Contribution of DNA breathing to physical interactions with transcription factors.

Interaction between transcription factors (TFs) and DNA plays a key role in regulating gene expression. It is generally believed that these interactions are controlled through recognition of DNA core motifs by TFs. Nevertheless, several studies pointed out the limitation of this view, in particular, DNA sequence variants influencing TF binding are often located outside of core motifs.

DNA breathing integration with deep learning foundational model advances genome-wide binding prediction of human transcription factors.

It was previously shown that DNA breathing, thermodynamic stability, as well as transcriptional activity and transcription factor (TF) bindings are functionally correlated. To ascertain the precise relationship between TF binding and DNA breathing, we developed the multi-modal deep learning model EPBDxDNABERT-2, which is based on the Extended Peyrard-Bishop-Dauxois (EPBD) nonlinear DNA dynamics model. To train our EPBDxDNABERT-2, we used chromatin immunoprecipitation sequencing (ChIP-Seq) data comprising 690 ChIP-seq experimental results encompassing 161 distinct TFs and 91 human cell types.

A nonlinear journey from structural phase transitions to quantum annealing.

Motivated by an exact mapping between equilibrium properties of a one-dimensional chain of quantum Ising spins in a transverse field (the transverse field Ising (TFI) model) and a two-dimensional classical array of particles in double-well potentials (the "ϕ4 model") with weak inter-chain coupling, we explore connections between the driven variants of the two systems. We argue that coupling between the fundamental topological solitary waves in the form of kinks between neighboring chains in the classical ϕ4 system is the analog of the competing effect of the transverse field on spin flips in the quantum TFI model. As an example application, we mimic simplified measurement protocols in a closed quantum model system by studying the classical ϕ4 model subjected to periodic perturbations.

Advancing Transcription Factor Binding Site Prediction Using DNA Breathing Dynamics and Sequence Transformers via Cross Attention.

Understanding the impact of genomic variants on transcription factor binding and gene regulation remains a key area of research, with implications for unraveling the complex mechanisms underlying various functional effects. Our study delves into the role of DNA's biophysical properties, including thermodynamic stability, shape, and flexibility in transcription factor (TF) binding. We developed a multi-modal deep learning model integrating these properties with DNA sequence data.

Examining DNA breathing with pyDNA-EPBD.

Motivation: The two strands of the DNA double helix locally and spontaneously separate and recombine in living cells due to the inherent thermal DNA motion. This dynamics results in transient openings in the double helix and is referred to as "DNA breathing" or "DNA bubbles." The propensity to form local transient openings is important in a wide range of biological processes, such as transcription, replication, and transcription factors binding.

Examining DNA Breathing with pyDNA-EPBD.

Motivation: The two strands of the DNA double helix locally and spontaneously separate and recombine in living cells due to the inherent thermal DNA motion.This dynamics results in transient openings in the double helix and is referred to as "DNA breathing" or "DNA bubbles." The propensity to form local transient openings is important in a wide range of biological processes, such as transcription, replication, and transcription factors binding.

Bubble Relaxation Dynamics in Homopolymer DNA Sequences.

Understanding the inherent timescales of large bubbles in DNA is critical to a thorough comprehension of its physicochemical characteristics, as well as their potential role on helix opening and biological function. In this work, we employ the coarse-grained Peyrard-Bishop-Dauxois model of DNA to study relaxation dynamics of large bubbles in homopolymer DNA, using simulations up to the microsecond time scale. By studying energy autocorrelation functions of relatively large bubbles inserted into thermalised DNA molecules, we extract characteristic relaxation times from the equilibration process for both adenine-thymine (AT) and guanine-cytosine (GC) homopolymers.

Patterns and Stability of Coupled Multi-Stable Nonlinear Oscillators.

Nonlinear isolated and coupled oscillators are extensively studied as prototypical nonlinear dynamics models. Much attention has been devoted to oscillator synchronization or the lack thereof. Here, we study the synchronization and stability of coupled driven-damped Helmholtz-Duffing oscillators in bi-stability regimes.

Measurement and memory in the periodically driven complex Ginzburg-Landau equation.

In the present work we illustrate that classical but nonlinear systems may possess features reminiscent of quantum ones, such as memory, upon suitable external perturbation. As our prototypical example, we use the two-dimensional complex Ginzburg-Landau equation in its vortex glass regime. We impose an external drive as a perturbation mimicking a quantum measurement protocol, with a given "measurement rate" (the rate of repetition of the drive) and "mixing rate" (characterized by the intensity of the drive).

Bubble lifetimes in DNA gene promoters and their mutations affecting transcription.

Relative lifetimes of inherent double stranded DNA openings with lengths up to ten base pairs are presented for different gene promoters and corresponding mutants that either increase or decrease transcriptional activity in the framework of the Peyrard-Bishop-Dauxois model. Extensive microcanonical simulations are used with energies corresponding to physiological temperature. The bubble lifetime profiles along the DNA sequences demonstrate a significant reduction of the average lifetime at the mutation sites when the mutated promoter decreases transcription, while a corresponding enhancement of the bubble lifetime is observed in the case of mutations leading to increased transcription.

Distributions of bubble lifetimes and bubble lengths in DNA.

We investigate the distribution of bubble lifetimes and bubble lengths in DNA at physiological temperature, by performing extensive molecular dynamics simulations with the Peyrard-Bishop-Dauxois (PBD) model, as well as an extended version (ePBD) having a sequence-dependent stacking interaction, emphasizing the effect of the sequences' guanine-cytosine (GC)/adenine-thymine (AT) content on these distributions. For both models we find that base pair-dependent (GC vs AT) thresholds for considering complementary nucleotides to be separated are able to reproduce the observed dependence of the melting temperature on the GC content of the DNA sequence. Using these thresholds for base pair openings, we obtain bubble lifetime distributions for bubbles of lengths up to ten base pairs as the GC content of the sequences is varied, which are accurately fitted with stretched exponential functions.

Metabolomics and the pig model reveal aberrant cardiac energy metabolism in metabolic syndrome.

Although metabolic syndrome (MS) is a significant risk of cardiovascular disease (CVD), the cardiac response (MR) to MS remains unclear due to traditional MS models' narrow scope around a limited number of cell-cycle regulation biomarkers and drawbacks of limited human tissue samples. To date, we developed the most comprehensive platform studying MR to MS in a pig model tightly related to human MS criteria. By incorporating comparative metabolomic, transcriptomic, functional analyses, and unsupervised machine learning (UML), we can discover unknown metabolic pathways connections and links on numerous biomarkers across the MS-associated issues in the heart.

Mechanical, elution, and antibacterial properties of simplex bone cement loaded with vancomycin.

Prosthetic joint infection (PJI) is one of the most devastating failures in total joint replacement (TJR). Infections are becoming difficult to treat due to the emergence of multi-drug resistant bacteria. These bacteria produce biofilm on the implant surface, rendering many antibiotics ineffective by compromising drug diffusion and penetration into the infected area.

Publisher Correction: Electrosynthesis of high-entropy metallic glass nanoparticles for designer, multi-functional electrocatalysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Electrosynthesis of high-entropy metallic glass nanoparticles for designer, multi-functional electrocatalysis.

Creative approaches to the design of catalytic nanomaterials are necessary in achieving environmentally sustainable energy sources. Integrating dissimilar metals into a single nanoparticle (NP) offers a unique avenue for customizing catalytic activity and maximizing surface area. Alloys containing five or more equimolar components with a disordered, amorphous microstructure, referred to as High-Entropy Metallic Glasses (HEMGs), provide tunable catalytic performance based on the individual properties of incorporated metals.

Speed-of-light pulses in the massless nonlinear Dirac equation with a potential.

We consider the massless nonlinear Dirac (NLD) equation in 1+1 dimension with scalar-scalar self-interaction g^{2}/2(Ψ[over ¯]Ψ)^{2} in the presence of three external electromagnetic real potentials V(x), a potential barrier, a constant potential, and a potential well. By solving numerically the NLD equation, we find different scenarios depending on initial conditions, namely, propagation of the initial pulse along one direction, splitting of the initial pulse into two pulses traveling in opposite directions, and focusing of two initial pulses followed by a splitting. For all considered cases, the final waves travel with the speed of light and are solutions of the massless linear Dirac equation.

Control of zeolite framework flexibility and pore topology for separation of ethane and ethylene.

The discovery of new materials for separating ethylene from ethane by adsorption, instead of using cryogenic distillation, is a key milestone for molecular separations because of the multiple and widely extended uses of these molecules in industry. This technique has the potential to provide tremendous energy savings when compared with the currently used cryogenic distillation process for ethylene produced through steam cracking. Here we describe the synthesis and structural determination of a flexible pure silica zeolite (ITQ-55).

Evaluating the role of coherent delocalized phonon-like modes in DNA cyclization.

The innate flexibility of a DNA sequence is quantified by the Jacobson-Stockmayer's J-factor, which measures the propensity for DNA loop formation. Recent studies of ultra-short DNA sequences revealed a discrepancy of up to six orders of magnitude between experimentally measured and theoretically predicted J-factors. These large differences suggest that, in addition to the elastic moduli of the double helix, other factors contribute to loop formation.

Variational approach to studying solitary waves in the nonlinear Schrödinger equation with complex potentials.

We discuss the behavior of solitary wave solutions of the nonlinear Schrödinger equation (NLSE) as they interact with complex potentials, using a four-parameter variational approximation based on a dissipation functional formulation of the dynamics. We concentrate on spatially periodic potentials with the periods of the real and imaginary part being either the same or different. Our results for the time evolution of the collective coordinates of our variational ansatz are in good agreement with direct numerical simulation of the NLSE.

Dynamical playground of a higher-order cubic Ginzburg-Landau equation: From orbital connections and limit cycles to invariant tori and the onset of chaos.

The dynamical behavior of a higher-order cubic Ginzburg-Landau equation is found to include a wide range of scenarios due to the interplay of higher-order physically relevant terms. We find that the competition between the third-order dispersion and stimulated Raman scattering effects gives rise to rich dynamics: this extends from Poincaré-Bendixson-type scenarios, in the sense that bounded solutions may converge either to distinct equilibria via orbital connections or to space-time periodic solutions, to the emergence of almost periodic and chaotic behavior. One of our main results is that third-order dispersion has a dominant role in the development of such complex dynamics, since it can be chiefly responsible (even in the absence of other higher-order effects) for the existence of periodic, quasiperiodic, and chaotic spatiotemporal structures.

Soliton dynamics in optical fibers using the generalized traveling-wave method.

The generalized traveling wave method (GTWM) is applied to the nonlinear Schrödinger (NLS) equation with general perturbations in order to obtain the equations of motion for an ansatz with six collective coordinates, namely the soliton position, the amplitude, the inverse of the soliton width, the velocity, the chirp, and the phase. The advantage of the new ansatz is that it yields three pairs of canonically conjugated coordinates and momenta that all are well-behaved. The new ansatz is applied to model the dynamics of a soliton in a dispersion-shifted optical fiber described by the generalized NLS, including dissipation, higher-order dispersion, Raman scattering, and self-steepening perturbations.

Possible Demonstration of a Polaronic Bose-Einstein(-Mott) Condensate in UO2(+x) by Ultrafast THz Spectroscopy and Microwave Dissipation.

Bose-Einstein condensates (BECs) composed of polarons would be an advance because they would combine coherently charge, spin, and a crystal lattice. Following our earlier report of unique structural and spectroscopic properties, we now identify potentially definitive evidence for polaronic BECs in photo- and chemically doped UO2(+x) on the basis of exceptional coherence in the ultrafast time dependent terahertz absorption and microwave spectroscopy results that show collective behavior including dissipation patterns whose precedents are condensate vortex and defect disorder and condensate excitations. That some of these signatures of coherence in an atom-based system extend to ambient temperature suggests a novel mechanism that could be a synchronized, dynamical, disproportionation excitation, possibly via the solid state analog of a Feshbach resonance that promotes the coherence.