The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase

Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver-related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate/NHC*-Ag-OAc (SBC3) is a reversible, high affinity inhibitor of E. coli thioredoxin reductase (TrxR; K_i=10.8±1.2 nM). Minimal inhibition concentration (MIC) tests with different E. coli and P. aeruginosa strains demonstrated that SBC3 can efficiently inhibit bacterial cell growth, especially in combination with established antibiotics like gentamicin. Our results show that SBC3 is a promising antibiotic drug candidate targeting bacterial TrxR.     

Fringing in tubular permanent-magnet machines: Part I. Magnetic field distribution, flux linkage, and thrust force

This paper extends an analysis developed for tubular permanent-magnet machines to account for the effect of fringing associated with the finite length of the ferromagnetic armature core. The magnetic field distribution, established by using an analytical technique formulated in the cylindrical coordinate system, provides an accurate means of evaluating the effect of the fringing flux on the thrust force and the back-electromotive force. Finite-element calculations confirm the analytically derived results. In Part II of the paper, the analysis is used to predict the cogging force that results from end effects and to facilitate minimization of the force.     

Test Case Generation as an AI Planning Problem

While Artificial Intelligence techniques have been applied to a variety of software engineering applications, the area of automated software testing remains largely unexplored. Yet, test cases for certain types of systems (e.g., those with command language interfaces and transaction based systems) are similar to plans. We have exploited this similarity by constructing an automated test case generator with an AI planning system at its core. We compared the functionality and output of two systems, one based on Software Engineering techniques and the other on planning, for a real application: the StorageTek robot tape library command language. From this, we showed that AI planning is a viable technique for test case generation and that the two approaches are complementary in their capabilities.     

Kinetic analysis of papaya proteinase omega

Papaya proteinase omega (pp omega) has been purified from dried latex both by immunoaffinity and traditional methods. Kinetic analysis revealed that (1), the pp omega-catalysed hydrolysis of N-benzoyl-L-arginine p-nitroanilide (BApNA) has a lower specificity (kcat/Km) than the same reaction catalysed by papain; (2), the pp omega-catalysed hydrolysis of a tripeptide substrate having phenylalanine at the second position (S2-site) showed a more similar specificity to that catalysed by papain; (3), the significant difference between the two enzymes is that steady state kinetics with both L-BApNA and a tripeptide enables the identification in pp omega of other ionizations affecting binding. The active sites of papain and pp omega can therefore be distinguished by pH-dependence of kcat/Km.     

The effect of interfacial energy and phase fraction on the particle shape and the dihedral angles in two-phase small particles containing a cusp-oriented interface; computational model

The equilibrium shape and dihedral angles at the solid–liquid–vapor tri-junctions of two-phase alloy small particles containing a cusp-oriented interface were modeled as a function of phase fraction, surface energy and the interfacial energy. The calculation was applied to different combinations of surface and/or interfacial energies to demonstrate the various possible particle shapes and dihedral angles that result for two-phase particles. The dihedral angles at the tri-junction vary with the phase fraction, due to the coupling between the relative amounts of each phase, interfacial energy relative to the two surface energies and the equilibrium conditions at the tri-junction. These features can be used to find the ratio of the interfacial energy to the surface energies of two-phase particles for any state of matter.     

Design optimization of radially magnetized, iron-cored, tubular permanent-magnet machines and drive systems

In this paper we deduce, from analytical field solutions, the influence of leading design parameters on the performance of a radially magnetized, iron-cored, tubular permanent-magnet machine and its drive system. We derive analytical formulas for predicting the open-circuit electromotive force, the thrust force, the iron loss, and the winding resistance and inductances, as well as the converter losses. The force density, the machine and drive system efficiencies, and the power factor and converter volt-ampere (VA) rating are established as functions of a set of machine dimensional ratios, with due account of magnetic saturation and subject to a specified thermal constraint. We validate the utility and accuracy of the analytically derived formulas by finite-element calculations. Finally, we show that the design optimization of such a linear drive system must account for the losses and VA rating of the converter as well as the design parameters of the tubular machine.     

Renal length in sickle cell disease: observations from a cohort study

Renal length has been measured by ultrasound in 237 subjects with homozygous sickle cell (SS) disease, 147 with sickle cell-hemoglobin C (SC) disease, and in 78 age-matched controls with a normal hemoglobin (AA) genotype. As expected, renal length increased with age in all genotypes but mean length was significantly greater in SS disease compared with SC disease (mean difference 4.3 mm after adjustment for height) and significantly greater in both genotypes than in AA controls (SS/AA difference 9.2 mm, SC/AA difference 5.0 mm after adjustment for height). Examination of relationships between renal length and some hematological indices (hemoglobin, fetal hemoglobin, reticulocyte counts, alpha thalassemia status) in SS or SC disease showed only a significant negative correlation with hemoglobin and positive correlation with reticulocyte count in SS disease. Further analysis suggested that the stronger relationship was between renal length and high reticulocyte count. The mechanism of renal enlargement is unknown although glomerular hypertrophy and increased renal blood volume are likely contributors.     

Value of transcranial Doppler indices in predicting raised ICP in infantile hydrocephalus. A study with review of the literature

Cerebral hemodynamic changes in infants with progressive hydrocephalus have been studied with the transcranial Doppler (TCD) technique. Several authors have referred to the correlation between the hemodynamic changes and increased intracranial pressure (ICP). Despite conflicting conclusions on the value of pulsatility index (PI) and resistance index (RI) measurements for monitoring infantile hydrocephalus, these pulsatility indices are the most commonly used for this purpose. Although clinical signs of raised ICP are highly variable and unreliable in infants, assumptions have been made in most of the studies about the presence of elevated ICP on the basis of the patient's clinical state. Few studies have reported on actual ICP values, however, and a direct relationship between ICP and TCD changes has never been adequately demonstrated. In the present study, this relationship was investigated in long-term simultaneous TCD/ICP measurements, in an attempt to develop a noninvasive method of monitoring the effect of ICP on intracranial hemodynamics. Two groups of data sets were established. Group I consisted of pre- and postoperative (shunt implantation) TCD/ICP measurements. Group II were long-term simultaneous TCD/ICP recordings showing significant ICP variations. In most of the postoperative measurements there was a decrease in the average PI and RI values. The correlation between PI or RI and ICP in the long-term simultaneous recordings, however, was generally poor. The risk of obtaining false positive or false negative PI or RI values in short-term measurements was also demonstrated. It can be concluded from our results, besides the wide range of reference values for the Doppler indices and extracranial influences upon them, that the present Doppler indices are inadequate for monitoring the complex intracranial dynamic responses in patients with raised ICP.     

Proceedings of the Joint US/EU Workshop: urinary biomarkers to detect significant effects of environmental and occupational exposure to nephrotoxins

Tear cytokines and growth factors are likely to modulate the wound healing process following corneal epithelial injury. Hepatocyte growth factor (HGF) is a paracrine mediator of epithelial proliferation, motility, and differentiation that is produced by keratocytes and the lacrimal gland. Tear samples were collected preoperatively and one, two, and seven days postoperatively in eyes undergoing excimer laser surface ablation [photorefractive keratoplasty (PRK) or phototherapeutic keratoplasty (PTK)]. Tear HGF concentration was measured with a sensitive ELISA assay. Tear HGF production was calculated using the tear flow rate in the collection capillary and HGF concentration. Although the instantaneous concentration of HGF in tears decreased significantly in the days following PRK, a large increase in tear flow resulted in a marked increase in HGF bioavailability. The heparin-binding characteristics of HGF would result in increased binding to glycosaminoglycans and other heparin-like matrix components and, therefore, increased growth factor availability to the cognate recptor. This is the first report documenting changes in tear film HGF production. HGF may have an important function in maintenance and wound healing of the ocular surface epithelium since HGF is present in the normal tear film and the HGF secretion rate increases markedly in parallel with aqueous tear production following corneal surgical injury.