Bax-induced cell death in Candida albicans

Bax is a pro-apoptotic member of the Bcl-2 family of proteins involved in the regulation of genetically programmed cell death in mammalian cells. It has been shown that heterologous expression of Bax in several yeast species, such as Saccharomyces cerevisiae, Schizosaccharomyces pombe and Pichia pastoris, also induces cell death. In this study we investigated the effects of Bax expression in the pathogenic yeast Candida albicans. Cell death inducing expression of Bax required a synthetic BAX gene that was codon-optimized for expression in Candida albicans. Expression of this BAX gene resulted in growth inhibition and cell death. By fusing Bax with the yeast enhanced green fluorescent protein of Aequoria victoria, the cell death-inducing effect of Bax was increased due to reduced proteolytic degradation of Bax. Using this fusion protein we showed that, upon expression in C. albicans, Bax co-localizes with the mitochondria. Furthermore, we showed for the first time that expression of Bax in yeast causes the mitochondria, which are normally distributed throughout the cell, to cluster in the perinuclear region.     

Fabrics for testing the ignition propensity of cigarettes

This paper reports an analysis of data from a study conducted by the cigarette industry to determine whether the fabrics used in a measurement method for cigarette ignition propensity reasonably represent the ignition behaviour of actual upholstery fabrics. A ‘consistency score’ is defined to evaluate objectively the relative agreement of ignition test results on various test fabrics compared with the cotton duck fabrics used in the measurement method. Particular attention is paid to those cases where the cigarettes show statistically significant differences by the chi-squared test. This analysis finds that the aggregated set of 79 industry fabrics ranks the four test cigarettes in the same order as do the three cotton duck fabrics in the measurement method. Thus, to the extent that the industry set is representative of those fabrics used in upholstery, it would be proper to use the three test fabrics as surrogates for the purpose of determining the relative ignition propensity of a cigarette. The analysis does identify six to ten fabrics that would be expected to show persistent reversals compared to the aggregate ordering; however, three-fourths of the fabrics rank the cigarettes consistently with the cotton duck fabrics. © 1997 John Wiley & Sons, Ltd.     

A novel method for chip formation analyses in deep hole drilling with small diameters

Recent trends of downsizing and miniaturization of components, e.g. in the automotive industry for the manufacturing of fuel injectors or in the medical industry for the production of bone screws or surgical instruments, increase the importance of mechanical deep hole drilling with small diameters. Unfortunately, there are still some open challenges regarding this process. In addition to the unfavorable ratio of the cutting edge rounding to the achievable feed rates and undeformed chip thicknesses which results in significant mechanical tool loads, the control of the chip formation and the removal constitutes a major difficulty. The slender tool dimensions, especially the small cross sections of the chip flutes, necessitate a favorable chip formation to achieve the required process safety and productivity. Therefore, analyses of the chip formation, when machining difficult-to-cut materials provide the means for an effective process design. This analysis, however, is particularly difficult due to the closed operating zone. Quick-stop devices used for the chip formation analyses so far are limited in the tool diameter respectively the revolution speed. Furthermore the informative value is limited, because a quick-stop test takes a significant time to stop and thus the instantaneous cutting conditions during the tool retraction are altered. To overcome these restrictions, a new method for the analysis of the chip formation in small diameter deep hole drilling is presented in this paper. It is based on the utilization of a high-speed camera and tailored material samples. The experimental set-up and the results of first analyses conducted under minimum quantity lubrication are presented. The chip formation process is analyzed for the single-lip gun drilling of the nickel-based alloy Inconel718 and the bainitic steel 20MnCrMo7.     

Numerical modelling of three-dimension stress rotation ahead of an advancing tunnel face

As underground excavations and construction works progress into deeper and more complex geological environments, understanding the three-dimensional redistribution of excavation-induced stresses becomes essential given the adverse consequences such stresses will have on the host rock strength and the subsequent excavation stability. This paper presents the results from a detailed three-dimensional finite-element study, which explores near-field stress paths during the progressive advancement of a tunnel face. These results demonstrate that as the tunnel face approaches and passes through a unit volume of rock, the spatial and temporal evolution of the three-dimensional stress field encompasses a series of deviatoric stress increases and/or decreases as well as several rotations of the principal stress axes. Particular emphasis is placed on the rotation of the principal stress axes as being a controlling factor in the direction of fracture propagation. If this orientation changes in time, i.e. during the progressive advancement of the tunnel face, the type of damage induced in the rock mass and the resulting failure mechanisms may also vary depending on the type and degree of stress rotation. The significance of these effects is discussed in terms of microfracture initiation and propagation, brittle fracture damage and rock strength degradation. Further analysis is also presented for varying tunnelling conditions including the effects of tunnel alignment with respect to the initial in situ stress field, excavation sequencing and elasto-plastic material yielding. Implications with respect to the new Gotthard base tunnel, currently under construction in Switzerland, are presented using examples from the nearby Furka tunnel.     

Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial

The ability of rats to learn the location of a hidden platform in a swim maze was compared in animals with excitotoxic lesions of the anterior or posterior (retrosplenial) cingulate cortex or radiofrequency lesions of the cingulum bundle or fimbria-fornix. Performance of this allocentric spatial task was unaffected by the posterior cingulate cortex lesions, while anterior cingulate cortex damage produced only a mild acquisition deficit. Transection of the fornix and lesions of the cingulum bundle produced similar patterns of impairment on initial acquisition, but the cingulum bundle lesions had less effect on reversal of the task. The results from the water maze, and from a subsequent T-maze alternation task, indicate that cingulum bundle lesions can produce a spatial deficit that is similar, but milder, to that observed after fornix transection. The results of the excitotoxic lesions suggest that previous studies examining conventional cingulate lesions may have been influenced by damage to adjacent fibre tracts, such as the cingulum bundle.     

ATP potentiates interleukin-1 beta-induced MMP-9 expression in mesangial cells via recruitment of the ELAV protein HuR

Renal mesangial cells express high levels of matrix metalloproteinase 9 (MMP-9) in response to inflammatory cytokines such as interleukin (IL)-1 beta. We demonstrate here that the stable ATP analog adenosine 5'-O-(thiotriphosphate) (ATP gamma S) potently amplifies the cytokine-induced gelatinolytic content of mesangial cells mainly by an increase in the MMP-9 steady-state mRNA level. A Luciferase reporter gene containing 1.3 kb of the MMP-9 5'-promoter region showed weak responses to ATP gamma S but conferred a strong ATP-dependent increase in Luciferase activity when under the additional control of the 3'-untranslated region of MMP-9. By in vitro degradation assay and actinomycin D experiments we found that ATP gamma S potently delayed the decay of MMP-9 mRNA. Gel-shift and supershift assays demonstrated that three AU-rich elements (AREs) present in the 3'-untranslated region of MMP-9 are constitutively bound by complexes containing the mRNA stabilizing factor HuR. The RNA binding of these complexes was markedly increased by ATP gamma S. Mutation of each ARE element strongly impaired the RNA binding of the HuR containing complexes. Reporter gene assays revealed that mutation of one ARE did not affect the stimulatory effects by ATP gamma S, but mutation of all three ARE motifs caused a loss of ATP-dependent increase in luciferase activity without affecting IL-1 beta-inducibility. By confocal microscopy we demonstrate that ATP gamma S increased the nucleo cytoplasmic shuttling of HuR and caused an increase in the cytosolic HuR level as shown by cell fractionation experiments. Together, our results indicate that the amplification of MMP-9 expression by extracellular ATP is triggered through mechanisms that likely involve a HuR-dependent rise in MMP-9 mRNA stability.     

Peripheral nerve stimulation by time-varying magnetic fields

PURPOSE: A study was performed to assess the stimulation threshold for healthy adults using sinusoidally oscillating gradients. METHOD: One hundred thirteen healthy adults were examined in the study. ECG and physiological parameters were measured. All measurements were performed of both the head and the abdomen. The subjects were measured in the supine position with the region of interest positioned in the center of the gradient coils. The measurement was performed for three orthogonal, four oblique, and double oblique orientations. RESULTS: No volunteer reported painful, severe stimulation. The mean thresholds for peripheral stimulation in head and body measurement were similar: 85.5% of stimulation during examination of the head and 87.6% during measurements of the abdomen were reported when the y-gradient was used. CONCLUSION: The greatest frequency of reported stimulations occurs when the y-gradient is used. This was confirmed by the results and supports the hypothesis that orthogonal to the y-axis the body has its largest conductive loop, resulting in the strongest peripheral stimulation.