Compensation States Approach in the Hybrid Diabatization Scheme: Extension to Multidimensional Data and Properties.

The diabatization of reactive systems for more than just a couple of states is a very demanding problem and generally requires advanced diabatization techniques. Especially for dissociative processes, the drastic changes in the adiabatic wave functions often would require large diabatic state bases, which quickly become impractical. Recently, we addressed this problem by the compensation states approach developed in the context of our hybrid diabatization scheme. This scheme utilizes wave function as well as energy data in combination with a diabatic potential model. In regions where the initial diabatic state basis becomes insufficient for an appropriate representation of the adiabatic states, new model states are generated. The new model states compensate for the state space not spanned by the initial diabatic basis. Such a compensation state is obtained by projecting the initial diabatic state space out of the adiabatic wave function. This yields a very efficient basis representation of the electronic Hamiltonian. The present work presents two new aspects. First, it is shown how other operators like the spin-orbit operator in the framework of the Effective Relativistic Coupling by Asymptotic Representation (ERCAR) can be evaluated in this compact model state space without losing the correct wave function information and accuracy. Second, the extension of the approach to multidimensional potential energy surface models is presented for methyl iodide including the C-I dissociation coordinate and the angular H3C-I bending coordinates.

A general method for the development of diabatic spin-orbit models for multi-electron systems.

Spin-orbit (SO) coupling can have significant effects on the quantum dynamics of molecular systems, but it is still difficult to account for accurately. One promising way to do this is to devise a diabatic SO model combined with the molecular potential energy. Few such models have been developed utilizing spatial and time-reversal symmetry. These models are tedious to derive and are specific for the molecular symmetry and included spin states. Here, we present a relatively simple approach to construct such models for various spin states with S≠12 from a basic one-electron SO case with S=12. The multi-electron fine structure states are expressed in terms of Slater determinants of single-electron spin functions (spinors). The properties of all single-electron matrix elements over the SO operator are derived and expressed as Taylor expansions in terms of symmetry-adapted nuclear coordinates. The SO matrix elements for the multi-electron case are then obtained from these single-electron matrix elements using the Slater-Condon rules. This yields the full SO matrix and symmetry properties of the multi-electron matrix elements in a straightforward way. The matrix elements are expressed as symmetry-adapted polynomials up to arbitrary order. This approach is demonstrated first for an abstract model of two electrons in a set of p orbitals in a C3v symmetric environment and then applied to set up a diabatic model for the photodissociation of methyl iodide (CH3I). The high accuracy of this new approach is demonstrated in comparison to an available analytic SO model for CH3I.

Immunological Aspects of AXL/GAS-6 in the Context of Human Liver Regeneration.

AXL and its corresponding ligand growth arrest-specific 6 (GAS-6) are critically involved in hepatic immunomodulation and regenerative processes. Pleiotropic inhibitory effects on innate inflammatory responses might essentially involve the shift of macrophage phenotype from a pro-inflammatory M1 to an anti-inflammatory M2. We aimed to assess the relevance of the AXL/GAS-6-pathway in human liver regeneration and, consequently, its association with clinical outcome after hepatic resection. Soluble AXL (sAXL) and GAS-6 levels were analyzed at preoperative and postoperative stages in 154 patients undergoing partial hepatectomy and correlated with clinical outcome. Perioperative dynamics of interleukin (IL)-6, soluble tyrosine-protein kinase MER (sMerTK), soluble CD163 (sCD163), and cytokeratin (CK) 18 were assessed to reflect pathophysiological processes. Preoperatively elevated sAXL and GAS-6 levels predicted postoperative liver dysfunction (area under the curve = 0.721 and 0.722; P < 0.005) and worse clinical outcome. These patients failed to respond with an immediate increase of sAXL and GAS-6 upon induction of liver regeneration. Abolished AXL pathway response resulted in a restricted increase of sCD163, suggesting a disrupted phenotypical switch to regeneratory M2 macrophages. No association with sMerTK was observed. Concomitantly, a distinct association of IL-6 levels with an absent increase of AXL/GAS-6 signaling indicated pronounced postoperative inflammation. This was further supported by increased intrahepatic secondary necrosis as reflected by CK18M65. sAXL and GAS-6 represent not only potent and easily accessible preoperative biomarkers for the postoperative outcome but also AXL/GAS-6 signaling might be of critical relevance in human liver regeneration. Refractory AXL/GAS-6 signaling, due to chronic overactivation/stimulation in the context of underlying liver disease, appears to abolish their immediate release following induction of liver regeneration, causing overwhelming immune activation, presumably via intrahepatic immune regulation.

Low-molecular-weight heparin use in coronavirus disease 2019 is associated with curtailed viral persistence: a retrospective multicentre observational study.

AIMS: Anticoagulation was associated with improved survival of hospitalized coronavirus disease 2019 (COVID-19) patients in large-scale studies. Yet, the development of COVID-19-associated coagulopathy (CAC) and the mechanism responsible for improved survival of anticoagulated patients with COVID-19 remain largely elusive. This investigation aimed to explore the effects of anticoagulation and low-molecular-weight heparin (LMWH) in particular on patient outcome, CAC development, thromboinflammation, cell death, and viral persistence. METHODS AND RESULTS: Data of 586 hospitalized COVID-19 patients from three different regions of Austria were evaluated retrospectively. Of these, 419 (71.5%) patients received LMWH and 62 (10.5%) received non-vitamin-K oral anticoagulants (NOACs) during hospitalization. Plasma was collected at different time points in a subset of 106 patients in order to evaluate markers of thromboinflammation (H3Cit-DNA) and the cell death marker cell-free DNA (cfDNA). Use of LMWH was associated with improved survival upon multivariable Cox regression (hazard ratio = 0.561, 95% confidence interval: 0.348-0.906). Interestingly, neither LMWH nor NOAC was associated with attenuation of D-dimer increase over time, or thromboinflammation. In contrast, anticoagulation was associated with a decrease in cfDNA during hospitalization, and curtailed viral persistence was observed in patients using LMWH leading to a 4-day reduction of virus positivity upon quantitative polymerase chain reaction [13 (interquartile range: 6-24) vs. 9 (interquartile range: 5-16) days, P = 0.009]. CONCLUSION: Time courses of haemostatic and thromboinflammatory biomarkers were similar in patients with and without LMWH, indicating either no effects of LMWH on haemostasis or that LMWH reduced hypercoagulability to levels of patients without LMWH. Nonetheless, anticoagulation with LMWH was associated with reduced mortality, improved markers of cell death, and curtailed viral persistence, indicating potential beneficial effects of LMWH beyond haemostasis, which encourages use of LMWH in COVID-19 patients without contraindications.