Browse Articles

Computation and resource efficient genome-wide association analysis for large-scale imaging studies

Exploiting the path-integral radius of gyration in open quantum dynamics

A major challenge in open quantum dynamics is the inclusion of Matsubara-decay terms in the memory kernel, which arise from the quantum-Boltzmann delocalization of the bath modes. This delocalization can be quantified by the radius of gyration squared R2(ω) of the imaginary-time Feynman paths of the bath modes as a function of the frequency ω. In a hierarchical equations of motion (HEOM) calculation with a Debye–Drude spectral density, R2(ω) is the only quantity that is treated approximately (assuming convergence with respect to hierarchy depth). Here, we show that the well-known Ishizaki–Tanimura correction is equivalent to separating smooth from “Brownian” contributions to R2(ω) and that modifying the correction leads to a more efficient HEOM in the case of fast baths. We also develop a simple “A4” adaptation of the “AAA” (adaptive Antoulas–Anderson) algorithm in order to fit R2(ω) to a sum over poles, which results in an extremely efficient implementation of the standard HEOM method at low temperatures.

Targeting leucine-rich repeat kinase 2 overcomes resistance to oncolytic herpes simplex virus-based therapies in glioblastoma

Windmilling clusters of active quadrupoles

Active matter has thrived in recent years, driven both by the insight that it underlies fundamental processes in nature and by its vast potential for applications. This allows for innovation, both inspired by experimental observations and by the construction of novel systems with desired properties. In this paper, we develop a novel system in the search for a new kind of pattern formation: microstructural motifs with orthogonal alignment. Taking a simple active Brownian particle model applied to dumbbell-shaped particles, we add a quadrupolar interaction by positioning two antiparallel magnetic dipolar moments on each particle. We find that the phase behavior is determined by the competition between active motion and the orthogonal alignment favored by quadrupolar attraction. By varying these quantities, we are able to tune both the internal structure of the aggregates and find a surprising stability of triangular aggregates, to the point of clusters of size N = 3 being strongly overrepresented. Although none of the component particles are chiral, the resulting structures spin in a random, fixed direction due to the combination of the polarity of the active motion. This results in an ensemble of windmilling (randomly spinning in a circular motion) aggregates with windmill-like shapes (due to the three or four core component dumbbells). Ultimately, this simple model shows an interesting range of microstructural motifs, with great potential for experimental implementations.

Template-directed vertical photopolymerization for construction of triphenylamine-based poly(diacetylene) nanofibers

Abstract Template-directed synthesis of macromolecules prevails in natural systems. However, artificial template-directed covalent polymerization that proceeds without sacrificing the delicate non-covalent order needed for precursor alignment remains a formidable challenge. Here we report a supramolecular-templating strategy for photopolymerization of triphenylamine-based diyne assemblies. Cooperative hydrogen- and halogen-bonding align C 3 -symmetric monomers into ordered stacks that evolve from nanodots into micron-scale nanofibers. Ultraviolet irradiation then triggers axial cross-linking of the diyne moieties, producing continuous one-dimensional conjugated polymers. Selective acid treatment cleaves the I···N halogen bond to remove the template while preserving nanofibrillar integrity, yielding a stable covalent network with red-shifted emission. We demonstrate that this self-assemble-then-cure strategy integrates reversible supramolecular organization with irreversible covalent fixation, providing a general and scalable route to vertically oriented conjugated polymer architectures.

Configurational entropy of randomly double-folding ring polymers

Topologically constrained genome-like polymers often double-fold into tree-like configurations. Here, we calculate the exact number of tightly double-folded configurations available to a ring polymer in ideal conditions. For this purpose, we introduce a scheme that allows us to define a “code” specifying how a ring wraps a randomly branching tree and calculate the number of admissible wrapping codes via a variant of Bertrand’s ballot theorem. As a validation, we demonstrate that data from Monte Carlo simulations of an elastic lattice model of non-interacting tightly double-folded rings with controlled branching activity are in excellent agreement with exact expressions for branch-node and tree size statistics that can be derived from our expression for the ring entropy.

Polyanion-stabilized amorphous halide electrolytes with low lithium content for all-solid-state lithium batteries

Low-lying excited correlated electronic states of cycloparaphenylene and cyclacene: An efficient symmetrized density matrix renormalization group study with periodic boundary condition

One-dimensional and quasi-one-dimensional correlated fermionic models can be studied efficiently using the Density Matrix Renormalization Group (DMRG) method with open boundary conditions. Although the implementation of the conventional DMRG technique in investigating a fermionic model with a periodic boundary condition (PBC) is still challenging due to the demand of high computational facility, this work reports the efficient use of the symmetrized DMRG (SDMRG) technique in studying the low-lying correlated excited-states of radially π-conjugated cycloparaphenylene ([6]CPP) and [n]cyclacene molecules within the Pariser–Parr–Pople (PPP) model Hamiltonian with adequate computational cost. The low-lying correlated singlet excited energies of [6]CPP calculated within the PPP model are in very good agreement with experiment. Compared to [6]CPP, the numerical accuracy of DMRG calculations for highly correlated [n]cyclacene depends on the number of DMEV basis (m). Such a study shows an efficient pathway to implement the SDMRG technique in studying fermionic systems with PBC in the future.

Asymmetric synthesis of Heteroatom-bridged [3.2.1]Octane scaffolds via enantioselective β-H elimination reaction

Corresponding orbitals in periodic frozen-density embedding: The case of alkaline-earth subnitrides, <i>Ae</i> 2N, by the example of Ba2N

The metallic metal-rich phase Ba2N, a representative example for the Ae2N alkaline-earth subnitrides, is examined using theoretical methods to investigate its electronic structure and chemical bonding, with a special focus on the “excess” electron found within these structures, alluding to an electride character. To quantify the latter phenomenon, the “corresponding orbital” formalism, introduced by Neese to the molecular quantum chemists about two decades ago [F. Neese, J. Phys. Chem. Solids 65, 781 (2004)], is adapted to the recently developed periodic frozen-density approach [M. Pauls et al., J. Phys. Chem. A 127, 6541 (2023)]. While the existence of Ba2N goes back to both constructive Ba-6s–N-2sp orbital interference (covalency) and significant ionic bonding, we identify that the “excess” electron engaged in a singlet ground state of the presumably non-paramagnetic phase contributes to intra-layer Ba–Ba bonding while destabilizing the inter-layer Ba–Ba bonding by occupying antibonding σ-type orbitals.

Cryo-EM structures of UBA6 reveal mechanisms of E1–E2 specificity and dual FAT10/ubiquitin thioester transfer

Free energy landscapes, nucleation, and morphological stability of biphasic nanodroplets dispersed in a liquid phase: A Monte Carlo simulation study of a ternary system

This work employs semigrand canonical ensemble Monte Carlo simulations to investigate the morphology of biphasic nanodroplets suspended in a liquid phase. Using a ternary Lennard-Jones system, we explore the free energy landscapes, nucleation pathways, and thermodynamic stability of core–shell, Janus, and dumbbell configurations that arise from internal phase separation within a parent nanodroplet. Our simulations confirm that the final morphology is dictated by the balance of interfacial free energies between the two droplet components and the surrounding liquid. While a thermodynamic model based on binary interfacial energies provides general predictions, the adsorption of a third component at the liquid–liquid interface alters the interfacial free energy, leading to discrepancies between the model and simulation, particularly for core–shell and crescent-shell morphologies. We also observe a link between the nucleation mechanism and the resulting morphology. Nucleation occurs at higher compositions for systems that form Janus droplets compared to those that form core–shell structures. These findings highlight the limitations of macroscopic models at the nanoscale and offer a more nuanced understanding of phase transitions in nanodroplets, which is essential for the rational design of complex nanoparticles.

Strong optical anisotropy in one-dimensional phosphorus wavy tubes

Abstract Anisotropic materials with intrinsic one-dimensional architectures, where chains or tubes align along a crystallographic axis, exhibit direction-dependent optical responses and serve as ideal building blocks for polarization-sensitive optoelectronics. While progress exists in engineered compounds, discovering elemental crystals with naturally ordered one-dimensional building blocks exhibiting giant optical anisotropy remains challenging. Here, we report the synthesis of a direct-bandgap semiconducting one-dimensional phosphorus single crystal composed of unique wavy polygonal tubes. The monoclinic lattice structure is revealed by single-crystal X-ray diffraction and advanced transmission electron microscopy. The crystal exhibits giant birefringence in the visible and near-infrared regions, stemming from electron localization and anisotropic transitions of the phosphorus 3 p orbital along the tube axis. The low-symmetry structure endows remarkable linear and nonlinear optical anisotropies, including orientation-dependent photoluminescence, Raman scattering, and second-harmonic generation. This study establishes a paradigm for designing giant optical anisotropies, opening avenues for on-chip polarization devices and nonlinear photonic circuits.

A large-scale dataset and physics-informed neural network for viscosity prediction in many-component aqueous and organic solutions

Modern industrial liquids—including coolants, lubricants, solvent blends, cryoprotectant cocktails, etc.—frequently employ complex, many-component formulations, but contemporary viscosity models and datasets are overwhelmingly limited to simplified binary or ternary compositions, leaving the most application-relevant compositional spaces broadly unexplored. This gap is attributable both to the limitations of classical viscosity correlations, which typically require either untenably idealized interaction assumptions or an untenably larger number of interaction parameters, and to the lack of systematic many-component viscosity datasets. Here, we provide a first-of-its-kind dataset of 44 316 viscosity measurements spanning 100 aqueous and organic solutions of up to 17-component complexity across temperatures from −20 to 35 °C, and we use it to power a physics-informed neural network (PINN) model that provides unprecedented predictive power and physical insight into many-component solution viscosity. We first show that predictive implementations of two prominent classical models (Katti–Chaudhuri and augmented Adam–Gibbs) systematically fail to describe these solutions but retain valuable trend-level information. We then use these models as physical guides for our PINN, embedding classical model insight as a training aid while machine learning the residual non-ideal contributions that dominate in many-component composition space. The resulting model, which we also provide as a software application, maintains stable performance across solution complexity, outperforming both classical correlations and data-only artificial neural networks on fully withheld test data. Finally, we compare residuals of both the classical and PINN models as a function of component number and entropy of mixing, suggesting that entropic phenomena unaccounted for in classical models may dominate the viscosity of many-component solutions.

Dynamic subcellular proteomics identifies regulators of adipocyte insulin action

Abstract Insulin acts on adipocytes to suppress lipolysis and increase glucose uptake to control whole-body glucose and lipid metabolism. Regulation of these processes by insulin signalling depends on changes in protein localisation. However, the extent of insulin-stimulated changes to the adipocyte spatial proteome, and the importance of these in the cellular insulin response, is unknown. Here, we use subcellular proteomics approaches to map acute insulin-stimulated protein relocalisation in adipocytes on a cell-wide scale. These data reveal extensive insulin-regulated protein redistribution, with hundreds of insulin-responsive proteins. These include the uncharacterised protein C3ORF18, which redistributes to the plasma membrane in response to insulin. Studies in C3ORF18-depleted adipocytes suggest this protein is required to maintain adipocyte insulin sensitivity. Overall, our data highlight the scale of protein relocalisation in the adipocyte insulin response, and provide an accessible resource to inform further studies into how changes in protein localisation contribute to cellular insulin responses.

Active phase separation triggered by chemotactic defects

When initial conditions are uniformly random, numerical simulations of Motility-Induced Phase Separation (MIPS) in active suspensions with average packing fractions above a specific (spinodal) threshold require relatively short run times. The question remains of how phase separation can be achieved within a feasible run time at lower packing fractions (binodal region). We demonstrate that defects functioning as attractive chemotactic centers can rapidly initiate the formation of local particle aggregates, which, under certain conditions, can detach and grow until phase separation is fully realized. Here, we provide a detailed investigation of defect-triggered MIPS in the binodal region. We suggest that this mechanism may facilitate the aggregation of bacteria into biofilms, with nutrient particles acting as chemotactic attractors.

Nanoporosity-driven deformation of additively manufactured nano-architected metals

Microwave and millimeter-wave spectroscopy of the potential interstellar carbonitrile cyclopropylacetonitrile

The pure rotational spectrum of cyclopropylacetonitrile has been investigated by jet-cooled impulse-excitation microwave spectroscopy and room-temperature chirped-pulse millimeter-wave spectroscopy. The spectra have been measured in the regions of 7–20 and 75–110 GHz, leading to the assignment of two trans and gauche conformations of this cyanoalkane. For both conformers, the spectral assignments were extended to all 13C and 15N mono-substituted isotopic species, allowing an accurate structural determination of the two conformers. Theoretical calculations [MP2/6-311++G(d,p), MP2/aug-cc-pVTZ, and B2PLYP/aug-cc-pVTZ] on the potential energy surface, electric properties, vibrational movements, and molecular structure complemented the experimental work. This comprehensive spectroscopic–computational study provides experimental rotational parameters of the ground and the lowest energy vibrational excited states, the 14N nuclear quadrupole coupling tensor, and the centrifugal distortion constants, permitting future radioastronomical investigations on the potential presence of this carbonitrile in the interstellar medium.

Physical echo state network based on the nonlinearity and dynamic response of ambipolar heterostructure transistors

Hydration and transport properties of cesium hydroxide and mixed cesium hydroxide–sodium nitrite aqueous solutions

This study explores the hydration and transport properties of aqueous cesium hydroxide (CsOH) solution, with or without 1 molar (M) sodium nitrite (NaNO2). Historic studies of electrolyte solutions indicate that Cs+ ions decrease viscosity and increase diffusion rates, whereas OH− ions have the opposite effect. Here, the influence of OH− was dominant in CsOH solutions, leading to increased viscosity and reduced diffusion rates. There was a linear relationship between diffusion coefficients and water activity, emphasizing the significant role of ion–water interactions in determining transport properties. This may be because the interaction between Cs+ and the anions is weak even when they are in direct contact with each other. The weakness of the ion-pairing was established through thermodynamic analysis. The findings suggest that ion-pairing is not the only important interaction controlling transport properties when ion-pairing is weak. Nonetheless, ion-pairing or obstructions did result in more sluggish transport properties as electrolyte concentrations increased. Overall, the research enhances the understanding of the complexities underlying ion interactions in multicomponent solutions.