bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure and mechanism of the RalGAP tumor suppressor complex
Authors: Rasche René , Klink Björn Udo , Apken Lisa Helene , Michalke Esther , Chen Minghao , Oeckinghaus Andrea , Gatsogiannis Christos , Kümmel Daniel
Published: November 2024

The RalGAP (GTPase activating protein) complexes are negative regulators of the Ral GTPases and thus crucial components that counteract (oncogenic) Ras signaling. However, no structural information on the architecture of this tumor suppressor complex is available hampering a mechanistic understanding of its functionality. Here, we present a cryo-EM structure of RalGAP that reveals an extended 58 nm tetrameric architecture comprising two heterodimers of the RalGAPα and RalGAPβ subunits. We show that the catalytic domain of RalGAPα requires stabilization by a unique domain of RalGAPβ, providing the molecular basis for why RalGAP complexes are obligatory heterodimers. Formation of RalGAP tetramers is not required for activityin vitro, but essential for function of the complexin vivo. Structural analysis of RalGAP subunit variants reported in cancer patients suggests effects on complex formation and thus functional relevance in tumor development, emphasizing the significance of the obtained structural information for medical research.
Genome-wide association studies identify promising QTL for freezing tolerance in winter and early spring as a basis for in-depth genetic analysis and implementation in winter faba bean (Vicia fabaL.) breeding
Authors: Windhorst Alex , Skovbjerg Cathrine Kiel , Angra Deepti , O’Sullivan Donal Martin , Andersen Stig Uggerhøj , Wolfgang Link
Published: November 2024

Interest in faba bean as a locally adapted high-protein grain legume crop has increased in Europe over the past decade. Winter faba bean, which can make use of soil moisture from autumn to spring and partially escape summer droughts, exhibit greater yield potential than the spring-type. However, due to insufficient winter hardiness, winterkill is a major constraint that prevents large-scale production of current winter-type cultivars in Central and Northern Europe. Here, we extend the understanding of freezing tolerance, the main component trait of winter hardiness, during winter and against late-frost in early spring and define genomic target regions for marker-assisted selection. Comparative analysis of genome-wide association studies revealed 13 treatment-specific major QTLs with partially pleiotropic effect on four freezing tolerance related traits. In addition, we identified five treatment-unspecific pleiotropic QTLs, including two major freezing tolerance loci on chromosomes 1 and 5. Our results thus indicate both a distinct and common genetic control of tolerance to winter- and late-frost in winter faba bean. In combination with the promising prediction abilities obtained from marker score-based prediction, our work highlights the potential for marker-assisted and genomic selection toward improved freezing tolerance and winter hardiness in winter faba bean breeding programs.
A novel framework for assessing the robustness of genomic animal models applied to a wild marine fish
Authors: Thia Joshua A. , Aguirre J. David , Hereward James , Evans Jennifer , Liggins Libby , Riginos Cynthia , McGuigan Katrina
Published: November 2024

Heritable genetic versus non-heritable plastic phenotypic variation determine how selection may shape evolutionary responses. Population genomic studies typically aim to identify associations between loci (SNPs) and phenotypes, missing broader insight into heritable basis of polygenic traits with quantitative genomic approaches.

Genomic animal models can facilitate estimates of trait heritability from genomic data but can be challenging to apply to wild organisms. This is because the populations of many wild organisms are large, comprising many distantly related individuals, which makes the sampling close-kin unlikely. This in turn limits the variation of relatedness in a sample, reducing the efficacy of genomic animal models.

We developed a novel framework for applying genomic animal models to wild organisms where sampling close-kin may be near impossible. Our framework combines resampling of genetic markers with simulating different levels of heritability to infer the power and reliability of genomic animal models fitted to datasets lacking kin structure.

We use our framework to estimate heritability of head shape traits in a wild marine intertidal fish,Bathygobius cocosensis(Bleeker 1854), using ddRAD SNP genotypes and phenotypes measured using geometric morphometric methods. In its eastern Australian range,B. cocosensisis highly abundant, has high effective gene flow, and occupies diverse habitats and microhabitats.

Placing our observed genomic animal model results in the context of simulated results, we conclude that two of the head shape traits were heritable (estimatedh2= 0.26 and 0.18). This suggests that head shape phenotypes could evolve through heritable genetic changes inB. cocosensis, although there is likely a large non- heritable component. We also found strong phenotypic differentiation (pairwisePST≤ 0.33) despite very weak genetic differentiation (pairwiseFST< 0.002), suggesting that environmental factors might structure phenotypes amidst processes homogenising genetic variation.

Our study addresses key methodological gaps for using quantitative genomic approaches on wild organisms, offering a rare example of partitioned heritable and non-heritable contributions to phenotypic variation in a non-model wild marine fish.

This would have been difficult without our new framework to overcome the challenges of a dataset lacking kin structure.
Sumatran orangutan mothers differ in the extent and trajectory of their expression of maternal behaviour
Authors: Revathe T , Mundry Roger , Utami-Atmoko Sri Suci , Umaira Aprilla Tazkia , A. van Noordwijk Maria , Fröhlich Marlen , Bürkner Paul-Christian , Schuppli Caroline
Published: November 2024

Mothers arguably play a crucial role in the early development and survival of mammalian offspring, and differences in maternal care may affect offspring’s physical and cognitive development. Whereas biological and socioecological factors contribute to differences among mothers, the individual as a source of variation remains understudied. We investigated between-individual variation in the average expression of and plasticity in six maternal behaviours in Sumatran orangutans, using 15 years of mother-offspring behavioural data. We found that mothers differed substantially in the average expression of four maternal behaviours, even after controlling for known predictors of these behaviours, and that not controlling for these confounding effects erroneously leads to larger estimated between-individual behavioural variation. Furthermore, orangutan mothers substantially differed in how they adjusted two maternal behaviours as their offspring aged – i.e., they showed variation in behavioural plasticity. Our study suggests that Sumatran orangutan mothers are constrained in the average expression of maternal behaviours and their plastic responses, potentially resulting in consistent differences among mothers, otherwise called maternal personality. Our findings highlight that individual variation around the population mean in maternal behaviour is more than noise but also that controlling for confounding effects is crucial to avoid the overestimation of individual variation.
RNF20-mediated H2B monoubiquitination protects stalled forks from degradation and promotes fork restart
Authors: Bhattacharya Debanjali , Dwivedi Harsh Kumar , Nagaraju Ganesh
Published: November 2024

Chromatin modifications play an important role in transcription, DNA replication and repair. Nonetheless, whether histone modifications regulate replication stress responses remains obscure. Here, we show that RNF20 localizes to and promotes H2B monoubiquitination (H2Bub) at replicating sites. Knockdown of RNF20 leads to degradation of stalled forks by MRE11 nuclease, which can be rescued by inhibition of MRE11 and co-depletion of SMARCAL1/HLTF/ZRANB3 fork remodelers. RNF20 facilitates the loading of RAD51 and RAD51C at the stalled fork sites and participates in the same pathway of RAD51/RAD51C-mediated fork protection and restart. Analyses with the RING domain and phosphorylation-deficient mutants of RNF20 showed that its catalytic activity and ATR/ATM-mediated phosphorylation are essential for its role in replication stress responses. Notably, treatment of RNF20-depleted cells with chromatin relaxing agents rescue the fork protection and restart defects. Collectively, our studies uncover the role of RNF20-mediated H2Bub in regulating the chromatin dynamics to safeguard the replicating genomes.
Influence of Contact Map Topology on RNA Structure Prediction
Authors: Faber Christian , Upadhyay Utkarsh , Taubert Oskar , Schug Alexander
Published: November 2024

The available sequence data of RNA molecules have highly increased in the past years. Unfortunately, while computational power is still under exponential growth, the computer prediction quality from sequence to final structure is still inferior to the labour intensive experimental work. Although a reliable end-to-end procedure was already developed for proteins since Alphafold2, while its successor AlphaFold3 can also predict RNA, its confidence in particular for novel sequences and folds appear still limited. Another strategy entails two steps: (i) predicting potential contacts in the form of a contact maps from evolutionary data, and (ii) simulating the molecule with a physical force field while using the contact map as restraint. However, the quality of the structure prediction crucially depends on the quality of the contact map. Until now, only the proportion of true positive contacts was considered as a quality characteristic. We propose to also include the distribution of these contacts, and have done so in our recent studies. We observed that the clustering of contacts, as is common for many AI algorithms, has a negative impact on prediction quality. In contrast, a more distributed topology is beneficial. We have applied these findings from computer experiments to current algorithms and introduced a measure of distribution, the Gaussian score.
Assessing Long-Read Mappers for Viral Genomics
Authors: Baudeau Thomas , Marchet Camille , Salson Mikaël
Published: November 2024

Long-read sequencing technologies from Pacific Biosciences and Oxford Nanopore Technologies (ONT) have advanced genomic research, producing reads over 10 kilobases and enabling rapid field-based viral surveillance. This study evaluates eight long-read mapping tools on viral genomic data, including modern and legacy methods. We assessed their performance on ONT reads and their impact on variant calling using bcftools and medaka. Using simulated and real datasets under varying conditions, reflecting different experimental and biological conditions, such as variable read lengths, error rates and the presence of multiple viral variants, we found that the majority of tools had great difficulty in correctly managing read edges. In addition, it was found that with a default setting, the performance of the tools decreased.
The presence of the Pacific Oyster OSHV-1 resistance marker on chromosome 8 does not impact susceptibility to infection by Vibrioaestuarianus
Authors: Surry Liam B. , Sutherland Ben J. G. , Lunda Spencer L. , Loudon Andrew H. , Divilov Konstantin , Langdon Chris J. , Green Timothy J.
Published: November 2024

The Pacific oyster,Crassostrea gigas, is an important species in global aquaculture, but its production is threatened by pathogenic infections such as Ostreid herpesvirus 1 (OsHV-1) andVibrio aestuarianus. A genetic marker for OsHV-1 resistance has been identified on chromosome 8 of the Pacific oyster genome, and selective breeding has been performed to produce OsHV-1-resistant oysters. However, the potential impact of this marker on susceptibility to other pathogens remains unknown. In this study, we assess the effect of the presence and allelic dosage of the OsHV-1 resistance marker on susceptibility toV. aestuarianusinfections in selectively bred oyster families from the Molluscan Broodstock Program of Oregon State University. Sixteen families were produced with various states of the OsHV-1 resistance marker, and a disease challenge withV. aestuarianuswas performed on these families to track mortality in each individual. Challenged oysters were genotyped at the OsHV-1 resistance locus, andVibriosusceptibility was compared among genotype groups within and between families. Additionally, double digest reduced representation sequencing (ddRADseq) was performed on challenged oysters, and a genome-wide association study was conducted for survivorship from theVibrioexposure. Results showed that prior to theVibrioexposure, the OsHV-1 resistance marker was not observed at the expected Mendelian inheritance ratios in families, with a significantly reduced presence of the homozygous alternate genotype in 75% of heterozygote family crosses. Among the 16 families, mortality rates differed significantly following exposure toV. aestuarianus(range: 85.4% to 47.9%), but there was no association found between the chromosome 8 marker and survival to Vibrio infection. No loci were found to be significantly associated to survivorship toVibrioinfection, suggesting Vibrio resistance in these families is not controlled by one or a few loci of large effect.
DOA/CLK2 phosphorylates Fl(2)d/WTAP to enhance m6A mRNA methyltransferase complex activity
Authors: McQuarrie David W. J. , Bian Wei , Soller Matthias
Published: November 2024

N6-methyladenosine (m6A) is the most abundant internal modification in messenger RNA (mRNA) providing an essential layer to the control of gene expression important to many biological processes. A megadalton writer complex deposits m6A methyl marks that are then read by YTH domain containing proteins. Deposition of m6A is thought to be regulated by cellular signalling but how remains uncertain. We identified the kinase DOA, a highly conserved homologue of human CLK2 by using the essential role of m6A in theDrosophilaSxl auto-regulation for sex determination and dosage compensation. We show that DOA kinase is required for m6A deposition andSxlalternative splicing. Overexpression of DOA can compensate writer complex insufficiency and rescue lethality of m6A in the context ofSxlmis- splicing, suggesting a key role in regulating activity of the m6A complex. Through genetic interaction experiments, we identify a phospho-site at the end of a conserved helical structure in Fl(2)d as DOA target. CLK2 phosphorylates the same helix in WTAP, the human homologue of Fl(2)d. CLK2 expands regulatory capacity through additional phospho-sites and changing of theDrosophilasite to a phosphomimetic-like glutamine, overall important for m6A directed regulation of dosage compensation genes in human cells.
Role of a TonB-dependent receptor and an oxygenase in iron-dependent copper resistance inCaulobacter crescentus
Authors: Cherry Pauline , Kasmo Hala , Godelaine Mauro , Tilquin Françoise , Dieu Marc , Renard Patsy , Matroule Jean-Yves
Published: November 2024

Copper (Cu) is potentially threatening for living organisms owing to its toxicity at high concentrations, requiring the onset of diverse detoxification strategies to maintain fitness. We previously showed that the environmental conditions modulate the response of the oligotrophic alphaproteobacteriumCaulobacter crescentusto Cu excess. In the present study, we investigated the role of the Fe-importing TonB-dependent receptor (TBDR) CciT and its partner, CciO, a 2-oxoglutarate/Fe2+-dependent oxygenase, in Cu resistance. CciT is specifically involved in Cu resistance in both rich and poor media. Using inductively coupled plasma optical emission spectrometry, we found that under Cu stress, the cellular Cu content is reduced by overexpression ofcciT, while Fe content increases. Mutations of the three known Fe-importing TBDRs reveal that CciT is the primary Fe importer in these conditions and the only TBDR required for Cu resistance. In addition, the extracellular Fe concentration is positively correlated with the cellular Fe content and negatively correlated with the cellular Cu content, resulting in the protection of the cells against Cu excess. The operon organization ofcciTandcciOis highly conserved across bacteria, indicating a functional link between the two proteins. Deletion ofcciT,cciO, or both genes leads to similar Cu sensitivity. Catalytic mutations in CciT and CciO also result in Cu sensitivity. While CciO is not required for Cu and Fe transport, its precise function remains unknown. Overall, this study provides new insights into the role of Fe uptake in Cu resistance, emphasizing the critical influence of environmental conditions on bacterial physiology.

Importance

Copper is an essential metal for many living organisms, as it helps to drive crucial chemical reactions. However, when present in excess, copper turns toxic due to its high reactivity with biological molecules. Bacteria may encounter excess copper in various environments, such as polluted soils, agricultural copper treatments, and within the vacuoles of infected macrophages. In this study, we investigated the copper response in the environmental bacteriumCaulobacter crescentus. Our findings reveal that environmental iron levels play a critical role in copper resistance, as increased iron prevents cellular copper accumulation and toxicity. We identified two essential proteins, CciT and CciO, that are involved in iron transport, providing protection against copper excess.
A Novel Actinobacteria-Specific Ribosome Hibernation Factor inMycobacterium tuberculosis
Authors: Majumdar Soneya , Li Yunlong , Manjari Swati R. , Gamper Howard B. , Hou Ya-Ming , Banavali Nilesh K. , Ojha Anil K. , Agrawal Rajendra K.
Published: November 2024

Mycobacterium tuberculosis(Mtb), the causative agent of tuberculosis (TB), persists within its host for long periods. Treatment of TB requires prolonged administration of antibiotics, some of which target Mtb ribosomes, the protein synthesizing machine of the cell. We determined high-resolution cryo-EM structures of Mtb ribosomes obtained from biofilms under zinc-depleted conditions that are expected to induce ribosome hibernation. In these structures, in addition to finding the Mtb homolog of the hibernation promoting factor Mpy that binds to the decoding center in the small ribosomal subunit, we discovered an actinobacteria-specific protein, previously of unknown function, bound in the nascent polypeptide-exit tunnel (NPET) within the large ribosomal subunit. We refer to this NPET-bound protein as a actinobacteria-specific ribosome tunnelocclusion factor (RTOF). RTOF is found with vacant or E-tRNA-bound 70S ribosomes, but not in actively translating Mtb ribosomes, suggesting that its binding coincides with ribosome hibernation. RTOF makes strong interactions through the entire stretch of NPET extending up to the peptidyl-transferase center (PTC), such that it would block the passage of nascent polypeptide chain. The highly conserved FRRKSG motif of RTOF also interferes with accommodation of the formyl-methionyl moiety of initiator fMet-tRNAfMetin the conformation required for translation initiation. A molar excess of mRNA and initiator fMet-tRNAfMetdisplaces RTOF by triggering a significant alteration to the conformation of FRRKSG motif, which suggests how RTOF-bound hibernating ribosomes can be reactivated under optimal cellular conditions. The presence of RTOF would interfere with the binding of PTC-targeting drugs, such as macrolides, lincosamides, and oxazolidines, thereby maintaining a drug-free pool of hibernating Mtb ribosomes.
Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12
Authors: Ingersoll Andrew J. , McCloud Devlon M. , Hu Jenny Y. , Rape Michael
Published: November 2024

The oxidative stress response is centered on the transcription factor NRF2 and protects cells from reactive oxygen species (ROS). While ROS inhibit the E3 ligase CUL3KEAP1to stabilize NRF2 and elicit antioxidant gene expression, cells recovering from stress must rapidly reactivate CUL3KEAP1to prevent reductive stress and oxeiptosis-dependent cell death. How cells restore efficient NRF2-degradation upon ROS clearance remains poorly understood. Here, we identify TRIP12, an E3 ligase dysregulated in Clark-Baraitser Syndrome and Parkinson’s Disease, as a component of the oxidative stress response. TRIP12 is a ubiquitin chain elongation factor that cooperates with CUL3KEAP1to ensure robust NRF2 degradation. In this manner, TRIP12 accelerates stress response silencing as ROS are being cleared, but limits NRF2 activation during stress. The need for dynamic control of NRF2-degradation therefore comes at the cost of diminished stress signaling, suggesting that TRIP12 inhibition could be used to treat degenerative pathologies characterized by ROS accumulation.
Integration of hunger and hormonal state gates infant-directed aggression
Authors: Cao Mingran , Ammari Rachida , Chen Maxwell Xiangheng , Wai Patty , Sahni Aashna , Liang Swang , Legrave Nathalie , MacRae James I , Strom Molly , Kohl Johannes
Published: November 2024

Social behaviour is profoundly shaped by internal physiological states. While significant progress has been made in understanding how individual states such as hunger, stress, or arousal modulate behaviour, animals experience multiple states at any given time. The neural mechanisms that integrate such orthogonal states - and how this integration affects behaviour - remain poorly understood. Here we report how hunger and estrous state converge on neurons in the medial preoptic area (MPOA) to shape infant-directed behaviour. We find that hunger promotes pup-directed aggression in normally non aggressive virgin female mice. This behavioural switch occurs through inhibition of MPOA neurons, driven by the release of neuropeptide Y (NPY) from Agouti-related peptide-expressing neurons in the arcuate nucleus (ArcAgRPneurons). The propensity for hunger induced aggression is set by reproductive state, with MPOA neurons detecting changes in progesterone (P4) to estradiol (E2) ratio across the estrous cycle. Hunger and estrous state converge on HCN (hyperpolarization-activated cyclic nucleotide-gated) channels, which sets the baseline activity and excitability of MPOA neurons. Using micro endoscopic imaging, we confirm these findingsin vivo, revealing that MPOA neurons encode a state for pup-directed aggression. This work thus provides a mechanistic understanding of how multiple physiological states are integrated to flexibly control social behaviour.
Dynamic whole-body models for infant metabolism
Authors: Zaunseder Elaine , Mohammad Faiz Khan , Mütze Ulrike , Kölker Stefan , Heuveline Vincent , Thiele Ines
Published: November 2024

1

Comprehensive, sex-specific whole-body models (WBMs) accounting for organ-specific metabolism have been developed to allow for the simulation of adult and infant metabolism. These WBMs are evaluated daily, giving insights into metabolic flux changes that occur in one day of an infant’s or adult’s life. However, for medical applications, such as in metabolic diseases and their treatment, an evaluation and concentration predictions on a shorter time scale would be beneficial. Therefore, we developed a dynamic infant-WBM that couples metabolite dynamics in short time frames through physiology-based pharma-cokinetic models with the existing infant whole-body models. We then tailored the dynamic infant-WBM enabling the prediction of isovalerylcarnitine (C5), a clinical biomarker used for the inherited metabolic disease isovaleric aciduria (IVA). Our results show that, as expected, the predicted C5 concentrations exceeded the newborn screening thresholds during the time (36 - 72 hours) newborn screening blood samples are taken in the IVA models but not in models simulating healthy infants. We also demonstrate how the dynamic infant-WBMs can be used to test the effect changes in dietary intake have on the biomarker. Since the dynamic infant-WBMs were parametrised with literature-derived experimental or estimated values, we show how uncertainty quantification can be applied to quantify the parameter uncertainties. We found that the fractional unbound plasma needed to be estimated correctly, as this parameter strongly impacted C5 concentration predictions of the dynamic infant-WBMs. Overall, the dynamic infant-WBMs hold promise for personalised medicine, as it enables personalised biomarker concentration predictions of healthy and diseased infant metabolism in various time intervals.
A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice
Authors: Maloney Susan E. , McCullough Katherine B. , Chaturvedi Sneha M. , Selmanovic Din , Chase Rebecca , Chen Jiayang , Wu Doris , Granadillo Jorge L. , Kroll Kristen L. , Dougherty Joseph D.
Published: November 2024

The transcription factor MYT1L supports proper neuronal differentiation and maturation during brain development. MYT1L haploinsufficiency results in a neurodevelopmental disorder characterized by intellectual disability, developmental delay, autism, behavioral disruptions, aggression, obesity and epilepsy. While MYT1L is expressed throughout the brain, how it supports proper neuronal function in distinct regions has not been assessed. Some features of MYT1L Neurodevelopmental Syndrome suggest disruption of hypothalamic function, such as obesity and endocrine issues, and previous research showed changes in hypothalamic neuropeptide expression following knockdown in zebrafish. Here, we leveraged our heterozygousMyt1lmutant, previously shown to recapitulate aspects of the human syndrome such as hyperactivity, social challenges, and obesity, to examine the impact of MYT1L loss on hypothalamic function. Examining the molecular profile of the MYT1L haploinsufficient hypothalamus revealed a similar scale of disruption to previously studied brain regions, yet with region-specific roles for MYT1L, including regulation of neuropeptide systems. Alterations in oxytocin and arginine vasopressin cell numbers were also found. Behaviors studied included maternal care, social group hierarchies, and aggression, all of which were unchanged. Feeding and metabolic markers were also largely unchanged in MYT1L haploinsufficient mice, yet an interaction was observed between diet and MYT1L genotype on weight gain. Our findings here suggest that gross endocrine function was not altered by MYT1L haploinsufficiency, and that key sex-specific behaviors related to proper hypothalamic function remain intact. Further study is needed to understand the functional impact of the altered hypothalamic molecular profile and changes in neuropeptide cell numbers that result from MYT1L haploinsufficiency.
Isolation of an infectious mammalian chu-like virus from tumor cells of the endangered Tasmanian devil (Sarcophilus harrisii)
Authors: Mélade Julien , Harvey Erin , Mahar Jackie E. , Darby Jocelyn M. , Flies Andrew S. , Holmes Edward C.
Published: November 2024

Jingchuvirales(negative-sense RNA viruses) were initially discovered in invertebrates, with both exogenous and endogenous jingchuviruses subsequently identified in fish, reptiles and mammals. To date, jingchuviruses have only been described metagenomically. By screening primary tumor tissues and tumor cell lines from the endangered Tasmanian devil (Sarcophilus harrisii), we isolated Tasmanian devil chu-like virus (TDCV) from cultures of Tasmanian devil facial tumor disease (DFTD) cells. Cell infection experiments demonstrated active virus replication in Tasmanian devil tumor cells, but not mosquito cells. The absence of viral replication in fibroblasts in cell culture and the lack of RNA detection in several organs suggested that replication was associated with tumor cells. Phylogenetic analysis revealed that TDCV likely represents a novel virus family. This is the first isolation of a jingchuvirus, demonstrating their capacity to infect mammalian cells, and providingin vitroavenues to understand the biology of TDCV and its association with tumor cell infection.
Multisensory integration across reference frames with additive feed-forward networks
Authors: Farahmandi Arefeh , Abedi Khoozani Parisa , Blohm Gunnar
Published: November 2024

The integration of multiple sensory inputs is essential for human perception and action in uncertain environments. This process includes reference frame transformations as different sensory signals are encoded in different coordinate systems. Studies have shown multisensory integration in humans is consistent with Bayesian optimal inference. However, neural mechanisms underlying this process are still debated. Different population coding models have been proposed to implement probabilistic inference. This includes a recent suggestion that explicit divisive normalization accounts for empirical principles of multisensory integration. However, whether and how divisive operations are implemented in the brain is not well understood. Indeed, all existing models suffer from the curse of dimensionality and thus fail to scale to real-world problems. Here, we propose an alternative model for multisensory integration that approximates Bayesian inference: a multilayer-feedforward neural network of multisensory integration (MSI) across different reference frames trained on the analytical Bayesian solution. This model displays all empirical principles of multisensory integration and produces similar behavior to that reported in Ventral intraparietal (VIP) neurons in the brain. The model achieved this without a neatly organized and regular connectivity structure between contributing neurons, such as required by explicit divisive normalization. Overall, we show that simple feedforward networks of purely additive units can approximate optimal inference across different reference frames through parallel computing principles. This suggests that it is not necessary for the brain to use explicit divisive normalization to achieve multisensory integration.

Significance Statement

This research presents an alternative model to divisive normalization models of multisensory integration in the brain. Our study demonstrates that a feed-forward neural network can achieve optimal multisensory integration across different reference frames without explicitly implementing divisive operations, challenging the long-held assumption that such operations are necessary for multisensory integration. The model displays all the empirical principles of multisensory integration, producing similar behavior to that reported in Ventral intraparietal (VIP) neurons in the brain. This work offers profound insights into the putative neural computations underlying multisensory processing.
Target sensitivity study of density transition-injected electrons in laser wakefield accelerators
Authors: Cobo C. C. , Arran C. , Bourgeois N. , Calvin L. , Carderelli J. , Cavanagh N. , Colgan C. , Dann S. J. D. , Fitzgarrald R. , Gerstmayr E. , Kettle B. , Los E. E. , Mangles S. P. D. , McKenna P. , Najmudin Z. , Rajeev P. P. , Ridgers C. P. , Sarri G. , Streeter M. J. V. , Symes D. R. , Thomas A. G. R. , Watt R. , Murphy C. D.
Published: November 2024

While plasma-based accelerators have the potential to positively impact a broad range of research topics, a route to application will only be possible through improved understanding of their stability. We present experimental results of a laser wakefield accelerator in the nonlinear regime in a helium gas jet target with a density transition produced by a razor blade in the flow. Modifications to the target setup are correlated with variations in the plasma density profile diagnosed via interferometry and the shot-to-shot variations of the density profile for nominally equal conditions are characterized. Through an in-depth sensitivity study using particle-in-cell simulations, the effects of changes in the plasma density profile on the accelerated electron beams are investigated. The results suggest that blade motion is more detrimental to stability than gas pressure fluctuations, and that early focusing of the laser may reduce the deleterious effects of such density fluctuations.

Published by the American Physical Society
2024
Influence of nanoparticulates and microgrooves on the secondary electron yield and electrical resistance of laser-treated copper surfaces
Authors: Krkotić P. , Madarász T. , Serafim C. , Neupert H. , Perez-Fontenla A. T. , Himmerlich M. , Calatroni S. , Wackerow S. , Abdolvand A.
Published: November 2024

Laser surface structuring has proven to be an effective technique for achieving a copper surface with secondary electron yield (SEY) values close to or below unity. However, the attributes that minimize SEY, such as moderately deep grooves and redeposited nanoparticles, may lead to undesirable consequences, including increased radio frequency surface resistance. This investigation systematically examined data about different cleaning procedures designed to eliminate redeposited adsorbed particulates. Various analysis techniques were used iteratively after each consecutive cleaning step, providing insights into the evolving surface characteristics. The collected experimental results identified distinct impacts of microgrooves, groove orientation, and associated particulates on secondary electron yield and surface resistance. Exposing the crests while retaining high particulate coverage in the grooves leads to reduced SEY values and surface resistance, suggesting that the tips of the grooves exert a more significant influence on surface current density than the groove depth. At the same time, nanoparticles in the grooves have a more significant impact on SEY values than the exposed tips at the surface.

Published by the American Physical Society
2024
Lattice spectra of the
DDK
three-body system with Lorentz covariant kinematic
Authors: Xiao Qi-Chao , Pang Jin-Yi , Wu Jia-Jun
Published: November 2024

The DDK system has gained increasing attention in recent research due to its potential to contain a three-hadron bound state. This paper utilizes an extension of the nonrelativistic effective field theory and the finite volume particle-dimer framework to derive Lorentz invariant quantization conditions for the DDK three-body system. Using current model input conditions, the finite volume energy spectrum of the DDK three-body system was calculated. This new calculation incorporates relativistic kinematics, allowing it to be applicable across a broader energy range starting from the threshold. In this work, we present a comprehensive O(p2) calculation. The spurious pole is effectively subtracted within the framework of relativistic kinematics. The spectra in the moving frame are also obtained. These analyses provide a broader testing ground for future lattice simulations. Based on this framework, it is expected to reveal more detailed properties of the DDK system and other three-hadron systems, if various higher-order effects, such as the isospin I=1 DK interactions and the coupled-channel effects are introduced.

Published by the American Physical Society
2024
Finite basis topologies for multiloop high-multiplicity Feynman integrals
Authors: Bargieła Piotr , Yang Tong-Zhi
Published: November 2024

In this work, we systematically analyze Feynman integrals in the ‘t Hooft-Veltman scheme. We write an explicit reduction resulting from partial fractioning the high-multiplicity integrands to a finite basis of topologies at any given loop order. We find all of these finite basis topologies at two loops in four external dimensions. Their maximal cut and the leading singularity are expressed in terms of the Gram determinant and Baikov polynomial. By performing an integration-by-parts reduction without any cut constraint on a numerical probe for one of these topologies, we show that the computational complexity drops significantly compared to the conventional dimensional regularization scheme. Formally, our work implies an upper bound on the rigidity of special functions appearing in the iterated integral solutions at each loop order in perturbative quantum field theory. Phenomenologically, the integrand-level reduction we present will substantially simplify the task of providing high-precision predictions for future high-multiplicity collider observables.

Published by the American Physical Society
2024
Path integral for chord diagrams and chaotic-integrable transitions in double scaled SYK
Authors: Berkooz Micha , Brukner Nadav , Jia Yiyang , Mamroud Ohad
Published: November 2024

We study transitions from chaotic to integrable Hamiltonians in the double scaled Sachdev-Ye-Kitaev (SYK) and p-spin systems. The dynamics of our models is described by chord diagrams with two species. We begin by developing a path integral formalism of coarse graining chord diagrams with a single species of chords, which has the same equations of motion as the bilocal (GΣ) Liouville action, yet appears otherwise to be different and in particular well defined. We then develop a similar formalism for two types of chords, allowing us to study different types of deformations of double scaled SYK and in particular a deformation by an integrable Hamiltonian. The system has two distinct thermodynamic phases: one is continuously connected to the chaotic SYK Hamiltonian, the other is continuously connected to the integrable Hamiltonian, separated at low temperature by a first order phase transition. We also analyze the phase diagram for generic deformations, which in some cases includes a zero-temperature phase transition.

Published by the American Physical Society
2024
Truly relativistic gravity mediated entanglement protocol using superpositions of rotational energies
Authors: Higgins Gerard , Di Biagio Andrea , Christodoulou Marios
Published: November 2024

Experimental proposals for testing quantum gravity-induced entanglement of masses (QGEM) typically involve two interacting masses which are each in a spatial superposition state. Here, we propose instead a QGEM experiment with two particles which are each in a superposition of rotational states; this amounts to a superposition of mass through mass-energy equivalence. In sharp contrast to the typical protocols studied, our proposal is genuinely relativistic. It does not consider a quantum positional degree of freedom and but relies on the fact that rotational energy gravitates: the effect we consider disappears in the c→∞ limit. Furthermore, this approach would test a feature unique to gravity since it amounts to sourcing a spacetime in superposition due to a superposition of “charge.”

Published by the American Physical Society
2024
Introducing quantum physics concepts and Dirac notation at the secondary school level: Insights into student reasoning from an acceptance survey
Authors: Hennig Fabian , Tóth Kristóf , Veith Joaquin , Bitzenbauer Philipp
Published: November 2024

Evidence from physics education research suggests that the introduction of a formalistic description of quantum phenomena can be beneficial to student learning, particularly in terms of helping students move away from naive realist views of quanta or space-time descriptions of quantum phenomena. However, the mathematical requirements for mastering quantum formalism are typically far beyond the scope of secondary school education. Therefore, in previous research, we have proposed a reduced Dirac notation tailored to the capabilities of secondary school students, which is included in a novel teaching-learning sequence. However, the cognitive processes of students when confronted with an introduction to quantum physics via a reduced Dirac notation have not been thoroughly investigated: In particular, it seems important to investigate whether this approach is actually beneficial to students’ learning and to explore the learning difficulties students are likely to encounter in such a setting. This paper contributes to this research gap by reporting the findings of an acceptance survey: N=14 learners participated in one-on-one interviews following a protocol consisting of four cyclical phases (information phase, acceptance evaluation, paraphrasing phase, and application phase). The findings of our study indicate that the instructional elements within our new teaching-learning sequence were generally well accepted by students but also revealed learning difficulties that students may encounter. Thus, on the one hand, the findings of this study pave the way for future research on students’ learning of quantum physics using Dirac notation. On the other hand, the in-depth findings reported here may guide teachers in designing learning environments that introduce Dirac notation at the upper secondary school and introductory university levels.

Published by the American Physical Society
2024
Universal heat superdiffusion in one-dimensional nonequilibrium lattices
Authors: Ren Yuanyang , Wang Yang , Wu Kai , Cubero David
Published: November 2024

We propose a generalized Fourier's law, based on recent mode-coupling calculations, for one-dimensional nonlinear lattices in nonequilibrium simulations, where the boundaries are kept at different temperatures. Though not useful for the typical textbook numerical examples, we are able to demonstrate numerically the theory for an anharmonic lattice with force field parameters similar to those of realistic low-dimensional structures such as covalently bonded molecular chains or carbon nanotubes, specifically showing that the asymptotic heat conductivity is described by the mode-coupling theory in good approximation, without any adjustable parameter.

Published by the American Physical Society
2024
Atom-Atom entanglement generation via collective states of atomic rings
Authors: Antman Ron Nadav , Carmi Maor , Bekenstein Rivka
Published: November 2024

Subwavelength atomic lattices have been established as a promising platform for quantum applications, utilizing collective superradiant and subradiant behavior to enhance atom-light interactions. While previous work has demonstrated high-fidelity atom-photon entanglement in these systems, the generation of atom–atom entanglement, a crucial ingredient for full scalability, remains a conceptual challenge. Here, we propose methods for high-fidelity entanglement generation between atomic qubits by identifying specific atoms within a ring array as qubits. The entanglement generation is achieved by collective atomic excitation involving both subradiant and superradiant states and leveraging the novel symmetry properties of the ring array. Specifically, we utilize symmetry breaking within the ring by preparing atomic qubits in a superpositions of detunings for our entanglement protocols. A fidelity analysis of the protocols provides practical experimental parameters for state-of-the-art setups.

Published by the American Physical Society
2024
Task Learning through Stimulation-Induced Plasticity in Neural Networks
Authors: Borra Francesco , Cocco Simona , Monasson Rémi
Published: November 2024

Synaptic plasticity dynamically shapes the connectivity of neural systems and is key to learning processes in the brain. To what extent the mechanisms of plasticity can be exploited to drive a neural network and make it perform some kind of computational task remains unclear. This question, relevant in a bioengineering context, can be formulated as a control problem on a high-dimensional system with strongly constrained and nonlinear dynamics. We present a self-contained procedure which, through appropriate spatiotemporal stimulations of the neurons, is able to drive rate-based neural networks with arbitrary initial connectivity towards a desired functional state. We illustrate our approach on two different computational tasks: a nonlinear association between multiple input stimulations and activity patterns (representing digit images), and the construction of a continuous attractor encoding a collective variable in a neural population. Our work thus provides a proof of principle for emerging paradigms of computation based on real neurons.

Published by the American Physical Society
2024
A Framework for Fully Programmable Frequency-Encoded Quantum Networks Harnessing Multioutput Quantum Pulse Gates
Authors: Folge Patrick , Stefszky Michael , Brecht Benjamin , Silberhorn Christine
Published: November 2024

Linear optical quantum networks, consisting of a quantum input state and a multiport interferometer, are an important building block for many quantum technological concepts, e.g., Gaussian boson sampling. Here, we propose the implementation of such networks based on frequency conversion by utilizing a so-called multioutput quantum pulse gate (MQPG). This approach allows the resource-efficient and therefore scalable implementation of frequency-bin-based, fully programmable interferometers in a single spatial and polarization mode. Quantum input states for this network can be provided by utilizing the strong frequency entanglement of a type-0 parametric down-conversion (PDC) source. Here, we develop a theoretical framework to describe linear networks based on an MQPG and PDC and utilize it to investigate the limits and scalabilty of our approach.

Published by the American Physical Society
2024
Optimal operation guidelines for direct recovery of high-purity precursor from spent lithium-ion batteries: hybrid operation model of population balance equation and data-driven classifier
Authors: Kim Jeongdong , Ga Seongbin , Suh Sungho , Kwon Joseph Sang-Il , Park Kiho , Kim Junghwan
Published: November 2024

The direct resynthesis of precursor from spent lithium-ion batteries (LIBs) via co-precipitation is a crucial step in closed-loop cathode recycling systems. However, design and operation strategies for producing high-purity precursors have not been comprehensively explored or optimized. Herein, we propose the optimization of co-precipitation during the recovery of spent LIBs to achieve impurity-free precursor resynthesis. By incorporating the thermodynamic equilibrium model of the leaching solution of spent LIBs into a population balance equation (PBE) model, we identified the operating ranges that prevented the formation of impurities. Bayesian optimization was employed within the screened operating ranges to determine the optimal operating conditions for minimizing both operation time and maximum particle size. This optimization was performed for both unseeded batch and semi-batch systems. The results demonstrate that the selection of an optimal semi-batch operation can reduce the operation time by 23.33% and increase the particle size by 54.75%, owing to the high nucleation and particle growth rate during the initial time step. By employing an optimization approach based on the PBE model, this study provides detailed operational guidelines for batch and semi-batch co-precipitation, enabling the production of high-purity precursor materials from spent LIBs, while minimizing both operating time and maximum particle size.
Examination of the influence of the integrated mission management system on the pilot’s situational awareness
Authors: Drupka Grzegorz , Grzybowski Piotr , Szczerba Piotr , Bichajło Lesław
Published: November 2024

Purpose

This paper aims to present research carried out on the influence of GUI graphical elements design for an integrated mission management system (IMMS) display flight planning process.

Design/methodology/approach

Surveys and research were conducted among students/pilots to explore graphic presentation methods for flight planning displays. Guidelines for graphical layout of the IMMS flight planning interface are proposed.

Findings

A research concept was obtained, enabling GUI tests for IMMS using prepared templates and questionnaires.

Practical implications

This study improves cockpit information readability, understanding and presentation, particularly for flight planning elements such as terrain, weather, traffic and zones influencing route organisation.

Social implications

This study targets possible improvements to the flight path planning process in aviation, inducing a reduction in errors related to human factors while processing the visual data on-board.

Originality/value

The study verified the impact of drawing and rendering methods on IMMS flight planning, suggesting that current display methods may be error-prone when showing hazard information from multiple sources on a single screen.