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Spatially defined Rabi spectroscopy for uninterrupted optical clock interrogation
Abstract Optical lattice clocks achieve fractional frequency uncertainties of 10⁻¹⁸, yet stability is constrained by the dead time between cooling, preparation, interrogation, and detection. This sampling aliases local-oscillator noise into the clock signal (the Dick effect) and prevents continuous accumulation of oscillator phase information. We demonstrate spatially defined Rabi spectroscopy of ultracold ⁸⁸Sr atoms continuously transported in a moving optical lattice. A longitudinal excitation geometry preserves Lamb–Dicke confinement and suppresses Doppler broadening. Clock excitation is enabled only within a localised region by a transverse magnetic mixing field, defining the atom–laser interaction in space rather than in time and decoupling interrogation from preparation and detection. Transporting atoms at 16 mm s⁻¹ through a 12-mm interaction region yields a 1.2-Hz-wide spectrum close to the transit-time Fourier limit while maintaining uninterrupted atom delivery. This approach provides a practical route toward dead-time-free optical clock interrogation of continuously delivered atomic ensembles.
A critical role of the histone lysine demethylase JmjC1 in regulating severe malaria-associated virulence genes in Plasmodium falciparum
Geometric programming of asymmetric colloidal dynamics via topological defect reconfiguration
Anionic solvation reconstruction stabilizes interfacial chemistry for high-temperature and high-voltage Li metal batteries
Phosphorene dominated integrative dual-electric field guiding charge flow for vapor-fed photocatalytic hydrogen evolution
Three-site cycloadditions within one reaction intermediate with site-selectivity controlled by electronic and size bias
PPARα activation overcomes fibroinflammatory liver microenvironment-associated anti-PD-1 resistance in hepatocellular carcinoma by mediating GSDME-dependent pyroptosis
Abstract The fibroinflammatory liver microenvironment (FILM), characterized by collagen-rich stroma and immunosuppressive inflammation, is prevalent in hepatocellular carcinoma (HCC) and correlates with poor response to programmed cell death protein 1 (PD-1) blockade. Here, we show that FILM suppresses gasdermin E (GSDME)-dependent pyroptosis and promotes immune suppression and anti-PD-1 resistance. Mechanistically, FILM-associated cancer-associated fibroblasts recruit and polarize macrophages toward a nitric oxide synthase 2 (NOS2)⁺ inflammatory phenotype. NOS2+ macrophage-derived nitric oxide induces SP1 S-nitrosylation, impairs SP1 binding to the peroxisome proliferator-activated receptor alpha (PPARA) promoter and transcriptionally represses PPARA in HCC cells. PPARα downregulation reduces pyruvate dehydrogenase kinase 4 (PDK4) expression, mitochondrial reactive oxygen species production, caspase-3 activation and GSDME cleavage. Conversely, ligand activation of tumor intrinsic PPARα restores the PDK4–ROS–caspase-3–GSDME axis, enhances dendritic cell and CD8⁺ T cell activation, and sensitizes HCC to anti–PD-1 therapy. The clinically approved PPARα agonist fenofibrate enhances anti-PD-1 efficacy in HCC models in male mice and is associated with improved clinical benefit in a retrospective cohort of patients with HCC. We propose a FILM–NOS2–SP1–PPARα–PDK4 axis that controls pyroptotic immunogenicity and immunotherapy response, supporting PPARα activation as a strategy to overcome FILM-associated immune resistance in HCC.
Identifiable learning of dissipative dynamics
Stress relief principles milestoning the industrial application of lithium metal battery systems
Dynamic magnetic capture-catalytic pyrolysis for aquatic micro- and nanoplastic management
Defective indium oxide as plasmonic catalyst for efficient photo-driven methanol steam reforming
Probing the atomic dynamics of ultrafast melting with femtosecond electron diffraction
Abstract Melting is an every-day phase transition that is determined by thermodynamic parameters like temperature and pressure. In contrast, ultra-fast melting is governed by the microscopic response to a rapid energy input and, thus, can reveal the strength and dynamics of atomic bonds as well as the energy flow rate to the lattice. Accurately describing these processes remains challenging and requires detailed insights into transient states encountered. Here, we present data from femtosecond electron diffraction measurements that capture the structural evolution of copper during the ultrafast solid-to-liquid phase transformations. At absorbed energy densities 2-4 times the melting threshold, melting begins at the surface slightly below the nominal melting point followed by rapid homogeneous melting throughout the volume. Molecular dynamics simulations reproduce these observations and reveal a weak electron-lattice energy transfer rate for the given experimental conditions. Both simulations and experiments show no indications of rapid lattice collapse when its temperature surpasses proposed limits of superheating, providing evidence that the inherent dynamics limits the speed of disordering in ultrafast melting of metals.
Retraction Note: Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma
Cell size reduction distinctly scales spindle elongation and chromosome segregation in C. elegans
Abstract How embryos adapt their internal cellular machinery to reductions in cell size during development remains a fundamental question in cell biology. Here, we use high-resolution lattice light-sheet fluorescence microscopy and automated image analysis to quantify lineage-resolved mitotic spindle and chromosome segregation dynamics from the 2- to 64-cell stages in Caenorhabditis elegans embryos. While spindle length scales with cell size across both wild-type and size-perturbed embryos, chromosome segregation dynamics remain largely invariant, suggesting that distinct mechanisms govern these mitotic processes. Combining femtosecond laser ablation with large-scale electron tomography, we find that mid-spindle microtubules mediate chromosome segregation dynamics and remain uncoupled from cell size across all stages of early development. In contrast, spindle elongation is driven by cortically anchored motor proteins and astral microtubules, rendering it sensitive to cell size. Incorporating these experimental results into an extended stoichiometric model for both the spindle and chromosomes, we find that allowing only cell size and microtubule catastrophe rates to vary reproduces spindle pole-to-pole dynamics across development. The same model also accounts for centrosome separation and pronuclear positioning in the one-cell C. elegans embryo, spindle-length scaling across nematode species spanning ~100 million years of divergence, and spindle rotation in human cells. Thus, a unified stoichiometric framework provides a predictive, mechanistic account of spindle and nuclear dynamics across scales and species.
Exopeptidase-assisted nanopore peptide sequence identification
Genome-targeted enrichment and sequencing of human-infecting Cryptosporidium spp.
Integrated in silico assessment of the regulatory and structural consequences of pulmonary tuberculosis-associated SP110 polymorphisms
Abstract The molecular mechanisms underlying conflicting findings of association of SP110 single nucleotide polymorphisms (SNPs) with susceptibility to pulmonary tuberculosis (PTB) remain unclear. We selected ten SP110 SNPs from publicly available genomic databases, based on prior PTB association and minor allele frequencies exceeding 1% in African populations and identified in a Ugandan cohort with PTB. We then applied in silico multi-tool framework, incorporating deep-learning splice predictors including SpliceAI, Pangolin, and AlphaGenome, to evaluate the regulatory and functional consequences of the SNPs on transcription factor binding, RNA splicing, RNA secondary structure, and protein-level effects. The model captured population-relevant SP110 variations rather than a directly genotyped Ugandan cohort. Our analysis revealed allele-specific gains and losses involving transcription factors TFAP2A, TFAP2C, TP63, Zfx, and IRF1, suggesting modulation of regulatory potential through altered transcription factor binding motifs. However, SpliceAI and Pangolin uniformly predicted low splice-disruptive effects across both exonic and intronic variants, while multiple protein pathogenicity tools consistently classified missense and stop-gained variants as benign or tolerated. RNA secondary structure analysis predicted that most variants preserved global thermodynamic stability. From our findings, SP110 variants are unlikely to exert major effects through splicing disruption or protein destabilization but may contribute to functional diversity through subtle regulatory mechanisms, including transcription factor binding modulation and RNA structural reorganization.
The influence of Lucilia sericata larval secretions on fibroblast lineage: an in vitro cell culture study
National trends in mortality involving acute pyelonephritis and obstructiveand reflux uropathy in the United States, 1999–2023
Crashworthiness enhancement of three-wheel vehicle structures under rear-end collision: a computational modelling approach
Abstract Worldwide, Three-wheeled vehicles (TWV) are becoming more and more ubiquitous for use in daily transportation. These vehicles are similar to motorcycles and scooters in that they have a steering wheel on the front, and they have a suspension system and differential on the back two wheels, just like a car. They typically consist of one front wheel and two rear wheels, with an open frame or sheet metal body. Their frontal design consists of an upright body and windscreen, a small cabin, a canvas roof, and a mudguard with an attached headlamp. These cars have a top speed of about 55 km/h. The front cabin houses the driver, while the back section is occupied by the passengers. It weighs about 650 kg, including the occupants. TWV are viewed as unsafe for two reasons: Auto rickshaws are thought to be dangerous for two reasons: first, the vehicle body and internal structure have no proper safety features, and second, the drivers are thought to be incompetent motorists who are ready to overload their cars and make numerous trips in a short amount of time. The driver’s seat and the back passenger bench are the only soft surfaces in the sparse, hard metal interior of auto-rickshaws, which are thought to be unstable and prone to turning turtle due to shunts from other vehicles, bumps in the road, or drivers who drive too fast. Because there are no doors, even at slow speeds, the occupants could be thrown onto the road and suffer serious injuries. Because of its materials’ and structures’ inadequate impact energy absorption, it also seriously jeopardizes pedestrian safety. The goal of this article was to reduce crash injuries by modifying the current three-wheeled vehicle to increase its crashworthiness during rear-end collisions. Accidents that happen to the rear ends of vehicles are the third most frequent type. Rear-impact collisions are frequent but rarely fatal. They do, however, cause a variety of injuries, the most frequent being whiplash trauma to the neck. In this study, the Federal Motor Vehicle Safety Standard (FMVSS)-301-inspired approach was followed when performing the Finite element analysis (FEA) rear-impact test on the TWV. Enhancing the crashworthiness of the car and the gasoline tank is another goal of the rear-impact test. Consequently, to see how occupants respond to a crash, human dummies are incorporated. Thus, modeling and analysis of the current three-wheeled vehicle structure with human dummies was the first task completed in this research. Following that, the outcome will be interpreted, and based on those findings, a new model will be developed to address the drawbacks of the three now in use. The outcomes of the original and modified models were then contrasted. Livermore Software Dynamic Nonlinear Analysis (LS-DYNA) was utilized for Finite element method (FEM) analysis, and CATIA was used for 3D modeling to accomplish this. From the result, the modified model is fitted with a rear bumper, so it reduces intrusion into the rear compartment of the vehicle. It deformed less, and as a result, 30% more protection was obtained for rear parts such as the fuel tank and engine. The rear bumper is made up of composite material, and this led to a greater absorption of energy with less deformation. The energy absorption of TWV was increased by 1.6 kJ. As a result, less energy is transferred to the occupants with the use of the modified model. With the use of the modified model, the force of impact was reduced by 22%; consequently, the occupants inside the modified model experienced fewer injuries. It can be observed that with little modification, the safety of the current TWV can be improved so that the owners and manufacturers can implement some of the safety development concepts discussed in this paper to improve the crashworthiness of the TWV.