Techniques for high-frequency integrated test and measurement

This paper describes techniques for the on-chip measurement of high-frequency and/or high-bandwidth electrical phenomena in ultra large-scale integration environments. The techniques rely on the integration of multiple compact and robust electronic test devices, or cores, at various locations within an integrated circuit. The cores consist primarily of signal generators that approximate the output of a sigma-delta modulator using finite repetitious bit patterns and a small set of highly robust analog components. They are capable of digitizing on-chip signals at gigahertz rates even using low-cost manufacturing processes. Simple communication between the multiple cores enables the migration of many "board-level" type measurements down to the chip level.     

Estimation of deformation gradient and strain from cine-PC velocity data

Phase contrast magnetic resonance imaging (MRI) can provide in vivo myocardial velocity field measurements. These data allow densely spaced material points to be tracked throughout the whole heart cycle using, for example, the Fourier tracking algorithm. To process the tracking results for myocardial deformation and strain quantification, we developed a method that is based on fitting the tracking results to an appropriate local deformation model. We further analyzed the accuracy and precision of the method and provided performance predictions for several local models. In order to validate the method and the theoretical performance analysis, we conducted controlled computer simulations and a phantom study. The results agreed well with expectations. Human heart data were also acquired and analyzed, and provided encouraging results. At the signal-to-noise ratio (SNR) level and spatial resolution expected in clinical settings, the study predicts strain quantification accuracy and precision that may allow the technique to become a practical and powerful noninvasive approach for the study of cardiac function, although clinically acceptable data acquisition strategies for three-dimensional (3-D) data are still a challenge.     

Platelet-derived growth factor activates a mammalian Ste20 coupled mitogen-activated protein kinase in airway smooth muscle

Attempts to immunise sheep against natural infestations by Lucilia cuprina larvae have not been effective. Yet it is known that the larvae excrete the immunosuppressant ammonium bicarbonate. The effect of larval ammonium and nonionic ammonia on immunopathobiology was evaluated in 12 infested sheep. The concentration of ammonium in veins draining infested sites was measured in another group of four sheep. Mean jugular unionized ammonia concentration increased 3.5 to 5.6 times above pre-infested control levels. Mean venous ammonium concentrations draining infested sites were 13 times higher than pre-infested jugular or carotid levels. Increases in jugular ammonia concentrations correlated with increased number of larvae, area of infestation, earlier death, neutropenia, eosinopenia, lymphocytopenia, large declines in serum globulins and zinc, and large rises in toxic neutrophils. The high concentrations of toxic unionized ammonia in blood directly permanently damaged neutrophils and lymphocytes and depressed serum globulin production. The results show that the ammonium from the excreta of larvae of L. cuprina may be highly immunosuppressive.     

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that produces Parkinsonism symptoms in man, has been examined as a substrate of recombinant human cytochrome P450 2D6. When cumene hydroperoxide is used as an oxygen and electron donor, a single product is formed, identified as 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) for formation of this product (130 microM) is in agreement with the dissociation constants for MPTP binding to the enzyme determined by optical and nuclear magnetic resonance (NMR) spectroscopy. When the reaction is carried out with nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) and recombinant human NADPH-cytochrome P450 reductase, a second product, identified as 1-methyl-4-(4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine, is formed in addition to 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) values for formation of these two products are 19 microM and 120 microM, respectively. Paramagnetic relaxation experiments have been used to measure distances between the protons of bound MPTP and the heme iron, and these have been used to construct models for the position and orientation of MPTP in the active site. For the cytochrome alone, a single mode of binding was observed, with the N-methyl close to the heme iron in a position appropriate for the observed N-demethylation reaction. In the presence of the reductase, the data were not consistent with a single mode of binding but could be explained by the existence of two alternative orientations of MPTP in the active site. One of these, characterized by a dissociation constant of 150 microM, is essentially identical to that observed in the absence of the reductase. In the second, which has a K(d) of 25 microM, the MPTP is oriented so that the aromatic ring is close to the heme iron, in a position appropriate for p-hydroxylation leading to the formation of the product seen only in the presence of the reductase. In the case of codeine, another substrate for cytochrome P450 2D6, the addition of reductase had no effect on the nature of the product formed, the dissociation constant, or the orientation in the binding site. These observations show that NADPH-cytochrome P450 reductase has an allosteric effect on the active site of cytochrome P450 2D6 that affects the binding of some substrates but not others.     

Should acyclovir prophylaxis be used in late pregnancy in women with recurrent genital herpes infection? How to use a clinical decision analysis

Contact stomatitis is rather uncommon because of the relative resistance of the oral mucosa to irritant agents and allergens. The clinical manifestations of contact stomatitis are extremely variable and include erythema, erosions, ulcerations, leukoplakia-like lesions, and lichenoid reactions. Clinical signs are frequently less pronounced than subjective symptoms, and patients commonly experience severe functional problems despite only mild mucosal alterations. Allergic stomatitis is rare and almost always attributable to metallic mercury and gold salts. A careful history and an accurate examination of the oral cavity, teeth, and dental restorations are essential for a correct diagnosis. Patch testing is indicated in all lesions that are not clearly related to trauma or physical injuries. Patch testing is not useful in the burning mouth syndrome. Evaluation of clinical relevance of patch test results is always very difficult and requires an interdisciplinary approach to the patient. Successful treatment requires the identification and elimination of the causative factor, when possible. It is important to bear in mind that replacement of dental restorations and prostheses may be very expensive and stressful for the patient and thus should not be recommended when their causative role is doubtful.     

The effect of particle distribution on damage formation in particulate reinforced metal matrix composites deformed in compression

Image analysis results are reported on the generation of damage in particulate reinforced metal matrix composites during compressive deformation. The technique allows the automated collection of data on the incidence of particle fracture and void formation in the matrix as a function of important microstructural parameters such as local particle volume fraction and particle size. There is a strong relationship between damage and the local volume fraction of the reinforcement proving that damage formation is accentuated in regions of particle clustering. With the SiC reinforced materials examined, there was observed to be a change in dominance of damage mechanism from particle fracture at low local volume fractions to void formation in the matrix within strongly clustered regions. The results are compared with finite element (FE) modelling of the compressive deformation of clustered particles using a simple cluster of equi-spaced particles. The FE results suggest that plastic flow is generally inhibited in clustered regions. In certain highly clustered configurations shielding is such that flow does not occur in the heart of the cluster even at high levels of average plastic strain. The modelling suggests that the change in dominance of damage mechanism is related to the dramatic increase in tensile hydrostatic stresses in the matrix with higher levels of particle clustering.     

Stochastic complexity measures for physiological signal analysis

Traditional feature extraction methods describe signals in terms of amplitude and frequency. This paper takes a paradigm shift and investigates four stochastic-complexity features. Their advantages are demonstrated on synthetic and physiological signals; the latter recorded during periods of Cheyne-Stokes respiration, anesthesia, sleep, and motor-cortex investigation     

Reaction time during cocaine versus alcohol withdrawal: longitudinal measures of visual and auditory suppression

Visual and auditory stimulus discrimination tasks, analogous to those used in the Reitan-Klove Sensory Perceptual Examination, were performed by 12 cocaine-dependent and 5 alcohol-dependent patients after 1 week, 3 weeks, and 3 months of verified abstinence. Sixteen control subjects, who were not substance-dependent, performed the same tasks after comparable intervals. During each task, either visual or auditory stimuli were presented in the left, in the right, or in both sensory fields. A simple key press was made to discriminate these conditions. Cocaine-dependent patients responded more slowly than control subjects during both tasks. The reaction-time slowing persisted across all three sessions, spanning a 3-month period of abstinence. There were no significant differences between the cocaine-dependent and control groups in response accuracy. In the context of other findings, these findings are interpreted as reflecting an enduring effect of prior cocaine dependence on motor as opposed to sensory functioning.     

Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2

Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma MCF-7 cells with PGA2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. These findings indicate that PGA2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of PGA2, particularly for suppressing growth of tumors lacking p53 function.