Studies of the increased gastrin release associated with Helicobacter pylori infection in duodenal ulcer disease

Duodenal ulcer disease is strongly associated with infection of the gastric antrum by Helicobacter pylori (H. pylori), possibly through the exaggerated plasma gastrin response associated with this organism. The work described in this thesis investigates aspects of both the cause and the effect of this increase in gastrin secretion in duodenal ulcer patients. Chapter 2 provides further evidence that H pylori is responsible for the exaggerated gastrin response since when duodenal ulcers are healed by sucralfate, which does not eradicate H pylori, the gastrin response is unchanged. However, unexpectedly, this treatment decreased basal gastric acid secretion. The results of studies described in chapter 3 suggest that the exaggerated gastrin response occurs by a mechanism independent of luminal pH and with no apparent change in the meal-stimulated secretion of acid or pepsin. Despite the fall in meal-stimulated gastrin the peak acid output also remained unchanged a year after the eradication of H pylori (chapter 4) but the basal acid output appeared to decrease in this small study. The work described in chapter 5 confirms this fact; successful eradication of the organism decreased both basal plasma gastrin concentrations and basal acid secretion, without altering the sensitivity of the parietal cell to circulating gastrin. This may be how the eradication of H pylori prevents ulcer recurrences. The cause of the hypergastrinaemia was addressed in the final chapters. Methods were developed to measure somatostatin mRNA from endoscopic biopsies as a surrogate marker of local somatostatin release. It was then established that the hypergastrinaemia seen in pernicious anaemia is associated with a deficiency of somatostatin mRNA (chapter 6). Finally, an increase in both somatostatin-secreting cells and somatostatin mRNA was found after the eradication of H pylori, implying that this bacterium increases gastrin release by the depletion of somatostatin

Market Segmentation and Energy Efficiency Program Design

The purpose of this paper is to describe the existing state of market segmentation among California’s electric utilities, with an emphasis on the investor-owned utilities (IOUs). In addition, how segmentation is applied in various other economic sectors is reviewed, in part to provide a framework to identify potential practices that could be effectively adopted in the utility industry

Fluorometabolite biosynthesis in streptomyces cattleya

Nature has evolved the ability to form a C-F bond, as exemplified by the bacterium Streptomyces cattleya, which elaborates fluoroacetate (FAc) and 4-fluorothreomne (4- FT). The mechanism of this bond formation are unknown. This thesis probes the biosynthesis of fluoroacetate and 4-fiuorothreonine and in doing so explores the C-F bond forming process. Feeding stable isotope enriched primary metabolites to S. cattleya, followed by (^19)F NMR and GCMS analysis of the resultant fluorometabolites, highlights the role of the glycolytic pathway in delivering a substrate for fluorination. 3-Fluoro-l- hydroxypropan-2-one was synthesised and feeding studies eliminate this as the initial product of fluorination. Fluoroacetaldehyde was identified as a common fluorinated intermediate in the biosynthesis of both FAc and 4-FT. Whole cell studies demonstrate the rapid oxidation of fluoroacetaldehyde to FAc. 4-FT is produced in low quantities by S. cattleya incubated with fluoroacetaldehyde. The synthesis and feeding of [1-(^2)H]- fluoroacetaldehyde provide evidence that the resultant 4-FT is biosynthesised from fluoroacetaldehyde. The biotransformation from fluoroacetaldehyde to FAc was shown in cell free studies to be mediated by an aldehyde dehydrogenase, requiring NAD(^4) as a co-factor. The substrate specificity of fluoroacetaldehyde dehydrogenase was probed by spectrophotometrically monitoring the production of NADH in the presence of different aldehydes. Further cell free experiments probed the biosynthetic origins of fluoroacetaldehyde. Glycolaldehyde phosphate and various phosphorylated glycolytic intermediates were incubated with cell free extracts of S. cattleya and a plethora of co-factors. In the absence of observing fluorination activity, it was shown that the cell free extract acts to dephosphorylate the substrates. The putative role of glycolaldehyde phosphate was explored by feeding isotopically labelled glycolaldehydes to whole cells of the bacterium. The results were not consistent with direct conversion from glycolaldehyde phosphate to fluoroacetaldehyde

Profit Patterns Across American Agriculture

To remain viable, agriculture in each location must offer returns that are competitive with those from alternative investments and sufficient to cover producers' financial obligations. Economic theory says that rates of return converge over time as resources flow into more-profitable industries and out of less-profitable industries, causing factor price changes. Both traditional growth and trade theories say factor markets will adjust to equalize commodity returns over time. This study examines spatial relationships in agriculture's profitability over time. Results show temporal and spatial convergence of returns consistent with trade and development theories. However, there are profit patterns unique to state/regional agriculture, raising policy implications.convergence, return on assets, "risk of ruin", Agribusiness,

A Re-emergent Analysis of Early Algebraic Learning

In this paper, we discuss a novel approach for collaborative retrospective analysis. One researcher was directly involved in a classroom teaching experiment, adopting an emergent perspective as an interpreter-witness of classroom interactions during a four-week algebra instructional unit with sixth-grade students. The other researcher experienced and analyzed the data in reverse chronological order. We describe how this re-emergent perspective revealed aspects of students’ early algebraic reasoning

Some buffet response characteristics of a twin-vertical-tail configuration

A rigid, 1/6 size, full span model of an F-18 airplane was fitted with flexible vertical tails of two different levels of stiffness that were buffet tested in the Langley Transonic Dynamics Tunnel. Vertical tail buffet response results that were obtained over the range of angles of attack from -10 to 40 degs, and over the range of Mach numbers from 0.30 to 0.95 are presented. These results indicate the following: (1) the response occurs in the first bending mode; (2) the response increases with increasing dynamic pressure, but changes in response are not linearly proportional to the changes in dynamic pressure; (3) the response is larger at M = 0.30 than it is at the higher Mach numbers; (4) the maximum intensity of the buffeting is described as heavy to severe using an assessment criteria proposed by another investigator; and (5) the data at different dynamic pressures and for the different tails correlate reasonably well using the buffet excitation parameter derived from the dynamic analysis of buffeting

REGIONAL CHANGES IN THE DISTRIBUTION OF NET VALUE ADDED IN U.S. AGRICULTURE, 1960-2002

This paper examines the effects of structural changes on the distribution of net value added and the difference between net value added and agricultural income over time. We present and discuss the changes in the distribution of net value added (land, labor, capital, and farm operator income) over time. Net value added by U.S. agriculture grew significantly from $18 billion to 1960 to$95 billion in 1996. We examine regional differences in net value added using the Theil entropy measure. The inequality (dispersion) of net value added increased over time. The increased inequality represented both increases in regional dispersion in net value added and increases in the average inequality in net value added in each region. Thus, the net value added is becoming less alike across the U.S. We also examined the inequality in the components of net value added. The greatest dispersion occurred in returns to land followed by returns to capital. Therefore, changes in the dispersion of net value added by agriculture are explained by differences in the payments to non-operator landlords and to capital.Agricultural Finance,

Synthesis and evaluation of N⁶-substituted apioadenosines as potential adenosine A₃ receptor modulators

Adenosine receptors (ARs) trigger signal transduction pathways inside the cell when activated by extracellular adenosine. Selective modulation of the A(3)AR subtype may be beneficial in controlling diseases such as colorectal cancer and rheumatoid arthritis. Here, we report the synthesis and evaluation of beta-D-apio-D-furano- and alpha-D-apio-L-furanoadenosines and derivatives thereof. Introduction of a 2-methoxy-5-chlorobenzyl group at N-6 of beta-D-apio-D-furanoadenosine afforded an A(3)AR antagonist (10c, K = 0.98 mu M), while a similar modification of an alpha-D-apio-L-furanoadenosine gave rise to a partial agonist (11c, K-i = 3.07 mu M). The structural basis for this difference was examined by docking to an A(3)AR model; the antagonist lacked a crucial interaction with Thr94

Development and testing of a scale model Clamshell Mucker, and validation by discrete element modelling.

Shaft sinking is an important part of the mining process, of which “mucking” (clearing the broken rock from the bottom of the shaft) plays a critical role. The aim of the research was to develop a scaled experimental replica of the so-called Clamshell Mucker and compare its performance, over a range of operating parameters, with those yielded by numerical simulations, for the long-term purpose of validating the simulation as a tool for optimizing the design of full-scale machines. Towards this end a scaled experimental rig of the clamshell mucker was developed and tested over an appropriate range of geometrical and operating parameters, for two different materials: hard plastic balls and thereafter 13 mm decomposed granite stone. Hydraulic actuator forces were established by measuring line pressures, while angular rotation of the jaws of the mucker was monitored using an angular potentiometer. Simple analysis provided a relationship between actuator force and torque on the buckets. The stone in the muck reservoir was agitated after each test run, to ensure random particle arrangements with no structuring, and a constant digging depth. Testing of the hard plastic balls was used to establish a qualitative comparison between Discrete Element Modelling (DEM) and physical testing, using both video and still photography comparisons, corresponding to the teeth initially touching the surface with a bucket closing velocity of 20 deg/s. Heuristic correlations obtained by this means were generally favourable. Quantitative testing using 13 mm granite stone yielded the bucket closing torque variation with bucket angle for various combinations of:- (a) bucket closing velocity, (b) initial distance of the bucket from the muck pile, (c) proximity of the bucket to the side and front walls of the container, and (d) the angle at which bucket assembly enters the muck pile. The main set of tests took place with the bucket entering vertically and positioned in the middle of the bed. Three different initial distances from the surface to the starting position of the bucket teeth were investigated (20 mm, 10 mm and 0 mm), with bucket angular velocities of 10 deg/s, 15 deg/s and 20 deg/s. Thereafter, testing was conducted at the forward (polycarbonate) boundary of the container and one of the lateral boundaries (steel) respectively, each for a single bucket velocity of 20 deg/s and covering the three above-mentioned initial distances from the surface. This testing was performed in an attempt to simulate the proximity effects that would be encountered in practice - for example, digging close to a side wall. Finally, torque variations with bucket angle were established at four different angles of attack (0±, 5±, 15± and 30±), at a constant bucket closing velocity of 20 deg/s, with the closest portion of the bucket initially touching the surface. Data was generally interpreted in the context of the fact the torque required to rotate the buckets appears to depend on an interplay between:- (a) the level of fluidization between particles in the bed, increasing with bucket closing velocity, results in a reduced torque; (b) particulate congestion, increasing as the initial distance from the surface of the granular material decreases, results in an increased torque; and (c) the momentum required to move the particles and change their direction, increasing with bucket velocity, results in an increased torque. Accordingly, for the larger initial distances from the surface momentum effects are dominant, generally leading to an increase of torque with angular velocity. However, as the initial distance reduces, congestion becomes increasingly important, until for the zero initial separation case, the lowest angular velocity yields the highest torques, probably because fluidization has been inhibited. Because particle to boundary interactions have lower friction than particle to particle interactions, torques in the presence of boundaries were lower than for the middle position in the initial stages. Beyond a certain point, proximity to the forward boundary led to congestion with a commensurate increase in torque above that of the middle case, whereas proximity to the lateral boundary led to no congestion, so the torques remained generally lower than for the middle case. When considering the effects of angle of penetration, it was found that the largest angle of penetration (30±) gave the highest torque in the initial stages, probably because the highest volumes of material are captured relative to other angles of attack. Beyond a bucket angle of about 14± congestion becomes increasingly dominant, with the rise in torque due to this effect generally delayed with increasing angles of attack. This phenomenon was ascribed to the fact that in all cases other than zero angle of penetration, only one jaw initially enters the material, with the second following at a later stage: therefore particles escape to a free surface for the mid-range bucket angles, with the onset of congestion commensurately delayed to the larger ones. Comparisons between DEM data and measurements for various testing parameters showed that the simulated and physical results display similar values of torque towards the beginning and end of the digging motion, but DEM predictions are low in the middle of the range. This is thought to arise primarily from the fact that simplified particle geometries (smooth, with no sharp edges) were incorporated into the DEM model because of computational resource limitations, whereas the real granular particles have sharp edges and are blocky, thus increasing particle interlocking effects and the high level of congestion frequently exhibited in the physical experimentation. This effect was generally reflected by poor comparisons between DEM data and experimentation in the context of torque variations with velocity in the middle range of angular positions. Because the coefficients of rolling friction and restitution were obtained from published data, additional simplified simulations were run to determine the sensitivity of these parameters (in addition to static friction coefficient, for comparative purposes) on the force characteristics of the model. It was established that specifically chosen percentage changes in all of the parameter values relative to the base system led to percentages of force deviation that were at least 3 to 5 times smaller, reinforcing the inference that particle interlocking effects were the dominant reason for poor mid-range correlations between experimentation and the DEM modelling. The maximum energy to fill the buckets was required at a zero angle of penetration, diminishing significantly to an angle of about 15± and then increasing once again. This trend is attributed to the fact that the 0± case is most affected by congestion, whereas the larger angles of attack (beyond about 20±) cause the weight of the material to significantly affect the energy required to close the buckets. While it was considered possible that similar trends would be observed in practice, that could potentially reflect in improved operational guidelines for the mucking process, further analysis suggested that an energy saving of less than 814.3 kJ might be attainable for clearing a 6 m diameter shaft during a single cycle. While this appears to be inconsequential in the broader context, it should be subjected to a more comprehensive investigation in the context of full-scale cleaning strategies. It is recommended that:- (a) the test facility be modified to extend the range of bucket angular velocities; (b) testing be conducted with a broader range of particle sizes; (c) research into the interlocking and frictional effects of rock be pursued, to create representative particulate shapes as input to the DEM model; (d) higher friction coefficients be attempted as a means of artificially compensating for interlocking effects that are impractical to achieve because of computer resource limitations; and (e) testing be conducted with a range of different bucket shapes and sizes for the purpose of optimizing the design by way of minimizing structural stresses and the specific energies required to collect individual loads