Assessment of membrane-based downstream purification processes as a replacement to traditional resin bead for monoclonal antibody purification.

Membrane chromatography devices are a viable alternative to packed-bed resins and enable highly productive purification cascades for monoclonal antibodies and Fc-fusion proteins. In this study, ion exchange and protein A membrane chromatography performances were assessed and compared with their resin counterparts. Protein A dynamic binding capacities were higher than 50 g/L for two of the tested membranes and with a residence time of 0.

Deconvolving microbial and environmental controls on marine sedimentary pyrite sulfur isotope ratios.

Reconstructions of past environmental conditions and biological activity are often based on bulk stable isotope proxies, which are inherently open to multiple interpretations. This is particularly true of the sulfur isotopic composition of sedimentary pyrite (δS), which is used to reconstruct ocean-atmosphere oxidation state and track the evolution of several microbial metabolic pathways. We present a microanalytical approach to deconvolving the multiple signals that influence δS, yielding both the unambiguous determination of microbial isotopic fractionation (ε) and new information about depositional conditions.

Sedimentary parameters control the sulfur isotope composition of marine pyrite.

Reconstructions of coupled carbon, oxygen, and sulfur cycles rely heavily on sedimentary pyrite sulfur isotope compositions (δS). With a model of sediment diagenesis, paired with global datasets of sedimentary parameters, we show that the wide range of δS (~100 per mil) in modern marine sediments arises from geographic patterns in the relative rates of diffusion, burial, and microbial reduction of sulfate. By contrast, the microbial sulfur isotope fractionation remains large and relatively uniform.

A randomized controlled trial of the intraoperative use of noninvasive ventilation versus supplemental oxygen by face mask for procedural sedation in an electrophysiology laboratory.

Purpose: The efficacy of noninvasive ventilation (NIV) during procedures that require sedation and analgesia has not been established. We evaluated whether NIV reduces the incidence of respiratory events.

Methods: In this randomized controlled trial, we included 195 patients with an American Society of Anesthesiologists Physical Status of III or IV during electrophysiology laboratory procedures.

Tunable biaxial strain device for low-dimensional materials.

Strain is attracting much interest as a mean to tune the properties of thin exfoliated two-dimensional materials and their heterostructures. Numerous devices to apply tunable uniaxial strain are proposed in the literature, but only few for biaxial strain, often with a trade-off between maximum strain and uniformity, reversibility, and device size. We present a compact device that allows for the controlled application of uniform in-plane biaxial strain, with maximum deformation and uniformity comparable to those found in much larger devices.

Exact Anomalous Current Fluctuations in a Deterministic Interacting Model.

We analytically compute the full counting statistics of charge transfer in a classical automaton of interacting charged particles. Deriving a closed-form expression for the moment generating function with respect to a stationary equilibrium state, we employ asymptotic analysis to infer the structure of charge current fluctuations for a continuous range of timescales. The solution exhibits several unorthodox features.

Transfer of continuous manufacturing process principles for mAb production in a GMP environment: A step in the transition from batch to continuous.

Implementation of continuous in lieu of batch upstream processing (USP) and downstream process (DSP) for the production of recombinant therapeutic protein is a significant paradigm change. The present report describes how the first kilograms of monoclonal antibody were produced with equipment originally designed for batch operations while using continuous manufacturing processes and principles. Project timelines for the delivery of clinical material have driven this ambition and helped the transition.

Strong local, not global, controls on marine pyrite sulfur isotopes.

Understanding variation in the sulfur isotopic composition of sedimentary pyrite (δS) is motivated by the key role of sulfur biogeochemistry in regulating Earth's surface oxidation state. Until recently, the impact of local depositional conditions on δS has remained underappreciated, and stratigraphic variations in δS were interpreted mostly to reflect global changes in biogeochemical cycling. We present two coeval δS records from shelf and basin settings in a single sedimentary system.

Acid digestion on river influenced shelf sediment organic matter: Carbon and nitrogen contents and isotopic ratios.

Rationale: Natural stable isotope ratios (δ C and δ N values) and associated elemental concentrations (i.e. total organic carbon and total nitrogen contents) preserved in marine sediments are frequently used for the determination of paleo-environmental processes such as the origin of organic matter.

Pyrite sulfur isotopes reveal glacial-interglacial environmental changes.

The sulfur biogeochemical cycle plays a key role in regulating Earth's surface redox through diverse abiotic and biological reactions that have distinctive stable isotopic fractionations. As such, variations in the sulfur isotopic composition (δS) of sedimentary sulfate and sulfide phases over Earth history can be used to infer substantive changes to the Earth's surface environment, including the rise of atmospheric oxygen. Such inferences assume that individual δS records reflect temporal changes in the global sulfur cycle; this assumption may be well grounded for sulfate-bearing minerals but is less well established for pyrite-based records.

IL-2 induces conformational changes in its preassembled receptor core, which then migrates in lipid raft and binds to the cytoskeleton meshwork.

While interleukin (IL)-2 clearly initiates the sequential assembly of its soluble receptor fragments (sIL-2R) in vitro (with sIL-2Rα first, sIL-2Rβ second, and sγc last), the assembly mechanism of full-length subunits (IL-2R) at the surface of living lymphocytes remains to be elucidated. Here we demonstrate by fluorescence cross-correlated spectroscopy that native IL-2Rβ and γc assemble spontaneously at the surface of living human leukemia T cells (Kit-225 cell line) in the absence of IL-2 and with 1:1 stoichiometry. The dissociation constant of the membrane-embedded IL-2Rβ/γc complex is measured in situ.

Autoimmunity during thymectomy-induced lymphopenia: role of thymus ablation and initial effector T cell activation timing in nonobese diabetic mice.

Autoimmune diseases develop in selected normal mouse strains when thymectomy (Tx) is performed at 3 days of age (d3-Tx). Insufficient T cell regulation after Tx may result from a defect in regulatory T (Treg) cells or from an augmented effector T (Teff) cell number/pathogenicity. We have previously shown that Tx at 3 wk (wk3-Tx), the age of massive islet Ag release, accelerates diabetes onset.

Mutual information and boson radius in a c=1 critical system in one dimension.

We study the generic scaling properties of the mutual information between two disjoint intervals, in a class of one-dimensional quantum critical systems described by the c=1 bosonic field theory. A numerical analysis of a spin-chain model reveals that the mutual information is scale invariant and depends directly on the boson radius. We interpret the results in terms of correlation functions of branch-point twist fields.

Classical dimers with aligning interactions on the square lattice.

We present a detailed study of a model of close-packed dimers on the square lattice with an interaction between nearest-neighbor dimers. The interaction favors parallel alignment of dimers, resulting in a low-temperature crystalline phase. With large-scale Monte Carlo and transfer matrix calculations, we show that the crystal melts through a Kosterlitz-Thouless phase transition to give rise to a high-temperature critical phase, with algebraic decays of correlations functions with exponents that vary continuously with the temperature.

Unconventional continuous phase transition in a three-dimensional dimer model.

Phase transitions occupy a central role in physics, due both to their experimental ubiquity and their fundamental conceptual importance. The explanation of universality at phase transitions was the great success of the theory formulated by Ginzburg and Landau, and extended through the renormalization group by Wilson. However, recent theoretical suggestions have challenged this point of view in certain situations.

Interacting classical dimers on the square lattice.

We study a model of close-packed dimers on the square lattice with a nearest neighbor interaction between parallel dimers. This model corresponds to the classical limit of quantum dimer models [D. S.

Defective interleukin-2-dependent STAT5 signalling in CD8 T lymphocytes from HIV-positive patients: restoration by antiretroviral therapy.

Background: CD8 T lymphocytes are critical in the control of HIV replication and disease progression. Our previous studies demonstrated that CD8 T cells from chronically infected patients with high virus load proliferated poorly in response to interleukin-2 (IL-2), a cytokine critical in CD8 T cell growth and differentiation, even though relatively high levels of IL-2 receptor (IL-2R) were expressed. This suggested that signal transduction defects in response to IL-2 might be involved.

Human immunodeficiency virus-1 envelope glycoproteins and anti-CD4 antibodies inhibit interleukin-2-induced Jak/STAT signalling in human CD4 T lymphocytes.

Human immunodeficiency virus (HIV) infection leads to a profound T cell dysfunction well before the clinical onset of acquired immunodeficiency syndrome (AIDS). We have been accumulating evidence that one of the mechanisms responsible for this T cell deficiency may be the dysregulation of signal transduction via the interleukin (IL)-2/IL-2 receptor (R) complex. In CD4 T cells, we have observed previously that viral envelope (env) glycoproteins induce IL-2 unresponsiveness and the down-regulation of the three chains making up the IL-2R (alpha, beta, gamma) in vitro.

Quantum dimer model on the kagome lattice: solvable dimer-liquid and ising gauge theory.

We introduce quantum dimer models on lattices made of corner-sharing triangles. These lattices include the kagome lattice and can be defined in arbitrary geometry. They realize fully disordered and gapped dimer-liquid phase with topological degeneracy and deconfined fractional excitations, as well as solid phases.

[Evaluation of a new form of care: the permanently maintained health care facility at the university hospital center in Nantes].

Considering the consequences of social instability within the health care system has become a public health priority. Each public hospital center in France is obliged to create a unit for welcoming impoverished and vulnerable people (Permanently Maintained Health Care Facilities). The university hospital in Nantes opened a socio-medical out-patient consultation service in November 1999 with the main objective being to bring these patients back into the usual ambulatory care system.

Unstimulated human CD4 lymphocytes express a cytoplasmic immature form of the common cytokine receptor gamma-chain.

As a component of various cytokine receptors, common cytokine receptor gamma-chain (gamma(c)) is essential in the development of the immune system and plays an important role in different stages of inflammatory and immune responses. Here we establish that resting CD4 T cells and the Jurkat CD4 T cell line do not express the mature form of gamma(c) (64 kDa) recognized by mAb Tugh4. However, these cells constitutively transcribe the corresponding gamma(c) gene.

129Xe NMR as a probe of the dynamics of gas confined in porous Vycor.

We use 129Xe NMR to probe the diffusion of xenon gas in the porous network of Vycor glass, by monitoring its relaxation properties. When the mean free path of the diffusing gas is larger than the pore size (Knudsen conditions), both 129Xe chemical shifts and relaxation rates are sensitive to the confinement of xenon gas within a porous solid. The influence of both temperature and xenon pressure are recorded on the 129Xe chemical shifts and relaxation rates, in order to characterise the xenon/Vycor interactions.