An assessment of electric vehicles: technology, infrastructure requirements, greenhouse-gas emissions, petroleum use, material use, lifetime cost, consumer acceptance and policy initiatives.

Concerns about climate change, urban air pollution and dependence on unstable and expensive supplies of foreign oil have led policy-makers and researchers to investigate alternatives to conventional petroleum-fuelled internal-combustion-engine vehicles in transportation. Because vehicles that get some or all of their power from an electric drivetrain can have low or even zero emissions of greenhouse gases (GHGs) and urban air pollutants, and can consume little or no petroleum, there is considerable interest in developing and evaluating advanced electric vehicles (EVs), including pure battery-electric vehicles, plug-in hybrid electric vehicles and hydrogen fuel-cell electric vehicles. To help researchers and policy-makers assess the potential of EVs to mitigate climate change and reduce petroleum use, this paper discusses the technology of EVs, the infrastructure needed for their development, impacts on emissions of GHGs, petroleum use, materials use, lifetime costs, consumer acceptance and policy considerations.

An investigation into the influence of boundary condition specification in finite difference methods on the behaviour of passive and active neuronal models.

Neuronal models provide a major aid to understanding the behaviour of individual neurons and networks of neurons. The solution of the model equations by finite difference methods is widespread because of the inherent simplicity of the technique. Error in the finite difference approach due to spatial and temporal discretisation is shown to be equivalent to a mis-specification of membrane current density. The effect of this mis-specification on the accuracy of the solution to the model equations is shown to depend on the structure of the model and its input, as well as the size of the discretisation intervals themselves. Through a theoretical analysis, illustrated by a number of examples on passive and active dendrites, this article demonstrates that the accuracy with which core current is implemented numerically at segment end-points in elementary models influences the behaviour of the numerical solution of these models, and consequently any physiological conclusions drawn from them.

The interaction between membrane kinetics and membrane geometry in the transmission of action potentials in non-uniform excitable fibres: a finite element approach.

By solving the partial differential equations for an axonal segment using a finite element method, the interaction between membrane kinetics and axonal inhomogeneities, measured by their influence on propagated action potentials and stochastic spike trains, is investigated for Morris-Lecar and Hodgkin-Huxley membrane models. To facilitate comparisons of both kinetic models, parameter values are matched to give approximately the same speed for propagated action potentials. In all cases examined, the Morris-Lecar membrane model is more sensitive to geometric inhomogeneities than the comparable Hodgkin-Huxley membrane model. This difference in sensitivity can, in part, be attributed to significant differences in the membrane current supplied by each kinetic model ahead of the action potential. Also, the Morris-Lecar membrane model did not generate reflected action potentials whereas these were observed over a narrow range of geometric parameters for the comparable Hodgkin-Huxley membrane model. Simulations using stochastic spike train input showed that the presence of a sharp flare could significantly modify the statistical characteristics of the spike train output. The behaviour of action potentials governed by Morris-Lecar kinetics were more sensitive to changes in axonal geometry than those generated by comparable Hodgkin-Huxley kinetics. As a consequence of the fine balance between membrane kinetics and axon geometry, local changes in membrane properties, such as those caused by synaptic activity, can be expected to have a strong influence on the behaviour of stochastic spike trains at regions of changing axonal geometry.

Dendritic subunits determined by dendritic morphology.

A theoretical framework is presented in which arbitrarily branched dendritic structures with nonhomogeneous membrane properties and nonuniform geometry can be transformed into an equivalent unbranched structure (equivalent cable). Rall's equivalent cylinder is seen to be one part of the equivalent cable in the special case of dendrites satisfying the Rall criteria. The relation between the branched dendrite and its equivalent unbranched representation is uniquely defined by an invertible mapping that connects configurations of inputs on the branched structure with those on the unbranched structure, and conversely. This mapping provides a new definition of dendritic subunit and provides a mechanism for characterizing local and nonlocal signal processing within dendritic structures.

Equivalence transformations for dendritic Y-junctions: a new definition of dendritic sub-unit.

A sequence of equivalence transformations is used to represent the mathematical model of a simply branched neuron with non-homogeneous membrane properties and non-uniform geometry by an entirely equivalent model of an unbranched structure. The analysis indicates how neuronal morphology, in combination with its biophysical properties, shapes neuronal output in response to current input. The equivalence transformations described here reveal the types of operations that are likely to feature in the analysis of complex multi-branched structures, neuronal or otherwise. These transformations provide a new definition of dendritic sub-unit and a basis of a mechanism for characterising local and non-local signal processing within dendritic structures. It is anticipated that the capacity to transform biological neurons into an equivalent unbranched structure will make an important contribution to the understanding of the functional role of neuron geometry as well as to the construction of silicon neurons with realistic biological properties.

The effect of severe undernutrition, and subsequent refeeding on digestive function in human patients.

BACKGROUND: Severe undernutrition may adversely affect gut function. AIMS: To investigate the effects of severe undernutrition and subsequent refeeding on human digestive function. METHODS: Severely undernourished patients (body mass index (BMI) < 17 kg/m2) were studied before, and after a period of intensive nutritional support. Standard intestinal absorption tests (faecal fat and urinary xylose excretion), pentagastrin-stimulated acid secretion, and cholecystokinin octapeptide (CCK-8)-stimulated pancreatic enzyme secretion tests were performed. In addition, duodenal biopies were taken to assess gut mucosal morphology. Findings were evaluated in comparison to a group of normal healthy volunteers. RESULTS: Mean BMI of the patients prior to nutritional support was 13.41 kg/m2, with improvement to 16.12 kg/m2 after. Duodenal histology showed evidence of villous atrophy in six of 14 (43%) undernourished patients. Mean xylose excretion following a 5 g oral dose was 0.62 g/5 h in the group of undernourished patients prior to nutritional support (normal > 1 g/5 h), with improvement to 1.40 g/5 h (P < 0.01) after feeding. Maximal gastric acid output was significantly impaired in the undernourished group, as compared to the controls (6.94 mEq/l vs 25.53 mEq/l, P < 0.02), with a significant improvement to 12.30 mEq/l (P < 0.05) following nutritional support. Pancreatic enzyme output was significantly reduced (amylase 830.9 U/h vs 2304 U/h, P < 0.01; lipase 38.0 U/h vs 118.6 U/h, P < 0.01; trypsin 119.7 U/h vs 341.4 U/h, P < 0.01). Following a period of nutritional support there was a significant improvement in amylase and lipase outputs to 1819 U/h and 85.5 U/h, respectively (P < 0.01). These levels were not significantly different from the normal controls. Trypsin output, however, remained significantly impaired at 174.3 U/h (P < 0.01). CONCLUSIONS: Severe undernutrition is associated with significant impairment of digestive function, with improvement occurring following nutritional support. These changes may affect initial tolerance to enteral feeding, particularly in those patients with co-existent gut disease.

The influence of intravenous infusions of glucose and amino acids of pancreatic enzyme and mucosal protein synthesis in human subjects.

BACKGROUND: Animal studies have shown that the synthesis and secretion of pancreatic enzymes and the turnover of mucosal proteins is strongly influenced by diet. METHODS: To determine whether the absorbed products of digestion are responsible for these changes, we investigated in groups of five healthy volunteers, the effects of i.v. infusions of amino acids (0.08 g/kg/h) and glucose (0.3 g/kg/h) on pancreatic enzyme and mucosal protein synthesis. Proteins were labeled in vivo by a 4-hours i.v. infusion of 14C-leucine and the enteric infusion of 3H-leucine tracer, during simultaneous cholecystokinin stimulation and duodenal collection of secreted pancreatic enzymes. Labeling of mucosal proteins was measured by endoscopic biopsy. RESULTS: The amino acid infusions elevated plasma amino acid levels, and the glucose infusions increased both glucose and insulin concentrations. The rates for amylase and trypsin secretion were significantly lower during the first 2 hours of glucose infusion and the rate of synthesis of trypsin was delayed by i.v. amino acid infusions from 52.1 +/- 4.1 to 77.6 +/- 8.5 minutes. Mucosal protein turnover rates were unaffected. 3H-labeling via the enteral route showed similar enzyme synthesis rates but variable mucosal incorporation rates. CONCLUSIONS: I.v. nutrients do not appear to stimulate the synthesis of pancreatic and mucosal proteins in human subjects.

Effect of buprenorphine on pancreatic enzyme synthesis and secretion in normal rats and rats with acute edematous pancreatitis.

Pancreatic enzyme secretion is inhibited during acute pancreatitis, resulting in an increase in acinar zymogen content. Since the premature activation of zymogens has been assigned a central role in the pathogenesis of acute pancreatitis, minimizing the amount of stored zymogens might lead to less severe acute pancreatitis. Inhibition of enzyme synthesis or stimulation of enzyme secretion would result in reduction of zymogen stores. Opiates have a varying effect on pancreatic secretion, depending on the dosage, site of administration, and presence of pancreatic stimulants. The effect of opiates and acute pancreatitis on individual pancreatic enzyme synthesis is unknown. The following study was undertaken in order to examine the effects of an opiate on pancreatic enzyme secretion and synthesis during experimental acute pancreatitis. Four groups of rats were studied. Group I received cerulein (25 micrograms/kg); group II received an opiate, buprenorphine (BPN, 0.5 mg/kg); and group III received cerulein and BPN. Drugs were dissolved in gelatin/saline and injected subcutaneously. A control group (group IV) received only gelatin/saline. Rats were sacrificed 4 hr after injection, and pancreatic mass was measured. Pancreatic acini were prepared and assayed for amylase and DNA content. Amylase, trypsinogen, chymotrypsinogen and lipase synthesis, and amylase secretion were measured for 2 hr. Results showed that, compared to controls, acini of rats with AP had increased amylase content, a finding consistent with decreased in vivo amylase secretion. Total protein and individual enzyme synthesis rates were significantly lower in the acini of the rats with AP than in those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenal juice total protein and pancreatic enzyme synthesis, turnover, and secretion in patients after acute pancreatitis.

It is controversial whether acute pancreatitis has longterm effects on pancreatic function. Pancreatic enzyme synthesis, turnover, and secretion were measured in 10 patients in clinical remission who had had one or more (one to six) attacks of acute alcoholic pancreatitis. The studies were done between two and 29 months after the most recent attack. A control group included five patients with no evidence of pancreatic disease. A four hour primed/continuous intravenous infusion of [14C]L-leucine tracer was given with secretin (2 U/kg/h) and cholecystokinin (0.5 U/kg/h) and secreted duodenal juice aspirated. Amylase and trypsin were extracted from duodenal juice by affinity chromatography, permitting measurement of the rate of isotope incorporation into total protein, amylase, and trypsin. The results showed non-parallel changes in enzyme synthesis and turnover with decreases in total enzyme protein and amylase synthesis and turnover but preservation of trypsin synthesis and turnover. The low turnover rates may be ascribed to continuing pancreatic cell malfunction after recovery from acute alcoholic pancreatitis and suggest that the decreased amylase secretion rates are partly a consequence of impaired amylase synthesis and not simply because of loss of pancreatic tissue.

The effect of fuel source on amino acid metabolism in critically ill patients.

The ideal energy substrate for critically ill patients receiving total parenteral nutrition (TPN) remains controversial. While glucose has been proved to have nitrogen sparing properties in postoperative patients, critically ill patients tolerate glucose loads poorly and fat appears to be an obligatory fuel in sepsis. Furthermore, it is not yet certain whether the changes in whole body protein metabolism induced by critical illness are influenced by the nature of the TPN provided. This study was conducted on patients admitted to a surgical intensive care unit (SICU) who fulfilled the criteria of requiring TPN and mechanical ventilation for at least four days. Patients were randomized to receive either glucose (G) or equicaloric proportions of glucose and lipid (GF) as an intravenous energy source. TPN was commenced early, within 24-48 hr of trauma or surgery and admission to the ICU. Nonprotein calorie intake was 125% of calculated basal energy expenditure. Nitrogen balance was calculated from 24-hr urinary urea excretion. Protein synthesis, turnover, and catabolism were measured on Day 4 of the study using an established radiolabeled C14-leucine technique. Degree of sepsis and illness were calculated using published scores. Fifty patients entered the trial but 32 were excluded by Day 4. Of the 18 patients completing an initial four day study, eight went on to complete a second study on the alternative regimen--a total of 26 studies (14 G, 12 GF). Net protein synthesis was achieved in 18 studies (12 G, 6 FG) and positive nitrogen balance by Day 4 in 22 studies. Four patients on the G regimen were withdrawn due to glucose intolerance while none of the patients on GF developed glucose intolerance or hyperlipidaemia. Both whole body protein synthesis and catabolism correlated significantly with degree of sepsis. The type of TPN fuel used, G and GF, did not appear to influence whole body protein dynamics, both regimens achieving greatly improved whole body protein kinetics.

Measurement of pancreatic enzyme synthesis in humans. Problems in patients with calcific pancreatitis.

Earlier studies have suggested that the rate of incorporation of labeled amino acids into duodenal juice proteins during pancreatic stimulation may be used to calculate pancreatic enzyme synthesis and function. In the present study, a pulse/4 h continuous intravenous infusion of 14C labeled leucine was used to compare synthesis rates in 6 patients with chronic calcific pancreatis(CP) to 4 controls. Analysis of duodenal juice protein demonstrated a delay of approximately 1 h in the appearance of labeled proteins, followed by a linear increase in specific activity, allowing calculation of synthesis that varied between 2.6-2.8 h in controls and 6-48 h in CP. The protein in controls was representative of enzyme protein, but that of CP was not, since it was heavily contaminated with albumin (up to 50%). The results indicate that enzyme secreted during the first hour of stimulation is derived from pancreatic stores and that the synthesis rate of enzymes secreted thereafter is approximately 2.7 h in normal humans. The method was, however, unable to determine rates in patients with CP owing to heavy contamination of enzymes with exudative proteins.

Single step affinity chromatographic purification of human alpha-amylase from aspirated duodenal juice and its application in the measurement of pancreatic alpha-amylase synthesis rates in man.

Human alpha-amylase was purified from aspirated duodenal juice to electrophoretic homogeneity in a single step by affinity chromatography with the competitive inhibitor acarbose (IC50 = 1.22 mumol/l) as ligand. Duodenal juice was applied to an agarose resin to which acarbose had been coupled covalently via a 1.9 nm spacer group. Pure alpha-amylase, eluted with free acarbose, had a molecular mass of 55,000, and isoelectrofocusing revealed the presence of six isozymes with pI values of 7.3, 6.8, 6.7, 6.5, 6.4 and 6.3, all of which possessed amylase activity based on positive starch/iodine staining. The potential usefulness of this one-step purification procedure in the measurement of pancreatic alpha-amylase synthesis rates was evaluated in two control patients with non-pancreatic disease. Aspirated duodenal juice was obtained during a pulse/continuous intravenous 4 h infusion of [14C]leucine together with secretin and pancreozymin, and alpha-amylase purified using our protocol. Pancreatic alpha-amylase synthesis rates were determined from the rate of incorporation of [14C]leucine into alpha-amylase; values of 4.4 and 5.1 h were obtained for the two control patients.

Severe malnutrition associated with alpha-heavy chain disease: response to tetracycline and intensive nutritional support.

A 20-yr-old black male was admitted with a 5-month history of profound weight loss and diarrhea. Appetite and dietary intake had been remarkably well preserved up until the week before admission. The severity of his depletion was evidenced by a body weight of only 38% of standard, multiple electrolyte deficiencies, and reduced metabolic expenditure, protein turnover, protein synthesis, and pancreatic function. Immunological defects included diminished lymphocyte numbers, lymphocyte transformation, gamma-globulin concentration, and cell-mediated immunity. A diagnosis of alpha-heavy chain disease (alpha-HCD) was made on endoscopic duodenal biopsy and serology--lymphoma being excluded by scanning and laparotomy. Treatment consisted initially of intravenous nutrition (because of the extreme malnutrition, severe diarrhea, and malabsorption of fluid, electrolytes, carbohydrates, and fat) and oral tetracycline. Response was dramatic, with a doubling of body weight within 6 wk, and resolution of malabsorption. He was discharged on a normal diet and long-term oral tetracycline (250 mg/day), and at 1-yr follow-up, nutritional status and gut function were normal despite persistence of duodenal mucosal abnormalities and markers of alpha-HCD and bacterial overgrowth. These results suggest that the malabsorption initially identified in this patient was not due simply to the mucosal abnormalities that characterize alpha-HCD, but was more a consequence of the superimposition of nutrient maldigestion and absorption resulting from the extreme state of protein deficiency and its effects on gut and pancreatic function.