Hydrophobic interaction chromatography of soluble interleukin I receptor type II to reveal chemical degradations resulting in loss of potency

A hydrophobic interaction chromatography method was developed to analyze recombinant soluble Interleukin 1 receptor type II (sIL-1R type II) drug substance and assess the stability of the drug under accelerated degradation studies. HIC resolved the degraded molecules into three peaks. A combination of several analytical techniques, including cyanogen bromide cleavage, reversed-phase chromatography, mass spectrometry, and N-terminal sequencing, were used to identify the origins of these peaks. We found that accelerated degradation resulted from three different events, deamidation and isomerization at asparagine 317 (Asn317), C-terminal cleavage, and aggregation. The iso-aspartate 317 (iso-Asp317)-containing species were shown to elute in HIC peak I and the Asp317-containing species in HIC peak II, respectively. Deamidation-isomerization to iso-Asp317, but not deamidation to Asp317, resulted in altered retention time on HIC companied by loss of potency, presumably by introducing a significant conformational change. CNBr C-terminal analysis showed that the inactive HIC peak I consisted of sIL-1R type II with "large" C-terminal truncations of 13 or 14 amino acids, whereas the active HIC peak II contained C-terminally full length and "small" C-terminal clips of two amino acids. Molecular modeling indicates that the short loop D317-S320, in the third domain of IL-1R type II, has a crucial impact on the stability of the molecule.     

Fireside Corrosion in Oxy-fuel Combustion of Coal

Oxy-fuel combustion is burning a fuel in oxygen rather than air for ease of capture of CO₂ from for reuse or sequestration. Corrosion issues associated with the environment change (replacement of much of the N₂ with CO₂ and higher sulfur levels) from air- to oxy-firing were examined. Alloys studied included model Fe–Cr alloys and commercial ferritic steels, austenitic steels, and nickel base superalloys. The corrosion behavior is described in terms of corrosion rates, scale morphologies, and scale/ash interactions for the different environmental conditions. Evidence was found for a threshold for severe attack between 10^?4 and 10^?3 atm of SO₃ at 700 °C.     

Evaluation of hydrogen and methanol fuel cell performance of sulfonated diels alder poly(phenylene) membranes

Hydrogen fuel cell performance of sulfonated diels alder poly(phenylene) (SDAPP) with IECs ≥ 1.8 meq g⁻¹ is comparable to Nafion 212 under fully humidified conditions at 80 °C. However, as relative humidity is reduced, performance loss is substantial for SDAPP when compared to Nafion 212. This loss can be attributed to the large drop in proton conductivity in SDAPP as relative humidity is reduced; the proton conductivity of SDAPP with an IEC of 2.3 meq g⁻¹ dropped from 0.117 S cm⁻¹ to 0.001 S cm⁻¹ as the relative humidity was reduced from 100% to 25% at 80 °C. Methanol fuel cell experiments using 3 M methanol result in a 60 mV performance improvement at 25 mA cm⁻² when using SDAPP with an IEC of 1.2 meq g⁻¹ instead of Nafion 212. This improvement is due to lower methanol permeability of SDAPP (1.4 meq g⁻¹) over Nafion 212, with SDAPP films having methanol permeabilities less than 25% of Nafion 212.     

Developmental relations between depressive symptoms, minor hassles, and major events from adolescence through age 30 years.

Stress generation and stress exposure models of the relations among depressive symptoms, minor hassles, and major event stress were investigated among 815 community-dwelling participants. Autoregressive latent trajectory models were constructed to examine latent growth patterns from ages 15 years to 30 years and to test 1-year lagged, reciprocal paths between depressive symptoms and stress constructs. Results indicated significant cross-sectional and longitudinal associations between depressive symptoms and both stress constructs at the latent level. At the manifest level, lagged paths from hassles at 1 year to depressive symptoms at the next year were significant between ages 17 years and 24 years. Significant cross-sectional paths between major events and depressive symptoms were found between ages 24 years and 28 years, and modest support was found for lagged paths from depressive symptoms to major events 1 year later. Findings generally suggest a high degree of covariation in depressive symptoms and stress concurrently and over time. One-year lagged predictive effects net of the associations between individuals' latent trajectories appear to be weak, constrained to specific time periods, and most consistent with a stress exposure effect of hassles on depressive symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An expert system for the compilation of engineering specification documents

An expert advisor (SPECIFAC) has been developed to assist design engineers in the creation of written engineering specification documents. A ‘mix & match’ style of clause library is used to provide a framework for the particular specifications. A proprietary shell was employed to build the advisor and the shell has been linked with a professional word processor to perform text handling. The advisor seeks to suggest clauses that should be included, based on pre-defined associations with relevant criteria.

Knowledge representation was facilitated by the use of a two-stage process. First, a conceptual picture of the knowledge was built up to assist in the acquisition, structuring and coding of the knowledge. Second, a shell-dependent coding scheme was enacted.

This paper describes the design and operation of the expert system and explains how it improves upon existing methods. Some of the main features are considered in detail and the issues surrounding the important design decisions are discussed.

The advisor was developed as a pilot system for British Rail, Civil Engineering Department. It has resulted in resources being committed to implement SPECIFAC on an operational basis.     

Mechanisms in the simultaneous erosion-oxidation attack of nickel and cobalt at high temperature

An apparatus is described by which a specimen may be exposed to a well-defined erosive gas stream containing 20 μm alumina particles. Samples of nickel and cobalt were exposed to conditions of erosion and high temperature oxidation simultaneously, using 90 deg impact angle, at velocities up to 140 m/s^-1 and at temperatures up to 800 °C. From the results of erosion kinetics, surface morphologies, and cross section metallographic observations it is concluded that several definite regimes of interaction between erosion and oxidation exist. These regimes are described in qualitative terms, and it is shown how they arise as a result of the balance between the relative intensities of the erosion and oxidation processes.     

Doping-induced bandwidth enhancement in metal-semiconductor-metal photodetectors

A novel technique is demonstrated for enhancing metal-semiconductor-metal photodetector bandwidths without reducing responsivity. The authors have observed bandwidth increases of up to 10 GHz from control to enhanced photodetectors which corresponds to about 70% enhancement. This technique involves modifying the internal electric field structure, by introducing a buried n-type doped layer that is completely depleted, to reduce the relatively long hole transit time.<>