bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exponential concentration in quantum kernel methods
Authors: Thanasilp Supanut , Wang Samson , Cerezo M. , Holmes Zoë 
Published: June 2024

AbstractKernel methods in Quantum Machine Learning (QML) have recently gained significant attention as a potential candidate for achieving a quantum advantage in data analysis. Among other attractive properties, when training a kernel-based model one is guaranteed to find the optimal model’s parameters due to the convexity of the training landscape. However, this is based on the assumption that the quantum kernel can be efficiently obtained from quantum hardware. In this work we study the performance of quantum kernel models from the perspective of the resources needed to accurately estimate kernel values. We show that, under certain conditions, values of quantum kernels over different input data can be exponentially concentrated (in the number of qubits) towards some fixed value. Thus on training with a polynomial number of measurements, one ends up with a trivial model where the predictions on unseen inputs are independent of the input data. We identify four sources that can lead to concentration including expressivity of data embedding, global measurements, entanglement and noise. For each source, an associated concentration bound of quantum kernels is analytically derived. Lastly, we show that when dealing with classical data, training a parametrized data embedding with a kernel alignment method is also susceptible to exponential concentration. Our results are verified through numerical simulations for several QML tasks. Altogether, we provide guidelines indicating that certain features should be avoided to ensure the efficient evaluation of quantum kernels and so the performance of quantum kernel methods.
Enhanced eMAGE applied to identify genetic factors of nuclear hormone receptor dysfunction via combinatorial gene editing
Authors: Ciaccia Peter N. , Liang Zhuobin , Schweitzer Anabel Y. , Metzner Eli , Isaacs Farren J. 
Published: June 2024

AbstractTechnologies that generate precise combinatorial genome modifications are well suited to dissect the polygenic basis of complex phenotypes and engineer synthetic genomes. Genome modifications with engineered nucleases can lead to undesirable repair outcomes through imprecise homology-directed repair, requiring non-cleavable gene editing strategies. Eukaryotic multiplex genome engineering (eMAGE) generates precise combinatorial genome modifications in Saccharomyces cerevisiae without generating DNA breaks or using engineered nucleases. Here, we systematically optimize eMAGE to achieve 90% editing frequency, reduce workflow time, and extend editing distance to 20 kb. We further engineer an inducible dominant negative mismatch repair system, allowing for high-efficiency editing via eMAGE while suppressing the elevated background mutation rate 17-fold resulting from mismatch repair inactivation. We apply these advances to construct a library of cancer-associated mutations in the ligand-binding domains of human estrogen receptor alpha and progesterone receptor to understand their impact on ligand-independent autoactivation. We validate that this yeast model captures autoactivation mutations characterized in human breast cancer models and further leads to the discovery of several previously uncharacterized autoactivating mutations. This work demonstrates the development and optimization of a cleavage-free method of genome editing well suited for applications requiring efficient multiplex editing with minimal background mutations.
PIP2 modulates TRPC3 activity via TRP helix and S4-S5 linker
Authors: Clarke Amy , Skerjanz Julia , Gsell Mathias A. F. , Wiedner Patrick , Erkan-Candag Hazel , Groschner Klaus , Stockner Thomas , Tiapko Oleksandra 
Published: June 2024

AbstractThe transient receptor potential canonical type 3 (TRPC3) channel plays a pivotal role in regulating neuronal excitability in the brain via its constitutive activity. The channel is intricately regulated by lipids and has previously been demonstrated to be positively modulated by PIP2. Using molecular dynamics simulations and patch clamp techniques, we reveal that PIP2 predominantly interacts with TRPC3 at the L3 lipid binding site, located at the intersection of pre-S1 and S1 helices. We demonstrate that PIP2 sensing involves a multistep mechanism that propagates from L3 to the pore domain via a salt bridge between the TRP helix and S4-S5 linker. Notably, we find that both stimulated and constitutive TRPC3 activity require PIP2. These structural insights into the function of TRPC3 are invaluable for understanding the role of the TRPC subfamily in health and disease, in particular for cardiovascular diseases, in which TRPC3 channels play a major role.
Epistasis mediates the evolution of the receptor binding mode in recent human H3N2 hemagglutinin
Authors: Lei Ruipeng , Liang Weiwen , Ouyang Wenhao O. , Hernandez Garcia Andrea , Kikuchi Chika , Wang Shengyang , McBride Ryan , Tan Timothy J. C. , Sun Yuanxin , Chen Chunke , Graham Claire S. , Rodriguez Lucia A. , Shen Ivana R. , Choi Danbi , Bruzzone Roberto , Paulson James C. , Nair Satish K. , Mok Chris K. P. , Wu Nicholas C. 
Published: June 2024

AbstractThe receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D and D190N in the hemagglutinin receptor-binding site have coevolved in two recent human H3N2 clades. X-ray crystallography results show that these mutations coordinately drive the evolution of the hemagglutinin receptor binding mode. Epistasis between G186D and D190N is further demonstrated by glycan binding and thermostability analyses. Immunization and neutralization experiments using mouse and human samples indicate that the evolution of receptor binding mode is accompanied by a change in antigenicity. Besides, combinatorial mutagenesis reveals that G186D and D190N, along with other natural mutations in recent H3N2 strains, alter the compatibility with a common egg-adaptive mutation in seasonal influenza vaccines. Overall, our findings elucidate the role of epistasis in shaping the recent evolution of human H3N2 hemagglutinin and substantiate the high evolvability of its receptor-binding mode.
Strain to shine: stretching-induced three-dimensional symmetries in nanoparticle-assembled photonic crystals
Authors: An Tong , Jiang Xinyu , Gao Feng , Schäfer Christian , Qiu Junjun , Shi Nan , Song Xiaokun , Zhang Manyao , Finlayson Chris E. , Zheng Xuezhi , Li Xiuhong , Tian Feng , Zhu Bin , Sui Tan , Han Xianhong , Baumberg Jeremy J. , Fan Tongxiang , Zhao Qibin 
Published: June 2024

AbstractStretching elastic materials containing nanoparticle lattices is common in research and industrial settings, yet our knowledge of the deformation process remains limited. Understanding how such lattices reconfigure is critically important, as changes in microstructure lead to significant alterations in their performance. This understanding has been extremely difficult to achieve due to a lack of fundamental rules governing the rearrangements. Our study elucidates the physical processes and underlying mechanisms of three-dimensional lattice transformations in a polymeric photonic crystal from 0% to over 200% strain during uniaxial stretching. Corroborated by comprehensive experimental characterizations, we present analytical models that precisely predict both the three-dimensional lattice structures and the macroscale deformations throughout the stretching process. These models reveal how the nanoparticle lattice and matrix polymer jointly determine the resultant structures, which breaks the original structural symmetry and profoundly changes the dispersion of photonic bandgaps. Stretching induces shifting of the main pseudogap structure out from the 1st Brillouin zone and the merging of different symmetry points. Evolutions of multiple photonic bandgaps reveal potential optical singularities shifting with strain. This work sets a new benchmark for the reconfiguration of soft material structures and may lay the groundwork for the study of stretchable three-dimensional topological photonic crystals.
Enhanced stress resilience in potato by deletion of Parakletos
Authors: Zahid Muhammad Awais , Kieu Nam Phuong , Carlsen Frida Meijer , Lenman Marit , Konakalla Naga Charan , Yang Huanjie , Jyakhwa Sunmoon , Mravec Jozef , Vetukuri Ramesh , Petersen Bent Larsen , Resjö Svante , Andreasson Erik 
Published: June 2024

AbstractContinued climate change impose multiple stressors on crops, including pathogens, salt, and drought, severely impacting agricultural productivity. Innovative solutions are necessary to develop resilient crops. Here, using quantitative potato proteomics, we identify Parakletos, a thylakoid protein that contributes to disease susceptibility. We show that knockout or silencing of Parakletos enhances resistance to oomycete, fungi, bacteria, salt, and drought, whereas its overexpression reduces resistance. In response to biotic stimuli, Parakletos-overexpressing plants exhibit reduced amplitude of reactive oxygen species and Ca2+ signalling, and silencing Parakletos does the opposite. Parakletos homologues have been identified in all major crops. Consecutive years of field trials demonstrate that Parakletos deletion enhances resistance to Phytophthora infestans and increases yield. These findings demark a susceptibility gene, which can be exploited to enhance crop resilience towards abiotic and biotic stresses in a low-input agriculture.
Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer’s disease
Authors: Babygirija Reji , Sonsalla Michelle M. , Mill Jericha , James Isabella , Han Jessica H. , Green Cara L. , Calubag Mariah F. , Wade Gina , Tobon Anna , Michael John , Trautman Michaela M. , Matoska Ryan , Yeh Chung-Yang , Grunow Isaac , Pak Heidi H. , Rigby Michael J. , Baldwin Dominique A. , Niemi Natalie M. , Denu John M. , Puglielli Luigi , Simcox Judith , Lamming Dudley W. 
Published: June 2024

AbstractDietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer’s disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.
Deep sequencing of Escherichia coli exposes colonisation diversity and impact of antibiotics in Punjab, Pakistan
Authors: Khawaja Tamim , Mäklin Tommi , Kallonen Teemu , Gladstone Rebecca A. , Pöntinen Anna K. , Mero Sointu , Thorpe Harry A. , Samuelsen Ørjan , Parkhill Julian , Izhar Mateen , Akhtar M. Waheed , Corander Jukka , Kantele Anu 
Published: June 2024

AbstractMulti-drug resistant (MDR) E. coli constitute a major public health burden globally, reaching the highest prevalence in the global south yet frequently flowing with travellers to other regions. However, our comprehension of the entire genetic diversity of E. coli colonising local populations remains limited. We quantified this diversity, its associated antimicrobial resistance (AMR), and assessed the impact of antibiotic use by recruiting 494 outpatients and 423 community dwellers in the Punjab province, Pakistan. Rectal swab and stool samples were cultured on CLED agar and DNA extracted from plate sweeps was sequenced en masse to capture both the genetic and AMR diversity of E. coli. We assembled 5,247 E. coli genomes from 1,411 samples, displaying marked genetic diversity in gut colonisation. Compared with high income countries, the Punjabi population generally showed a markedly different distribution of genetic lineages and AMR determinants, while use of antibiotics elevated the prevalence of well-known globally circulating MDR clinical strains. These findings implicate that longitudinal multi-regional genomics-based surveillance of both colonisation and infections is a prerequisite for developing mechanistic understanding of the interplay between ecology and evolution in the maintenance and dissemination of (MDR) E. coli.
Structural basis for hyperpolarization-dependent opening of human HCN1 channel
Authors: Burtscher Verena , Mount Jonathan , Huang Jian , Cowgill John , Chang Yongchang , Bickel Kathleen , Chen Jianhan , Yuan Peng , Chanda Baron 
Published: June 2024

AbstractHyperpolarization and cyclic nucleotide (HCN) activated ion channels are critical for the automaticity of action potentials in pacemaking and rhythmic electrical circuits in the human body. Unlike most voltage-gated ion channels, the HCN and related plant ion channels activate upon membrane hyperpolarization. Although functional studies have identified residues in the interface between the voltage-sensing and pore domain as crucial for inverted electromechanical coupling, the structural mechanisms for this unusual voltage-dependence remain unclear. Here, we present cryo-electron microscopy structures of human HCN1 corresponding to Closed, Open, and a putative Intermediate state. Our structures reveal that the downward motion of the gating charges past the charge transfer center is accompanied by concomitant unwinding of the inner end of the S4 and S5 helices, disrupting the tight gating interface observed in the Closed state structure. This helix-coil transition at the intracellular gating interface accompanies a concerted iris-like dilation of the pore helices and underlies the reversed voltage dependence of HCN channels.
Competing climate feedbacks of ice sheet freshwater discharge in a warming world
Authors: Li Dawei , DeConto Robert M. , Pollard David , Hu Yongyun 
Published: June 2024

AbstractFreshwater discharge from ice sheets induces surface atmospheric cooling and subsurface ocean warming, which are associated with negative and positive feedbacks respectively. However, uncertainties persist regarding these feedbacks’ relative strength and combined effect. Here we assess associated feedbacks in a coupled ice sheet-climate model, and show that for the Antarctic Ice Sheet the positive feedback dominates in moderate future warming scenarios and in the early stage of ice sheet retreat, but is overwhelmed by the negative feedback in intensive warming scenarios when the West Antarctic Ice Sheet undergoes catastrophic collapse. The Atlantic Meridional Overturning Circulation is affected by freshwater discharge from both the Greenland and the Antarctic ice sheets and, as an interhemispheric teleconnection bridge, exacerbates the opposing ice sheet’s retreat via the Bipolar Seesaw. These results highlight the crucial role of ice sheet-climate interactions via freshwater flux in future ice sheet retreat and associated sea-level rise.
Daily station-level records of air temperature, snow depth, and ground temperature in the Northern Hemisphere
Authors: Tran Vinh Ngoc , Zhou Wenbo , Kim Taeho , Mazepa Valeriy , Valdayskikh Victor , Ivanov Valeriy Y. 
Published: June 2024

AbstractAir temperature (Ta), snow depth (Sd), and soil temperature (Tg) are crucial variables for studying the above- and below-ground thermal conditions, especially in high latitudes. However,in-situobservations are frequently sparse and inconsistent across various datasets, with a significant amount of missing data. This study has assembled a comprehensive dataset ofin-situobservations of Ta, Sd, and Tg for the Northern Hemisphere (higher than 30°N latitude), spanning 1960–2021. This dataset encompasses metadata and daily data time series for 27,768, 32,417, and 659 gages for Ta, Sd, and Tg, respectively. Using the ERA5-Land reanalysis data product, we applied deep learning methodology to reconstruct the missing data that account for 54.5%, 59.3%, and 74.3% of Ta, Sd, and Tg daily time series, respectively. The obtained high temporal resolution dataset can be used to better understand physical phenomena and relevant mechanisms, such as the dynamics of land-surface-atmosphere energy exchange, snowpack, and permafrost.
Unravelling the effects of nano SiO2, nano TiO2 and their nanocomposites on Zea mays L. growth and soil health
Authors: Kumari Kusum , Rani Neelam , Hooda Vinita 
Published: June 2024

AbstractAmidst the challenges posed by climate change, exploring advanced technologies like nanotechnology is crucial for enhancing agricultural productivity and food security. Consequently, this study investigated the impact of nano SiO2 (nSiO2), nano TiO2 (nTiO2) and SiO2/TiO2 nanocomposites (NCs) on 30-day-old Zea mays L. plants and soil health at concentrations of 100 and 200 ppm. Results showed that nSiO2 and nTiO2 at 100 ppm and SiO2/TiO2 NCs at both concentrations, positively influenced plant growth, with the best stimulation observed at 200 ppm of SiO2/TiO2 NCs. Improved plant growth was associated with higher chlorophyll content, photosynthetic rate, transpiration rate, stomatal conductance, rhizospheric N-fixing and phosphate solubilizing bacterial population and plant nutrient uptake. Additionally, treated plants exhibited increased cellulose and starch levels. Malondialdehyde (MDA) content was lower or similar to that of the control, except at 200 ppm of nTiO2-treated shoots. Antioxidant enzyme activities fluctuated, indicating physiological adjustments. Overall, 100 ppm of nTiO2 as well as nSiO2 and 100 and 200 ppm of SiO2/TiO2 NCs improved soil fertility and Z. mays growth, suggesting potential benefits for sustainable agriculture. The findings lay the foundation for more comprehensive investigations into the long-term fate of nanomaterials in soil and their intricate molecular-level interactions with Z. mays.
Classification of coal bursting liability of some chinese coals using machine learning methods
Authors: Wang Chao , Liu Yv , Li Yuefeng , Liu Xiaofei , Wang Qiwei 
Published: June 2024

AbstractThe classification of coal bursting liability (CBL) is essential for the mitigation and management of coal bursts in mining operations. This study establishes an index system for CBL classification, incorporating dynamic fracture duration (DT), elastic strain energy index (WET), bursting energy index (KE), and uniaxial compressive strength (RC). Utilizing a dataset comprising 127 CBL measurement groups, the impacts of various optimization algorithms were assessed, and two prominent machine learning techniques, namely the back propagation neural network (BPNN) and the support vector machine (SVM), were employed to develop twelve distinct models. The models’ efficacy was evaluated based on accuracy, F1-score, Kappa coefficient, and sensitivity analysis. Among these, the Levenberg–Marquardt back propagation neural network (LM-BPNN) model was identified as superior, achieving an accuracy of 96.85%, F1-score of 0.9113, and Kappa coefficient of 0.9417. Further validation in Wudong Coal Mine and Yvwu Coal Industry confirmed the model, achieving 100% accuracy. These findings underscore the LM-BPNN model’s potential as a viable tool for enhancing coal burst prevention strategies in coal mining sectors.
Body size predicts ontogenetic nitrogen stable-isotope (δ15N) variation, but has little relationship with trophic level in ectotherm vertebrate predators
Authors: Villamarín Francisco , Jardine Timothy D. , Bunn Stuart E. , Malvasio Adriana , Piña Carlos Ignacio , Jacobi Cristina Mariana , Araújo Diogo Dutra , de Brito Elizângela Silva , de Moraes Carvalho Felipe , da Costa Igor David , Verdade Luciano Martins , Lara Neliton , de Camargo Plínio Barbosa , Miorando Priscila Saikoski , Portelinha Thiago Costa Gonçalves , Marques Thiago Simon , Magnusson William E. 
Published: June 2024

AbstractLarge predators have disproportionate effects on their underlying food webs. Thus, appropriately assigning trophic positions has important conservation implications both for the predators themselves and for their prey. Large-bodied predators are often referred to as apex predators, implying that they are many trophic levels above primary producers. However, theoretical considerations predict both higher and lower trophic position with increasing body size. Nitrogen stable isotope values (δ15N) are increasingly replacing stomach contents or behavioral observations to assess trophic position and it is often assumed that ontogenetic dietary shifts result in higher trophic positions. Intraspecific studies based on δ15N values found a positive relationship between size and inferred trophic position. Here, we use datasets of predatory vertebrate ectotherms (crocodilians, turtles, lizards and fishes) to show that, although there are positive intraspecific relationships between size and δ15N values, relationships between stomach-content-based trophic level (TPdiet) and size are undetectable or negative. As there is usually no single value for 15N trophic discrimination factor (TDF) applicable to a predator species or its prey, estimates of trophic position based on δ15N in ectotherm vertebrates with large size ranges, may be inaccurate and biased. We urge a reconsideration of the sole use of δ15N values to assess trophic position and encourage the combined use of isotopes and stomach contents to assess diet and trophic level.
Use of phase plate cryo-EM reveals conformation diversity of therapeutic IgG with 50 kDa Fab fragment resolved below 6 Å
Authors: Lin Hsin-Hung , Wang Chun-Hsiung , Huang Shih-Hsin , Lin Sung-Yao , Kato Takayuki , Namba Keiichi , Hosogi Naoki , Song Chihong , Murata Kazuyoshi , Yen Ching-Hsuan , Hsu Tsui-Ling , Wong Chi-Huey , Wu Yi-Min , Tu I.-Ping , Chang Wei-Hau 
Published: June 2024

AbstractWhile cryogenic electron microscopy (cryo-EM) is fruitfully used for harvesting high-resolution structures of sizable macromolecules, its application to small or flexible proteins composed of small domains like immunoglobulin (IgG) remain challenging. Here, we applied single particle cryo-EM to Rituximab, a therapeutic IgG mediating anti-tumor toxicity, to explore its solution conformations. We found Rituximab molecules exhibited aggregates in cryo-EM specimens contrary to its solution behavior, and utilized a non-ionic detergent to successfully disperse them as isolated particles amenable to single particle analysis. As the detergent adversely reduced the protein-to-solvent contrast, we employed phase plate contrast to mitigate the impaired protein visibility. Assisted by phase plate imaging, we obtained a canonical three-arm IgG structure with other structures displaying variable arm densities co-existing in solution, affirming high flexibility of arm-connecting linkers. Furthermore, we showed phase plate imaging enables reliable structure determination of Fab to sub-nanometer resolution from ab initio, yielding a characteristic two-lobe structure that could be unambiguously docked with crystal structure. Our findings revealed conformation diversity of IgG and demonstrated phase plate was viable for cryo-EM analysis of small proteins without symmetry. This work helps extend cryo-EM boundaries, providing a valuable imaging and structural analysis framework for macromolecules with similar challenging features.