On Entangled Singlet Pure Diradicals.

This work addresses a class of conjugated hydrocarbons that are expected to be singlet diradicals according to the topological Hückel Hamiltonian while possibly satisfying full on-bond electron pairing. These systems possess two degenerate singly occupied molecular orbitals (SOMOs), but aromaticity brought by properly positioned six-membered rings does prevent Jahn-Teller distortions. Density functional theory (DFT) calculations performed on two emblematic examples confirm the strong bond-length alternation in the closed-shell solutions and the clear spatial symmetry in the open-shell spin-unrestricted determinants, the latter solution always being found to have significantly lower energy. Since the SOMOs are here of different symmetry, the wave function is free from ionic valence-bond component, and spin decontamination of the unrestricted DFT solutions and wave function calculations at the CASSCF-plus-second-order-perturbation level confirm the expected pure diradical character of such molecules. In contrast to disjoint diradicals, the SOMOs of present systems have large amplitudes on neighbor atoms, and we propose to name them entangled pure diradicals, further providing some prescription rules for their design. Additional calculations point out the qualitative contrast between these molecules and the related diradicaloids.

What governs magnetic exchange couplings in radical-bridged dinuclear complexes?

Coupling transition metal or lanthanide ions through a radical bridging ligand is a promising route to increase performances in the area of single molecular magnets. A better understanding of the underlying physical mechanisms governing the magnetic exchange couplings is thus of valuable importance to design future compounds. Here, couplings in three series of metal-radical-metal compounds based on transition metal ions are investigated by means of the decomposition/recomposition methods. This work presents the generalisation and first application of the method to systems with an arbitrary number of magnetic centres featuring several unpaired electrons. Thanks to the decomposition into the three main contributions (direct exchange, kinetic exchange, and spin polarisation) as well as a description in terms of electron-electron interactions, we study the influence of the nature of the metal centre and the radical ligand on the couplings. We combine the energetic contributions extracted with orbital and charge population analysis to rationalise the results.

Revisiting magnetic exchange couplings in heterodinuclear complexes through the decomposition method in KS-DFT.

Providing tools to understand the physical mechanisms governing magnetic properties in transition metal-based compounds is still of great interest. Here, the magnetic exchange coupling in a series of heterodinuclear complexes is investigated by means of the decomposition method. This work presents the first application of the decomposition method to systems where magnetic centres may bear more than one unpaired electron. By decomposing the coupling into three physical contributions (direct exchange, kinetic exchange, and spin polarisation), we provide numerical arguments to confirm or infirm the rationalisation allowed by the conceptual analysis of the magnetic d orbitals. We also take advantage of the recently proposed generalisation of the method [David et al., J. Chem. Theory Comput., 2023, 19, 157] to get more insights into the underlying mechanisms by disentangling the coupling between centres into its electron-electron interactions.

Consistent Evaluation of Magnetic Exchange Couplings in Multicenter Compounds in KS-DFT: The Recomposition Method.

The use of broken-symmetry calculations in Kohn-Sham density functional theory has offered an affordable route to study magnetic exchange couplings in transition-metal-based compounds. However, computing this property in compounds exhibiting several couplings is still challenging and especially due to the difficulties to overcome the well-known problem of spin contamination. Here, we present a new and general method to compute magnetic exchange couplings in systems featuring several spin sites. To provide a consistent spin decontamination of J values, our strategy exploits the decomposition method of the magnetic exchange coupling proposed by Coulaud et al. and generalizes our previous work on diradical compounds where the overall magnetic exchange coupling is defined as the sum of its three main and properly extracted physical contributions (direct exchange, kinetic exchange, and spin polarization). In this aim, the generalized extraction of all contributions is presented to systems with multiple spin sites bearing one unpaired electron. This is done by proposing a new paradigm to treat the kinetic exchange contribution, which proceeds through monorelaxations of the magnetic orbitals. This method, so-called the recomposition method, is applied to a compound featuring three Cu(II) ions with a linear arrangement and to a recently synthesized complex containing a Cu4O4 cubane unit presenting an unusual magnetic behavior.

An Embedded Fragment Method for Molecules in Strong Magnetic Fields.

An extension of the embedded fragment method for calculations on molecular clusters is presented, which includes strong external magnetic fields. The approach is flexible, allowing for calculations at the Hartree-Fock, current-density-functional theory, Møller-Plesset perturbation theory, and coupled-cluster levels using London atomic orbitals. For systems consisting of discrete molecular subunits, calculations using London atomic orbitals can be performed in a computationally tractable manner for systems beyond the reach of conventional calculations, even those accelerated by resolution-of-the-identity or Cholesky decomposition methods. To assess the applicability of the approach, applications to water clusters are presented, showing how strong magnetic fields enhance binding within the clusters. However, our calculations suggest that, contrary to previous suggestions in the literature, this enhanced binding may not be directly attributable to strengthening of hydrogen bonding. Instead, these results suggest that this arises for larger field strengths as a response of the system to the presence of the external field, which induces a charge density build up between the monomer units. The approach is embarrassingly parallel and its computational tractability is demonstrated for clusters of up to 103 water molecules in triple-ζ basis sets, which would correspond to conventional calculations with more than 12 000 basis functions.

Difficulty of the evaluation of the barrier height of an open-shell transition state between closed shell minima: The case of small C4n rings.

C4n cyclacenes exhibit strong bond-alternation in their equilibrium geometry. In the two equivalent geometries, the system keeps an essentially closed-shell character. The two energy minima are separated by a transition state suppressing the bond-alternation, where the wave function is strongly diradical. This paper discusses the physical factors involved in this energy difference and possible evaluations of the barrier height. The barrier given as the energy difference between the restricted density functional theory (DFT)/B3LYP for the equilibrium and the broken symmetry DFT/B3LYP of the transition state is either negative or small, in contradiction with the most reliable Wave Function Theory calculations. The minimal (two electrons in two molecular orbitals) Complete Active Space self-consistent field (CASSCF) overestimates the barrier, and the subsequent second-order perturbation cancels it. Due to the collective character of the spin-polarization effect, it is necessary to perform a full π CASSCF + second-order perturbation to reach a reasonable value of the barrier, but this type of treatment cannot be applied to large molecules. DFT procedures treating on an equal foot the closed-shell and open-shell geometries have been explored, such as Mixed-Reference Spin-Flip Time-dependent-DFT and a new spin-decontamination proposal, namely, DFT-dressed configuration interaction, but the results still depend on the density functional. M06-2X without or with spin-decontamination gives the best agreement with the accurate wave function results.

Biocomposites from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and lignocellulosic fillers: Processes stored in data warehouse structured by an ontology.

Due to the rising amount of plastic waste generated each year, multiple questions are emerging about their harmful long-term effects on the environment, the eco-systems and human health. One possible strategy to mitigate these issues is to substitute conventional plastics by materials fully biodegradable in natural conditions, such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). In order to decrease the overall cost and environmental impact of PHBV-based materials while modulating their technical performance, PHBV can be combined with lignocellulosic fillers. In this article, a total of 88 formulations of PHBV-based biocomposites has been collected, distributed over 5 interdisciplinary projects involving computer scientists, data scientists and biomass processing experts for food and bio-based material production. Available data concern the technical process descriptions, including the description of each step and the different observations measured. These data are stored in a knowledge base that can be queried on the Web.

Self-Consistent Field Methods for Excited States in Strong Magnetic Fields: a Comparison between Energy- and Variance-Based Approaches.

Self-consistent field methods for excited states offer an attractive low-cost route to study not only excitation energies but also properties of excited states. Here, we present the generalization of two self-consistent field methods, the maximum overlap method (MOM) and the σ-SCF method, to calculate excited states in strong magnetic fields and investigate their stability and accuracy in this context. These methods use different strategies to overcome the well-known variational collapse of energy-based optimizations to the lowest solution of a given symmetry. The MOM tackles this problem in the definition of the orbital occupations to constrain the self-consistent field procedure to converge on excited states, while the σ-SCF method is based on the minimization of the variance instead of the energy. To overcome the high computational cost of the variance minimization, we present a new implementation of the σ-SCF method with the resolution of identity approximation, allowing the use of large basis sets, which is an important requirement for calculations in strong magnetic fields. The accuracy of these methods is assessed by comparison with the benchmark literature data for He, H2, and CH+. The results reveal severe limitations of the variance-based scheme, which become more acute in large basis sets. In particular, many states are not accessible using variance optimization. Detailed analysis shows that this is a general feature of variance optimization approaches due to the masking of local minima in the optimization. In contrast, the MOM shows promising performance for computing excited states under these conditions, yielding results consistent with available benchmark data for a diverse range of electronic states.

Early remodeling of the colonic mucosa after allogeneic hematopoietic stem cells transplantation: An open-label controlled pilot study on 19 patients.

BACKGROUND: Graft-versus-host disease (GVHD), particularly acute digestive GVHD (aDGVHD), is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is necessary to identify predictive factors of GVHD to adapt prophylactic treatment. OBJECTIVE: In this context, our pilot study aimed (i) to determine whether an early remodeling of the colonic mucosa occurred after allo-HSCT and (ii) to identify potential predictive mucosal markers of aDGVHD after allo-HSCT. METHODS: Between day 21 and day 28 after the allo-HSCT, 19 allo-HSCT patients were included and had a rectosigmoidoscopy with probe-based confocal laser endomicroscopy (pCLE) recording and biopsies. Sixteen patients were included in the control group. Morphological (pCLE), functional (intestinal permeability), and inflammatory parameters (cytokine multiplex immunoassay) were assessed. RESULTS: Among allo-HSCT patients, 11 patients developed GVHD, and 6 of them developed aDGVHD. Morphological and functional changes of the colonic mucosa occurred after allo-HSCT. Indeed, the perimeter of colonic crypts was significantly increased in allo-HSCT patients compared to controls as well as crypt lumen fluorescein leakage (53% vs. 9%), whereas crypts sphericity, roundness, Feret diameter, and mean vessel area were significantly decreased in allo-HSCT patients compared to the control group. In addition, interleukin-6 (IL-6), IL-33, and IL-15 levels in the supernatants of 24 h explant cultures of colonic biopsies were significantly increased in allo-HSCT patients compared to controls. Finally, there was no difference in pCLE parameters, intestinal permeability, and inflammatory cytokines between patients who developed aDGVHD and those who did not. CONCLUSION: This pilot study identified early colonic mucosa remodeling after allo-HSCT conditioning therapy, that is morphological and functional mucosal alterations as well as mucosal inflammation. As to whether these changes are first steps in GVHD initiation and could be considered as predictive biomarkers of aDGVHD need to be determined in a larger cohort of patients.

Optimizing Molecular Geometries in Strong Magnetic Fields.

An efficient implementation of geometrical derivatives at the Hartree-Fock (HF) and current-density functional theory (CDFT) levels is presented for the study of molecular structure in strong magnetic fields. The required integral derivatives are constructed using a hybrid McMurchie-Davidson and Rys quadrature approach, which combines the amenability of the former to the evaluation of derivative integrals with the efficiency of the latter for basis sets with high angular momentum. In addition to its application to evaluating derivatives of four-center integrals, this approach is also applied to gradients using the resolution-of-the-identity approximation, enabling efficient optimization of molecular structure for many-electron systems under a strong magnetic field. The CDFT contributions have been implemented for a wide range of density functionals up to and including the meta-GGA level with current-density dependent contributions and (range-separated) hybrids for the first time. Illustrative applications are presented to the OH and benzene molecules, revealing the rich and complex chemistry induced by the presence of an external magnetic field. Challenges for geometry optimization in strong fields are highlighted, along with the requirement for careful analysis of the resulting electronic structure at each stationary point. The importance of correlation effects is examined by comparison of results at the HF and CDFT levels. The present implementation of molecular gradients at the CDFT level provides a cost-effective approach to the study of molecular structure under strong magnetic fields, opening up many new possibilities for the study of chemistry in this regime.

Consistent spin decontamination of broken-symmetry calculations of diradicals.

Broken-symmetry calculations of diradicals exploit the mean-field energies of determinants that are not eigenfunctions of the S2 operator, the mean value of which is close to 1 for the ms = 0 solution. This spin contamination must be corrected. Two different contributions affect ⟨S2⟩, namely, the mixing between neutral and ionic valence bond components, the so-called kinetic exchange, which decreases ⟨S2⟩, and the spin polarization of the supposedly closed shell orbitals, which increases ⟨S2⟩. The popular Yamaguchi formula is valid for the first effect but irrelevant for the second one. From a few constrained broken-symmetry calculations, one may treat separately the two contributions and apply their specific spin decontamination correction. This work proposes a consistent spin-decontaminated procedure for the evaluation of singlet-triplet gaps in diradicals.

[Pancreatic insufficiency†: diagnostic insufficiency†?] / Insuffisance pancréatique†: insuffisance diagnostique†?

Exocrine pancreatic insufficiency is characterized by insufficient secretion of pancreatic enzymes with subsequent inability to maintain adequate digestion of food. Maldigestion may lead to malnutrition with associated various morbidities. Exocrine pancreatic insufficiency is also associated with a reduced quality of life and, in some studies, increased mortality. Exocrine pancreatic insufficiency may develop due to numerous causes and is often underdiagnosed and not adequately treated. Particularly in the early stages, diagnosis of exocrine pancreatic insufficiency may be difficult, as steatorrhea may be absent and a specific diagnostic test currently does not exist. Hence, it is crucial to recall the situations at risk for exocrine pancreatic insufficiency in order not to miss its diagnosis. In this article, we will provide a summary of the main causes of exocrine pancreatic insufficiency as well as its diagnosis and management.

L'insuffisance pancréatique exocrine (IPE) est caractérisée par une activité pancréatique enzymatique insuffisante pour maintenir une digestion adéquate des nutriments. Cette maldigestion peut mener à un état de malnutrition avec de nombreuses conséquences en termes de morbidité. L'IPE est également associée à une diminution de la qualité de vie et à une augmentation de la mortalité. Elle peut se retrouver dans de nombreuses circonstances et plusieurs études suggèrent que sa prise en charge est insuffisante. Son diagnostic, surtout précoce, peut s'avérer difficile car les symptômes classiques de stéatorrhée ne sont pas toujours présents et il n'existe actuellement pas de test diagnostique de certitude. Il est donc essentiel de savoir reconnaître les situations à risque. Dans cet article, nous passerons en revue les principales causes, méthodes diagnostiques et possibilités thérapeutiques de l'IPE.

Improved evaluation of spin-polarization energy contributions using broken-symmetry calculations.

Spin-polarization effects may play an important role in free radicals and in the magnetic coupling between radical centers. Starting from restricted open-shell calculations, i.e., a closed-shell description of the non-magnetic core electrons, a low-order perturbation expansion identifies the spin-polarization contribution to the energy of mono-radicals and to singlet-triplet energy differences in diradicals. Broken-symmetry (BS) single-determinant calculations introduce only a fraction of spin-polarization effects, and in a biased manner, since BS determinants are not spin eigenfunctions. We propose a simple technique to correctly evaluate spin-polarization energies by taking into account the effect of spin-flip components on one-hole one-particle excited configurations. Spin-decontamination corrections are shown to play a non-negligible role in the BS evaluation of bond energies. The importance of spin decontamination is illustrated in cases for which spin polarization is the leading contribution to the singlet-triplet gap, which characterizes twisted conjugated double bonds and disjoint diradicals.

Eco-Conversion of Two Winery Lignocellulosic Wastes into Fillers for Biocomposites: Vine Shoots and Wine Pomaces.

Two winery residues, namely vine shoots (ViSh) and wine pomace (WiPo), were up-cycled as fillers in PHBV-based biocomposites. Answering a biorefinery approach, the impact of a preliminary polyphenols extraction step using an acetone/water mixture on the reinforcing effect of fillers was assessed. Biocomposites (filler content up to 20 wt%) were prepared by melt-mixing and compared in terms of final performance (thermal, mechanical and barrier). It was shown that the reinforcing effect was slightly better in the case of vine shoots, while it was not significantly affected by the pre-treatment, demonstrating that these two winery residues could be perfectly used as fillers in composite materials even after an extraction process to maximize their potential of valorization.

Analyzing Magnetically Induced Currents in Molecular Systems Using Current-Density-Functional Theory.

A suite of tools for the analysis of magnetically induced currents is introduced. These are applicable to both the weak-field regime, well described by linear response perturbation theory, and to the strong-field regime, which is inaccessible to such methods. A disc-based quadrature scheme is proposed for the analysis of magnetically induced current susceptibilities, providing quadratures that are consistently defined between different molecular systems and applicable to both planar 2D and general 3D molecular systems in a black-box manner. The applicability of the approach is demonstrated for a range of planar ring systems, the ground and excited states of the benzene molecule, and the ring, bowl, and cage isomers of the C20 molecule in the presence of a weak magnetic field. In the presence of a strong magnetic field, the para- to diamagnetic transition of the BH molecule is studied, demonstrating that magnetically induced currents present a visual interpretation of this phenomenon, providing insight beyond that accessible using linear response methods.

[Abecedary of colonic polyps]. / ABC des polypes coliques.

Colonic polyps are very common in the general population. Some polyps present a cancerization risk and their screening and management by endoscopy reduce the risk of colorectal cancer. Other polyps do not need specific follow-up. There are different types of polyps whose classification has been updated over the last ten years. Serrated polyps now intersect hyperplastic polyps, sessile serrated adenomas and traditional serrated adenomas. Current recommendations are to resect and histologically analyze each colonic polyp to define a personalized endoscopic surveillance strategy. Some colonic polyposis syndromes require management in a specialized center.

Les polypes coliques sont très fréquents dans la population générale. Certains sont à risque de cancérisation et leurs dépistage et prise en charge par le biais de l'endoscopie permettent une diminution du risque de cancer colorectal. D'autres ne nécessitent pas de surveillance. La classification des polypes a été remise à jour au cours de ces dix dernières années et, à côté des adénomes conventionnels, on reconnaît à présent les festonnés ou dentelés qui regroupent les polypes hyperplasiques, les adénomes dentelés sessiles et les dentelés traditionnels. Les recommandations actuelles sont de réséquer et d'analyser histologiquement chaque polype colique afin de définir une stratégie de surveillance endoscopique personnalisée. Certains syndromes dits de polypose colique nécessitent une prise en charge en centre spécialisé.

Quantum Package 2.0: An Open-Source Determinant-Driven Suite of Programs.

Quantum chemistry is a discipline which relies heavily on very expensive numerical computations. The scaling of correlated wave function methods lies, in their standard implementation, between O(N5) and O(eN) , where N is proportional to the system size. Therefore, performing accurate calculations on chemically meaningful systems requires (i) approximations that can lower the computational scaling and (ii) efficient implementations that take advantage of modern massively parallel architectures. Quantum Package is an open-source programming environment for quantum chemistry specially designed for wave function methods. Its main goal is the development of determinant-driven selected configuration interaction (sCI) methods and multireference second-order perturbation theory (PT2). The determinant-driven framework allows the programmer to include any arbitrary set of determinants in the reference space, hence providing greater methodological freedom. The sCI method implemented in Quantum Package is based on the CIPSI (Configuration Interaction using a Perturbative Selection made Iteratively) algorithm which complements the variational sCI energy with a PT2 correction. Additional external plugins have been recently added to perform calculations with multireference coupled cluster theory and range-separated density-functional theory. All the programs are developed with the IRPF90 code generator, which simplifies collaborative work and the development of new features. Quantum Package strives to allow easy implementation and experimentation of new methods, while making parallel computation as simple and efficient as possible on modern supercomputer architectures. Currently, the code enables, routinely, to realize runs on roughly 2 000 CPU cores, with tens of millions of determinants in the reference space. Moreover, we have been able to push up to 12 288 cores in order to test its parallel efficiency. In the present manuscript, we also introduce some key new developments: (i) a renormalized second-order perturbative correction for efficient extrapolation to the full CI limit and (ii) a stochastic version of the CIPSI selection performed simultaneously to the PT2 calculation at no extra cost.

Mitigating the Impact of Cellulose Particles on the Performance of Biopolyester-Based Composites by Gas-Phase Esterification.

Materials that are both biodegradable and bio-sourced are becoming serious candidates for substituting traditional petro-sourced plastics that accumulate in natural systems. New biocomposites have been produced by melt extrusion, using bacterial polyester (poly(3-hydroxybutyrate-co-3-hydroxyvalerate)) as a matrix and cellulose particles as fillers. In this study, gas-phase esterified cellulose particles, with palmitoyl chloride, were used to improve filler-matrix compatibility and reduce moisture sensitivity. Structural analysis demonstrated that intrinsic properties of the polymer matrix (crystallinity, and molecular weight) were not more significantly affected by the incorporation of cellulose, either virgin or grafted. Only a little decrease in matrix thermal stability was noticed, this being limited by cellulose grafting. Gas-phase esterification of cellulose improved the filler's dispersion state and filler/matrix interfacial adhesion, as shown by SEM cross-section observations, and limiting the degradation of tensile properties (stress and strain at break). Water vapor permeability, moisture, and liquid water uptake of biocomposites were increased compared to the neat matrix. The increase in thermodynamic parameters was limited in the case of grafted cellulose, principally ascribed to their increased hydrophobicity. However, no significant effect of grafting was noticed regarding diffusion parameters.

IL-7 receptor influences anti-TNF responsiveness and T cell gut homing in inflammatory bowel disease.

It remains unknown what causes inflammatory bowel disease (IBD), including signaling networks perpetuating chronic gastrointestinal inflammation in Crohn's disease (CD) and ulcerative colitis (UC), in humans. According to an analysis of up to 500 patients with IBD and 100 controls, we report that key transcripts of the IL-7 receptor (IL-7R) pathway are accumulated in inflamed colon tissues of severe CD and UC patients not responding to either immunosuppressive/corticosteroid, anti-TNF, or anti-α4ß7 therapies. High expression of both IL7R and IL-7R signaling signature in the colon before treatment is strongly associated with nonresponsiveness to anti-TNF therapy. While in mice IL-7 is known to play a role in systemic inflammation, we found that in humans IL-7 also controlled α4ß7 integrin expression and imprinted gut-homing specificity on T cells. IL-7R blockade reduced human T cell homing to the gut and colonic inflammation in vivo in humanized mouse models, and altered effector T cells in colon explants from UC patients grown ex vivo. Our findings show that failure of current treatments for CD and UC is strongly associated with an overexpressed IL-7R signaling pathway and point to IL-7R as a relevant therapeutic target and potential biomarker to fill an unmet need in clinical IBD detection and treatment.