Magnetic hexamers interacting in layers in the (Na,K)2_2Cu3_3O(SO4)3_4)_3 minerals

Magnetic properties and underlying magnetic models of the synthetic A$_2$Cu$_3$O(SO$_4)_3$ fedotovite (A = K) and puninite (A = Na) minerals, as well as the mixed euchlorine-type NaKCu$_3$O(SO$_4)_3$ are reported. We show that all these compounds contain magnetic Cu$_6$ hexamer units, which at temperatures below about 100 K act as single spin-1 entities. Weak interactions between these magnetic molecules lead to long-range order below $T_N$ = 3.4 K (A = Na), 4.7 K (A = NaK), and about 3.0 K (A = K). The formation of the magnetic order is elucidated by ab initio calculations that reveal two-dimensional inter-hexamer interactions within crystallographic $bc$ planes. This model indicates the presence of a weakly distorted square lattice of $S=1$ magnetic ions and challenges the earlier description of the A$_2$Cu$_3$O(SO$_4)_3$ minerals in terms of Haldane spin chains.Comment: published version, re-worked compared to the initial submissio

Clinical trial simulation to evaluate power to compare the antiviral effectiveness of two hepatitis C protease inhibitors using nonlinear mixed effect models: a viral kinetic approach.

International audienceBACKGROUND: Models of hepatitis C virus (HCV) kinetics are increasingly used to estimate and to compare in vivo drug's antiviral effectiveness of new potent anti-HCV agents. Viral kinetic parameters can be estimated using non-linear mixed effect models (NLMEM). Here we aimed to evaluate the performance of this approach to precisely estimate the parameters and to evaluate the type I errors and the power of the Wald test to compare the antiviral effectiveness between two treatment groups when data are sparse and/or a large proportion of viral load (VL) are below the limit of detection (BLD). METHODS: We performed a clinical trial simulation assuming two treatment groups with different levels of antiviral effectiveness. We evaluated the precision and the accuracy of parameter estimates obtained on 500 replication of this trial using the stochastic approximation expectation-approximation algorithm which appropriately handles BLD data. Next we evaluated the type I error and the power of the Wald test to assess a difference of antiviral effectiveness between the two groups. Standard error of the parameters and Wald test property were evaluated according to the number of patients, the number of samples per patient and the expected difference in antiviral effectiveness. RESULTS: NLMEM provided precise and accurate estimates for both the fixed effects and the inter-individual variance parameters even with sparse data and large proportion of BLD data. However Wald test with small number of patients and lack of information due to BLD resulted in an inflation of the type I error as compared to the results obtained when no limit of detection of VL was considered. The corrected power of the test was very high and largely outperformed what can be obtained with empirical comparison of the mean VL decline using Wilcoxon test. CONCLUSION: This simulation study shows the benefit of viral kinetic models analyzed with NLMEM over empirical approaches used in most clinical studies. When designing a viral kinetic study, our results indicate that the enrollment of a large number of patients is to be preferred to small population sample with frequent assessments of VL

Changes in liver mitochondrial plasticity induced by brain tumor

BACKGROUND: Accumulating data suggest that liver is a major target organ of systemic effects observed in the presence of a cancer. In this study, we investigated the consequences of the presence of chemically induced brain tumors in rats on biophysical parameters accounting for the dynamics of water in liver mitochondria. METHODS: Tumors of the central nervous system were induced by intraveinous administration of ethylnitrosourea (ENU) to pregnant females on the 19th day of gestation. The mitochondrial crude fraction was isolated from the liver of each animal and the dynamic parameters of total water and its macromolecule-associated fraction (structured water, H(2)Ost) were calculated from Nuclear Magnetic Resonance (NMR) measurements. RESULTS: The presence of a malignant brain tumor induced a loss of water structural order that implicated changes in the physical properties of the hydration shells of liver mitochondria macromolecules. This feature was linked to an increase in the membrane cholesterol content, a way to limit water penetration into the bilayer and then to reduce membrane permeability. As expected, these alterations in mitochondrial plasticity affected ionic exchanges and led to abnormal features of mitochondrial biogenesis and caspase activation. CONCLUSION: This study enlightens the sensitivity of the structured water phase in the liver mitochondria machinery to external conditions such as tumor development at a distant site. The profound metabolic and functional changes led to abnormal features of ion transport, mitochondrial biogenesis and caspase activation

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Common Building Motifs in Ba2Fe3(PO4)4·2H2O, BaFe3(PO4)3, and Na3Fe3(PO4)4 Labile Fe2+/Fe3+ Ordering and Charge-Dependent Magnetism

International audienceTwo new mixed-valence Fe2/3+ barium phosphates have been synthesized in hydrothermal conditions and characterized Ba2Fe2.66+3(PO4)4·2H2O (compound 1, ratio Fe3+/Fe2+ = 21, orthorhombic space group Pbca, a = 6.71240(10) Å, b = 10.6077(2) Å, c = 20.9975(5) Å, R1 = 3.39%) and BaFe2.33+3(PO4)3 (compound 2, ratio Fe3+/Fe2+ = 12, orthorhombic, space group Imma with a = 10.5236(3) Å, b = 13.4454(4) Å, c = 6.6411(2) Å, R1 = 1.63%). 1 has a two-dimensional crystal structure built of [Fe2.5+2Fe3+1(PO4)4]4- layers with charge segregation on two individual Fe crystal sites, in contrast to the single valence on these two sites found in similar layers of Na3Fe3+3(PO4)4. The crystal structure of 2 is formed of the same layers but condensed into a 3D [Fe2+2Fe3+1(PO4)3]2- framework. The complete Fe2+ vs Fe3+ charge ordering on the two available sites differs from what was found in the two previous cases and denotes a remarkable charge adaptability of the common elementary units. Compared to the antiferromagnetic Na3Fe3+3(PO4)4 the partial iron reduction into Fe2+ is responsible for strong ferromagnetic components along the c-easy axis for both 1 and 2. Additionally 1 shows multiple magnetization steps in the perpendicular direction, giving raise to atypical anisotropic magnetism into a complex magnetic phase diagram. © 2016 American Chemical Society

Common Building Motifs in Ba2Fe3(PO4)4·2H2O, BaFe3(PO4)3, and Na3Fe3(PO4)4 Labile Fe2+/Fe3+ Ordering and Charge-Dependent Magnetism

Two new mixed-valence Fe2/3+ barium phosphates have been synthesized in hydrothermal conditions and characterized Ba2Fe2.66+3(PO4)4·2H2O (compound 1, ratio Fe3+/Fe2+ = 21, orthorhombic space group Pbca, a = 6.71240(10) Å, b = 10.6077(2) Å, c = 20.9975(5) Å, R1 = 3.39%) and BaFe2.33+3(PO4)3 (compound 2, ratio Fe3+/Fe2+ = 12, orthorhombic, space group Imma with a = 10.5236(3) Å, b = 13.4454(4) Å, c = 6.6411(2) Å, R1 = 1.63%). 1 has a two-dimensional crystal structure built of [Fe2.5+2Fe3+1(PO4)4]4- layers with charge segregation on two individual Fe crystal sites, in contrast to the single valence on these two sites found in similar layers of Na3Fe3+3(PO4)4. The crystal structure of 2 is formed of the same layers but condensed into a 3D [Fe2+2Fe3+1(PO4)3]2- framework. The complete Fe2+ vs Fe3+ charge ordering on the two available sites differs from what was found in the two previous cases and denotes a remarkable charge adaptability of the common elementary units. Compared to the antiferromagnetic Na3Fe3+3(PO4)4 the partial iron reduction into Fe2+ is responsible for strong ferromagnetic components along the c-easy axis for both 1 and 2. Additionally 1 shows multiple magnetization steps in the perpendicular direction, giving raise to atypical anisotropic magnetism into a complex magnetic phase diagram. © 2016 American Chemical Society

Triple Co-II,Co- (III,) (IV) charge ordering and spin states in modular cobaltites: a systematization through experimental and virtual compounds

International audienceThe series of modular compounds [BanCo2+nO3n+2][BaCo6O9] (n = 1 to 3) including experimental and hypothetical terms, was investigated using DFT calculations and several experimental results. A systematic evolution of the electronic and magnetic states was evidenced along the series leading to ordered Co-II/Co-III versus mixed Co-III/IV charge segregation in two distinct structural motifs. In essence, using different packing modes within the labile [BanCo2+nO3n+2] block, we have systematized the spin state dependence on the CoO6 connectivity, i.e. corner-sharing (HS states) against face-sharing (LS states). We also show that the electronic and magnetic features of the [BaCo6O9] blocks do not vary trough the series, (i.e. HS-Co-II and LS-Co-III charge ordering) whereas the [BanCo2+nO3n+2] blocks hold drastic changes from n = 1 to 3. In particular, the later carries a mixed III/IV cobalt charge for n >= 2. It leads to a triple valence cobalt state. For n = 2, we experimentally observe at 4 K a superstructure (2a, 2c) superstructure accompanied by a perfect Co-II/Co-III/Co-IV charge ordering. The charge ordering occurs at Tt = 160 K and is accompanied by a transition in the electronic transport leading to a 2D-VRH behaviour below Tt

Triple Co-II,Co- (III,) (IV) charge ordering and spin states in modular cobaltites: a systematization through experimental and virtual compounds

International audienceThe series of modular compounds [BanCo2+nO3n+2][BaCo6O9] (n = 1 to 3) including experimental and hypothetical terms, was investigated using DFT calculations and several experimental results. A systematic evolution of the electronic and magnetic states was evidenced along the series leading to ordered Co-II/Co-III versus mixed Co-III/IV charge segregation in two distinct structural motifs. In essence, using different packing modes within the labile [BanCo2+nO3n+2] block, we have systematized the spin state dependence on the CoO6 connectivity, i.e. corner-sharing (HS states) against face-sharing (LS states). We also show that the electronic and magnetic features of the [BaCo6O9] blocks do not vary trough the series, (i.e. HS-Co-II and LS-Co-III charge ordering) whereas the [BanCo2+nO3n+2] blocks hold drastic changes from n = 1 to 3. In particular, the later carries a mixed III/IV cobalt charge for n >= 2. It leads to a triple valence cobalt state. For n = 2, we experimentally observe at 4 K a superstructure (2a, 2c) superstructure accompanied by a perfect Co-II/Co-III/Co-IV charge ordering. The charge ordering occurs at Tt = 160 K and is accompanied by a transition in the electronic transport leading to a 2D-VRH behaviour below Tt