An Extensible Meta-Model for Program Analysis

Software maintenance tools for program analysis and refactoring rely on a metamodel capturing the relevant properties of programs. However, what is considered relevant may change when the tools are extended with new analyses, refactorings, and new programming languages. This paper proposes a language independent metamodel and an architecture to construct instances thereof, which is extensible for new analyses, refactorings, and new front-ends of programming languages. Due to the loose coupling between analysis, refactoring, and front-end components, new components can be added independently and reuse existing ones. Two maintenance tools implementing the metamodel and the architecture, VIZZANALYZER and X-DEVELOP, serve as proof of concept.     

An Extensible Metamodel for Program Analysis (abstract only)

Software maintenance tools for program analysis and refactoring rely on a metamodel capturing the relevant properties of programs. However, what is considered relevant may change when the tools are extended with new analyses, refactorings, and new programming languages. This paper proposes a language independent metamodel and an architecture to construct instances thereof, which is extensible for new analyses, refactorings, and new front-ends of programming languages. Due to the loose coupling between analysis, refactoring, and front-end components, new components can be added independently and reuse existing ones. Two maintenance tools implementing the metamodel and the architecture, VlZZANALYZER and X-DEVELOP, serve as proof of concept.     

Distribution Modeling of Nonlinear Inverse Controllers Under a Bayesian Framework

The inverse controller is traditionally assumed to be a deterministic function. This paper presents a pedagogical methodology for estimating the stochastic model of the inverse controller. The proposed method is based on Bayes' theorem. Using Bayes' rule to obtain the stochastic model of the inverse controller allows the use of knowledge of uncertainty from both the inverse and the forward model in estimating the optimal control signal. The paper presents the methodology for general nonlinear systems and is demonstrated on nonlinear single-input-single-output (SISO) and multiple-input-multiple-output (MIMO) examples     

The Dependence of the Melting Temperature of Cobalt–Carbon Eutectic on the Morphology of its Microstructure

Fixed points provide a reliable way to realize and verify temperature scales. High-temperature fixed points are being developed based upon alloys, since single-phase materials are impractical to use above the copper freezing point. In particular, eutectic alloys have been shown to be sufficiently reproducible to warrant consideration as a way to significantly improve high-temperature metrology. However, eutectic alloys have certain characteristics requiring that they are used differently from the current ITS-90 fixed points. As their freezing temperature depends on the freezing rate, the melting temperature is preferred, though it has been shown that for some alloys, notably iron–carbon and cobalt–carbon, the apparent melting temperature can depend on the rate of the preceding freeze. This behavior will need to be explained and quantified if such fixed points are to be acceptable. The effect of varying the freezing rate on subsequent melting has been investigated for cobalt–carbon eutectic fixed points. The apparent melting temperature varies by up to 50 mK. Measurements were made of two different fixed-point blackbodies with very similar results. Optical microscopy of samples produced at different freeze rates shows a change in scale of the microstructure. Electron back-scatter diffraction (EBSD) shows evidence of high levels of residual strain in rapidly frozen samples. The effect of annealing on the melting behavior and microstructure has also been investigated. It is suggested that disordered phase boundaries and residual strain lead to changes in the melting behavior as nonequilibrium conditions may lead to a significant level of pre-melting. Whether this actually changes the liquidus temperature, or whether the melting temperature variation is due to the way the melting point is defined, is also discussed. The variation requires consideration if the highest accuracy is to be achieved, and will be a contributory factor to any uncertainty budget.     

Success of surgery for primary aldosteronism judged by residual autonomous aldosterone production

Since February 1996 we have prospectively assessed residual adrenal autonomy by the fludrocortisone suppression test (FST) in 23 patients 3 months after unilateral adrenalectomy for Conn syndrome and in 45 patients after a longer interval. In regard to blood pressure, 36 (53%) patients were cured of hypertension and the remaining 32 (47%) patients had improved hypertension control at the time of their latest postoperative clinical assessment. In regard to the outcome of surgery, patients who achieved normal suppressibility of aldosterone were regarded as cured, and those who had greater suppressibility after surgery were considered improved. Time since surgery for the whole group averaged 26 months. By these biochemical criteria, 42 patients (62%) were cured by surgery, and the rest improved; 16 (76%) of 21 women were cured, and 26 (55%) of 47 men. The women (mean +/- SD age 47 +/- 11 years) were significantly (p < 0.05) younger than the men (52 +/- 9 years). Preoperative aldosterone levels before and after FST were similar in the cured and improved groups and fell significantly (p < 0.01) in both groups following surgery. After surgical reduction of autonomous aldosterone production, mean plasma renin activity levels increased sixfold in the cured group and threefold in the improved group. Surgical mortality in this group of 68 patients with Conn syndrome was zero.     

Application of Biological Acidification to Improve the Quality and Processability of Wort Produced from 50% Raw Barley

In this study four strains of lactic acid bacteria (LAB) were chosen to bioacidify a mash containing 50% barley and 50% malt. The strains were isolated from malted and unmalted barley and assayed for extracellular enzymatic activities (proteases, amylases, β‐glucanases). The biologically acidified mash was compared to a chemically acidified mash, 100% malt mash un‐acidified and 50% malt and 50% barley mash unacidified. Characteristics such as pH, extract, colour, viscosity, total soluble nitrogen (TSN), free amino nitrogen (FAN), apparent fermentability, β‐glucan and lautering performance of the resultant worts were determined. A model lautering system replicating one used in a brewery was designed and built in University College Cork (UCC) to measure the lautering performance of the bioacidified mashes. The new system was compared to the filtration method used in EBC method 4.5.1. Overall the addition of LAB to bioacidify a mash of 50% barley and 50% malt resulted in faster filtration times, which correlated with decreased β‐glucan levels. Proteolytic LAB had a positive influence on the quality of wort and resulted in increased FAN levels. Lighter colour worts were observed along with increased extract levels.     

Subcellular localization of prostaglandin endoperoxide H synthases-1 and -2 by immunoelectron microscopy

Prostaglandin endoperoxide H synthases-1 and -2 (PGHS-1 and -2) are the major targets of nonsteroidal anti-inflammatory drugs like aspirin and ibuprofen. These enzymes catalyze the committed step in the formation of prostanoids from arachidonic acid. Although PGHS-1 and -2 are similar biochemically, a number of studies suggest that PGHS-1 and PGHS-2 function independently to form prostanoids that subserve different cellular functions. We have hypothesized that these isozymes may reside, at least in part, in different subcellular compartments and that their compartmentation may affect their access to arachidonic acid and serve to separate the functions of the enzymes. To obtain high resolution data on the subcellular locations of PGHS-1 and -2, we employed immunoelectron microscopy with multiple antibodies specific to each isozyme. Both PGHS-1 and -2 were found on the lumenal surfaces of the endoplasmic reticulum (ER) and nuclear envelope of human monocytes, murine NIH 3T3 cells, and human umbilical vein endothelial cells. Within the nuclear envelope, PGHS-1 and -2 were present on both the inner and outer nuclear membranes and in similar proportions. Western blotting data showed a similar distribution of PGHS-1 and -2 in subcellular fractions, and product analysis using isozyme-specific inhibitors suggested that both enzymes generate the same products in NIH 3T3 cells. Thus, we are unable to attribute the independent functioning of PGHS-1 and PGHS-2 to differences in their subcellular locations. Instead, the independent operation of these isozymes may be attributable to subtle kinetic differences (e.g. negative allosteric regulation of PGHS-1 at low concentrations of arachidonate (500-1000 nM)). A further conclusion of importance from a cell biological perspective is that membrane proteins such as PGHS-1 and -2, which are located on the lumenal surface of the ER, are able to diffuse freely among the ER and the inner and outer membranes of the nuclear envelope.     

Identification of a gene that causes primary open angle glaucoma

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.     

Live animal performance, carcass traits, and meat palatability of calf- and yearling-fed cloned steers

Two groups of Brangus steers produced by nuclear transplantation cloning were used in parallel studies investigating the impact of calf- and yearling-feeding. The first group (n = 8) were fed as calves (CF; n = 4) or yearlings (YF; n = 4) to a constant age end point of 16 mo. The second group (n = 10) were fed as calves (CF; n = 5) or yearlings (YF; n = 5) to a constant live weight end point (530 kg). When slaughtered at the same age, CF and YF steers did not differ (P > .05) in feedlot ADG, but the CF steers were heavier and had higher dressing percentages, numeric yield grades, and quality grades (P < .05). Top loin steaks from the groups of steers did not differ (P > .05) in palatability traits. When fed to a constant live weight, the YF steers gained more rapidly (P < .05) and had lower (P < .05) numeric yield grades than did CF steers. Again CF steers had higher (P < .05) dressing percentages. There was no difference (P > .05) between the treatments in carcass quality grade or meat palatability characteristics. Thus, when finished to a constant weight end point, YF steers gained more rapidly, with no adverse effects on carcass quality grade or palatability traits; however, CF steers consistently produced higher dressing percentages, largely due to greater external fatness.     

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study

Simultaneous extracellular recordings were performed in stratum radiatum and stratum pyramidale of hippocampal slices 7 days following unilateral intracerebroventricular injections of kainic acid. In this ex vivo experimental model of human temporal lobe epilepsy, stimulation of the surviving commissural fibres in stratum radiatum produced graded epileptiform activity in the CA1 area. The oxidizing reagent 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) acting at NMDA receptors redox sites decreases NMDA receptor-mediated responses by half and suppresses evoked epileptiform discharges. We have examined the effect of DTNB on NMDA-dependent bidirectional synaptic plasticity and EPSP/spike coupling. DTNB treatment did not prevent either long-term potentiation induced by tetanic stimulation or long-term depression induced by low frequency stimulation of field EPSPs. Application of DTNB alone did not induce EPSP/spike dissociation. However, both high and low frequency stimulations induced EPSP/spike potentiation indicating that neurons had a high probability to discharge in synchrony. These results suggest that oxidizing reagents may provide novel antiepileptic treatments since they decrease NMDA-dependent evoked epileptiform activity but do not interfere with either NMDA-dependent synaptic plasticity or the probability of synchronous discharge.