Multimerization of Peptide Mimotopes for Blocking of Factor VIII Neutralizing Antibodies

About 30 % of patients with severe hemophilia A develop neutralizing antibodies (inhibitors) to coagulation factor VIII (FVIII) upon treatment with exogenous factor preparations. Two peptides, C6 (NPVENMMDRDSQ) and H10 (QSPWQTWFTRAL), that mimic putative inhibitor epitopes (mimotopes), were previously selected by phage display screening of plasma samples from patients with inhibitors. Synthetic peptide mimotopes inhibited IgG binding to FVIII (IC₅₀: 30–50 μM ). This effect was increased by an equimolar combination of both mimotopes. Mimotopes were fused to the C‐terminal multimerization domain of the C4bp α‐chain and expressed as multimers in 293T cells. Multimerized mimotopes showed improved binding to anti‐FVIII IgG and prolonged in vitro half‐life relative to synthetic peptides. The two mimotopes were combined in heteromultimers by co‐transfection of 293T cells with respective vectors, resulting in bi‐specific molecules that almost completely blocked polyclonal antibody binding to FVIII (IC₅₀: 2–3 μM ). This strategy is capable of functionally improving synthetic peptides by multimerization and could provide a basis for novel therapeutic approaches for patients with hemophilia A and inhibitors.     

Concurrent and legacy economic and environmental impacts from establishing a marine energy sector in Scotland

We examine the economic and environmental impact that the installation of 3 GW of marine energy capacity would have on Scotland. This is not a forecast, but a projection of the likely effects of meeting the Scottish Government's targets for renewable energy through the development of a marine energy sector. Energy, with a particular focus on renewables, is seen by the Scottish Government as a “key sector”, with high growth potential and the capacity to boost productivity (Scottish Government, 2007a. The Government Economic Strategy. The Scottish Government, Edinburgh). The key nature of this sector has been identified through targets being set for renewable energy to achieve environmental and economic benefits. Using a regional computable general equilibrium (CGE) model of Scotland we show that the development of a marine energy sector can have substantial and beneficial impacts on GDP, employment and the environment over the lifetime of the devices, given the encouragement of strong indigenous inter-industry linkages. Furthermore, there are also substantial “legacy” effects that persist well beyond the design life of the devices.     

Use of reactable light stabilizers to prevent migration and to improve durability of coatings on plastic substrates

One of the challenges of coating plastic substrates for exterior automotive applications involves the tendency for light stabilizers, which inhibit UV degradation of the coating, to migrate out of the topcoat and into the underlying plastic substrate. The consequent depletion of the stabilizer from the topcoat could account for significantly poorer durability for coatings applied on plastic than on a nonpermeable substrate such as steel. These studies investigate the migration of both nonreactable and reactable UV absorbers (UVAs) and hindered amine light stabilizers (HALS) in fully formulated 2K urethane coatings applied on thermoplastic olefin (TPO) and steel substrates. Extensive migration of the nonreactable stabilizers occurs during accelerated exposure of the cured coating, and this migration correlates with poorer performance on TPO. Functionalization of the stabilizer with a group which covalently reacts into the coating will prevent much of this migration, and the improved degree of retention of the reactable light stabilizers in the topcoat correlates with improved performance on TPO substrates. In addition, stabilizer variables, such as the type and extent of functionalization as well as their chemical structure, have an effect on both the migration and performance of the stabilizers.     

The Perceptions of Science Classes Survey: What undergraduate science reform efforts really need to address.

Nine-hundred twenty two undergraduates completed an 80-item survey that assessed their perceptions of undergraduate science classes. Factor analysis of the items yielded 6 factors: (1) Pedagogical Strategies, (2) Faculty Interest in Teaching, (3) Student Interest and Perceived Competence in Science, (4) Passive Learning, (5) Grades as Feedback, and (6) Laboratory Experiences. Women differed significantly from men on the Pedagogical Strategies, Passive Learning, Grades as Feedback, and Laboratory Experiences factors. Correlational analyses and evidence from distinct groups supported the survey's construct validity. Students reported room for improvement of the science faculty's pedagogical practices. From the students' perspective, how information is taught appears to be at least as much of a concern as what information is taught. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

3D Viscoelastic analysis of a polymer solution in a complex flow

A mixed low-order finite element technique based on the Discrete Elastic Viscous Stress Splitting (DEVSS)/Discontinuous Galerkin (DG) method has been developed for the analysis of three-dimensional viscoelastic flows in the presence of multiple relaxation times. In order to evaluate the predictive capabilities of some established nonlinear constitutive relations like the Giesekus and the Phan-Thien–Tanner (PTT) model results of 3D calculations are compared with experimental results in a cross-slot flow geometry. Moreover, the performance of a new viscoelastic constitutive equation that provides enhanced independent control of the shear and elongational properties is investigated. Steady shear flows and a combined shear/elongational flow are analyzed for a polyisobutylene solution. A general method is introduced to compare calculated stresses along the depth of the flow with birefringence measurements using the stress optical rule. In particular at and downstream of the stagnation point in the cross-slot flow geometry, the numerical/experimental evaluation shows that the multi-mode Giesekus and the PTT model are unable to describe the stress-related experimental observations. The new viscoelastic constitutive relation proves to perform significantly better for this stagnation flow.     

Production of CO2 clathrate hydrate frozen desserts by flash freezing

CO₂ clathrate hydrate is a crystalline water–carbon dioxide structure that can enable novel, strongly carbonated frozen desserts. A CO₂ flash-freezing process has been developed to form CO₂ hydrates during freezing of a dessert mixture. In the process, liquid CO₂ and liquid dessert mixture are emulsified and then sprayed into a chamber in which the CO₂ flashes to a vapor causing the dessert mixture to freeze into a low-density powder. To ensure CO₂ hydrate formation it is important to avoid ice formation because ice to CO₂ hydrate conversion proceeds too slowly to occur during flash freezing. To avoid ice formation it is important to flash the emulsion to a pressure greater than 4.7 bars and disperse the mixture in fine droplets. In this work the key parameters of the process are described, which will enable development of commercial dispensers.     

Anabolic–androgenic steroids: User characteristics, motivations, and deterrents.

The use of anabolic–androgenic steroids (AAS) is increasing internationally. The present study addresses the paucity of information regarding the characteristics and motivations of AAS users. This sample of 100 AAS (94% male) users was unlike other samples of Australian illicit drug users. They were typically male, well educated, and employed and had a higher disposable income than the general Australian population. They were also involved in rigorous training directly related to their AAS use. Recreational drug use was low, with gay participants largely responsible for the polydrug use among this sample. The main motivations for AAS use were improved physical appearance and increased size. Different subgroups of users had varied expectations about the psychological effects of AAS use that were also important in motivating use. Concern about physical health was the main deterrent to use. This information will be useful in the development of educational initiatives. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Toward credible IT testing and certification

Accessible, rigorous measurement and test methods are key to creating quality software and increasing IT market competition. At the US National Institute of Standards and Technology's Information Technology Laboratory, work focuses on establishing comprehensive certification capability for the IT industry. This article describes NIST's work and how it can be applied