Negative Cooperativity in NAD(P)H Quinone Oxidoreductase 1 (NQO1)

NAD(P)H quinone oxidoreductase-1 (NQO1) is a homodimeric protein that acts as a detoxifying enzyme or as a chaperone protein. Dicourmarol interacts with NQO1 at the NAD(P)H binding site and can both inhibit enzyme activity and modulate the interaction of NQO1 with other proteins. We show that the binding of dicoumarol and related compounds to NQO1 generates negative cooperativity between the monomers. This does not occur in the presence of the reducing cofactor, NAD(P)H, alone. Alteration of Gly150 (but not Gly149 or Gly174) abolished the dicoumarol-induced negative cooperativity. Analysis of the dynamics of NQO1 with the Gaussian network model indicates a high degree of collective motion by monomers and domains within NQO1. Ligand binding is predicted to alter NQO1 dynamics both proximal to the ligand binding site and remotely, close to the second binding site. Thus, drug-induced modulation of protein motion might contribute to the biological effects of putative inhibitors of NQO1.     

Remote monitoring technology and servitised strategies – factors characterising the organisational application

This paper introduces factors that characterise the organisational application of remote monitoring technology (RMT) for servitised strategies. Factors were developed through in-depth case studies of four manufacturers operating in aerospace, industrial equipment, marine and transportation sector. They suggest a very complex, multi-levelled, multifaceted and circular relationship between RMT and servitisation. When unfolding this relationship we need to consider: the value proposition, nature of the product and its hierarchical position in the customer’s business, RMT functionality, type and amount of data required, and a number of other factors that either complement or constrain the use of RMT. By providing the necessary lenses, the proposed factors can help in exploring this complexity. One such exploration questions our understanding of outcome-based contracting.     

Effects of hip-loading input on simulated wear of Al2O3–PTFE materials

The objective of this study was to compare the effects of static, sinusoidal and physiological load-profiles on wear of Al₂O₃–PTFE materials. This was an accelerated wear model of clinical relevance. In nine experiments, the peak load-levels were varied from 1 to 4 kN in a hip simulator with multi-directional kinematics and with bovine serum used as the lubricant. Systematic wear differences were checked using three sizes of femoral heads in each experiment. The Paul load-profile used was found to be more aggressive than sinusoidal, raising the polytetrafluoroethylene (PTFE) wear-rates by 28%. The PTFE cups showed a very mild response to increased load magnitudes, only 11–20% increase evident in volumetric wear per 1 kN increase in load. One recommendation was that simulator wear-studies adopt a 0.25–2.5 kN Paul load-profile as their standard. An experiment with 0.84 kN constant-load also performed satisfactorily, with PTFE wear-rates actually higher than with the 1 kN sine and Paul load-profiles. Some wear anomalies were encountered due to the use of serum lubrication. Combinations of large head size, high load-magnitudes, the Paul load-profile and the high serum protein concentrations used in this study were at times contributing factors. Use of low-protein serum solution may be advisable for wear studies, not only to properly simulate the polymeric wear characteristics but also to minimize the degradation artifacts more prevalent in higher protein-concentrations.     

METHODS FOR PROCESSING EXPERIMENTAL DRYING KINETICS DATA

This paper provides a review of methods for processing the data obtained from drying kinetics rigs and pilot-plant trials. Different methods for fitting and smoothing drying curves are compared, aiming to generate curves that are usable in industrial design without losing vital information by oversmoothing. Generally, plots of drying rate need more smoothing than moisture content data. Special care is needed at low drying rates and moisture contents. It is shown that some popular methods of processing data, including use of smoothing programs or fitting to equations, may generate drying curves which are seriously in error. Recommendations are made for reliable methods of processing data; cubic splines have been found to be effective for moisture-time curves. It is important to retain the original raw experimental data as a cross-check, as smoothing can conceal valuable information.     

Measurement of hydrodynamic data of gas-phase polymerization reactors using non-intrusive methods

The hydrodynamic characteristics of polyethylene resins are studied in detail through a combination of different techniques in our laboratory. Computer Assisted Tomography is used to determine voidage distribution under different operating conditions. Radioactive particle tracking is used to determine the solid particle trajectories, the horizontal and vertical velocities of the solids and the residence time distribution of the solids. X-ray fluoroscopy is used to determine bubble frequency and velocity. All these techniques are then combined with the information obtained through monitoring pressure fluctuations in the fluidized bed columns. All experiments are performed in Plexiglas columns of diameters that vary between 10 and 30 cm in diameter. The materials used are polyethylene and air, respectively. The combination of these techniques provides the unique opportunity to study the fluidized bed systems in great detail. Unfortunately, all techniques cannot be implemented in a single experiment. As a result, the same experiment is repeated as many times as necessary to collect the required data. The column is moved from one imaging system to the next and the experiment is repeated under the same operating conditions. It is believed that the data collected can be used as if all the data were collected during the same test. This paper presents preliminary experimental results for each set of experiments along with the nature and limitations of each set of experimental data. The results from each different system are combined in an effort to describe the complex hydrodynamics of the bed. The incremental information obtained in each set of experiments compared to the macroscopic measurements (flow rate and pressure drop) is demonstrated.     

Accuracy and reproducibility of the electrochemical profiler

The electrochemical CV profiler (ECV) plays a key role in the characterisation of compound epitaxial structures. Epi suppliers and their customers need a procedure that ensures that the carrier concentration in any given layer lies within agreed limits. Carrier concentrations in optoelectronic device structures and HBTs are usually specified around ±20%, with tighter limits being applied to MESFET and HEMT structures. By understanding the factors that affect the accuracy and reproducibility of the ECV method, the standard deviation of the measurement, for uniformly doped epilayers, can be reduced to around 2%.     

Modernist Town Planning And Metropolitan Planning: Reflections From Gordon Stephenson

Gordon Stephenson died on March 29th this year, aged 88. We were fortunate enough to have spoken in depth with Stephenson late in 1995. We dedicate this piece to a person who was described in a recent obituary in The Australian (10.4.97) as “one of the great town planners of this century”.     

Optimal fluid control can normalize cardiovascular risk markers and limit left ventricular hypertrophy in thrice weekly dialysis patients

Increased hemodialysis frequency can make fluid overload easier to treat, although most patients are still treated thrice weekly. Chronic fluid overload is associated with left ventricular hypertrophy and elevated serum cardiac biomarkers, recognized as mortality risk factors. Serum cardiac troponin T (cTnT), N‐terminal prohormone brain natriuretic peptide (NT‐proBNP), left ventricular mass index by cardiac magnetic imaging, and ambulatory blood pressure was measured in 30 thrice weekly hemodiafiltration patients. Time‐averaged fluid overload (TAFO) was quantified by bioimpedance spectroscopy. In the study group, left ventricular hypertrophy was found to be 26% by cardiac magnetic resonance. Ambulatory blood pressure was 130 mmHg (112–151) requiring a low equivalent dose of medication of 0.25 units (0–1). Significantly, lower levels of left ventricular mass index (P < 0.05) were associated in those patients with TAFO <1 L or NT‐proBNP <1200 pg/mL or cTnT <0.1 ug/L. In the subgroups, 16 patients had normal cTnT (<0.03 ug/L), 16 patients had NT‐proBNP <400 pg/mL, and 20 patients had TAFO <1 L. Nine patients had both cTnT <0.03 ug/L and NT‐proBNP <400 pg/mL. Normally hydrated thrice‐weekly hemodiafiltration patients can have cardiac biomarker and TAFO levels indistinguishable from the normal healthy population. Obtaining TAFO by bioimpedance monitoring can offer a practical alternative to serum cardiac biomarkers.