Colloidal stability of tannins: astringency, wine tasting and beyond

Tannin-tannin and tannin-protein interactions in water-ethanol solvent mixtures are studied in the context of red wine tasting. While tannin self-aggregation is relevant for visual aspect of wine tasting (limpidity and related colloidal phenomena), tannin affinities for salivary proline-rich proteins is fundamental for a wide spectrum of organoleptic properties related to astringency. Tannin-tannin interactions are analyzed in water-ethanol wine-like solvents and the precipitation map is constructed for a typical grape tannin. The interaction between tannins and human salivary proline-rich proteins (PRP) are investigated in the framework of the shell model for micellization, known for describing tannin-induced aggregation of beta-casein. Tannin-assisted micellization and compaction of proteins observed by SAXS are described quantitatively and discussed in the case of astringency

Phonons and d-wave pairing in the two-dimensional Hubbard model

We analyze the influence of phonons on the d-wave pairing instability in the Hubbard model on the two-dimensional square lattice at weak to moderate interaction U, using a functional renormalization group scheme with frequency-dependent interaction vertices. As measured by the pairing scale, the B1g buckling mode enhances the pairing, while other phonon modes decrease the pairing. When various phonon modes are included together, the net effect on the scale is small. However, in situations where d-wave superconductivity and other tendencies, e.g. antiferromagnetism, are closely competing, the combined effect of different phonons may be able to tip the balance towards pairing.Comment: 4 pages, 3 figure

d-wave superconductivity and Pomeranchuk instability in the two-dimensional Hubbard model

We present a systematic stability analysis for the two-dimensional Hubbard model, which is based on a new renormalization group method for interacting Fermi systems. The flow of effective interactions and susceptibilities confirms the expected existence of a d-wave pairing instability driven by antiferromagnetic spin fluctuations. More unexpectedly, we find that strong forward scattering interactions develop which may lead to a Pomeranchuk instability breaking the tetragonal symmetry of the Fermi surface.Comment: 4 pages (RevTeX), 4 eps figure

Spontaneous symmetry breaking in the colored Hubbard model

The Hubbard model is reformulated in terms of different ``colored'' fermion species for the electrons or holes at different lattice sites. Antiferromagnetic ordering or d-wave superconductivity can then be described in terms of translationally invariant expectation values for colored composite scalar fields. A suitable mean field approximation for the two dimensional colored Hubbard model shows indeed phases with antiferromagnetic ordering or d-wave superconductivity at low temperature. At low enough temperature the transition to the antiferromagnetic phase is of first order. The present formulation also allows an easy extension to more complicated microscopic interactions.Comment: 19 pages, 5 figure

Imatinib ameliorates renal disease and survival in murine lupus autoimmune disease

n/

Exact integral equation for the renormalized Fermi surface

The true Fermi surface of a fermionic many-body system can be viewed as a fixed point manifold of the renormalization group (RG). Within the framework of the exact functional RG we show that the fixed point condition implies an exact integral equation for the counterterm which is needed for a self-consistent calculation of the Fermi surface. In the simplest approximation, our integral equation reduces to the self-consistent Hartree-Fock equation for the counterterm.Comment: 5 pages, 1 figur

Exact renormalization group flow equations for non-relativistic fermions: scaling towards the Fermi surface

We construct exact functional renormalization group (RG) flow equations for non-relativistic fermions in arbitrary dimensions, taking into account not only mode elimination but also the rescaling of the momenta, frequencies and the fermionic fields. The complete RG flow of all relevant, marginal and irrelevant couplings can be described by a system of coupled flow equations for the irreducible n-point vertices. Introducing suitable dimensionless variables, we obtain flow equations for generalized scaling functions which are continuous functions of the flow parameter, even if we consider quantities which are dominated by momenta close to the Fermi surface, such as the density-density correlation function at long wavelengths. We also show how the problem of constructing the renormalized Fermi surface can be reduced to the problem of finding the RG fixed point of the irreducible two-point vertex at vanishing momentum and frequency. We argue that only if the degrees of freedom are properly rescaled it is possible to reach scale-invariant non-Fermi liquid fixed points within a truncation of the exact RG flow equations.Comment: 20 Revtex pages, with 4 figures; final version to appear in Phys. Rev. B; references and some explanations adde

Aggregation of antibody drug conjugates at room temperature: SAXS and light scattering evidence for colloidal instability of a specific subpopulation

Coupling an hydrophobic drug onto monoclonal antibodies via Lysine residues is a common route to prepare antibody-drug conjugates (ADC), a promising class of biotherapeutics. But a few chemical modifications on protein surface often increases aggregation propensity, without clear understanding of the aggregation mechanisms at stake (loss of colloidal stability, self- assemblies, denaturation...), and the statistical nature of conjugation introduces polydispersity in the ADC population, which raises questions on whether the whole ADC population becomes unstable. To characterize the average interactions between ADC, we monitored small angle X-ray scattering in solutions of monoclonal IgG1 human antibody drug conjugate, with average degree of conjugation of 0, 2, or 3 drug molecules per protein. To characterize stability, we studied kinetics of aggregation at room temperature. Intrinsic Fuchs stability ratio of the ADC was estimated from the variation over time of scattered light intensity and hydrodynamic radius, in buffers of varying pH, and at diverse sucrose (0% or 10%) and NaCl (0 or 100 mM) concentrations. We show that stable ADC stock solutions became unstable upon pH shift, well below the pH of maximum average attraction between IgGs. Data indicates that aggregation can be ascribed to a fraction of ADC population usually representing less than 30 mol% of the sample. In contrast to the case of (monodisperse) monoclonal antibodies, our results suggest that a poor correlation between stability and average interaction parameters should be expected as a corollary of dispersity of ADC conjugation. In practice, the most unstable fraction of the ADC population can be removed by filtrations, which affects remarkably the apparent stability of the samples. Finally, the lack of correlation between the kinetic stability and variations of the average inter-ADC interactions is tentatively attributed to the uneven nature of charge distributions and the presence of patches on the drug-modified antibodies.This work was supported by the French National Research Agency (program Blanc International, grant ANR 2010-INT 1501, and program Investissement d’Avenir ANR-11- LABX-0011-01, and by SANOFI research grant to BFP. Authors are grateful to Javier Perez and Aurélien Thureau for their help and advice in SAXS measurements at SOLEIL. We thank Sophie Norvez from MMC laboratory in ESPCI for her help with circular dichroism.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/acs.langmuir.6b0065

Aggregation of Antibody Drug Conjugates at Room Temperature: SAXS and Light Scattering Evidence for Colloidal Instability of a Specific Subpopulation

Coupling a hydrophobic drug onto monoclonal antibodies via lysine residues is a common route to prepare antibody–drug conjugates (ADC), a promising class of biotherapeutics. But a few chemical modifications on protein surface often increase aggregation propensity, without a clear understanding of the aggregation mechanisms at stake (loss of colloidal stability, self-assemblies, denaturation, etc.), and the statistical nature of conjugation introduces polydispersity in the ADC population, which raises questions on whether the whole ADC population becomes unstable. To characterize the average interactions between ADC, we monitored small-angle X-ray scattering in solutions of monoclonal IgG1 human antibody drug conjugate, with average degree of conjugation of 0, 2, or 3 drug molecules per protein. To characterize stability, we studied the kinetics of aggregation at room temperature. The intrinsic Fuchs stability ratio of the ADC was estimated from the variation over time of scattered light intensity and hydrodynamic radius, in buffers of varying pH, and at diverse sucrose (0% or 10%) and NaCl (0 or 100 mM) concentrations. We show that stable ADC stock solutions became unstable upon pH shift, well below the pH of maximum average attraction between IgGs. Data indicate that aggregation can be ascribed to a fraction of ADC population usually representing less than 30 mol % of the sample. In contrast to the case of (monodisperse) monoclonal antibodies, our results suggest that a poor correlation between stability and average interaction parameters should be expected as a corollary of dispersity of ADC conjugation. In practice, the most unstable fraction of the ADC population can be removed by filtration, which affects remarkably the apparent stability of the samples. Finally, the lack of correlation between the kinetic stability and variations of the average inter-ADC interactions is tentatively attributed to the uneven nature of charge distributions and the presence of patches on the drug-modified antibodies