The role of cysteine oxidation in the thermal inactivation of T4 lysozyme

Wild-type T4 lysozyme contains unpaired cysteine residues atpositions 54 and 97. To investigate the role these residuesplay in the thermal inactivation of the wild-type, we constructeda double mutant with these cysteines replaced with valine andserine. This molecule, T4 lysozyme (C54V/C97S), is more stablethan the wild-type to inactivation at 70°C at pH 6.5 and8.0. Guanidine hydrochloride reactivation experiments and SDS-PAGEon the inactivated products show that the wild-type is susceptibleto varying degrees of oxidative damage, depending on bufferconditions, while the cysteine-minus mutant inactivates onlyby other pathways. The products of thermal, oxidative inactivationof the wild-type are disulfide-linked oligomers. The dependenceof inactivation rate on temperature suggests that the formationof these aggregates depends on prior thermal unfolding of theT4 lysozyme molecule.     

Preferences as expectation-driven inferences: Effects of affective expectations on affective experience.

Presents a model arguing that affect and emotion are often formed in an expectation-driven fashion. A pilot study and 2 experiments manipulated undergraduate Ss' affective expectations (e.g., how funny they expected a set of cartoons to be) and whether Ss' expectations were confirmed (e.g., whether the cartoons really were funny). When the value of a stimulus was consistent with an affective expectation, people formed evaluations relatively quickly. Even when the value of a stimulus was discrepant from an affective expectation, people sometimes assimilated the value of the stimulus to their expectations. Other times, such as when making a more fine-grained evaluation of the cartoons, people noticed that they were discrepant from their affective expectations. Under these conditions, people appeared to have more difficulty forming preferences. They took longer to evaluate and spent more time thinking about the cartoons. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Computational Aspects of Pathology Image Classification and Retrieval

We are investigating the role of high performance computing for support of a comprehensive pathology image atlas. The primary computing component is a database access mechanism providing retrieval by content based image matching (CBIR) along with traditional term based queries. An organization based on information theoretic and Bayesian principles using decision trees and signature files is being developed. The essential role of HPC is the discovery, selection, and optimization of medically useful image feature sets via genetic algorithm and simulated annealing methods. This paper outlines the problem area along with aspects of the underlying theoretical basis and distinguishing computing characteristics. Efficiency of key portions of the computations can be greatly improved by using parallelism within the computer word length using bit counting instructions to implement voting and multimedia style instruction sets for low level image processing.     

An immune cell-selective interleukin 4 agonist

Interleukin 4 (IL-4) is a pleiotropic cytokine. Of the cell types responsive to IL-4, T cells express one IL-4 receptor (IL-4R) type, IL-4Ralpha/IL-2Rgamma (class I IL-4R), whereas endothelial cells express another type, IL-4Ralpha/IL-13Ralpha (class II IL-4R). It was hypothesized that IL-4 variants could be generated that would be selective for cell types expressing the different IL-4Rs. A series of IL-4 muteins were generated that were substituted in the region of IL-4 implicated in interactions with IL-2Rgamma. These muteins were evaluated in T cell and endothelial cell assays. One of these muteins, containing the mutation Arg-121 to Glu (IL-4/R121E), exhibited complete biological selectivity for T cells, B cells, and monocytes, but showed no activity on endothelial cells. Receptor binding studies indicated that IL-4/R121E retained physical interaction with IL-2Rgamma but not IL-13Ralpha; consistent with this observation, IL-4/R121E was an antagonist of IL-4-induced activity on endothelial cells. IL-4/R121E exhibits a spectrum of activities in vitro that suggest utility in the treatment of certain autoimmune diseases.     

Impaired priming on the general knowledge task in amnesia.

The status of priming on the general knowledge test was examined in amnesia. Twenty amnesic and 20 control participants studied words (e.g., CHEETAH) under semantic and nonsemantic encoding conditions and attempted to answer general knowledge questions (e.g., "What is the fastest animal on earth"?) under implicit and explicit retrieval instructions. The measure of memory was how many more test questions participants answered correctly using studied than nonstudied words. Amnesic patients showed impaired memory under implicit and explicit retrieval instructions. Control participants showed equal memory under implicit and explicit retrieval instructions, a result indicating that they engaged in explicit retrieval in both instruction conditions. General-knowledge priming appears to involve explicit retrieval that depends on medial-temporal and diencephalic regions damaged in amnesia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of scale‐up methods for dispersive mixing in twin‐screw extruders

Twin‐screw extrusion processes are commonly refined on laboratory‐scale extruders then scaled‐up to manufacturing systems. When using twin‐screw extrusion to compound filler into a polymer, the dispersion of the filler must be considered during scale‐up. In this work, two scale‐up methods are evaluated for how accurately they scale dispersion as measured by the Residence Stress Distribution, an experimental method that quantifies stress developed in a twin‐screw extruder. The first scale‐up method evaluated is the industry‐standard scaling based on maintaining equivalent volumetric flow rate across extruder sizes. Volumetric scaling is compared to a second, novel scale‐up method, the percent drag flow rule, which maintains the same degree of fill in the strongest dispersive screw elements on all extruder sizes. Both scale‐up rules have been used to scale between three extruder sizes and have been evaluated for how accurately the larger extruders recreate the dispersive mixing of the smallest machine. Results indicate that the percent drag flow scale‐up more accurately maintains dispersive mixing behavior than the volumetric scaling. Furthermore, percent drag flow scale‐up resulted in all three extruder sizes behaving similarly to changes in operating conditions. These results indicate that percent drag flow scale‐up is a valid technique to scale real industrial processes. POLYM. ENG. SCI., 57:345–354, 2017. © 2016 Society of Plastics Engineers     

Improving multifunctional behavior in structural electrolytes through copolymerization of structure- and conductivity-promoting monomers

Polymer electrolytes were developed to improve simultaneous demonstration of mechanical and electrochemical properties. Solvent-free random copolymers were synthesized using one monomer with poly(ethylene glycol) sidechains that promote lithium ion conduction and one crosslinking monomer that promotes high modulus. Sixty unique systems of monomer pairs were developed in this manner. The properties of the resulting copolymers were influenced by the monomer ratio and chemistry. The copolymers consistently exhibited improved electrochemical-mechanical multifunctionality with respect to the analogous homopolymers. The most promising systems included highly conductive components paired with highly structural components, suggesting that improved multifunctionality may be achieved through interpenetrating multicomponent systems in which each component demonstrates high efficiency in a single property. Electrochemical, mechanical, and viscoelastic properties are discussed with respect to composition and the glass transition temperature. Modeling of conductivity and modulus was employed to enable prediction of copolymer properties based on the ratio and properties of the constituents.     

Longitudinal MRI and cognitive change in healthy elderly.

Cross-sectional studies of normal aging indicate an association between memory and hippocampal volume, and between executive functioning and subcortical-frontal circuits. Much less is known, however, about the relationship between longitudinal MRI changes and cognitive decline. The authors hypothesized that longitudinal change in memory would be best predicted by change in hippocampal volumes, whereas change in executive functioning would be best predicted by cortical atrophy and progression of MRI markers of cerebrovascular disease. For this study, 50 healthy elderly subjects underwent structural MRI and cognitive testing at baseline and again at follow-up, with a mean follow-up interval of 45 months. Volumetric MRI measures were hippocampus, cortical gray matter, white matter signal hyperintensity (WMSH), and lacunae. Neuropsychological measures were psychometrically robust composite scores of episodic memory (MEM) and executive functioning (EXEC). Hierarchical multiple regression indicated that a decrease in hippocampus was associated with a decline in MEM, whereas decreased cortical gray matter and increased WMSH were independently associated with a decline in EXEC. Results suggest that in normal aging, cognitive functioning declines as cortical gray matter and hippocampus decrease, and WMSH increases. The association between WMSH and EXEC further highlights the cognitive sequealae associated with cerebrovascular disease in normal elderly. (PsycINFO Database Record (c) 2010 APA, all rights reserved)