Aggregation of human plasma and of human blood induced in vitro by pegfilgrastim originator formulation buffer and pegfilgrastim products.

PEGylated recombinant human granulocyte colony stimulating factor (pegfilgrastim) is used clinically to reduce the incidence and duration of severe neutropenia in patients who have received chemotherapy treatment. Pegfilgrastim products are administered by subcutaneous injection. We herein report that solutions of pegfilgrastim originator product Neulasta®, of a biosimilar product candidate, and also of the pegfilgrastim originator formulation buffer, induced aggregate formation when mixed in vitro with human plasma, and formation of large membranous aggregated structures when mixed with human blood.

Aggregation of human plasma and of human blood induced in vitro by filgrastim originator product; effect of PEGylation.

We herein report that filgrastim product Neupogen® and the filgrastim formulation buffer induced aggregate formation when mixed in vitro with human plasma, and formation of large membranous erythrocyte aggregates when mixed with human blood, similar to the aggregation induced by pegfilgrastim and by pegfilgrastim buffer [T. Arvinte, E. Poirier, N.

Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC.

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6   6   6 m liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light.

Search for Electron Antineutrino Appearance in a Long-Baseline Muon Antineutrino Beam.

Electron antineutrino appearance is measured by the T2K experiment in an accelerator-produced antineutrino beam, using additional neutrino beam operation to constrain parameters of the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) mixing matrix. T2K observes 15 candidate electron antineutrino events with a background expectation of 9.3 events.

Part 2: Physicochemical characterization of bevacizumab in 2 mg/mL antibody solutions as used in human i.v. administration: Comparison of originator with a biosimilar candidate.

The physicochemical properties of Avastin® manufactured in the USA (Originator USA) and in Europe (Originator EU) and ABX-BEV, a bevacizumab biosimilar drug product candidate produced by Apobiologix Inc., were characterized at a clinically relevant concentration of 2 mg/mL following dilution of the 25 mg/mL drug products with 0.9% NaCl.

Part 1: Physicochemical characterization of bevacizumab in undiluted 25 mg/mL drug product solutions: Comparison of originator with a biosimilar candidate.

The biosimilarity assessment of the physicochemical properties of high-concentration biopharmaceuticals is usually performed with measurements on diluted solutions, at concentrations below 1 mg/mL. In this study 13 orthogonal, spectroscopy and particle size determination methods were used to characterize the structure and aggregation of undiluted, 25 mg/mL bevacizumab drug products Avastin® manufactured in the USA and in Europe, and ABX-BEV, a bevacizumab biosimilar candidate produced by Apobiologix Inc. Secondary structure, conformation and the potential occurrence of chemical degradation of the monoclonal antibodies were characterized and compared using infrared spectroscopy, intrinsic fluorescence and ANS fluorescence spectroscopy.

Search for CP Violation in Neutrino and Antineutrino Oscillations by the T2K Experiment with 2.2×10^{21} Protons on Target.

The T2K experiment measures muon neutrino disappearance and electron neutrino appearance in accelerator-produced neutrino and antineutrino beams. With an exposure of 14.7(7.

Combined Analysis of Neutrino and Antineutrino Oscillations at T2K.

T2K reports its first results in the search for CP violation in neutrino oscillations using appearance and disappearance channels for neutrino- and antineutrino-mode beams. The data include all runs from January 2010 to May 2016 and comprise 7.482×10^{20} protons on target in neutrino mode, which yielded in the far detector 32 e-like and 135  μ-like events, and 7.

Precision Measurement of the Longitudinal Double-Spin Asymmetry for Inclusive Jet Production in Polarized Proton Collisions at sqrt[s]=200 GeV.

We report a new measurement of the midrapidity inclusive jet longitudinal double-spin asymmetry, A_{LL}, in polarized pp collisions at center-of-mass energy sqrt[s]=200  GeV. The STAR data place stringent constraints on polarized parton distribution functions extracted at next-to-leading order from global analyses of inclusive deep-inelastic scattering (DIS), semi-inclusive DIS, and RHIC pp data. The measured asymmetries provide evidence at the 3σ level for positive gluon polarization in the Bjorken-x region x>0.

Enhanced potency of human calcitonin when fibrillation is avoided.

The peptide hormone calcitonin (CT) is a potent drug for the therapy of different bone diseases. Salmon CT (sCT) is reported to be more active than human CT (hCT). Human CT, but not sCT, has a strong tendency to aggregate and fibrillate in aqueous solutions.

Ipriflavone directly inhibits osteoclastic activity.

Ipriflavone, an isoflavone derivative, is a new drug used in an attempt to decrease bone loss in osteoporosis. Experimental studies have shown that this compound acts by inhibiting osteoclastic bone resorption both in vivo and in vitro, but the mechanism of its inhibitory action on resorbing cells remains unclear. Using bone resorption assays, video image analysis together with measurements of intracellular free calcium in isolated osteoclasts, we show here that IP directly inhibits osteoclastic activity by the modulation of intracellular free calcium.

The structure and mechanism of formation of human calcitonin fibrils.

Turbidity measurements of the kinetics of human calcitonin (hCT) fibrillation showed a linear dependence of the logarithm of fibrillation time (the time the sample is not fibrillated) and the logarithm of hCT concentration. This ln/ln plot linearity and electron microscope observations of fibrils indicate that the fibrillation process can be explained by the double nucleation mechanism that was proposed for the gelation of sickle cell hemoglobin (Ferrone, F. A.

Formation of cage-like particles by poly(amino acid)-based block copolymers in aqueous solution.

When dissolved in N,N-dimethylformamide and then dialyzed against phosphate-buffered saline, A-B-A block copolymers composed of poly [N5-(2-hydroxyethyl)-L-glutamine]-block-poly(gamma-benzyl-L-glutamate)- block-poly [N5-(2-hydroxyethyl)-L-glutamine] form particles. The particles are cage-like structures with average diameters of 300 nm (average polydispersity, 0.3-0.

Specific interaction of CD4-bearing liposomes with HIV-infected cells.

The CD4 molecule was reconstituted into the bilayers of large liposomes. Fluorescence microscopy and electron microscopy showed that these liposomes interact with HIV-infected H9-HT cells, delivering their contents to the cell interior. Liposomes bearing CD4 did not interact in this way with noninfected H9-HT cells nor did liposomes without CD4 interact significantly with HIV-infected cells.

Dextran protection of erythrocytes from low-pH-induced hemolysis.

Low-pH-induced hemolysis of erythrocytes is inhibited by dextrans. The protective effect was observed with dextrans larger than 40 kDa. Electron microscopy showed dextrans of 150 kDa in a tight association with the erythrocyte membrane.

Low-pH association of proteins with the membranes of intact red blood cells. II. Studies of the mechanism.

The low-pH interaction of proteins with erythrocyte membranes has been found to be correlated with pH-induced changes in the erythrocyte membrane. Using a 90 degree lightscattering method it was shown that red blood cell hemolysis was slow between pH 5.8 and 5 (t1/2 above 1 h) but became fast at and below pH 4.

Low-pH association of proteins with the membranes of intact red blood cells. I. Exogenous glycophorin and the CD4 molecule.

Glycophorin and CD4 proteins are tightly associated with intact human erythrocyte membranes after a short-time incubation at low pH (1-2 min, pH lower than 5, 37 degrees C). Flow cytometry and epifluorescence microscope observations showed that after incubation of red cells with fluorescein isothiocyanate (FITC) labeled glycophorin at pH values lower than 5, the erythrocyte membrane and subsequently formed ghost membranes were fluorescent. Unlabeled glycophorin was reacted with mouse erythrocytes using the same low-pH conditions.

Liposomes as carriers of DNA.

A recombinant plasmid encoding for rat preproinsulin I was encapsulated in large liposomes and injected intravenously into rats. Glycemia and blood, splenic and hepatic insulin were assayed from 6 h after inoculation. Control animals received (1) empty liposomes, (2) liposomes carrying the E.

On the use of Percoll as a marker for liposomes in electron microscopy of mouse spleen tissue.

Liposomes encapsulating Percoll were prepared by reverse phase evaporation and characterized by electron microscopy (EM). Encapsulated Percoll was contained between lipid bilayers and in the lumen of the liposomes. The largest population of liposomes had diameters between 110 and 140 nm (22.

Interaction of intravenously injected liposomes with mouse liver mitochondria. A fluorescence and electron microscopy study.

Megamitochondria, resulting from cuprizone feeding of Swiss ICR mice, were fluorescent in hepatocytes after the intravenous injection to mice of a liposome-encapsulated acridine orange-DNA complex (AO-DNA). Flow cytofluorimetric analysis of isolated megamitochondria showed that the proportion of liposome-encapsulated AO-DNA which localized in megamitochondria increased from 0.02% of the dose injected per liver cell at 3 min after injection to an average of 0.

Intracellular fate of liposome-encapsulated DNA in mouse liver. Analysis using electron microscope autoradiography and subcellular fractionation.

Transient expression of liposome-encapsulated DNA in liver after intravenous injection to rats and mice has raised questions concerning the intracellular fate of this DNA. Electron microscope autoradiography shows that at 10 min after injection the highest concentration of liposomal DNA which is taken up by the liver is associated with lysosomes and vesicles. The proportion of DNA associated with the mitochondria steadily increases for 1 h after injection, up to 48% of the exogenous DNA found in the tissue.

Liposomes injected intravenously into mice associate with liver mitochondria.

Liposomes encapsulating uranyl acetate or ferritin were injected intravenously into mice. At periods of 20 min, 1 h and 4 h post-injection, animals were killed, and livers were excised. Transmission electron micrographs of liver tissue showed association of oligolamellar liposomes with mitochondria for each time period.