High-resolution computer simulations of stacking of weak bases using a transient pH boundary in capillary electrophoresis. 1. Concept and impact of sample ionic strength

The dynamics of focusing weak bases using a transient pH boundary was examined via high-resolution computer simulation software. Emphasis was placed on the mechanism and impact that the presence of salt, namely, NaCl, has on the ability to focus weak bases. A series of weak bases with mobilities ranging from 5 x 10(-9) to 30 x 10(-9) m2/V x s and pKa values between 3.0 and 7.5 were examined using a combination of 65.6 mM formic acid, pH 2.85, for the separation electrolyte, and 65.6 mM formic acid, pH 8.60, for the sample matrix. Simulation data show that it is possible to focus weak bases with a pKa value similar to that of the separation electrolyte, but it is restricted to weak bases having an electrophoretic mobility of 20 x 10(-9) m2/V x s or quicker. This mobility range can be extended by the addition of NaCl, with 50 mM NaCl allowing stacking of weak bases down to a mobility of 15 x 10(-9) m2/V x s and 100 mM extending the range to 10 x 10(-9) m2/V x s. The addition of NaCl does not adversely influence focusing of more mobile bases, but does prolong the existence of the transient pH boundary. This allows analytes to migrate extensively through the capillary as a single focused band around the transient pH boundary until the boundary is dissipated. This reduces the length of capillary that is available for separation and, in extreme cases, causes multiple analytes to be detected as a single highly efficient peak.

Dystrophic cardiomyopathy: amplification of cellular damage by Ca2+ signalling and reactive oxygen species-generating pathways

AIMS: Cardiac myopathies are the second leading cause of death in patients with Duchenne and Becker muscular dystrophy, the two most common and severe forms of a disabling striated muscle disease. Although the genetic defect has been identified as mutations of the dystrophin gene, very little is known about the molecular and cellular events leading to progressive cardiac muscle damage. Dystrophin is a protein linking the cytoskeleton to a complex of transmembrane proteins that interact with the extracellular matrix. The fragility of the cell membrane resulting from the lack of dystrophin is thought to cause an excessive susceptibility to mechanical stress. Here, we examined cellular mechanisms linking the initial membrane damage to the dysfunction of dystrophic heart. METHODS AND RESULTS: Cardiac ventricular myocytes were enzymatically isolated from 5- to 9-month-old dystrophic mdx and wild-type (WT) mice. Cells were exposed to mechanical stress, applied as osmotic shock. Stress-induced cytosolic and mitochondrial Ca(2+) signals, production of reactive oxygen species (ROS), and mitochondrial membrane potential were monitored with confocal microscopy and fluorescent indicators. Pharmacological tools were used to scavenge ROS and to identify their possible sources. Osmotic shock triggered excessive cytosolic Ca(2+) signals, often lasting for several minutes, in 82% of mdx cells. In contrast, only 47% of the WT cardiomyocytes responded with transient and moderate intracellular Ca(2+) signals. On average, the reaction was 6-fold larger in mdx cells. Removal of extracellular Ca(2+) abolished these responses, implicating Ca(2+) influx as a trigger for abnormal Ca(2+) signalling. Our further experiments revealed that osmotic stress in mdx cells produced an increase in ROS production and mitochondrial Ca(2+) overload. The latter was followed by collapse of the mitochondrial membrane potential, an early sign of cell death. CONCLUSION: Overall, our findings reveal that excessive intracellular Ca(2+) signals and ROS generation link the initial sarcolemmal injury to mitochondrial dysfunctions. The latter possibly contribute to the loss of functional cardiac myocytes and heart failure in dystrophy. Understanding the sequence of events of dystrophic cell damage and the deleterious amplification systems involved, including several positive feed-back loops, may allow for a rational development of novel therapeutic strategies.

Speech understanding in quiet and in noise with the bone-anchored hearing aids Baha Compact and Baha Divino

CONCLUSIONS: Speech understanding is better with the Baha Divino than with the Baha Compact in competing noise from the rear. No difference was found for speech understanding in quiet. Subjectively, overall sound quality and speech understanding were rated better for the Baha Divino. OBJECTIVES: To compare speech understanding in quiet and in noise and subjective ratings for two different bone-anchored hearing aids: the recently developed Baha Divino and the Baha Compact. PATIENTS AND METHODS: Seven adults with bilateral conductive or mixed hearing losses who were users of a bone-anchored hearing aid were tested with the Baha Compact in quiet and in noise. Tests were repeated after 3 months of use with the Baha Divino. RESULTS: There was no significant difference between the two types of Baha for speech understanding in quiet when tested with German numbers and monosyllabic words at presentation levels between 50 and 80 dB. For speech understanding in noise, an advantage of 2.3 dB for the Baha Divino vs the Baha Compact was found, if noise was emitted from a loudspeaker to the rear of the listener and the directional microphone noise reduction system was activated. Subjectively, the Baha Divino was rated statistically significantly better in terms of overall sound quality.

Minimal assumption derivation of a weak Clauser-Horne inequality

According to Bell's theorem a large class of hidden-variable models obeying Bell's notion of local causality (LC) conflict with the predictions of quantum mechanics. Recently, a Bell-type theorem has been proven using a weaker notion of LC, yet assuming the existence of perfectly correlated event types. Here we present a similar Bell-type theorem without this latter assumption. The derived inequality differs from the Clauser-Horne inequality by some small correction terms, which render it less constraining.

PyGirl: Generating Whole-System VMs from High-Level Prototypes Using PyPy

Virtual machines (VMs) emulating hardware devices are generally implemented in low-level languages for performance reasons. This results in unmaintainable systems that are difficult to understand. In this paper we report on our experience using the PyPy toolchain to improve the portability and reduce the complexity of whole-system VM implementations. As a case study we implement a VM prototype for a Nintendo Game Boy, called PyGirl, in which the high-level model is separated from low-level VM implementation issues. We shed light on the process of refactoring from a low-level VM implementation in Java to a high-level model in RPython. We show that our whole-system VM written with PyPy is significantly less complex than standard implementations, without substantial loss in performance.