Browse Articles

Active phase discovery in heterogeneous catalysis via topology-guided sampling and machine learning

Increased thermal conductivity of β-Ga2O3 using Al substitution: Full spectrum phonon engineering

Improving the thermal conductivity of β-Ga2O3 is critical for optimizing its performance in high-power electronic devices, as effective thermal management significantly influences their output power and reliability. In this work, the thermal conductivities of β-Ga2O3 and (AlxGa1−x)2O3 alloys along the (2¯ 0 1) direction were first computed using a non-equilibrium molecular dynamics method based on the deep learning potential. Our results indicate that the calculated thermal conductivity of β-Ga2O3 is 16.6 W m−1K−1 along the (2¯ 0 1) direction, which is in excellent agreement with experimental measurements. In our findings, an Al to Ga ratio of 1:1 leads to the thermal conductivity of the (AlxGa1−x)2O3 alloy being more than twice that of β-Ga2O3, regardless of the Al substitution sites. The (Al0.5Ga0.5)2O3 alloy exhibits enhanced thermal conductivity due to the improved transport properties of optical phonon modes, including the increased group velocities, the enhanced participation, and the induced new vibrational modes at higher frequencies. This research provides theoretical predictions regarding the optimal Al to Ga ratio to enhance the thermal conductivity of (AlxGa1−x)2O3 alloys, offering crucial insights for the design and thermal management of β-Ga2O3 power devices.

Fluid flow inside slit-shaped nanopores: The role of surface morphology at the molecular scale

Non-equilibrium molecular dynamics (NEMD) simulations of fluid flow have highlighted the peculiarities of nanoscale flows compared to classical fluid mechanics; in particular, boundary conditions can deviate from the no-slip behavior at macroscopic scales. For fluid flow in slit-shaped nanopores, we demonstrate that surface morphology provides an efficient control on the slip length, which approaches zero when matching the molecular structures of the pore wall and the fluid. Using boundary-driven, energy-conserving NEMD simulations with a pump-like driving mechanism, we examine two types of pore walls—mimicking a crystalline and an amorphous material—that exhibit markedly different surface resistances to flow. The resulting flow velocity profiles are consistent with Poiseuille theory for incompressible, Newtonian fluids when adjusted for surface slip. For the two pores, we observe partial slip and no-slip behavior, respectively. The hydrodynamic permeability corroborates that the simulated flows are in the Darcy regime. However, the confinement of the fluid gives rise to an effective viscosity below its bulk value; wide pores exhibit a crossover between boundary and bulk-like flows. In addition, the thermal isolation of the flow causes a linear increase in fluid temperature along the flow, which we relate to strong viscous dissipation and heat convection, utilizing conservation laws of fluid mechanics. Noting that the investigated fluid model does not form droplets, our findings challenge the universality of previously reported correlations between slippage, solvophobicity, and a depletion zone. Furthermore, they underscore the need for molecular-scale modeling to accurately capture the fluid dynamics near boundaries and in nanoporous materials, where macroscopic models may not be applicable.

Expression of ENL YEATS domain tumor mutations in nephrogenic or stromal lineage impairs kidney development

Abstract Recurrent gain-of-function mutations in the histone reader protein ENL have been identified in Wilms tumor, the most prevalent pediatric kidney cancer. However, their pathological significance in kidney development and tumorigenesis in vivo remains elusive. Here, we generate mouse models mimicking ENL tumor (ENLT) mutations and show that heterozygous mutant expression in Six2 + nephrogenic or Foxd1 + stromal lineages leads to severe, lineage-specific kidney defects, both resulting in neonatal lethality. Six2-ENLT mutant kidneys display compromised cap mesenchyme, scant nephron tubules, and cystic glomeruli, indicative of premature progenitor commitment and blocked differentiation. Bulk and spatial transcriptomic analyses reveal aberrant activation of Hox and Wnt signaling genes in mutant nephrogenic cells. In contrast, Foxd1-ENLT mutant kidneys exhibit expansion in renal capsule and cap mesenchyme, with dysregulated stromal gene expression affecting stroma-epithelium crosstalk. Our findings uncover distinct pathways through which ENL mutations disrupt nephrogenesis, providing a foundation for further investigations into their role in tumorigenesis.

Two-temperature model for predicting heating and melting in metallic and semiconductor materials irradiated by x-ray pulses

The interaction of x-ray pulses with metallic and semiconductor materials has a wide range of applications in defense, nuclear fusion, and material processing. As such, thermal analysis of x-ray interactions with materials is crucial, particularly for ultrashort and short pulses (ranging from femtoseconds to a few nanoseconds). Similar to optical lasers, pulsed x rays can induce melting, evaporation, and ablation of materials through various physical mechanisms. A two-temperature model (TTM) is developed and applied to investigate the effects of soft x rays on the heating, melting, and ablation of metallic and semiconductor materials, which are commonly used in spacecraft solar cells, fusion devices, and high-energy physics applications. This model is particularly suited for analyzing these processes at very short time scales. The applicability of TTM for x-ray pulses lasting a few nanoseconds is also explored. The results are validated against the experimental data, offering valuable insights into the electron-lattice dynamics in metals and semiconductors during and after exposure to x-ray pulses.

Method-independent cusps for atomic orbitals in quantum Monte Carlo

We present an approach for augmenting Gaussian atomic orbitals with correct nuclear cusps. Like the atomic orbital basis set itself and unlike previous cusp corrections, this approach is independent of the many-body method used to prepare wave functions for quantum Monte Carlo. Once the basis set and molecular geometry are specified, the cusp-corrected atomic orbitals are uniquely specified, regardless of which density functionals, quantum chemistry methods, or subsequent variational Monte Carlo optimizations are employed. We analyze the statistical improvement offered by these cusps in a number of molecules and find them to offer similar advantages as molecular-orbital-based approaches while remaining independent of the choice of many-body method.

Three-dimensional flexible thermoelectric fabrics for smart wearables

The OH + CH3SH process: Potential energy surface and theoretical dynamics study

In the present work, an analytical full-dimensional potential energy surface, PES-2024, was developed for the first time, describing the polyatomic OH + CH3SH gas-phase reaction. This reaction presents some intrinsic difficulties, such as 18 degrees of freedom; two possible reactive channels; methyl- and thiol-H abstraction reactions, (R1) and (R2), respectively; and the presence of intermediate complexes in the entrance and exit channels. In the valence bond-molecular mechanics, VB-MM, framework, we have developed this potential based on a reduced number of high-level ab initio calculations, the input data. The new PES has been subjected to a series of stringent tests. PES-2024 simultaneously describes both (R1) and (R2) reaction paths, forming the water molecule and describing reasonably the topology of the reaction: high exothermicities, low barriers, and the presence of intermediate complexes. Based on this surface, quasi-classical trajectory calculations were performed at room temperature for both paths, with special emphasis on the H2O(v1, v2, v3) product stretching (v1 and v3 modes) and bending (v2 mode) vibrational excitations, comparing the results with the recent experimental evidence. The available energy was mostly deposited as water vibrational energy, 44% and 47%, respectively, simulating the experimental evidence. These detailed state-to-state results lend confidence to the new surface.

Author Correction: Biophysical neural adaptation mechanisms enable artificial neural networks to capture dynamic retinal computation

Stepwise microsolvation of HCl revisited: Infrared investigation of selectively deuterated (HCl)m(H2O)n (m + n ≤ 4) cluster molecules

In a recent theoretical investigation of DCl–H2O, HCl–D2O, and DCl–D2O [Felker et al., J. Phys. Chem. A, 125(29), 6437 (2021)] employing an accurate 9D permutation invariant polynomial-neural network potential energy surface and a highly efficient bound-state methodology, all the intramolecular vibrational eigenstates and dimerization spectral shifts of the three isotopic binary 1:1 complexes have been predicted. By means of dedicated annealing procedures, relative concentration dependencies, and a specialized dual inlet deposition procedure enabling complexation between specific isotopically substituted subunits, the present work identifies the intramolecular vibrational transitions experimentally for these three isotopologues of the binary complex and the most stable cyclic conformations of selectively deuterated mixed (HCl)m(H2O)n (m + n ≤ 4) cluster molecules embedded in inert neon “quantum matrices” at 4 K. The vibrational assignments up to mixed ternary cluster molecules are supported by harmonic CCSD(T)-F12b/cc-pVTZ-F12 frequency predictions in conjunction with anharmonic corrections employing second-order vibrational perturbation theory (VPT2) at the MP2/aug-cc-pVTZ level of theory. While the assigned O–H and O–D stretching transitions in neon are systematically spectrally redshifted by 0.2%–0.5% relative to previously reported observations in supersonic jets, the assigned H–Cl and D–Cl stretching transitions all reveal anomalous excessive spectral redshifts in neon increasing with the size of the cluster molecules. These cluster-size dependent excessive H–Cl/D–Cl spectral redshifts in neon indicate that the extent of charge transfer is enhanced strongly with the complexation of an increasing number of H2O molecules as predicted by quantum chemical models for more than a decade.

Cholecystokinin neurons in the spinal trigeminal nucleus interpolaris regulate mechanically evoked predatory hunting in male mice

Structures and properties of Ca–Xe compounds at extreme pressure and temperature

Calcium, one of the most abundant elements in the Earth’s mantle, does not react easily with noble gases (e.g., He and Xe) under ambient conditions. However, high pressure can alter electron configurations in atoms, leading to the formation of unconventional compounds. In this study, we systematically investigate Ca–Xe compounds across pressures of 0–150 GPa using calypso structure prediction methods combined with first-principles calculations. We identify four novel Ca–Xe compounds Pm3̄m-CaXe, P4/mmm-CaXe2, I4/m-Ca3Xe, and P4/mmm-Ca2Xe3 that demonstrate stability over a wide pressure range from 37.5 to 150 GPa. All these compounds exhibit metallic properties and are dynamically stable, as indicated by the absence of imaginary frequencies in their phonon dispersion spectra. Ionic bonding between Ca and Xe is observed due to electron transfer from Ca to Xe. Ab initio molecular dynamics simulations show that Pm3̄m-CaXe, P4/mmm-CaXe2, and P4/mmm-Ca2Xe3 remain solid up to pressures of 135 GPa and temperatures of 4000 K. In contrast, I4/m-Ca3Xe undergoes a transition from solid to liquid at temperatures above 3500 K due to weakened Ca–Xe bonds. The findings suggest that these Ca–Xe compounds could potentially be synthesized experimentally under high-pressure conditions. The results offer theoretical guidance for discovering new high-pressure Xe compounds and provide valuable insights into Xe chemistry.

Astrocytic pleiotrophin deficiency in the prefrontal cortex contributes to stress-induced depressive-like responses in male mice

Theory of frequency fluctuation of intramolecular vibration in solution phase: Application to C–N stretching mode of organic compounds

We formulate frequency fluctuations of intramolecular vibrations of a solute by exploring the fluctuation of the electrostatic potential by solvents. We present a numerical methodology for estimating the frequency fluctuations; the methodology is based on the reference interaction site model self-consistent field with a constrained spatial electron density distribution, a theoretical model of solvation fields based on classical statistic mechanics. By applying the present theory to the C–N stretching vibrations of several nitrile compounds, our estimated frequency fluctuation scale and bandwidth shift by changing solvent kinds reproduced the experimental data. Furthermore, we regard the standard deviation of the electrostatic potential as the multiple random variables for analyzing the frequency fluctuations. Our results reveal that the dominant fluctuation of the electrostatic field is almost parallel to the vibrational axis. In addition, the fluctuations of electrostatic potential become spatially nonuniform as the solvents form stronger hydrogen bonds with the solute. The development of the solvation field confirms that the nonuniformity of the electrostatic field is crucial to the frequency fluctuations.

Polaritonic Fourier crystal

USP7 V517F mutation as a mechanism of inhibitor resistance

FKBP51 in glutamatergic forebrain neurons promotes early life stress inoculation in female mice

Abstract Early life stress (ELS) can increase vulnerability to psychiatric disorders, but also trigger resilience. FKBP51 has been associated with an increased risk for developing psychiatric disorders, specifically in interaction with ELS exposure. Here, the contribution of FKBP51 in glutamatergic forebrain neurons to the long-term consequences of ELS was investigated in both sexes. In female wild-type Fkbp5 lox/lox mice, ELS exposure led to an anxiolytic phenotype and improved memory performance in a stressful context, however this ELS effect was absent in Fkbp5 Nex mice. These interactive FKBP51 x ELS effects in female mice were also reflected in reduced brain region volumes, and on structural and electrophysiological properties of CA1 pyramidal neurons of the dorsal hippocampus. In contrast, the behavioral, structural and functional effects in male ELS mice were less pronounced and independent of FKBP51. RNA sequencing of the hippocampus revealed the transcription factor 4 (TCF4) as a potential regulator of the female interactive effects. Cre-dependent viral overexpression of TCF4 in female Nex-Cre mice led to similar beneficial effects on behavior as the ELS exposure. This study demonstrates a sex-specific role for FKBP51 in mediating the adaptive effects of ELS on emotional regulation, cognition, and neuronal function, implicating TCF4 as a downstream effector.

ER O-glycosylation in synovial fibroblasts drives cartilage degradation

Abstract How arthritic synovial fibroblasts (SFs) activate cartilage ECM degradation remains unclear. GALNT enzymes initiate O-glycosylation in the Golgi; when relocated to the ER, their activity stimulates ECM degradation. Here, we show that in human rheumatoid and osteoarthritic synovial SFs, GALNTs are relocated to the ER. In an RA mouse model, GALNTs relocation occurs shortly before arthritis symptoms and abates as the animal recovers. An ER GALNTs inhibitor prevents cartilage ECM degradation in vitro and expression of this chimeric protein in SFs results in the protection of cartilage. One of the ER targets of GALNTs is the resident protein Calnexin, which is exported to the cell surface of arthritic SFs. Calnexin participates in matrix degradation by reducing ECM disulfide bonds. Anti-Calnexin antibodies block ECM degradation and protect animals from RA. In sum, ER O-glycosylation is a key switch in arthritic SFs and glycosylated surface Calnexin could be a therapeutic target.

Deep representation learning for clustering longitudinal survival data from electronic health records

Abstract Precision medicine requires accurate identification of clinically relevant patient subgroups. Electronic health records provide major opportunities for leveraging machine learning approaches to uncover novel patient subgroups. However, many existing approaches fail to adequately capture complex interactions between diagnosis trajectories and disease-relevant risk events, leading to subgroups that can still display great heterogeneity in event risk and underlying molecular mechanisms. To address this challenge, we implemented VaDeSC-EHR, a transformer-based variational autoencoder for clustering longitudinal survival data as extracted from electronic health records. We show that VaDeSC-EHR outperforms baseline methods on both synthetic and real-world benchmark datasets with known ground-truth cluster labels. In an application to Crohn’s disease, VaDeSC-EHR successfully identifies four distinct subgroups with divergent diagnosis trajectories and risk profiles, revealing clinically and genetically relevant factors in Crohn’s disease. Our results show that VaDeSC-EHR can be a powerful tool for discovering novel patient subgroups in the development of precision medicine approaches.

Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization

Abstract The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O2 or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres apparent in the pluripotent Inner Cell Mass (ICM) and persisting after organogenesis. Identical defects of elevated mtROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. We further demonstrate that telomere elongation during ICM formation is controlled by mitochondrial-nuclear communication at fertilization. Using mitochondrially-targeted therapeutics (BGP-15, MitoQ, SS-31, metformin) we demonstrate that it is possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length.