A novel contact model of piezoelectric traveling wave rotary ultrasonic motors with the finite volume method.

The operating principle of the piezoelectric traveling wave rotary ultrasonic motor is based on two energy conversion processes: the generation of the stator traveling wave and the rectification of the stator movement through the stator-rotor contact mechanism. This paper presents a methodology to model in detail the stator-rotor contact interface of these motors. A contact algorithm that couples a model of the stator which is discretized with the finite volume method and an analytical model of the rotor is presented. The outputs of the proposed model are the normal and tangential force distribution produced at the stator-rotor contact interface, contact length, height and shape of the stator traveling wave and rotor speed. The torque-speed characteristic of the USR60 is calculated with the proposed model, and the results of the model are compared versus the real torque-speed of the motor. A good agreement between the proposed model results and the torque-speed characteristic of the USR60 was observed.

White matter integrity in physically fit older adults.

BACKGROUND: White matter (WM) integrity declines with normal aging. Physical activity may attenuate age-related WM integrity changes and improve cognitive function. This study examined brain WM integrity in Masters athletes who have engaged in life-long aerobic exercise training. We tested the hypothesis that life-long aerobic training is associated with improved brain WM integrity in older adults. METHODS: Ten Masters athletes (3 females, age=72.2 ± 5.3 years, endurance training >15 years) and 10 sedentary older adults similar in age and educational level (2 females, age=74.5 ± 4.3 years) participated. MRI fluid-attenuated-inversion-recovery (FLAIR) images were acquired to assess white matter hyperintensities (WMH) volume. Diffusion tensor imaging (DTI) was performed to evaluate the WM microstructural integrity with a DTI-derived metric, fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: After normalization to whole-brain volume, Masters athletes showed an 83% reduction in deep WMH volume relative to their sedentary counterparts (0.05 ± 0.05% vs. 0.29 ± 0.29%, p<0.05). In addition, we found an inverse relationship between aerobic fitness (VO2max) and deep WMH volume (r=-0.78, p<0.001). Using TBSS, Masters athletes showed higher FA values in the right superior corona radiata (SCR), both sides of superior longitudinal fasciculus (SLF), right inferior fronto-occipital fasciculus (IFO), and left inferior longitudinal fasciculus (ILF). In addition, Masters athletes also showed lower MD values in the left posterior thalamic radiation (PTR) and left cingulum hippocampus. CONCLUSIONS: These findings suggest that life-long exercise is associated with reduced WMH and may preserve WM fiber microstructural integrity related to motor control and coordination in older adults.

A novel approach for normalizing the photoreflectance spectrum by using polymer-dispersed liquid crystal.

This study developed a novel type of normalization procedure for modulation reflectance spectroscopy experiments to obtain the relative change in the reflectance spectrum, ΔR/R. This technique uses a polymer-dispersed liquid crystal to ensure that the dc component of the signal from the detector remained constant by varying the intensity of the light striking the sample. This method is particularly useful for photoreflectance measurement, which may encounter background problems because of scattered pump light and/or photoluminescence. It does not require a change in the gain of the detector or the use of a variable neutral density filter mounted on a servo-motor.

Regenerated mdx mouse skeletal muscle shows differential mRNA expression.

Despite over 3,000 articles published on dystrophin in the last 15 years, the reasons underlying the progression of the human disease, differential muscle involvement, and disparate phenotypes in different species are not understood. The present experiment employed a screen of 12,488 mRNAs in 16-wk-old mouse mdx muscle at a time when the skeletal muscle is avoiding severe dystrophic pathophysiology, despite the absence of a functional dystrophin protein. A number of transcripts whose levels differed between the mdx and human Duchenne muscular dystrophy were noted. A fourfold decrease in myostatin mRNA in the mdx muscle was noted. Differential upregulation of actin-related protein 2/3 (subunit 4), beta-thymosin, calponin, mast cell chymase, and guanidinoacetate methyltransferase mRNA in the more benign mdx was also observed. Transcripts for oxidative and glycolytic enzymes in mdx muscle were not downregulated. These discrepancies could provide candidates for salvage pathways that maintain skeletal muscle integrity in the absence of a functional dystrophin protein in mdx skeletal muscle.

Protection against TNF-induced liver parenchymal cell apoptosis during endotoxemia by a novel caspase inhibitor in mice.

Excessive apoptotic cell death is implicated in a growing number of acute and chronic disease states. Caspases are critical for the intracellular signaling pathway leading to apoptosis. The aim of this investigation was to evaluate the efficacy and the mechanism of action of the novel caspase inhibitor CV1013 in a well-characterized model of TNF-induced apoptosis. Administration of 700 mg/kg galactosamine/100 microg/kg endotoxin (Gal/ET) induced hepatocellular apoptosis in C3Heb/FeJ mice as indicated by increased caspase-3 activity (706% above controls) and enhanced DNA fragmentation (3400% above controls) at 6 h. In addition, apoptosis was aggravated by the neutrophil-induced injury at 7 h (ALT activities: 4220 +/- 960 U/L and 48 +/- 4% necrosis). All animals died 8-12 h after Gal/ET treatment from shock and liver failure. A dose of 10 or 1 mg/kg of CV1013 administered three times (3, 4.5, and 5.5 h after Gal/ET) effectively prevented caspase-3 activation and parenchymal cell apoptosis at 6 h as well as the subsequent neutrophil-induced aggravation of the injury at 7 h after Gal/ET treatment. Animals treated with 10 mg/kg CV1013 survived for 24 h without liver injury. CV1013 reduced the processing of caspase-3 and caspase-8. This suggests that CV1013 may have inhibited the small amount of active caspase-8 generated at the receptor level. Because of the multiple amplification loops used to activate the entire caspase cascade, blocking the initial intracellular signal by CV1013 was highly effective in preventing apoptotic cell death. CV1013 has therapeutic potential for disease states with excessive apoptosis.

The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain.

The progressive aggregation and deposition of amyloid beta-protein (Abeta) in brain regions subserving memory and cognition is an early and invariant feature of Alzheimer's disease, the most common cause of cognitive failure in aged humans. Inhibiting Abeta aggregation is therapeutically attractive because this process is believed to be an exclusively pathological event. Whereas many studies have examined the aggregation of synthetic Abeta peptides under nonphysiological conditions and concentrations, we have detected and characterized the oligomerization of naturally secreted Abeta at nanomolar levels in cultures of APP-expressing CHO cells [Podlisny, M. B., Ostaszewski, B. L., Squazzo, S. L., Koo, E. H., Rydell, R. E., Teplow, D. B., and Selkoe, D. J. (1995) J. Biol. Chem. 270, 9564-9570 (1); Podlisny, M. B., Walsh, D. M., Amarante, P., Ostaszewski, B. L., Stimson, E. R., Maggio, J. E., Teplow, D. B., and Selkoe, D. J. (1998) Biochemistry 37, 3602-3611 (2)]. To determine whether similar species occur in vivo, we probed samples of human cerebrospinal fluid (CSF) and detected SDS-stable dimers of Abeta in some subjects. Incubation of CSF or of CHO conditioned medium at 37 degrees C did not lead to new oligomer formation. This inability to induce oligomers extracellularly as well as the detection of oligomers in cell medium very early during the course of pulse-chase experiments suggested that natural Abeta oligomers might first form intracellularly. We therefore searched for and detected intracellular Abeta oligomers, principally dimers, in primary human neurons and in neuronal and nonneural cell lines. These dimers arose intracellularly rather than being derived from the medium by reuptake. The dimers were particularly detectable in neural cells: the ratio of intracellular to extracellular oligomers was much higher in brain-derived than nonbrain cells. We conclude that the pathogenically critical process of Abeta oligomerization begins intraneuronally.

Pulmonary hypoplasia in the myogenin null mouse embryo.

Although fetal breathing movements are required for normal lung development, there is uncertainty concerning the specific effect of absent fetal breathing movements on pulmonary cell maturation. We set out to evaluate pulmonary development in a genetically defined mouse model, the myogenin null mouse, in which there is a lack of normal skeletal muscle fibers and thus skeletal muscle movements are absent in utero. Significant decreases were observed in lung:body weight ratio and lung total DNA at embryonic days (E)14, E17, and E20. Reverse transcriptase/polymerase chain reaction, in situ immunofluorescence, and electron microscopy revealed early lung cell differentiation in both null and wild-type lungs as early as E14. However at E14, myogenin null lungs had decreased 5'-bromo-2-deoxyuridine incorporation compared with that of wild-type littermates, whereas at E17 and E20, increased Bax immunolabeling and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining were detected in the myogenin null mice but not in the wild-type littermates. These observations highlight the importance of skeletal muscle contractile activity in utero for normal lung organogenesis. Null mice lacking the muscle-specific transcription factor myogenin exhibit a secondary effect on lung development such that decreased lung cell proliferation and increased programmed cell death are associated with lung hypoplasia.

Autonomous decision-making: a data mining approach.

The researchers and practitioners of today create models, algorithms, functions, and other constructs defined in abstract spaces. The research of the future will likely be data driven. Symbolic and numeric data that are becoming available in large volumes will define the need for new data analysis techniques and tools. Data mining is an emerging area of computational intelligence that offers new theories, techniques, and tools for analysis of large data sets. In this paper, a novel approach for autonomous decision-making is developed based on the rough set theory of data mining. The approach has been tested on a medical data set for patients with lung abnormalities referred to as solitary pulmonary nodules (SPNs). The two independent algorithms developed in this paper either generate an accurate diagnosis or make no decision. The methodolgy discussed in the paper depart from the developments in data mining as well as current medical literature, thus creating a variable approach for autonomous decision-making.

Deposition of monomeric, not oligomeric, Abeta mediates growth of Alzheimer's disease amyloid plaques in human brain preparations.

Senile plaques composed of the peptide Abeta contribute to the pathogenesis of Alzheimer's disease (AD), and mechanisms underlying their formation and growth may be exploitable as therapeutic targets. To examine the process of amyloid plaque growth in human brain, we have utilized size exclusion chromatography (SEC), translational diffusion measured by NMR, and in vitro models of Abeta amyloid growth to identify the oligomerization state of Abeta that is competent to add onto an existing amyloid deposit. SEC of radiolabeled and unlabeled Abeta over a concentration range of 10(-)(10)-10(-)(4) M demonstrated that the freshly dissolved peptide eluted as a single low molecular weight species, consistent with monomer or dimer. This low molecular weight Abeta species isolated by SEC was competent to deposit onto preexisting amyloid in preparations of AD cortex, with first-order kinetic dependence on soluble Abeta concentration, establishing that solution-phase oligomerization is not rate limiting. Translational diffusion measurements of the low molecular weight Abeta fraction demonstrate that the form of the peptide active in plaque deposition is a monomer. In deliberately aged (>6 weeks) Abeta solutions, a high molecular weight (>100 000 M(r)) species was detectable in the SEC column void. In contrast to the active monomer, assembled Abeta isolated from the column showed little or no focal association with AD tissue. These studies establish that, at least in vitro, Abeta exists as a monomer at physiological concentrations and that deposition of monomers, rather than of oligomeric Abeta assemblies, mediates the growth of existing amyloid in human brain preparations.

Transcriptional up-regulation of paxillin expression by heregulin in human breast cancer cells.

Activation of heregulin (HRG) signaling has been implicated in the development of aggressive phenotype in breast cancer cells. The mechanisms through which HRG regulates the progression of breast cancer cells to a more invasive or motile phenotype are currently unknown. Because the process of cell migration must involve dynamic changes in the formation of new focal adhesions at the leading edge and dissolution of preexisting focal points, we explored the potential HRG regulation of paxillin, a major component of focal adhesion. Here, we report that HRG stimulation of noninvasive breast cancer MCF-7 cells resulted in the up-regulation of paxillin mRNA and protein. The observed HRG stimulation of paxillin mRNA expression was completely blocked by actinomycin D (a transcriptional inhibitor) as well as by cycloheximide (a protein synthesis inhibitor), suggesting the involvement of an inducible protein factor(s) and transcriptional regulation of paxillin mRNA by HRG. Extension of these observations to other HRG-responsive human cell lines also demonstrated that HRG has a significant capacity to up-regulate the paxillin expression. Furthermore, the levels of paxillin expression were closely linked with the coexpression of human epidermal growth factor receptor 2 (HER2)/HER3 receptors in breast cancer cell lines and in grade III human breast tumors. This study is the first demonstration of regulation of paxillin expression by a polypeptide growth factor, and it suggests a potential role for paxillin in the HER2 pathway in breast cancer.

Human bHLH transcription factor gene myogenin (MYOG): genomic sequence and negative mutation analysis in patients with severe congenital myopathies.

The myogenin gene encodes an evolutionarily conserved basic helix-loop-helix transcription (bHLH) factor that is required for differentiation of skeletal muscle, and its homozygous deletion in mice results in perinatal death from respiratory failure due to the lack of muscle fibers. Since the histology of skeletal muscle in myogenin null mice is reminiscent of that found in severe congenital myopathy patients, many of whom also die of respiratory complications, we sought to test the hypothesis that an aberrant human myogenin (myf4) coding region could be associated with some congenital myopathy conditions. With PCR amplification, we found similarly sized PCR products for the three exons of the myogenin gene in DNA from 37 patient and 40 control individuals. In contrast to previously reported sequencing of human myogenin (myf4), we describe with automated sequencing several base differences in flanking and coding regions plus an additional 659 and 498 bp in the first and second introns, respectively, in all 37 patient and 40 control samples. We also find a variable length (CA)-dinucleotide repeat in the second intron, which may have utility as a marker for future linkage studies. In summary, no causative mutations were detected in the myogenin coding locus of genomic DNA from 37 patients with severe congenital myopathy.

Molecular and cellular adaptation of muscle in response to physical training.

Molecular biology tools can be used to answer questions as to how adaptations occur in skeletal muscle with training that could provide new frameworks to improve physical performance. A number of mRNAs for transfer of metabolic substrates into muscle cells increase after a single bout of exercise demonstrating the responsiveness of some gene expression to exercise. In stretch-induced hypertrophy SRE1 of the skeletal alpha-actin promoter is required to transactivate the promoter. Less retardation of SRF in crude nuclear extracts from the stretched muscle implies a conformational change in SRF because of the stretch. Transgenic animals will provide a tool to test questions concerned with how exercise signals adaptive changes in gene expression. Molecular biological approaches will be able to evaluate the interaction between physical activity levels and the expression of genes that modulate the susceptibility to many chronic diseases. Benefits of exercise extend beyond fitness to better health. Molecular biology is an important tool which should lead to improved physical performance and health in both elite athletes and the general public.

Dual-function detector-modulator smart-pixel module.

We describe a smart-pixel circuit that permits the use of a GaAs/AlGaAs multiple quantum well diode to be used both as a detector for data input and a modulator for data output. The module provides the ability to double the number of inputs or outputs to the array and is well suited to cascaded optoelectronic system architectures that require bidirectional communition.

Photonic page buffer based on GaAs multiple-quantum-well modulators bonded directly over active silicon complementary-metal-oxide-semiconductor (CMOS) circuits.

We present a 2-kbit, 50-Mpage/s, photonic first-in, first-out page buffer based on gallium arsenide/aluminium-gallium arsenide multiple-quantum-well diodes that are flip-chip bonded to submicrometer silicon complementary-metal-oxide-semiconductor circuits. This photonic chip provides nonvolatile storage (buffering), asynchronous-to-synchronous conversion, bandwidth smoothing, tolerance to jitter or skew, spatial format conversion, wavelength conversion, and independent flow control for the input and the output channels. It serves as an interface chip for parallel-accessed optical bit-plane data. It represents the first smart-pixel array that accomplishes the vertical integration of multiple-quantum-well modulators and detectors directly over active silicon VLSI circuits and provides over 340 transistors per optical input-output. Results from high-speed single-channel testing and real-time array operation of the photonic page buffer are reported.

Photonic page buffer based on GaAs multiple-quantum-well modulators bonded directly over active silicon complementary-metal-oxide-semiconductor (CMOS) circuits: errata.

Owing to printing errors, [Appl. Opt. 35, 2439 (1996)] several figures were illegible. The figures are reprinted and briefly reviewed.

Strength and aerobic training attenuate muscle wasting and improve resistance to the development of disability with aging.

By the age of 50 yrs old, humans become aware that they are losing muscle strength (mass) and endurance (mitochondria). A frequent symptom of neuromuscular disorders is muscle weakness (Walton, 1988). We define the aging-associated muscle wasting as a progressive neuromuscular syndrome that will lower the quality of life in the elderly by (1) decreasing the ability to lift loads (progressing to difficulty arising from a chair), and (2) decreasing endurance (leading to an inability to perform the activities of daily living, which increases health care costs). Campion (1994) states that the most successful outcome would be for the very elderly to take control of the last stage of their life and make it worth living. To obtain this goal, prevention of muscle wasting is an absolute requirement. Muscle mass and motor unit number, activation, and synchronization are highly related to strength; both decrease with aging (Rodgers and Evans, 1993). Resistance-training is the best way to increase muscle mass, neural coordination, and strength. Mitochondrial concentration is highly related to endurance capacity in young and old (Holloszy and Coyle, 1984). Both muscle contractile and mitochondrial protein decrease with aging in sedentary humans (reviewed by Rodgers and Evans, 1993). Endurance training, which is the best exercise to increase/maintain mitochondrial concentration with aging, has generally resulted in relatively small functional benefits to nursing home patients (Fiatarone et al., 1994).(ABSTRACT TRUNCATED AT 250 WORDS)