Browse Articles

A Gaussian kernel Monte Carlo resampling method to construct smooth free energy surface from discrete simulation data

Constructing a free energy surface based on discrete molecular simulation data is a common practice in computational chemistry and biophysics. As a general strategy, histogram-based methods have substantial limitations in producing smooth free energy surfaces from sparse samples. Most histogram-free methods allow for possible smooth global free energy surface mapping but likely lead to significantly compromised local features. This issue is particularly severe when both the global shape and the local free energy transition need to be quantitatively depicted, as often aimed for in general ensemble simulation studies. In this work, we introduce a Gaussian kernel Monte Carlo (GKMC) resampling method to robustly construct a smooth free energy surface from discrete simulation data. In GKMC resampling, the target free energy surface is mapped as the sum of local Gaussian basis functions; the height of each Gaussian basis function is recursively obtained through MC resampling of the simulation data. In this work, the GKMC resampling method is illustrated based on the data from a generalized orthogonal space tempering simulation study of deca-alanine peptide conformational changes in aqueous solution. As revealed in the case study, smooth free energy surfaces that can accurately represent simulated probability distributions could be robustly generated through the GKMC resampling strategy. Because data noise can be effectively removed, local free energy features could be displayed in an informative way. Notably, without impacting the global free energy shape, local free energy smoothness can be conveniently adjusted via the choice of the Gaussian kernel function width. As demonstrated, GKMC resampling is a robust approach for high-quality free energy surface construction.

Correlated vibration–solvent and Duschinsky effects on electron transfer dynamics and optical spectroscopy

Understanding the effects of vibrations in electron transfer (ET) dynamics and optical spectroscopies is essential to precisely interpret the role of decoherence, especially for systems embedded in solvents. In this work, we study the correlated Duschinsky and solvent effects on ET and spectroscopy. Exploited is a novel extended dissipaton-equation-of-motion approach, which is an exact and non-Markovian, non-perturbative method for quadratic system–bath couplings. The unified bath description, in terms of multiple Brownian oscillators (BOs), comprises the solvent modes and also intramolecular vibrations. Both ET dynamics and spectroscopy show the complex interplay among linear displacements, frequency shifts, Duschinsky rotations, and solvent-induced BO-mode correlations. The reduced ET system density operator evolution is further analyzed in the context of the Bloch sphere representation, which is basis-set independent due to its geometric nature.

Broadband shot-to-shot transient absorption anisotropy

Transient absorption (TA) is the most widespread method to follow ultrafast dynamics in molecules and materials. The related method of TA anisotropy (TAA) reports on the ultrafast reorientation dynamics of transition dipole moments, reporting on phenomena ranging from electronic dephasing to orientational diffusion. While these are fundamental aspects complementary to TA, TAA is generally less widely used. The main reason is that TAA signals are usually not measured directly but are retrieved from two consecutive TA measurements with parallel (R‖) and perpendicular (R⊥) polarization of pump and probe pulses. This means that even minor systematic errors in these measurements lead to drastic changes in the TAA signal. In this work, the authors demonstrate alternating shot-to-shot detection of R‖ and R⊥, minimizing systematic errors due to laser fluctuations. The employed broadband detection lets us discuss effects dependent on detection wavelength in the ultrafast anisotropy decay of 2,3-naphthalocyanine, a system previously scrutinized by David Jonas and co-workers. In particular, we compare timescales of population relaxation and decoherence and support the proposals for isotropic type of relaxation in square symmetric molecules.

A new six-dimensional <i>ab initio</i> potential energy surface and rovibrational spectra for the CO–CO2 complex

New six-dimensional potential energy surfaces containing the stretching vibration of CO and the Q3 normal mode for the ν3 antisymmetric stretching vibration of CO2 were constructed for the CO–CO2 complex at the CCSD(T)-F12/AVTZ level. We obtained the effective vibrational interaction potentials by integration over the two intramolecular coordinates, and these potentials are found to exhibit a global T-shaped minimum (the C-bonded isomer) with the C atom in CO pointed toward CO2 and a local T-shaped minimum (the O-bonded isomer) but with the CO monomer flipped by 180°. The rovibrational energy levels and bound states were computed by employing the radial discrete variable representation/angular finite basis representation approach and the Lanczos algorithm. The band origin shifts of infrared spectra in the stretching range of CO are +5.022 and −3.589 cm−1 for the two isomers, which are in accordance with the measured data of +4.970 and −2.982 cm−1, respectively, and better than the values of +5.3/+3.6 and −0.6/−0.4 cm−1 obtained from previous theoretical studies. In addition, the wavefunctions of the intermolecular ground and lower excited vibrational states distribute around the T-shaped minima, and the obtained intermolecular vibrational frequencies for both isomers performed on the averaged potential energy surfaces are close to the available observed values. The spectroscopic constants fitted from the rovibrational levels exhibit that the CO–CO2 dimer is a near antisymmetric prolate top. The obtained pure rotational transition energies and the infrared fundamental and combination bands of the CO–CO2 dimer and the isotopomer 13CO–CO2 dimer well reproduce the experimental spectra.

Finetuning laser-pulse frequencies for optimizing information content of femtosecond nonlinear spectroscopy: <i>Ab initio</i> simulations

We have performed a series of numerical ab initio experiments, in which we simulated several popular nonlinear femtosecond signals—time-resolved fluorescence, transient-absorption pump–probe, and electronic two-dimensional—for different carrier frequencies of the pump and probe pulses. As a system under study, we took the molecule of pyrazine in the gas phase. Our results demonstrate that variation of frequencies of the pulses increases the amount of information extracted from the spectroscopic signals, helps explore rarely visiting areas of the potential energy landscapes, and compensates for the unavailability of extra-broadband transform-limited pulses.

Testing exact-factorization-based density functional approximation on a continuous density model

In this work, we test the performance of an exact-factorization-based density functional approximation (DFA) for electron–nuclear correlation beyond the Born–Oppenheimer approximation that was derived in Li et al. [J. Chem. Phys.148, 084110 (2018)]. The present work extends beyond the Hubbard model that was used previously in a two-electron Shin–Metiu model with continuous electronic density in one dimension. Using new iteration techniques, we managed to solve coupled Kohn–Sham equations that embody nonadiabatic corrections with a nuclear Schrödinger equation. Our results show that the DFA can successfully capture the nonadiabatic effect caused by electron–nuclear correlation as manifested in the correct shift of the critical nuclear position where the proton-coupled electron transfer takes place. The nonadiabatic correction to the Kohn–Sham potential also leads to a shift of orbital energies, which can potentially be useful to study band renormalization induced by electron–phonon interactions in bulk materials.

A combined statistical mechanical and <i>ab initio</i> approach to understanding H2O/CO2 co-adsorption in mmen-Mg2(dobpdc)

We study the effects of H2O on CO2 adsorption in an amine-appended variant of the metal–organic framework Mg2(dobpdc), which is known to exhibit chaining behavior that presents in a step-shaped adsorption isotherm. We first show how the presence of different levels of local H2O affects this chaining behavior and the energetics of CO2 adsorption, based on a series of ab initio calculations, giving insight into the atomic-scale environment. In particular, we predict a novel adsorbed configuration, in which H2O and CO2 intertwine to make a braided chain down the MOF pore. We then show how an existing lattice model can be adapted to incorporate the effect of water and predict the CO2 isotherms for the various water levels, observing a sharp shift in the uptake at low partial pressures. The manifestation of this braided chain in the lattice model points to the potential emergence of a shift from cooperative capture to that of a phase transition. In addition to the physical insights, this work may serve as a launching off point for further work on this and related materials.

Quantum geometry and adiabaticity in molecules and in condensed matter

The adiabatic theorem states that when the time evolution of the Hamiltonian is “infinitely slow,” a system, when started in the ground state, remains in the instantaneous ground state at all times. This, however, does not mean that the adiabatic evolution of a generic observable obtains simply as its expectation value over the instantaneous eigenstate. As a general principle, there is an additional adiabatic term, of quantum-geometrical nature, which is the relevant one for several static or adiabatic observables. This is shown explicitly for the cases of polarizability and infrared tensors (in molecules and condensed matter) and rotational g factor and magnetizability (in molecules only). Quantum geometry allows for a transparent derivation and a compact expression for these observables, alternative to the well-known sum-over-states Kubo formulas.

Rotational investigation of volatile anesthetics: Conformational equilibrium, molecular structure, and complex hyperfine interactions of methoxyflurane

The volatile anesthetic methoxyflurane was investigated in the 2–8 GHz region by chirp-excitation Fourier-transform broadband microwave spectroscopy. The presence of two conformers—gauche–trans (C1) and trans–trans (Cs)—each containing two quadrupolar chlorine nuclei and one methyl internal rotor, results in a very dense spectrum with complex rotational hyperfine effects, where contributions from nuclear quadrupole interactions and internal rotation couple to the overall molecular rotation. For the spectrally more complicated C1-conformer, additional impulse-excitation cavity measurements were carried out in the region of 10–21 GHz. To the best of our knowledge, there is no published code that can handle two quadrupolar nuclei in a non-coplanar orientation with respect to the internal rotor, so we developed our own codes interfacing with Pickett’s SPFIT rovibrational fitting program to allow for a near-experimental accuracy fit of the relatively abundant isotopologues, comprising all isotopologue combinations of the 35Cl and 37Cl nuclei. Furthermore, the Hartwig–Herbers’ XIAM-NQ code was later extended to treat a second quadrupolar nucleus, and global fits with this new code XIAM-2NQ were validated against SPFIT results. The relative transition intensities of the two conformers were used to estimate the relative room-temperature population as N(Cs)/N(C1) = 0.88 ± 0.30 corresponding to a difference in the Gibbs free energy of −1.4 ± 1.1 kJ/mol. A computational characterization using density functional theory [CAM-B3LYP-D3 (BJ)] complemented the experimental results. This work completes the rotational investigations on the conformational and structural panorama of the most important halogenated inhalational anesthetics, potentially enabling their monitoring through rotational spectroscopic fingerprints.

Pr and Pfr structures of plant phytochrome A

Abstract Phytochromes are biliprotein photoreceptors widespread amongst microorganisms and ubiquitous in plants where they control developmental processes as diverse as germination, stem elongation and floral induction through the photoconversion of inactive Pr to the Pfr signalling state. Here we report crystal structures of the chromophore-binding module of soybean phytochrome A, including ~2.2 Å XFEL structures of Pr and Pfr at ambient temperature and high resolution cryogenic structures of Pr. In the Pfr structure, the chromophore is exposed to the medium, the D-ring remaining α-facial following the likely clockwise photoflip. The chromophore shifts within its pocket, while its propionate side chains, their partners as well as three neighbouring tyrosines shift radically. Helices near the chromophore show substantial shifts that might represent components of the light signal. These changes reflect those in bacteriophytochromes despite their quite different signalling mechanisms, implying that fundamental aspects of phytochrome photoactivation have been repurposed for photoregulation in the eukaryotic plant.

High isolation quad ports MIMO antenna loaded with FSS for 5G communication

Abstract This paper introduces a high isolation quad ports MIMO (Multiple-Input Multiple-Output) antenna with a frequency selective surface (FSS) structure for higher frequency bands in 5G communication systems. The recommended antenna is designed for 28 GHz application. The single unit of the antenna consists of a microstrip feed line on one side and a rectangular slot in the ground plane on the other side. The four MIMO antennas are arranged orthogonally on a Rogers RO4003C substrate with a permittivity of 3.38, a loss tangent (tan δ) of 0.002, and a height of 0.203 mm. The substrate features a cross-shaped cut to enhance the isolation between ports. An FSS is placed beneath the MIMO system to improve the overall gain across the desired frequency band. The antenna size is 25.7 × 25.7 mm². The design and simulation of the proposed structure were carried out using CST MW Studio. The antenna with and without the FSS structure was constructed and tested to verify the simulation results. The results indicate that the suggested structure is worked from 25.5 GHz up to 30 GHz with insertion loss ≤ -22 dB and peak gain of around 8dBi. As well, the envelope correlation coefficient (ECC), diversity gain (DG), and channel capacity loss (CCL) are measured and achieved ≤ 0.002, ≥ 9.99 dB, ≤ 0.2 bit/s/Hz, respectively. Also, extra MIMO parameters such as mean effective gain (MEG), channel capacity, and total active reflection coefficient (TARC) are extracted and achieve good outcomes confirming the ability of the antenna to be applicable for 5G networks.

Attention-driven UNet enhancement for accurate segmentation of bacterial spore outgrowth in microscopy images

Abstract Analyzing microscopy images of large growing cell samples using traditional methods is a complex and time-consuming process. In this work, we have developed an attention-driven UNet-enhanced model using deep learning techniques to efficiently quantify the position, area, and circularity of bacterial spores and vegetative cells from images containing more than 10,000 bacterial cells. Our attention-driven UNet algorithm has an accuracy of 96%, precision of 82%, sensitivity of 81%, and specificity of 98%. Therefore, it can segment cells at a level comparable to manual annotation. We demonstrate the efficacy of this model by applying it to a live-dead decontamination assay. The model is provided in three formats: Python code, a Binder that operates within a web browser without needing installation, and a Flask Web application for local use.

Microfacies analysis and diagenetic history of Lower to Middle Eocene carbonates at Umm Russies area in the northeastern desert of Egypt

Abstract An integrated study, incorporating field observations and petrographic analysis, has been conducted on the Lower-Middle Eocene carbonates of the Umm Russies area, North Eastern Desert, Egypt. These carbonate sequence represented, from base to top, by Minia, Gebel Hof, and Observatory formations, primarily consisting of marl, dolomite, and limestone. The microfacies analysis allowed the identification of seven distinct microfacies types: bioclastic floatstone, ferruginous dolomite, bioclastic packstone, ferruginous peloidal grainstone, sandy rudstone, foraminiferal wackestone, and bioclastic packstone. These microfacies types reflect a deposition in a wide range of environments from high-energy inner ramp to low-energy middle ramp settings. The performed petrographic analysis indicates that the investigated carbonate rocks underwent significant modification through a range of diagenetic processes, such as micritization, glauconitization, and dolomitization, representing marine-phreatic, meteoric-phreatic, burial, and meteoric-vadose environments. These environments are part of three successive diagenetic stages; eogenesis, mesogenesis, and telogenesis. The relationship between diagenetic episodes and depositional settings highlights that high-energy inner ramp environments facilitated early cementation and micritization, while middle ramp conditions promoted dissolution and neomorphism. Restricted platform margin environments favored dolomitization and glauconitization. Integrating microfacies analysis with these diagenetic interpretations facilitates reconstructing paleoenvironmental conditions and provides a framework for understanding carbonate rock formation in various geological settings.

Algorithm-based intraoperative diagnosis of liver tumors using infrared spectroscopy

Abstract Liver cancer, including hepatocellular carcinoma (HCC), cholangiocellular carcinoma (CCC), and metastases, presents diagnostic challenges during surgery due to its infiltrative nature. Accurate intraoperative classification and margin assessment are crucial for improving outcomes. Current methods, like frozen section analysis, are time-consuming and subjective, necessitating rapid, objective alternatives. This study assessed fiber-based attenuated total reflection infrared (ATR IR) spectroscopy combined with supervised machine learning for intraoperative liver tumor classification based on a holistic biochemical signature approach. Fresh liver tissue from 69 surgical patients was analyzed using a probe consisting of Ge ATR crystal and silver halide fibers. Supervised algorithms reliably classified normal tissue and tumor subtypes (HCC, CCC, metastases) using cross-validation and independent test sets. Normal liver tissue was distinguished primarily by differences in glycogen content and structural compactness of tumor tissue. Normal and tumor tissues were differentiated with a sensitivity of 0.89 and a specificity of 0.92. The accuracy of spectroscopic classification is 0.90. The three-group classification of tumor subtypes also yielded an average accuracy of 0.90. HCC is characterized by a higher glycogen content compared to CCC and metastases and can be identified spectroscopically with high reliability. CCC showed distinct protein-associated spectral signatures, while metastases exhibited unique profiles reflecting their different origins. In a minority of cases, misclassifications occurred, indicating potential for further refinement. Fiber-based ATR IR spectroscopy in combination with machine learning provides a rapid, objective, and highly accurate intraoperative tool for liver tumor classification. This label-free biochemical approach may enhance surgical precision and reduce recurrence risks across the full range of solid tumor entities.

Modeling of potential field data for detecting structural and tectonic framework of Esh El Mellaha area, Red Sea, Egypt

Birth mode is associated with layer-specific mechanical changes in fetal membranes

Abstract Rupture of fetal membranes and subsequent full-term birth are prerequisites for neonatal health, and a preterm rupture can lead to life-threatening complications. Our study determines the mechanical properties of term fetal membranes to identify perinatal structural changes by a unique biophysical multiscale approach, including atomic force microscopy, shear rheology, tabletop magnetic resonance elastography (MRE), and high-resolution optical microscopy. Fetal membranes from term spontaneous vaginal deliveries were compared to those from primary cesarean sections, used as a control group for pre-labor membranes. Spontaneously delivered term fetal membranes are softer and easier to deform in MRE experiments (median stiffness: 1.9 kPa, IQR 1.6–2.4) compared to controls (4.7 kPa, IQR 3.8–5.6); p &lt; 0.001) and show increased water diffusion (median: 1.78 × 10−3 mm2/s, IQR: (1.65–1.84) × 10−3 vs. 1.66 × 10−3 mm2/s, IQR (1.60–1.73) × 10−3; p = 0.047). Their intermediate connective tissue layer (i.e. the collagen-rich area enclosed by the amnion and chorion) exhibits less ordered fiber alignment (median order parameter: 0.52, IQR 0.44–0.58 vs. 0.55, IQR 0.47–0.62; p = 0.04) and a looser fiber structure, as indicated by a significantly lower fiber area fraction (median: 0.33, IQR 0.25–0.46 vs. 0.73, IQR 0.63–0.88; p &lt; 0.001) compared to the control membranes. These layer-specific changes in both structure and viscoelasticity are evidence for the dominant role of the intermediate connective tissue in maintaining membrane stability and the onset of rupture. Our mechanical and histopathological findings highlight the potential of mechanics-based screening-methods to assess the risk of preterm rupture and preterm birth to reduce neonatal morbidity.

Age-related changes in the proteome and mitochondrial metabolism of rabbit adipose-derived stromal/stem cells

Abstract Adipose tissue is continuously regenerated by stromal mesenchymal stem cells throughout life. This study hypothesises that early age-related changes in the proteome and metabolic properties of subcutaneous (s) and visceral (v) adipose tissue-derived stromal/stem cells (ASCs) from young and old rabbits contribute to a loss of stem cell plasticity and function. To test this, the proteome and metabolic properties of ASCs from young and old rabbits were analysed using mass spectrometry-based label-free quantification and mitochondrial respiration measurements (Seahorse Mito Cell Stress Test). Both sASCs and vASCs from old rabbits exhibited comparable clusters of differentially expressed proteins. However, age-related changes were more pronounced in sASCs, suggesting that ageing affects ASCs differently depending on anatomical origin. In particular, a cluster of mitochondrial proteins in sASCs was differentially expressed with age, correlating with a shift in metabolic profile. The increase in mitochondrial respiration indicates that ageing ASCs lose their quiescent state and plasticity, leading to accelerated proliferation and differentiation. These proteomic findings were validated by Western Blot analysis, which confirmed the differential expression of key mitochondrial proteins. These results highlight the role of cellular origin in stem cell ageing and provide insights into the mechanisms underlying age-related stem cell dysfunction.

Effects of K-wire diameter and insertion angle on femoral bone medial closing-wedge osteotomies: a finite element study

Abstract Medial closing-wedge surgery for distal femoral osteotomy is employed to correct genu valgum by correcting coronal plane malalignment. This procedure involves pre-surgery planning, creating a wedge incision, performing the osteotomy, and stabilizing with plates and screws. However, hinge fractures during wedge closure present significant challenges, often necessitating revisions. Contemporary solutions have explored the use of k-wires, and this study investigates their biomechanical implications. The interplay between k-wire insertion angle and diameter, often overlooked in existing literature, is a critical determinant of their efficacy in achieving successful osteotomies, highlighting gaps in our understanding of these key parameters. We hypothesize that k-wire mechanics vary with insertion angle and diameter. This study examines the introduction of k-wires at different angles (30°, 45°, and 60°) and diameters (1.6, 1.8, and 2 mm) using computed tomography-based finite element models to assess structural integrity during femoral medial closing-wedge osteotomy. Results reveal angle-dependent stress variations, with 60° configurations exhibiting favorable patterns that reduce tensile and compressive loads and plastic deformation—crucial in preventing hinge fractures. Diameter variations show no significant differences in stresses or system stiffness. It was also found that while angle significantly affects stresses, lower diameters appear optimal only in combination with higher angles. Comparative analysis of k-wire systems with a naïve model demonstrates that k-wires at a 60° angle reduce tensile and compressive loadings and plastically deformed volume fractions, thus lowering fracture risk. This study underscores the importance of optimizing k-wire placement and configuration, particularly highlighting the significance of the insertion angle. Future research should expand the range of angles and diameters tested and examine different femoral geometries and osteotomy angles to provide a more comprehensive understanding and enhanced clinical application.

Electrical equivalent circuit for analyzing the effect of signal shape on power distribution in cochlear implant electrodes and surrounding tissue

Abstract Cochlear implants are a well-established solution for restoring hearing in severe impairment and profound deafness. However, cochlear implants still have limitations, such as speech recognition in noisy environments caused by intra-cochlear current spread across different auditory spiral ganglion neurons as a consequence of, e.g., the large distance of the stimulation electrodes to the target cells in a highly conductive environment. Stimulation in cochlear implants is typically done with charge balanced biphasic rectangular current pulses in a monopolar arrangement. However, several studies have shown that a rectangular stimulation pulse is not optimal for stimulating spiral ganglion neurons. For example, stimulation with a ramped pulse, such as a sawtooth pulse, has been shown to be more energy-efficient and achieves a similar threshold profile in spiral ganglion neurons. In this study, a new but simple equivalent electrical circuit model is introduced that describes the complex impedance between two stimulation electrodes of a cochlear implant with high accuracy (mean relative error ≤ 8%). Based on this bipolar model, a monopolar equivalent electrical circuit model is developed to describe the stimulation between one stimulation electrode and a counter electrode located outside the cochlea. These two models now allow for analyzing the effect of stimulation pulse shape on power distribution in cochlear implant electrodes and surrounding tissue providing a tool for investigating stimulation efficiency with respect to energy losses in the cochlear implant electrode.

Exploring the anticancer potential of green silver Nanoparticles–Paclitaxel nanocarrier on MCF-7 breast Cancer cells: an in vitro approach

Abstract Paclitaxel (PTX) is a potent chemotherapeutic agent limited by poor solubility and adverse effects. To address these challenges, we developed a novel nanocomposite combining PTX purified from the endophytic fungus A. fumigatiaffinis PP235788.1 with biosynthesized silver nanoparticles (AgNPs) from the same fungal strain. The PTX-AgNP conjugate (28.48 ± 0.13 nm) was characterized by UV-Vis, XRD, and TEM, revealing monodisperse AgNPs (14.50 ± 0.58 nm) as the core component. In vitro studies demonstrated significant cytotoxicity against MCF-7 breast cancer cells (IC₅₀= 1.7 µg/mL, p &lt; 0.001), with 5-10-fold greater efficacy than AgNPs alone. Annexin V/PI staining and DNA fragmentation assays confirmed apoptosis induction, highlighting the conjugate’s enhanced anticancer activity. This eco-friendly nano platform synergizes PTX’s therapeutic effects with AgNP-mediated targeting, offering a promising strategy to reduce side effects while improving tumor-specific cytotoxicity for advanced cancer therapy.