Fluorescent Probes for Studying Thioamide Positional Effects on Proteolysis Reveal Insight into Resistance to Cysteine Proteases

Thioamide substitutions of the peptide backbone have been shown to reduce proteolytic degradation, and this property can be used to generate competitive protease inhibitors and to stabilize peptides toward degradation in vivo. Here, we present a straightforward sensor design that allows a systematic study of the positional effects of thioamide substitution by using real-time fluorescence. Thioamide scanning in peptide substrates of five papain family cysteine proteases demonstrates that a thioamide at or near the scissile bond can slow proteolysis in all cases, but that the magnitude of the effects varies with position and protease in spite of high sequence homology. Mechanistic investigation of papain proteolysis reveals that the thioamide effects derive from reductions in both affinity (K_M) and turnover number (k_cat). Computational modeling allows these effects to be understood based on disruption of key enzyme–substrate hydrogen bonds, providing a model for future rational use of thioamides to confer cysteine protease resistance.     

Comparison of PIV and PDA droplet velocity measurement techniques on two high-pressure water mist nozzles

The need for reliable measurement of droplet velocities and droplet size has increased with the more widespread use of water mist systems. Two optical measuring techniques have been investigated, Particle Image Velocimetry (PIV) and phase Doppler anemometry (PDA). Measurements have been performed on two high-pressure nozzles, a hollow cone nozzle and a full cone nozzle. Both methods performed well close to the nozzle and further away from the nozzle. In the intermediate region the results obtained with PIV are biased against the larger droplets. The two methods complement each other, PIV giving the instantaneous velocity field and PDA giving both the droplet velocity and droplet size at a point. The measurement indicates that higher throw length can be archived with a full cone nozzle compared to the hollow cone nozzle, if both nozzles have the same cone angle and flow rate.     

Statistical Threat Assessment for General Road Scenes Using Monte Carlo Sampling

This paper presents a threat-assessment algorithm for general road scenes. A road scene consists of a number of objects that are known, and the threat level of the scene is based on their current positions and velocities. The future driver inputs of the surrounding objects are unknown and are modeled as random variables. In order to capture realistic driver behavior, a dynamic driver model is implemented as a probabilistic prior, which computes the likelihood of a potential maneuver. A distribution of possible future scenarios can then be approximated using a Monte Carlo sampling. Based on this distribution, different threat measures can be computed, e.g., probability of collision or time to collision. Since the algorithm is based on the Monte Carlo sampling, it is computationally demanding, and several techniques are presented to increase performance without increasing computational load. The algorithm is intended both for online safety applications in a vehicle and for offline data analysis.     

Potential bioethanol and biogas production using lignocellulosic biomass from winter rye, oilseed rape and faba bean

To meet the increasing need for bioenergy several raw materials have to be considered for the production of e.g. bioethanol and biogas. In this study, three lignocellulosic raw materials were studied, i.e. (1) winter rye straw (Secale cereale L), (2) oilseed rape straw (Brassica napus L.) and (3) faba bean straw (Viciafaba L.). Their composition with regard to cellulose, hemicellulose, lignin, extractives and ash was evaluated, as well as their potential as raw materials for ethanol and biogas production. The materials were pretreated by wet oxidation using parameters previously found to be optimal for pretreatment of corn stover (195 °C, 15 min, 2 g l⁻¹ Na₂CO₃ and 12 bar oxygen). It was shown that pretreatment was necessary for ethanol production from all raw materials and gave increased biogas yield from winter rye straw. Neither biogas productivity nor yield from oilseed rape straw or faba bean straw was significantly affected by pretreatment. Ethanol was produced by the yeast Saccharomyces cerevisiae during simultaneous enzymatic hydrolysis of the solid material after wet oxidation with yields of 66%, 70% and 52% of theoretical for winter rye, oilseed rape and faba bean straw, respectively. Methane was produced with yields of 0.36, 0.42 and 0.44 l g⁻¹ volatile solids for winter rye, oilseed rape and faba bean straw, respectively, without pretreatment of the materials. However, biogas productivity was low and it took over 50 days to reach the final yield. It could be concluded that all three materials are possible raw materials for either biogas or ethanol production; however, improvement of biogas productivity or ethanol yield is necessary before an economical process can be achieved.     

An experimental and numerical study of shape stability in laminated timber columns

The study concerns the question of how the shape stability features of laminated columns of Norway spruce can be improved in terms of twist through optimal orientation of the individual laminates. Both experimental testing and numerical simulations were employed for evaluating twist stability. In all the columns studied, deformations were measured experimentally at different moisture content levels. A number of columns were also selected for numerical analysis in order to obtain a more thorough understanding of the twist behavior involved, their geometries and material properties of interest being determined. The experimental results showed the twist stability of the columns to be highly dependant upon the internal orientation of the individual laminates. It was also found that high quality columns in terms of shape stability could be manufactured, even when the center-core material has a strong twist tendency. The numerical simulations performed were in close agreement with the experimental results.     

Ideation methods applied in a cross-functional inter-organizational group: an exploratory case study from the railway sector

The conceptual design phase is a critical step, since it influences the subsequent steps during product development with regard to cost, quality and performance. Previous research has focused on cross-functional teams within an organization. However, many product development projects benefit from the participation of members from different organizations, not least during the conceptual design phase of technical products, where it is essential to consider different aspects of the product-to-be. Therefore, we conducted an in-depth case study of a cross-functional inter-organizational group testing ideation methods in a real-life setting within a development project in the railway sector. The group comprised participants from an infrastructure manager, a supplier, a maintenance contractor and research bodies. The tested ideation methods were Method 635, the gallery method and the SIL method. The participants found working in a cross-functional inter-organizational group to be beneficial both during the group-analysis of the topics and during the generation of ideas on how to address the ideation topic. Applying the ideation methods to the ideation topics facilitated the sharing of information between participants, and the diversity of the group manifested itself in several ways during ideation. Overall, the gallery method was most popular, and the SIL method was least popular among the participants.     

Treatment of acute upper gastrointestinal bleeding: a retrospective study of the results in a surgical clinic

OBJECTIVE: To review our results of the treatment of acute upper gastrointestinal bleeding since 1990. DESIGN: Retrospective study. SETTING: District hospital. SUBJECTS: 226 patients who presented with acute upper gastrointestinal bleeding between January 1990 and April 1992. INTERVENTIONS: Upper gastrointestinal endoscopy and, in 15 cases, emergency laparotomy. MAIN OUTCOME MEASURES: Morbidity and mortality, and the incidence of emergency operations. RESULTS: There were 5 deaths (4%) and 11 emergency operations (10%) in 1990, compared with one death (1%) and 4 operations (4%) during the subsequent 16 months. Duration of hospital stay was reduced from a mean of 7 days to a mean of 6 days and the amount of blood transfused from a mean of 3.4 units to a mean of 2.4 (p < 0.02) over the same period. 149 patients (66%) were over the age of 65 years, 82 (36%) were taking potentially dangerous drugs, and 129 (57%) had serious coexistent diseases. CONCLUSION: We conclude that the natural history of acute upper gastrointestinal bleeding may be changing, and that our "one team" approach comprising immediate resuscitation, urgent endoscopy, emergency operation when indicated, and intensive nursing, is responsible for the improvement in our results over the period of time studied.     

Slope constrained topology optimization

The problem of minimum compliance topology optimization of an elastic continuum is considered. A general continuous density–energy relation is assumed, including variable thickness sheet models and artificial power laws. To ensure existence of solutions, the design set is restricted by enforcing pointwise bounds on the density slopes. A finite element discretization procedure is described, and a proof of convergence of finite element solutions to exact solutions is given, as well as numerical examples obtained by a continuation/SLP (sequential linear programming) method. The convergence proof implies that checkerboard patterns and other numerical anomalies will not be present, or at least, that they can be made arbitrarily weak. © 1998 John Wiley & Sons, Ltd.     

SO2 promoted oxidation of ethyl acetate, ethanol and propane

The effect of SO₂ addition on the oxidation of ethyl acetate, ethanol, propane and propene, over Pt/γ-Al₂O₃ and Pt/SiO₂ has been investigated. The reactants (300–800 vol. ppm) were mixed with air and led through the catalyst bed. The conversions below and above light-off were recorded both in the absence and in the presence of 1–100 vol. ppm SO₂. For the alumina-supported catalyst, the conversion of ethyl acetate, ethanol and propane was promoted by the addition of SO₂, while the conversion of propene was inhibited. The effect of SO₂ was reversible, i.e. the conversion of the reactants returned towards the initial values when SO₂ was turned off. However, this recovery was quite slow. The oxidation of propane was inhibited by water, both in absence and presence of SO₂. For the silica-supported catalyst no significant effect of SO₂ could be observed on the conversion of ethyl acetate, ethanol or propane, whereas the conversion of propene was inhibited by the presence of SO₂. In situ FTIR measurements revealed the presence of surface sulphates on the Pt/γ-Al₂O₃ catalyst with and after SO₂ addition. It is proposed that these sulphate groups enhance the oxidation of propane, ethyl acetate and ethanol by creating additional reaction pathways to Pt on the surface of the Pt/γ-Al₂O₃ catalyst.