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The vibrational wavepackage dynamics and phase modulation via the resonant Rydberg states in molecules
The observation of vibrational coherence has become significant because it reflects the spatial and temporal localization of a nucleus in a specific mode and characterizes energy flow and multiple kinetic relaxations in chemical dynamics. Vibrational coherence in the S1 state of 2,4-difluoroanisole has been investigated in real time by femtosecond time-resolved photoelectron spectroscopy and time-of-flight mass spectroscopy. Quantum beats of superpositions exhibit temporal oscillations with a frequency of 78 cm−1. Combining the structure computations, oscillations derive from the structure change from planar to nonplanar geometry, which correspond the coherence wavepackets moving from the Franck–Condon region toward the minimum point of the potential energy surface, elucidating the energy flows following the excitation of 2,4-difluoroanisole in the S1 state. The phases of the quantum beat via the resonant Rydberg states exhibit a shift of π rad. The vibrational coherent phase modulation via the resonant Rydberg states will facilitate the chemical coherence control in complex molecular systems.
The anti-GD2 monoclonal antibody naxitamab plus GM-CSF for relapsed or refractory high-risk neuroblastoma: a phase 2 clinical trial
Abstract In this single-arm, non-randomized, phase 2 trial (NCT03363373), 74 patients with relapsed/refractory high-risk neuroblastoma and residual disease in bone/bone marrow (BM) received naxitamab on Days 1, 3, and 5 (3 mg/kg/day) with granulocyte-macrophage colony-stimulating factor (Days -4 to 5) every 4 weeks, until complete response (CR) or partial response (PR) followed by 5 additional cycles every 4 weeks. Primary endpoint in the prespecified interim analysis was overall response (2017 International Neuroblastoma Response Criteria). Among 26 responders (CR + PR) in the efficacy population (N = 52), 58% had refractory disease, and 42% had relapsed disease. Overall response rate (ORR) was 50% (95% CI: 36-64%), and CR and PR were observed in 38% and 12%, respectively. With the 95% CI lower limit for ORR exceeding 20%, the primary endpoint of overall response was met. Patients with evaluable bone disease had a 58% (29/50) bone compartment response (CR, 40%; PR, 18%). BM compartment response was 74% (17/23; CR, 74%). One-year overall survival and progression-free survival (secondary endpoints) were 93% (95% CI: 80-98%) and 35% (95% CI: 16-54%), respectively. Naxitamab-related Grade 3 adverse events included hypotension (58%) and pain (54%). Overall, naxitamab demonstrated clinically meaningful efficacy with manageable safety in patients with residual neuroblastoma in bone/BM.
RENEB interlaboratory comparison for biological dosimetry based on dicentric chromosome analysis and cobalt-60 exposures higher than 2.5 Gy
Abstract In previous RENEB interlaboratory comparisons based on the manual scoring of dicentric chromosomes, a tendency for systematic overestimation for doses > 2.5 Gy was found. However, these exercises included only very few doses in the high dose range, and they were heterogeneous in terms of radiation quality and evaluation mode, and comparable only to a limited extent. Here, this presumed deviation was explored by investigating three doses > 2.5 Gy. Blood samples were irradiated (2.56, 3.41 and 4.54 Gy) using a 60Co source and sent to 14 member laboratories of the RENEB network, which performed the dicentric chromosome assay (manual and/or semi-automatic scoring) and reported dose estimates. Most participants provided estimates that agreed very well with the physical reference doses and all provided dose estimates were in the correct clinical category (> 2 Gy). The previously observed tendency for a systematic bias across all laboratories was not confirmed. However, tendencies for systematic underestimation were detected for dose estimations for reference doses given in terms of absorbed dose to blood and for some participants, a laboratory-specific trend of systematic under- or overestimation was observed. The importance of regularly performed quality checks for a broad dose range became obvious to avoid misinterpretation of results.
The role of functionalization in the translocation of peptides through multilayer graphene nanopores
The rapid translocation speed of peptides through graphene nanopores poses a challenge, hindering the accurate sensing of the biomarkers. Employing the functionalized graphene nanopores is at the forefront of reducing the translocation speed. The current work details the translocation of a negatively charged peptide endothelin-1 through a bare multilayer graphene nanopore, a hydrogen-functionalized graphene nanopore, and a hydroxyl-functionalized graphene nanopore by applying electric fields. The hydroxyl-functionalized graphene nanopore significantly reduces the peptide’s translocation speed. The time required for the peptide to translocate through the hydroxyl-functionalized graphene nanopore is 2.25 times longer than in the non-functionalized graphene nanopore and 1.25 times longer than in the hydrogen-functionalized graphene nanopore. We critically analyze the factors influencing the reduced translocation speed, including the interactions between the pore and the peptide, the conformational changes of the peptide within the pore, the solvent velocity inside the pore, and the solvent’s viscosity near the peptide. The altered solvent velocities within functionalized pores have a minimal role in the speed reduction of peptides. When a constant force is applied to the peptide without any electric field, the hydroxyl-functionalized graphene nanopore delivers the lowest diffusion rate. The persistence time, which serves as a measure of the solvent viscosity near the peptide, is the highest within the hydroxyl-functionalized pore. Finally, we conclude that the Coulombic interactions between the peptide and the pore play a major role in its speed reduction inside the hydroxyl-functionalized graphene nanopore.
Expression of foetal gene Pontin is essential in protecting heart against pathological remodelling and cardiomyopathy
Abstract Cardiac remodelling is a key process in the development of heart failure. Reactivation of foetal cardiac genes is often associated with cardiac remodelling. Here we study the role of Pontin (Ruvbl1), which is highly expressed in embryonic hearts, in mediating adverse remodelling in adult mouse hearts. We observe that Pontin deficiency in cardiomyocytes leads to induced apoptosis, increased hypertrophy and fibrosis, whereas Pontin overexpression improves survival, increases proliferation and reduces the hypertrophic response. Moreover, RNAseq analysis show that genes involved in cell cycle regulation, cell proliferation and cell survival/apoptosis are differentially expressed in Pontin knockout. Specifically, we detect changes in the expression of Hippo pathway components in the Pontin knockout mice. Using a cellular model we show that Pontin induces YAP activity, YAP nuclear translocation, and transcriptional activity. Our findings identify Pontin as a modulator of adverse cardiac remodelling, possibly via regulation of the Hippo pathway. This study may lead to the development of a new approach to control cardiac remodelling by targeting Pontin.
Pan-serological antibodies and liver cancer risk: a nested case-control analysis
Abstract Recently, studies have reported that pan-viral serology signatures may be predictive for liver cancer development. However, whether these same findings are observed for prospective studies has not been previously investigated. The nested case-control analysis included 191 persons who developed liver cancer and 382 controls from the PLCO prospective cohort. The presence of circulating antibodies, measured by VirScan, was determined in serum samples obtained at study recruitment. The presence of antibodies was compared between cases and controls using multivariable conditional logistic regressions, and prediction models were used to estimate whether exposures predicted liver cancer development. No significant associations were found between antibodies to viruses, bacteria or allergens and liver cancer risk after adjustment for multiple testing. The agent most significantly associated with risk was hepatitis C virus (HCV), but it was only detected among 23 participants (odds ratio (OR): 3.98; 95% confidence intervals (CI):1.59–9.99; p = 0.0032, False Discovery Rate (FDR) = 0.35). In prediction models based on 109 antibody features, no associations with liver cancer risk were observed (area under the curve [AUC]: 0.52–0.54). In analyses restricted to the most common type of liver cancer, hepatocellular carcinoma, the association with HCV was stronger (OR: 23.16, 95% CI: 4.55-117.68; FDR p-value = 0.0016), although prediction models based on all detected antibodies were similar (AUC = 0.55; 95% CI:0.43–0.68). Antibodies to no infectious agents, other than HCV, were found to be prospectively associated with liver cancer risk. The utility of using an antibody exposure signature prospectively for liver cancer development needs to be further explored.
Unveiling nucleosome dynamics: A comparative study using all-atom and coarse-grained simulations enhanced by principal component analysis
The conformational dynamics of the DNA in the nucleosome may play a role in governing gene regulation and accessibility and impact higher-order chromatin structure. This study investigates nucleosome dynamics using both all-atom and coarse-grained (CG) molecular dynamics simulations, focusing on the SIRAH force field. Simulations are performed for two nucleosomal DNA sequences—alpha satellite palindromic and Widom-601—over 6 μs at physiological salt concentrations. A comparative analysis of structural parameters, such as groove widths and base pair geometries, reveals good agreement between atomistic and CG models, although CG simulations exhibit broader conformational sampling and greater breathing motion of DNA ends. Principal component analysis is applied to DNA structural parameters, revealing multiple free energy minima, especially in CG simulations. These findings highlight the potential of the SIRAH CG force field for studying large-scale nucleosome dynamics, offering insights into DNA repositioning and sequence-dependent behavior.
Dynamic properties of transcriptional condensates modulate CRISPRa-mediated gene activation
Nitrogen addition restricts key soil ecological enzymes and nutrients by reducing microbial abundance and diversity
Electron-propagator methods versus experimental ionization energies
Select electron-propagator (EP) methods agree as closely with experimental standards for molecular vertical ionization energies as they do with computational data of nearly full-configuration-interaction quality. Several EP methods consistently attain higher accuracy than alternatives with equal arithmetic bottlenecks expressed in terms of occupied (O) and virtual (V) orbital dimensions. The cubically scaling methods realize a mean absolute error (MAE) below 0.2 eV and are feasible whenever conventional self-consistent-field calculations are performed. O2V3-scaling EP self-energies achieve an MAE slightly above 0.1 eV and are as feasible as conventional second-order perturbative calculations of total energies. OV4 methods are more accurate (MAEs ∼0.075 eV) than ΔCCSD(T) and are more efficient than third-order total-energy calculations. An equally accurate generalization with full self-energy matrices and non-iterative O2V4 contractions produces Dyson orbitals in their most general form. Composite EP models that accurately estimate the effects of basis-set saturation drastically improve efficiency without sacrificing accuracy. No adjustable parameters are employed in the self-energy formulas or in the generation of reference-state orbitals. When Dyson-orbital probability factors indicate that Koopmans’s theorem is qualitatively valid, simple perturbative corrections suffice to approach chemical accuracy.
Protective catalytic layer powering activity and stability of electrocatalyst for high-energy lithium-sulfur pouch cell
Characterizing variability in passive myocardial stiffness in healthy human left ventricles using personalized MRI and finite element modeling
An efficient approach to estimate electronic couplings in molecular pairs using molecular orbital grids
The estimation of electronic couplings between diabatic states is crucial for the comprehension of electron transfer phenomena between molecular systems. Therefore, the development of efficient approximations that enable a very fast, yet accurate, estimation of electronic couplings is an important research goal in the context of organic semiconductors. The most popular methods (diabatization schemes, projection approximations, or methods using fragment molecular orbitals) usually involve the use of electronic structure calculations and can be computationally prohibitive if a large number of electronic coupling estimations is required. In this paper, we propose a novel strategy (CubeMap) to evaluate electronic couplings between molecular pairs in an extremely efficient manner. CubeMap employs the well-established linear relationship between the electronic coupling and the overlap integral between the corresponding molecular orbitals localized on the interacting molecules. In particular, CubeMap is based on the efficient calculation of the overlap integral in real space using molecular orbital grids of moderate size. The CubeMap efficiency partly comes from the fact that only a single electronic structure calculation of an individual molecule (reference geometry) is enough for the subsequent evaluation of overlap integrals and electronic couplings in multiple dimer dispositions. We show that CubeMap is particularly appealing to rapidly estimate the electronic coupling distributions in molecular crystals due to thermal fluctuations (dynamic disorder), which is an important effect for the accurate description of charge transport in organic semiconductors. Compared with the methods usually employed to evaluate electronic couplings, the CubeMap approach drastically reduces the computational cost by several orders of magnitude.
Reply to: Failure to replicate a superiority effect in crowding
Dual observers based sliding mode control for QUAVs with unknown disturbances and time varying delays
Abstract This paper presents a dual-observers-based nonsingular fast terminal sliding mode control scheme for quadrotor unmanned aerial vehicles (QUAVs) with unknown disturbances and time-varying delays. Firstly, to facilitate the controller design, the QUAVs model is decoupled into two subsystems: position subsystem and attitude subsystem. Secondly, for the position subsystem, a sliding mode controller is presented to control the position of the QUAVs. For the attitude subsystem, by introducing an exponential term, a nonsingular fast terminal sliding mode controller is obtained to ensure the fast convergence of the attitude angles. Moreover, based on the exponential term, the singularity problem of the conventional terminal sliding mode is solved. Thirdly, the disturbance and time-varying delay observers are presented by considering the time-varying delayed signals and unknown disturbances. Finally, the effectiveness and feasibility of the proposed control scheme are demonstrated by some computer simulations.
CUT-E as a 1/<i>N</i> expansion for multiscale molecular polariton dynamics
Molecular polaritons arise when the collective coupling between an ensemble of N molecules and an optical mode exceeds individual photon and molecular linewidths. The complexity of their description stems from their multiscale nature, where the local dynamics of each molecule can, in principle, be influenced by the collective behavior of the entire ensemble. To address this, we previously introduced a formalism called collective dynamics using truncated equations (CUT-E). CUT-E approaches the problem in two stages. First, it exploits permutational symmetries to obtain a substantial simplification of the problem. However, this is often insufficient for parameter regimes relevant to most experiments. Second, it takes the exact solution of the problem in the N → ∞ limit as a reference and derives systematic finite-N corrections. Here, we provide a novel derivation of CUT-E based on recently developed bosonization techniques. We lay down its connections with 1/N expansions that are ubiquitous in other fields of physics and present previously unexplored key aspects of this formalism, including various types of approximations and extensions to high-excitation manifolds.
A dominant role of transcriptional regulation during the evolution of C4 photosynthesis in Flaveria species
Abstract C 4 photosynthesis exemplifies convergent evolution of complex traits. Herein, we construct chromosome-scale genome assemblies and perform multi-omics analysis for five Flaveria species, which represent evolutionary stages from C 3 to C 4 photosynthesis. Chromosome-scale genome sequence analyses reveal a gradual increase in genome size during the evolution of C 4 photosynthesis attributed to the expansion of transposable elements. Systematic annotation of genes encoding C 4 enzymes and transporters identify additional copies of three C 4 enzyme genes through retrotranspositions in C 4 species. C 4 genes exhibit elevated mRNA and protein abundances, reduced protein-to-RNA ratios, and comparable translation efficiencies in C 4 species, highlighting a critical role of transcriptional regulation in C 4 evolution. Furthermore, we observe an increased abundance of ethylene response factor (ERF) transcription factors and cognate cis -regulatory elements associated with C 4 genes regulation. Altogether, our study provides valuable genomic resources for the Flaveria genus and sheds lights on evolutionary and regulatory mechanisms underlying C 4 photosynthesis.
Artificial intelligence for automatic diagnosis and pleomorphic morphological characterization of malignant biliary strictures using digital cholangioscopy
Analytical solution for the hydrodynamic resistance of a disk in a compressible fluid layer with odd viscosity on a rigid substrate
Chiral active fluids can exhibit odd viscosity, a property that breaks the time-reversal and parity symmetries. Here, we examine the hydrodynamic flows of a rigid disk moving in a compressible 2D fluid layer with odd viscosity, supported by a thin lubrication layer of a conventional fluid. Using the 2D Green’s function in Fourier space, we derive an exact analytical solution for the flow around a disk of arbitrary size, as well as its resistance matrix. The resulting resistance coefficients break the Onsager reciprocity, but satisfy the Onsager–Casimir reciprocity to any order in odd viscosity.