We present new rigid body potentials that should favour efficient self-assembly of pentagonal and hexagonal pyramids into icosahedral shells over a wide range of temperature. By adding an extra repulsive site opposite the existing apex sites of the pyramids considered in a previously published model, frustrated energy landscapes are transformed into systems identified with self-assembling properties. The extra interaction may be considered analogous to a hydrophobic-hydrophilic repulsion, as in micelle formation.

The behavior of small water clusters, (H2O)n, n=2-5 and n=8, in a uniform electric field is investigated for three related rigid-body models. Changes in the properties of the low-lying potential energy minima and the rearrangement pathways between them are examined. Results for certain structural transitions are compared with recent ab initio calculations. The models are found to give qualitatively similar trends, and there is some evidence that as the applied field strength is increased the quantitative differences between the models are also reduced.

Background: Iohexol clearance is an accurate and precise exogenous marker of glomerular filtration rate (GFR), but protocols are generally lengthy or require multiple sampling. Shorter or simpler protocols would be more practicable. Methods: Two clearance estimates, two weeks apart, were undertaken in 11 healthy individuals and 26 diabetic patients with minimal to moderate renal impairment (chronic kidney disease stages 1-3). Blood specimens withdrawn at 60, 90, 120, 150, 180 and 240 min post-iohexol were analysed for iohexol. Results: Visit 1 demonstrated excellent correlation with visit 2 (slope 1.00, confidence interval [CI] 0.88 to 1.13, intercept 0.94 mL/min/1.73 m2, CI -9.9 to 11.8, P=0.43). The within-individual coefficient of variation (CV) of the 240 min reference method was 5.4% at a mean GFR of 84.1 mL/min/1.73 m2. Single point estimates between 120 and 240 min had CVs of 4.5-7.0%, and did not differ from the reference method CV by more than 2.0 mL/min/1.73 m2. Two and three point estimates in the interval 60-120 min post iohexol injection offered no advantages over these single-point estimates and overestimated at lower GFRs. Conclusions: An iohexol clearance estimate of GFR derived from a single sample taken between 2 to 4 h after infusion may provide a suitable tool for routine clinical use.

We study the water octamer in a uniform electric field using the all-exchanges parallel tempering Monte Carlo method in the canonical ensemble. The heat capacity, quenched energy configurations, and the order parameter Q(4) are employed to understand the phase changes observed as a function of temperature and the strength of the applied electric field. At a low field strength of 0.1 V A(-1) a solidlike to liquidlike "melting" transition is detected. The corresponding heat capacity peak appears around 206 K, where Q(4) shows a significant change of slope. For E> or =0.5 V A(-1) such features are absent. However, at E=0.5 V A(-1) we find a solidlike to solidlike transition between cubic and extended structures around T approximately 25 K.

Normothermic preservation has been shown to be advantageous in an experimental model of preservation of non-heart-beating donor (NHBD) livers, which have undergone significant warm ischemic injury. The logistics of clinical organ retrieval might dictate a period of cold preservation prior to warm perfusion. We have investigated the effects of a brief period of cold preservation on NHBD livers prior to normothermic preservation. Porcine livers were subjected to 60 minutes of warm ischaemia and then assigned to following groups: Group W (n = 5), normothermic preservation for 24 hours; and Group C (n = 6), cold preservation in University of Wisconsin solution for 1 hour followed by normothermic preservation for 23 hours (total preservation time, 24 hours). Synthetic function (bile production and factor V production) and cellular damage were compared on the ex vivo circuit during preservation. There was no significant difference in the synthetic function of the livers (bile production and factor V production). Markers of hepatocellular damage (alanine aminotransferase and aspartate aminotransferase release), sinusoidal endothelial cell dysfunction (hyaluronic acid), and Kupffer cell injury (beta-galactosidase) were significantly higher in Group C. The histology of the livers at the end of perfusion was similar. In conclusion, a brief-period cold preservation prior to normothermic perfusion maintains the synthetic function and metabolic activity but results in significant hepatocellular damage, sinusoidal endothelial cell dysfunction, and Kupffer cell injury. Transplant studies are required to establish whether livers treated in this way are viable for transplantation.

Candidate global minimum structures are reported for (H2O)n clusters for n⩽21 described by the rigid-body TIP5P potential. These structures are compared with previously published results for the related TIP4P potential, and with ab initio calculations at the MP2 level. The variation of the energy gap from the putative global minimum to the next-lowest structure as a function of system size is analysed. Comparisons with previously reported structural trends in water clusters are made.

The properties of low-lying stationary points on the potential energy surfaces of singly protonated water clusters (H(2)O)(n)H(+), are investigated using an empirical valence bond potential. Candidate global minima are reported for n=2-4, 8, and 20-22. For n=8, the variation in the energies and structures of low-lying minima with the number of valence bond states included in the model is studied. For n=4 and 8, disconnectivity graphs are also reported and are compared to results for the equivalent neutral water clusters as described by the rigid TIP3P potential. For the larger clusters, n=20-22, the structural properties of the low energy minima are compared with recently published spectroscopic data on these systems. The observed differences between the n=20 and n=21 systems are qualitatively reproduced by the model potential, but the similarities between the n=21 and n=22 systems are not.

BACKGROUND:The enzyme beta-galactosidase present in the Kupffer cells of the liver has potential as a marker of liver dysfunction prior to transplantation. Spectrophotometric methods have insufficient sensitivity. METHODS:Fluorimetric methods have the required sensitivity and we have optimised such a method in a microtitre plate format to improve its utility. beta-galactosidase acts on the substrate 4-methylumbelliferyl-galactoside (MUG) to produce 4-methylumbelliferone (4-MU), detected fluorimetrically with excitation wavelength 355 nm and emission wavelength 460 nm. RESULTS:Reaction conditions in a citrate-phosphate buffer were optimised to give maximal enzyme activity: pH was optimal at 4.4 (range investigated 3.6-5.0) and substrate concentration at 3.33 mmol/l. A small specimen volume (10 microl) in 80 microl of substrate solution produced adequate fluorescent yield after an incubation period of 30 to 60 min at 37 degrees C. Reaction was terminated by addition of 200 microl of glycine-NaOH, pH 12.8. The assay is linear to 3,000 U/ml. The intra-assay coefficient of variation (CV%) at 50, 502, and 2,012 U/ml was 4.7, 3.1, and 3.4, respectively (n=10). Inter-assay CV% at 51, 496, and 1,986 U/ml was 7.0, 4.0, and 3.9, respectively (n=10). CONCLUSIONS:The assay has greater practical utility and demonstrated significant differences in the perfusate beta-galactosidase between cold-stored and warm-perfused livers in a porcine model of transplantation.

BACKGROUND:To minimize the ischemia-reperfusion injury that occurs to the liver with the current method of preservation and transplantation, we have used an extracorporeal circuit to preserve the liver with normothermic, oxygenated, sanguineous perfusion. In this study, we directly compared preservation by the standard method of simple cold storage in University of Wisconsin (UW) solution with preservation by perfusion.METHODS:Porcine livers were harvested from large white sows weighing between 30 and 50 kg by the standard procedure for human retrieval. The livers were preserved for 24 hr by either cold storage in UW solution (n=5) or by perfusion with oxygenated autologous blood at body temperature (n=5). The extracorporeal circuit used included a centrifugal pump, heat exchanger, and oxygenator. Both groups were then tested on the circuit for a 24 hr reperfusion phase, analyzing synthetic function, metabolic capacity, hemodynamics, markers of hepatocyte and reperfusion injury, and histology.RESULTS:Livers preserved with normothermic perfusion were significantly superior (P=0.05) to cold-stored livers in terms of bile production, factor V production, glucose metabolism, and galactose clearance. Cold-stored livers showed significantly higher levels of hepatocellular enzymes in the perfusate and were found to have significantly more damage by a blinded histological scoring system.CONCLUSIONS:Normothermic sanguineous oxygenated perfusion is a superior method of preservation compared with simple cold storage in UW solution. In addition, perfusion allows the possibility to assess viability of the graft before transplantation.

Glycohydrolases are a group of enzymes contained predominantly within lysosomes, which are released during Kupffer cell activation or death. One of these, beta-galactosidase, has been proposed as a marker of ischemia-reperfusion injury in the liver because Kupffer cell activation represents a primary event in the injurious reperfusion cascade. In this study, we compared B-galactosidase with more traditional indicators of liver injury and function in a porcine model of liver preservation. Porcine livers were allocated into two groups: group C (n = 5), preserved in University of Wisconsin solution by standard cold storage for 24 hours, and group W (n = 5), perfused with oxygenated autologous blood on an extracorporeal circuit for 24 hours. Both groups were subsequently tested on the circuit during a 24-hour reperfusion phase. The perfusate was sampled for levels of beta-galactosidase, as well as traditional markers of liver injury and function. A sharp increase in beta-galactosidase levels was seen on reperfusion of cold preserved livers to a level of 1,900 IU/mL. This contrasted dramatically with normothermically preserved livers, in which the level never exceeded 208 IU/mL (P =.002). beta-Galactosidase levels showed much earlier and greater increases compared with transaminase levels in livers injured by ischemia. A rapid elevation in beta-galactosidase levels corresponded well with poor liver function and more liver injury. Measurement of beta-galactosidase is a simple test that quantifies ischemia-reperfusion injury of preserved livers. It is more sensitive than transaminases, with faster and larger increases in levels after ischemic injury. It can be useful in assessing the viability of a liver during machine preservation.

In this note it is shown that if constant marginal costs find linear demand are assumed then it is possible to derive a simple relationship between monopoly welfare losses as a proportion of the value of sales and the level of elasticity in the monopoly outcome.

This article presents the results of an empirical study into the marketing of UK sport associations. A 44-item scale is used to investigate the extent to which UK sport associations are marketing-oriented. The results suggest a low degree of marketing orientation amongst such organisations. Key variables identified as influencing the degree of marketing orientation are the size of an association and respondents' subjective assessments of the spectating and playing status of their sport. The majority of sport associations possess only a limited understanding of marketing, and view the discipline principally as a promotional or money-making vehicle.