Excipient Effects on Humanized Monoclonal Antibody Interactions with Silicone Oil Emulsion

Silicone oil is a lubricant used for plunger depression in prefilled glass syringes. Many therapeutic protein products are stored in prefilled syringes and may be exposed to the silicone oil-water interface for up to 18-24 months. At the present, our understanding of how proteins interact with this interface remains poorly understood. In this work, the interaction of three humanized monoclonal antibodies (humAbs) with silicone oil emulsion was assessed in presence of sodium chloride, sucrose, Tween® 20, Tween® 80, and poloxamer 188. It was found that the amount of humAb adsorbed was antibody- and excipient-dependent. Once adsorbed, the tryptophan exposure to solvent resembled that of unfolded protein and was independent of the identity of different excipients present in the formulation buffer. Protein aggregation was not detected in solution. But, colloidal destabilization of silicone oil emulsion resulting from protein adsorption lowered the activation energy barrier to flocculation thereby enabling heterogeneous aggregates comprised of protein-coated silicone oil microdroplets to form. The size of these flocs was dependent on the solution ionic strength. Flocculation occurred in the presence of all excipients examined except in the presence of surfactant. In formulations containing surfactant, there was competition between humAb and surfactant molecules for adsorption sites at the silicone oil-water interface. The results suggest that the kinetics of humAb displacement from the silicone oil interface was surfactant-dependent. Whether the mechanism of this replacement involved the formation of protein-surfactant complex remains uncertain

Performance Models for Split-execution Computing Systems

Split-execution computing leverages the capabilities of multiple computational models to solve problems, but splitting program execution across different computational models incurs costs associated with the translation between domains. We analyze the performance of a split-execution computing system developed from conventional and quantum processing units (QPUs) by using behavioral models that track resource usage. We focus on asymmetric processing models built using conventional CPUs and a family of special-purpose QPUs that employ quantum computing principles. Our performance models account for the translation of a classical optimization problem into the physical representation required by the quantum processor while also accounting for hardware limitations and conventional processor speed and memory. We conclude that the bottleneck in this split-execution computing system lies at the quantum-classical interface and that the primary time cost is independent of quantum processor behavior.Comment: Presented at 18th Workshop on Advances in Parallel and Distributed Computational Models [APDCM2016] on 23 May 2016; 10 page

The Vehicle, Spring 1995

Table of Contents Poetry The SwimmersJennifer Moropage 2 Everlasting ArmsSue Songerpage 2 Talking to an AddictBridgett Jensenpage 3 SecretsTiffany Abbottpage 5 CryingMatthew Berrypage 6 winter fieldsKeith Spearpage 7 untitledKemp Nishan Munizpage 7 Rainy Night in ParisDiana Matijaspage 8 nap timeKelly A. Pricepage 10 Angel of the EarthHeather Anne Winterspage 10 Color DreamsMatthew J. Nelsonpage 12 Dandelion PaintSandy Beauchamppage 13 Merry Go Round MarathonElizabeth Bromleypage 14 The ArmadilloKeith Spearpage 15 The Shoe SagaJennifer Moropage 16 Coffee Cup Confessional BoothSue Songerpage 18 What Gravity, A Rock And A Rabbit Have To Do With My Love LifeMartin Paul Brittpage 19 Good Bye, Good KnightRich Birdpage 20 Photography Railroad Station IKelly A. Pricepage 22 1000 VinesKelly A. Pricepage 23 Self PortraitKelly A. Pricepage 24 Prose Queen of Dead AirBryan Levekpage 26 Closer to the noiseMichell Heidelpage 29 Somewhere in BetweenKimberly Hunterpage 32 Miss SteakBryan Levekpage 37 Chasing the ChasteTerry Bassettpage 43 Biographies Authors, editorspage 48https://thekeep.eiu.edu/vehicle/1065/thumbnail.jp

Mechanism of selective benzene hydroxylation catalyzed by iron-containing zeolites

A direct, catalytic conversion of benzene to phenol would have wide-reaching economic impacts. Fe zeolites exhibit a remarkable combination of high activity and selectivity in this conversion, leading to their past implementation at the pilot plant level. There were, however, issues related to catalyst deactivation for this process. Mechanistic insight could resolve these issues, and also provide a blueprint for achieving high performance in selective oxidation catalysis. Recently, we demonstrated that the active site of selective hydrocarbon oxidation in Fe zeolites, named α-O, is an unusually reactive Fe(IV)=O species. Here, we apply advanced spectroscopic techniques to determine that the reaction of this Fe(IV)=O intermediate with benzene in fact regenerates the reduced Fe(II) active site, enabling catalytic turnover. At the same time, a small fraction of Fe(III)-phenolate poisoned active sites form, defining a mechanism for catalyst deactivation. Density-functional theory calculations provide further insight into the experimentally defined mechanism. The extreme reactivity of α-O significantly tunes down (eliminates) the rate-limiting barrier for aromatic hydroxylation, leading to a diffusion-limited reaction coordinate. This favors hydroxylation of the rapidly diffusing benzene substrate over the slowly diffusing (but more reactive) oxygenated product, thereby enhancing selectivity. This defines a mechanism to simultaneously attain high activity (conversion) and selectivity, enabling the efficient oxidative upgrading of inert hydrocarbon substrates

Three-weekly doses of azithromycin for Indigenous infants hospitalized with bronchiolitis: a multicentre, randomized, placebo-controlled trial

Background: Bronchiolitis is a major health burden in infants globally, particularly among Indigenous populations. It is unknown if 3 weeks of azithromycin improve clinical outcomes beyond the hospitalization period. In an international, double-blind randomized controlled trial, we determined if 3 weeks of azithromycin improved clinical outcomes in Indigenous infants hospitalized with bronchiolitis.Methods: Infants aged ≤24 months were enrolled from three centers and randomized to receive three once-weekly doses of either azithromycin (30 mg/kg) or placebo. Nasopharyngeal swabs were collected at baseline and 48 h later. Primary endpoints were hospital length of stay (LOS) and duration of oxygen supplementation monitored every 12 h until judged ready for discharge. Secondary outcomes were: day-21 symptom/signs, respiratory rehospitalizations within 6 months post-discharge and impact upon nasopharyngeal bacteria and virus shedding at 48 h.Results: Two hundred nineteen infants were randomized (n = 106 azithromycin, n = 113 placebo). No significant between-group differences were found for LOS (median 54 h for each group, difference = 0 h, 95% CI: −6, 8; p = 0.8), time receiving oxygen (azithromycin = 40 h, placebo = 35 h, group difference = 5 h, 95% CI: −8, 11; p = 0.7), day-21 symptom/signs, or rehospitalization within 6 months (azithromycin n = 31, placebo n = 25 infants, p = 0.2). Azithromycin reduced nasopharyngeal bacterial carriage (between-group difference 0.4 bacteria/child, 95% CI: 0.2, 0.6; p < 0.001), but had no significant effect upon virus detection rates.Conclusion: Despite reducing nasopharyngeal bacterial carriage, three large once-weekly doses of azithromycin did not confer any benefit over placebo during the bronchiolitis illness or 6 months post hospitalization. Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis.Clinical trial registration: The trial was registered with the Australian and New Zealand Clinical Trials Register: Clinical trials number: ACTRN1261000036099