THz conductivity of Sr1−x_{1-x}Cax_xRuO3_3

We investigate the optical conductivity of Sr$_{1-x}$Ca$_x$RuO$_3$ across the ferromagnetic to paramagnetic transition that occurs at $x=0.8$. The thin films were grown by metalorganic aerosol deposition with $0 \leq x \leq 1$ onto NdGaO$_3$ substrates. We performed THz frequency domain spectroscopy in a frequency range from 3~cm$^{-1}$ to 40~cm$^{-1}$ (100~GHz to 1.4~THz) and at temperatures ranging from 5~K to 300~K, measuring transmittivity and phase shift through the films. From this we obtained real and imaginary parts of the optical conductivity. The end-members, ferromagnetic SrRuO$_3$ and paramagnetic CaRuO$_3$, show a strongly frequency-dependent metallic response at temperatures below 20~K. Due to the high quality of these samples we can access pronounced intrinsic electronic contributions to the optical scattering rate, which at 1.4~THz exceeds the residual scattering rate by more than a factor of three. Deviations from a Drude response start at about 0.7~THz for both end-members in a remarkably similar way. For the intermediate members a higher residual scattering originating in the compositional disorder leads to a featureless optical response, instead. The relevance of low-lying interband transitions is addressed by a calculation of the optical conductivity within density functional theory in the local density approximation (LDA)

Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome

BackgroundSymptoms lasting longer than 12  weeks after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection are called post-coronavirus disease (COVID) syndrome (PCS). The identification of new biomarkers that predict the occurrence or course of PCS in terms of a post-viral syndrome is vital. T-cell dysfunction, cytokine imbalance, and impaired autoimmunity have been reported in PCS. Nevertheless, there is still a lack of conclusive information on the underlying mechanisms due to, among other things, a lack of controlled study designs.MethodsHere, we conducted a prospective, controlled study to characterize the humoral and cellular immune response in unvaccinated patients with and without PCS following SARS-CoV-2 infection over 7 months and unexposed donors.ResultsPatients with PCS showed as early as 6 weeks and 7 months after symptom onset significantly increased frequencies of SARS-CoV-2-specific CD4+ and CD8+ T-cells secreting IFNγ, TNF, and expressing CD40L, as well as plasmacytoid dendritic cells (pDC) with an activated phenotype. Remarkably, the immunosuppressive counterparts type 1 regulatory T-cells (TR1: CD49b/LAG-3+) and IL-4 were more abundant in PCS+.ConclusionThis work describes immunological alterations between inflammation and immunosuppression in COVID-19 convalescents with and without PCS, which may provide potential directions for future epidemiological investigations and targeted treatments

Calculation of Absolute Molecular Entropies and Heat Capacities Made Simple

We propose a fully automated composite scheme for the calculation of molecular entropies efficiently, accurately and numerically stable by a combination of DFT, semiempirical quantum chemical (SQM) and force-field (FF) levels. A modified rigid-rotor-harmonic-oscillator (msRRHO) approximation and the Gibbs-Shannon formula for extensive conformer ensembles (CEs) are applied and efficiently account for effects of anharmonicity. CEs of systematically increasing quality are generated by a modified metadynamics search algorithm and extrapolated to completeness. Variations of the ro-vibrational entropy over the CE are accounted for by a Boltzmann population average for the first time consistently. The proposed procedure was extensively tested with two standard DFT methods (B97-3c and B3LYP) and at GFN-SQM/FF levels for the conformation term in comparison with experimental gas phase entropies and heat capacities. Excellent performance is observed with mean deviations 14H30-C16H34),unprecedentedly small errors of about 3 cal/mol K are obtained. For 25 typical drug molecules, the conformational entropy depends weakly to strongly on the underlying theory level revealing the complex potential energy surfaces as main source of error. The approach is systematically expandable and moreover can be applied straightforward together with continuum solvation models.<br /

Finding Excited-State Minimum Energy Crossing Points on a Budget: Non-Self-Consistent Tight-Binding Methods.

The automated exploration and identification of minimum energy conical intersections (MECIs) is a valuable computational strategy for the study of photochemical processes. Due to the immense computational effort involved in calculating non-adiabatic derivative coupling vectors, simplifications have been introduced focusing instead on minimum energy crossing points (MECPs), where promising attempts were made with semiempirical quantum mechanical methods. A simplified treatment for describing crossing points between almost arbitrary diabatic states based on a non-self-consistent extended tight-binding method, GFN0-xTB, is presented. Involving only a single diagonalization of the Hamiltonian, the method can provide energies and gradients for multiple electronic states, which can be used in a derivative coupling-vector-free scheme to calculate MECPs. By comparison with high-lying MECIs of benchmark systems, it is demonstrated that the identified geometries are good starting points for further MECI refinement with ab initio methods.- Feodor Lynden Fellowship of the Alexander von Humboldt Foundation - German Federal Ministry of Education and Research (BMBF) and the Ministry of Culture and Science of the German State of North Rhine-Westphalia (MKW) under the Excellence Strategy of the Federal Government and the Lände

Multilevel Framework for Analysis of Protein Folding Involving Disulfide Bond Formation.

Publication status: PublishedIn this study, a three-layered multicenter ONIOM approach is implemented to characterize the naive folding pathway of bovine pancreatic trypsin inhibitor (BPTI). Each layer represents a distinct level of theory, where the initial layer, encompassing the entire protein, is modeled by a general all-atom force-field GFN-FF. An intermediate electronic structure layer consisting of three multicenter fragments is introduced with the state-of-the-art semiempirical tight-binding method GFN2-xTB. Higher accuracy, specifically addressing the breaking and formation of the three disulfide bonds, is achieved at the innermost layer using the composite DFT method r2SCAN-3c. Our analysis sheds light on the structural stability of BPTI, particularly the significance of interlinking disulfide bonds. The accuracy and efficiency of the multicenter QM/SQM/MM approach are benchmarked using the oxidative formation of cystine. For the folding pathway of BPTI, relative stabilities are investigated through the calculation of free energy contributions for selected intermediates, focusing on the impact of the disulfide bond. Our results highlight the intricate trade-off between accuracy and computational cost, demonstrating that the multicenter ONIOM approach provides a well-balanced and comprehensive solution to describe electronic structure effects in biomolecular systems. We conclude that multiscale energy landscape exploration provides a robust methodology for the study of intriguing biological targets.Engineering and Physical Sciences Research Council Alexander von Humboldt Foundatio

A Robust Non-Self-Consistent Tight-Binding Quantum Chemistry Method for large Molecules

We propose a semiempirical quantum chemical method, designed for the fast calculation of molecular Geometries, vibrational Frequencies and Non-covalent interaction energies (GFN) of systems with up to a few thousand atoms. Like its predecessors GFN-xTB and GFN2-xTB, the new method termed GFN0-xTB is parameterized for all elements up to radon (Z = 86) and mostly shares well-known density functional tight-binding approximations as well as basis set and integral approximations. The main new feature is the avoidance of the self-consistent charge iterations leading to speed-ups of a factor of 2-20 depending on the size and electronic complexity of the system. This is achieved by including only quantum mechanical contributions up to first-order which are incorporated similar to the previous versions without any pair-specific parameterization. The essential electrostatic electronic interaction is treated by a classical electronegativity equilibration charge model yielding atomic partial charges that enter the electronic Hamiltonian indirectly. Furthermore, the atomic charge-dependent D4 dispersion correction is included to account for long range London correlation effects. Formulas for analytical total energy gradients with respect to nuclear displacements are derived and implemented in the xtb code allowing numerically very precise structure optimizations. The neglect of self-consistent energy terms not only leads to a large gain in computational speed but also can increase robustness in electronically difficult situations because ill-convergence or artificial charge-transfer (CT) is avoided. The comparison of GFN0-xTB and GFN/GFN2-xTB allows dissection of quantum electronic polarization and CT effects thereby improving our understanding of chemical bonding. Compared to the most sophisticated multipole-based GFN2-xTB model (which approaches DFT accuracy for the target properties closely), GFN0-xTB performs slightly worse for non-covalent interactions and molecular structures, while very good results are observed for conformational energies. Vibrational frequencies are obtained less accurately than with GFN/GFN2-xTB but they may still be useful for various purposes like estimating relative thermostatistical reaction energies. Most exceptional is the fact that even relatively complicated transition metal complex structures can be accurately optimized with a non-self-consistent quantum approach. The new method bridges the gap between force-fields and traditional semiempirical methods with its excellent computational cost to accuracy ratio and is intended to explore the chemical space of large molecular systems and solids.<br /

Multilevel Framework for Analysis of Protein Folding Involving Disulfide Bond Formation.

In this study, a three-layered multicenter ONIOM approach is implemented to characterize the naive folding pathway of bovine pancreatic trypsin inhibitor (BPTI). Each layer represents a distinct level of theory, where the initial layer, encompassing the entire protein, is modeled by a general all-atom force-field GFN-FF. An intermediate electronic structure layer consisting of three multicenter fragments is introduced with the state-of-the-art semiempirical tight-binding method GFN2-xTB. Higher accuracy, specifically addressing the breaking and formation of the three disulfide bonds, is achieved at the innermost layer using the composite DFT method r2SCAN-3c. Our analysis sheds light on the structural stability of BPTI, particularly the significance of interlinking disulfide bonds. The accuracy and efficiency of the multicenter QM/SQM/MM approach are benchmarked using the oxidative formation of cystine. For the folding pathway of BPTI, relative stabilities are investigated through the calculation of free energy contributions for selected intermediates, focusing on the impact of the disulfide bond. Our results highlight the intricate trade-off between accuracy and computational cost, demonstrating that the multicenter ONIOM approach provides a well-balanced and comprehensive solution to describe electronic structure effects in biomolecular systems. We conclude that multiscale energy landscape exploration provides a robust methodology for the study of intriguing biological targets.Engineering and Physical Sciences Research Council Alexander von Humboldt Foundatio

High accuracy quantum-chemistry-based calculation and blind prediction of macroscopic pKa values in the context of the SAMPL6 challenge

Recent advances in the development of low-cost quantum chemical methods have made the prediction of conformational preferences and physicochemical properties of medium-sized drug-like molecules routinely feasible, with significant potential to advance drug discovery. In the context of the SAMPL6 challenge, macroscopic pKa values were blindly predicted for a set of 24 of such molecules. In this paper we present two similar quantum chemical based approaches based on the high accuracy calculation of standard reaction free energies and the subsequent determination of those pKa values via a linear free energy relationship. Both approaches use extensive conformational sampling and apply hybrid and double-hybrid density functional theory with continuum solvation to calculate free energies. The blindly calculated macroscopic pKa values were in excellent agreement with the experiment

SAR and scan-time optimized 3D whole-brain double inversion recovery imaging at 7T

Purpose The aim of this project was to implement an ultra-high field (UHF) optimized double inversion recovery (DIR) sequence for gray matter (GM) imaging, enabling whole brain coverage in short acquisition times ( math formula5 min, image resolution 1 mm3). Methods A 3D variable flip angle DIR turbo spin echo (TSE) sequence was optimized for UHF application. We implemented an improved, fast, and specific absorption rate (SAR) efficient TSE imaging module, utilizing improved reordering. The DIR preparation was tailored to UHF application. Additionally, fat artifacts were minimized by employing water excitation instead of fat saturation. Results GM images, covering the whole brain, were acquired in 7 min scan time at 1 mm isotropic resolution. SAR issues were overcome by using a dedicated flip angle calculation considering SAR and SNR efficiency. Furthermore, UHF related artifacts were minimized. Conclusion The suggested sequence is suitable to generate GM images with whole-brain coverage at UHF. Due to the short total acquisition times and overall robustness, this approach can potentially enable DIR application in a routine setting and enhance lesion detection in neurological diseases

Double-Bridging Increases the Stability of Zinc(II) Metal-Organic Cages.

A key feature of coordination cages is the dynamic nature of their coordinative bonds, which facilitates the synthesis of complex polyhedral structures and their post-assembly modification. However, this dynamic nature can limit cage stability. Increasing cage robustness is important for real-world use cases. Here we introduce a double-bridging strategy to increase cage stability, where designed pairs of bifunctional subcomponents combine to generate rectangular tetratopic ligands within pseudo-cubic Zn8L6 cages. These cages withstand transmetalation, the addition of competing ligands, and nucleophilic imines, under conditions where their single-bridged congeners decompose. Our approach not only increases the stability and robustness of the cages while maintaining their polyhedral structure, but also enables the incorporation of additional functional units in proximity to the cavity. The double-bridging strategy also facilitates the synthesis of larger cages, which are inaccessible as single-bridged congeners