator of β-cell function in pancreatic islets and that a better understanding of this adhesion molecule may provide new opportunities to combat type 1 diabetes.
Bromodomain-containing protein 4 (BRD4) as an epigenetic regulator of fatty acid metabolism genes and ferroptosis
Authors: Yang Minghua , Liu Ke , Chen Pan , Zhu Hongyi , Wang Junjie , Huang Jun
Published: October 2022

Reprogramming lipid metabolism is considered a fundamental step in tumourigenesis that influences ferroptosis. However, molecular mechanisms between lipid metabolism and ferroptosis remain largely unknown. Results from the drug screening of 464 inhibitors (for 164 targets) applied to ferroptosis cells indicated that 4 inhibitors targeted bromodomain-containing protein 4 (BRD4) significantly inhibiting erastin-induced ferroptosis. Functional studies proved that the loss of BRD4 weakened oxidative catabolism in mitochondria, protecting cells from the excessive accumulation of lipid peroxides. Mechanism research revealed that the transcriptional levels of fatty acid metabolism-related genes (HADH, ACSL1 and ACAA2) participating in the β-oxidation of fatty acids (FAO) and polyunsaturated fatty acids (PUFAs) synthesis depended on the activity of super-enhancers (SEs) formed by BRD4 and HMGB2 in their promoter regions. Conclusively, this study demonstrated that BRD4 was indispensable for fatty acid metabolism based on its epigenetic regulatory mechanisms and affecting erastin-induced ferroptosis, providing a new theoretical reference for understanding the relationship between lipid metabolism and ferroptosis deeply.
The impact of phosphorus on projected Sub-Saharan Africa food security futures
Authors: Magnone Daniel , Niasar Vahid J. , Bouwman Alexander F. , Beusen Arthur H. W. , van der Zee Sjoerd E. A. T. M. , Sattari Sheida Z.
Published: October 2022

Sub-Saharan Africa must urgently improve food security. Phosphorus availability is one of the major barriers to this due to low historical agricultural use. Shared socioeconomic pathways (SSPs) indicate that only a sustainable (SSP1) or a fossil fuelled future (SSP5) can improve food security (in terms of price, availability, and risk of hunger) whilst nationalistic (SSP3) and unequal (SSP4) pathways worsen food security. Furthermore, sustainable SSP1 requires limited cropland expansion and low phosphorus use whilst the nationalistic SSP3 is as environmentally damaging as the fossil fuelled pathway. The middle of the road future (SSP2) maintains today’s inadequate food security levels only by using approximately 440 million tonnes of phosphate rock. Whilst this is within the current global reserve estimates the market price alone for a commonly used fertiliser (DAP) would cost US$ 130 ± 25 billion for agriculture over the period 2020 to 2050 and the farmgate price could be two to five times higher due to additional costs (e.g. transport, taxation etc.). Thus, to improve food security, economic growth within a sustainability context (SSP1) and the avoidance of nationalist ideology (SSP3) should be prioritised.
The cell-free DNA methylome captures distinctions between localized and metastatic prostate tumors
Authors: Chen Sujun , Petricca Jessica , Ye Wenbin , Guan Jiansheng , Zeng Yong , Cheng Nicholas , Gong Linsey , Shen Shu Yi , Hua Junjie T. , Crumbaker Megan , Fraser Michael , Liu Stanley , Bratman Scott V. , van der Kwast Theodorus , Pugh Trevor , Joshua Anthony M. , De Carvalho Daniel D. , Chi Kim N. , Awadalla Philip , Ji Guoli , Feng Felix , Wyatt Alexander W. , He Housheng Hansen
Published: October 2022

Metastatic prostate cancer remains a major clinical challenge and metastatic lesions are highly heterogeneous and difficult to biopsy. Liquid biopsy provides opportunities to gain insights into the underlying biology. Here, using the highly sensitive enrichment-based sequencing technology, we provide analysis of 60 and 175 plasma DNA methylomes from patients with localized and metastatic prostate cancer, respectively. We show that the cell-free DNA methylome can capture variations beyond the tumor. A global hypermethylation in metastatic samples is observed, coupled with hypomethylation in the pericentromeric regions. Hypermethylation at the promoter of a glucocorticoid receptor geneNR3C1is associated with a decreased immune signature. The cell-free DNA methylome is reflective of clinical outcomes and can distinguish different disease types with 0.989 prediction accuracy. Finally, we show the ability of predicting copy number alterations from the data, providing opportunities for joint genetic and epigenetic analysis on limited biological samples.
Structural insights into light-driven anion pumping in cyanobacteria
Authors: Astashkin R. , Kovalev K. , Bukhdruker S. , Vaganova S. , Kuzmin A. , Alekseev A. , Balandin T. , Zabelskii D. , Gushchin I. , Royant A. , Volkov D. , Bourenkov G. , Koonin E. , Engelhard M. , Bamberg E. , Gordeliy V.
Published: October 2022

Transmembrane ion transport is a key process in living cells. Active transport of ions is carried out by various ion transporters including microbial rhodopsins (MRs). MRs perform diverse functions such as active and passive ion transport, photo-sensing, and others. In particular, MRs can pump various monovalent ions like Na+, K+, Cl−, I−, NO3−. The only characterized MR proposed to pump sulfate in addition to halides belongs to the cyanobacterium Synechocystis sp. PCC 7509 and is named Synechocystis halorhodopsin (SyHR). The structural study of SyHR may help to understand what makes an MR pump divalent ions. Here we present the crystal structure of SyHR in the ground state, the structure of its sulfate-bound form as well as two photoreaction intermediates, the K and O states. These data reveal the molecular origin of the unique properties of the protein (exceptionally strong chloride binding and proposed pumping of divalent anions) and sheds light on the mechanism of anion release and uptake in cyanobacterial halorhodopsins. The unique properties of SyHR highlight its potential as an optogenetics tool and may help engineer different types of anion pumps with applications in optogenetics.
Integration of Hi-C with short and long-read genome sequencing reveals the structure of germline rearranged genomes
Authors: Schöpflin Robert , Melo Uirá Souto , Moeinzadeh Hossein , Heller David , Laupert Verena , Hertzberg Jakob , Holtgrewe Manuel , Alavi Nico , Klever Marius-Konstantin , Jungnitsch Julius , Comak Emel , Türkmen Seval , Horn Denise , Duffourd Yannis , Faivre Laurence , Callier Patrick , Sanlaville Damien , Zuffardi Orsetta , Tenconi Romano , Kurtas Nehir Edibe , Giglio Sabrina , Prager Bettina , Latos-Bielenska Anna , Vogel Ida , Bugge Merete , Tommerup Niels , Spielmann Malte , Vitobello Antonio , Kalscheuer Vera M. , Vingron Martin , Mundlos Stefan
Published: October 2022

Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than expected in lamina-associated domains (LADs) and that a majority reshuffle topologically associating domains (TADs). By applying phased RNA-seq, we observe an enrichment of genes showing allelic imbalanced expression (AIG) within 100 kb around the breakpoints. Interestingly, the AIGs hit by a breakpoint (19/22) display both up- and downregulation, thereby suggesting different mechanisms at play, such as gene disruption and rearrangements of regulatory information. However, the majority of interpretable genes located 200 kb around a breakpoint do not show significant expression changes. Thus, there is an overall robustness in the genome towards large-scale chromosome rearrangements.
Competing instabilities reveal how to rationally design and control active crosslinked gels
Authors: Najma Bibi , Varghese Minu , Tsidilkovski Lev , Lemma Linnea , Baskaran Aparna , Duclos Guillaume
Published: October 2022

How active stresses generated by molecular motors set the large-scale mechanics of the cell cytoskeleton remains poorly understood. Here, we combine experiments and theory to demonstrate how the emergent properties of a biomimetic active crosslinked gel depend on the properties of its microscopic constituents. We show that an extensile nematic elastomer exhibits two distinct activity-driven instabilities, spontaneously bending in-plane or buckling out-of-plane depending on its composition. Molecular motors play a dual antagonistic role, fluidizing or stiffening the gel depending on the ATP concentration. We demonstrate how active and elastic stresses are set by each component, providing estimates for the active gel theory parameters. Finally, activity and elasticity were manipulated in situ with light-activable motor proteins, controlling the direction of the instability optically. These results highlight how cytoskeletal stresses regulate the self-organization of living matter and set the foundations for the rational design and optogenetic control of active materials.
Observation of a new type of self-generated current in magnetized plasmas
Authors: Na Yong-Su , Seo Jaemin , Lee Yoonji , Choi Gyungjin , Park Minseo , Park Sangjin , Yi Sumin , Wang Weixing , Yoo Min-Gu , Cha Minsoo , Kim Beomsu , Lee Young-Ho , Han Hyunsun , Kim Boseong , Lee Chanyoung , Kim SangKyeun , Yang SeongMoo , Byun Cheol-Sik , Kim Hyun-Seok , Ko Jinseok , Lee Woochang , Hahm Taik Soo
Published: October 2022

A tokamak, a torus-shaped nuclear fusion device, needs an electric current in the plasma to produce magnetic field in the poloidal direction for confining fusion plasmas. Plasma current is conventionally generated by electromagnetic induction. However, for a steady-state fusion reactor, minimizing the inductive current is essential to extend the tokamak operating duration. Several non-inductive current drive schemes have been developed for steady-state operations such as radio-frequency waves and neutral beams. However, commercial reactors require minimal use of these external sources to maximize the fusion gain, Q, the ratio of the fusion power to the external power. Apart from these external current drives, a self-generated current, so-called bootstrap current, was predicted theoretically and demonstrated experimentally. Here, we reveal another self-generated current that can exist in a tokamak and this has not yet been discussed by present theories. We report conclusive experimental evidence of this self-generated current observed in the KSTAR tokamak.
Multiple sources of aerobic methane production in aquatic ecosystems include bacterial photosynthesis
Authors: Perez-Coronel Elisabet , Michael Beman J.
Published: October 2022

Aquatic ecosystems are globally significant sources of the greenhouse gas methane to the atmosphere. Until recently, methane production was thought to be a strictly anaerobic process confined primarily to anoxic sediments. However, supersaturation of methane in oxygenated waters has been consistently observed in lakes and the ocean (termed the ‘methane paradox’), indicating that methane can be produced under oxic conditions through unclear mechanisms. Here we show aerobic methane production from multiple sources in freshwater incubation experiments under different treatments and based on biogeochemical, metagenomic, and metatranscriptomic data. We find that aerobic methane production appears to be associated with (bacterio)chlorophyll metabolism and photosynthesis, as well as with Proteobacterial degradation of methylphosphonate. Genes encoding pathways for putative photosynthetic- and methylphosphonate-based methane production also co-occur in Proteobacterial metagenome-assembled genomes. Our findings provide insight into known mechanisms of aerobic methane production, and suggest a potential co-occurring mechanism associated with bacterial photosynthesis in aquatic ecosystems.
Genome-wide rare variant score associates with morphological subtypes of autism spectrum disorder
Authors: Chan Ada J. S. , Engchuan Worrawat , Reuter Miriam S. , Wang Zhuozhi , Thiruvahindrapuram Bhooma , Trost Brett , Nalpathamkalam Thomas , Negrijn Carol , Lamoureux Sylvia , Pellecchia Giovanna , Patel Rohan V. , Sung Wilson W. L. , MacDonald Jeffrey R. , Howe Jennifer L. , Vorstman Jacob , Sondheimer Neal , Takahashi Nicole , Miles Judith H. , Anagnostou Evdokia , Tammimies Kristiina , Zarrei Mehdi , Merico Daniele , Stavropoulos Dimitri J. , Yuen Ryan K. C. , Fernandez Bridget A. , Scherer Stephen W.
Published: October 2022

Defining different genetic subtypes of autism spectrum disorder (ASD) can enable the prediction of developmental outcomes. Based on minor physical and major congenital anomalies, we categorize 325 Canadian children with ASD into dysmorphic and nondysmorphic subgroups. We develop a method for calculating a patient-level, genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD have a significantly higher GRVS compared to those with nondysmorphic ASD (P = 0.03). Using the polygenic transmission disequilibrium test, we observe an over-transmission of ASD-associated common variants in nondysmorphic ASD probands (P = 2.9 × 10−3). These findings replicate using WGS data from 442 ASD probands with accompanying morphology data from the Simons Simplex Collection. Our results provide support for an alternative genomic classification of ASD subgroups using morphology data, which may inform intervention protocols.
Natural scene sampling reveals reliable coarse-scale orientation tuning in human V1
Authors: Roth Zvi N. , Kay Kendrick , Merriam Elisha P.
Published: October 2022

Orientation selectivity in primate visual cortex is organized into cortical columns. Since cortical columns are at a finer spatial scale than the sampling resolution of standard BOLD fMRI measurements, analysis approaches have been proposed to peer past these spatial resolution limitations. It was recently found that these methods are predominantly sensitive to stimulus vignetting - a form of selectivity arising from an interaction of the oriented stimulus with the aperture edge. Beyond vignetting, it is not clear whether orientation-selective neural responses are detectable in BOLD measurements. Here, we leverage a dataset of visual cortical responses measured using high-field 7T fMRI. Fitting these responses using image-computable models, we compensate for vignetting and nonetheless find reliable tuning for orientation. Results further reveal a coarse-scale map of orientation preference that may constitute the neural basis for known perceptual anisotropies. These findings settle a long-standing debate in human neuroscience, and provide insights into functional organization principles of visual cortex.
Pauli blocking of stimulated emission in a degenerate Fermi gas
Authors: Jannin Raphael , van der Werf Yuri , Steinebach Kees , Bethlem Hendrick L. , Eikema Kjeld S. E.
Published: October 2022

The Pauli exclusion principle in quantum mechanics has a profound influence on the structure of matter and on interactions between fermions. Almost 30 years ago it was predicted that the Pauli exclusion principle could lead to a suppression of spontaneous emission, and only recently several experiments confirmed this phenomenon. Here we report that this so-called Pauli blockade not only affects incoherent processes but also, more generally, coherently driven systems. It manifests itself as an intriguing sub-Doppler narrowing of a doubly-forbidden transition profile in an optically trapped Fermi gas of 3He. By actively pumping atoms out of the excited state, we break the coherence of the excitation and lift the narrowing effect, confirming the influence of Pauli blockade on the transition profile. This insight into the interplay between quantum statistics and coherent driving is a promising development for future applications involving fermionic systems.
Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications
Authors: Ye Yan , Chen Zechuan , Jiang Shan , Jia Fengyun , Li Teng , Lu Xia , Xue Jing , Lian Xinyue , Ma Jiaqiang , Hao Pei , Lu Liangjing , Ye Shuang , Shen Nan , Bao Chunde , Fu Qiong , Zhang Xiaoming
Published: October 2022

Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) is an autoimmune condition associated with rapidly progressive interstitial lung disease and high mortality. The aetiology and pathogenesis of MDA5+ DM are still largely unknown. Here we describe the immune signatures of MDA5+ DM via single-cell RNA sequencing, flow cytometry and multiplex immunohistochemistry in peripheral B and T cells and in affected lung tissue samples from one patient. We find strong peripheral antibody-secreting cell and CD8+ T cell responses as cellular immune hallmarks, and over-stimulated type I interferon signaling and associated metabolic reprogramming as molecular immune signature in MDA5+ DM. High frequency of circulating ISG15+ CD8+ T cells at baseline predicts poor one-year survival in MDA5+ DM patients. In affected lungs, we find profuse immune cells infiltration, which likely contributes to the pro-fibrotic response via type I interferon production. The importance of type I interferons in MDA5+ DM pathology is further emphasized by our observation in a retrospective cohort of MDA5+ DM patients that combined calcineurin and Janus kinase inhibitor therapy show superior efficacy to calcineurin inhibitor monotherapy. In summary, this study reveals key immune-pathogenic features of MDA5+ DM and provides a potential basis for future tailored therapies.
Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation
Authors: Zenke Simon , Sica Mauricio P. , Steinberg Florian , Braun Julia , Zink Alicia , Gavrilov Alina , Hilger Alexander , Arra Aditya , Brunner-Weinzierl Monika , Elling Roland , Beyersdorf Niklas , Lämmermann Tim , Smulski Cristian R. , Rohr Jan C.
Published: October 2022

Intercellular communication is crucial for collective regulation of cellular behaviors. While clustering T cells have been shown to mutually control the production of key communication signals, it is unclear whether they also jointly regulate their availability and degradation. Here we use newly developed reporter systems, bioinformatic analyses, protein structure modeling and genetic perturbations to assess this. We find that T cells utilize trogocytosis by competing antagonistic receptors to differentially control the abundance of immunoregulatory ligands. Specifically, ligands trogocytosed via CD28 are shuttled to the T cell surface, enabling them to co-stimulate neighboring T cells. In contrast, CTLA4-mediated trogocytosis targets ligands for degradation. Mechanistically, this fate separation is controlled by different acid-sensitivities of receptor-ligand interactions and by the receptor intracellular domains. The ability of CD28 and CTLA4 to confer different fates to trogocytosed ligands reveals an additional layer of collective regulation of cellular behaviors and promotes the robustness of population dynamics.
Surface chemical heterogeneous distribution in over-lithiated Li1+xCoO2 electrodes
Authors: Sun Gang , Yu Fu-Da , Lu Mi , Zhu Qingjun , Jiang Yunshan , Mao Yongzhi , McLeod John A. , Maley Jason , Wang Jian , Zhou Jigang , Wang Zhenbo
Published: October 2022

In commercial Li-ion batteries, the internal short circuits or over-lithiation often cause structural transformation in electrodes and may lead to safety risks. Herein, we investigate the over-discharged mechanism of LiCoO2/graphite pouch cells, especially spatially resolving the morphological, surface phase, and local electronic structure of LiCoO2 electrode. With synchrotron-based X-ray techniques and Raman mapping, together with spectroscopy simulations, we demonstrate that over-lithiation reaction is a surface effect, accompanied by Co reduction and surface structure transformation to Li2CoO2/Co3O4/CoO/Li2O-like phases. This surface chemical distribution variation is relevant to the depth and exposed crystalline planes of LiCoO2 particles, and the distribution of binder/conductive additives. Theoretical calculations confirm that Li2CoO2-phase has lower electronic/ionic conductivity than LiCoO2-phase, further revealing the critical effect of distribution of conductive additives on the surface chemical heterogeneity evolution. Our findings on such surface phenomena are non-trivial and highlight the capability of synchrotron-based X-ray techniques for studying the spatial chemical phase heterogeneity.
A biomimetic laminated strategy enabled strain-interference free and durable flexible thermistor electronics
Authors: Hao Sanwei , Fu Qingjin , Meng Lei , Xu Feng , Yang Jun
Published: October 2022

The development of flexible thermistor epidermal electronics (FTEE) to satisfy high temperature resolution without strain induced signal distortion is of great significance but still challenging. Inspired by the nacre microstructure capable of restraining the stress concentration, we exemplify a versatile MXene-based thermistor elastomer sensor (TES) platform that significantly alleviates the strain interference by the biomimetic laminated strategy combining with the in-plane stress dissipation and nacre-mimetic hierarchical architecture, delivering competitive advantages of superior thermosensitivity (−1.32% °C−1), outstanding temperature resolution (~0.3 °C), and unparalleled mechanical durability (20000 folding fatigue cycles), together with considerable improvement in strain-tolerant thermosensation over commercial thermocouple in exercise scenario. By a combination of theoretical model simulation, microstructure observation, and superposed signal detection, the authors further reveal the underlying temperature and strain signal decoupling mechanism that substantiate the generality and customizability of the nacre-mimetic strategy, possessing insightful significance of fabricating FTEE for static and dynamic temperature detection.
Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity
Authors: Rosás-Umbert Miriam , Gunst Jesper D. , Pahus Marie H. , Olesen Rikke , Schleimann Mariane , Denton Paul W. , Ramos Victor , Ward Adam , Kinloch Natalie N. , Copertino Dennis C. , Escribà Tuixent , Llano Anuska , Brumme Zabrina L. , Brad Jones R. , Mothe Beatriz , Brander Christian , Fox Julie , Nussenzweig Michel C. , Fidler Sarah , Caskey Marina , Tolstrup Martin , Søgaard Ole S.
Published: October 2022

In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8+ T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8+ T cell responses that are associated with ART-free virologic control.
Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma
Authors: Tomaszewski William H. , Waibl-Polania Jessica , Chakraborty Molly , Perera Jonathan , Ratiu Jeremy , Miggelbrink Alexandra , McDonnell Donald P. , Khasraw Mustafa , Ashley David M. , Fecci Peter E. , Racioppi Luigi , Sanchez-Perez Luis , Gunn Michael D. , Sampson John H.
Published: October 2022

Glioblastoma (GBM) is notorious for its immunosuppressive tumor microenvironment (TME) and is refractory to immune checkpoint blockade (ICB). Here, we identify calmodulin-dependent kinase kinase 2 (CaMKK2) as a driver of ICB resistance. CaMKK2 is highly expressed in pro-tumor cells and is associated with worsened survival in patients with GBM. Host CaMKK2, specifically, reduces survival and promotes ICB resistance. Multimodal profiling of the TME reveals that CaMKK2 is associated with several ICB resistance-associated immune phenotypes. CaMKK2 promotes exhaustion in CD8+ T cells and reduces the expansion of effector CD4+ T cells, additionally limiting their tumor penetrance. CaMKK2 also maintains myeloid cells in a disease-associated microglia-like phenotype. Lastly, neuronal CaMKK2 is required for maintaining the ICB resistance-associated myeloid phenotype, is deleterious to survival, and promotes ICB resistance. Our findings reveal CaMKK2 as a contributor to ICB resistance and identify neurons as a driver of immunotherapeutic resistance in GBM.
Tracing the international arrivals of SARS-CoV-2 Omicron variants after Aotearoa New Zealand reopened its border
Authors: Douglas Jordan , Winter David , McNeill Andrea , Carr Sam , Bunce Michael , French Nigel , Hadfield James , de Ligt Joep , Welch David , Geoghegan Jemma L.
Published: October 2022

In the second quarter of 2022, there was a global surge of emergent SARS-CoV-2 lineages that had a distinct growth advantage over then-dominant Omicron BA.1 and BA.2 lineages. By generating 10,403 Omicron genomes, we show that Aotearoa New Zealand observed an influx of these immune-evasive variants (BA.2.12.1, BA.4, and BA.5) through the border. This is explained by the return to significant levels of international travel following the border’s reopening in March 2022. We estimate one Omicron transmission event from the border to the community for every ~5,000 passenger arrivals at the current levels of travel and restriction. Although most of these introductions did not instigate any detected onward transmission, a small minority triggered large outbreaks. Genomic surveillance at the border provides a lens on the rate at which new variants might gain a foothold and trigger new waves of infection.
Spontaneous time-reversal symmetry breaking in twisted double bilayer graphene
Authors: Kuiri Manabendra , Coleman Christopher , Gao Zhenxiang , Vishnuradhan Aswin , Watanabe Kenji , Taniguchi Takashi , Zhu Jihang , MacDonald Allan H. , Folk Joshua
Published: October 2022

Twisted double bilayer graphene (tDBG) comprises two Bernal-stacked bilayer graphene sheets with a twist between them. Gate voltages applied to top and back gates of a tDBG device tune both the flatness and topology of the electronic bands, enabling an unusual level of experimental control. Metallic states with broken spin and valley symmetries have been observed in tDBG devices with twist angles in the range 1.2–1.3°, but the topologies and order parameters of these states have remained unclear. We report the observation of an anomalous Hall effect in the correlated metal state of tDBG, with hysteresis loops spanning hundreds of mT in out-of-plane magnetic field (B⊥) that demonstrate spontaneously broken time-reversal symmetry. The B⊥ hysteresis persists for in-plane fields up to several Tesla, suggesting valley (orbital) ferromagnetism. At the same time, the resistivity is strongly affected by even mT-scale values of in-plane magnetic field, pointing to spin-valley coupling or to a direct orbital coupling between in-plane field and the valley degree of freedom.
Flexible hyperspectral surface plasmon resonance microscopy
Authors: Liu Ziwei , Wu Jingning , Cai Chen , Yang Bo , Qi Zhi-mei
Published: October 2022

Optical techniques for visualization and quantification of chemical and biological analytes are always highly desirable. Here we show a hyperspectral surface plasmon resonance microscopy (HSPRM) system that uses a hyperspectral microscope to analyze the selected area of SPR image produced by a prism-based spectral SPR sensor. The HSPRM system enables monochromatic and polychromatic SPR imaging and single-pixel spectral SPR sensing, as well as two-dimensional quantification of thin films with the measured resonance-wavelength images. We performed pixel-by-pixel calibration of the incident angle to remove pixel-to-pixel differences in SPR sensitivity, and demonstrated the HSPRM’s capabilities by using it to quantify monolayer graphene thickness distribution, inhomogeneous protein adsorption and single-cell adhesion. The HSPRM system has a wide spectral range from 400 nm to 1000 nm, an optional field of view from 0.884 mm2 to 0.003 mm2 and a high lateral resolution of 1.2 μm, demonstrating an innovative breakthrough in SPR sensor technology.