Hollow waveguides with low intrinsic photoluminescence fabricated with Ta(2)O(5) and SiO(2) films

A type of integrated hollow core waveguide with low intrinsic photoluminescence fabricated with Ta(2)O(5) and SiO(2) films is demonstrated. Hollow core waveguides made with a combination of plasma-enhanced chemical vapor deposition SiO(2) and sputtered Ta(2)O(5) provide a nearly optimal structure for optofluidic biofluorescence measurements with low optical loss, high fabrication yield, and low background photoluminescence. Compared to earlier structures made using Si(3)N(4), the photoluminescence background of Ta(2)O(5) based hollow core waveguides is decreased by a factor of 10 and the signal-to-noise ratio for fluorescent nanobead detection is improved by a factor of 12.     

Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.     

Can an immunologically, nonreactive potential allograft recipient undergo transplantation without a donor-specific crossmatch?

Performance of the pretransplant crossmatch requires 4 or more hours . Delays in the crossmatch might alter operating room availability and thereby increase donor organ cold ischemia time that might then result in increased risk of delayed graft function. To avoid these problems, recipients could be identified who would be expected to display negative donor crossmatches and who could be transplanted with a concurrent or retrospective rather than a pretransplant crossmatch. We, therefore, evaluated the percent reactive antibodies and donor IgG-antihuman globulin (AHG) crossmatch results of 1165 sera from 220 potential allograft recipients. Twenty-five (11%) of 220 recipients consistently displayed a 0% PRA and, with only one exception, their sera (n= 156) tested IgG-AHG crossmatch-negative against potential cadaveric donors (a 0.6% IgG-AHG positive crossmatch risk). These data suggest that the timing of the pretransplant serum crossmatch could be altered for a highly selected group of immunologically nonreactive recipients.     

The transepicondylar axis approximates the optimal flexion axis of the knee

The traditional understanding of knee kinematics holds that no single fixed axis of rotation exists in the knee. In contrast, a recent hypothesis suggests that knee kinematics are better described simply as two simultaneous rotations occurring about fixed axes. Knee flexion and extension occurs about an optimal flexion axis fixed in the femur, whereas tibial internal and external rotations occur about a longitudinal rotation axis fixed in the tibia. No other translations or rotations exist. This hypothesis has been tested. Tibiofemoral kinematics were measured for 15 cadaveric knees undergoing a realistic loadbearing activity (simulated squatting). An optimization technique was used to identify the locations of the optimal flexion and longitudinal rotation axes such that simultaneous rotations about them could best represent the measured kinematics. The optimal flexion axis was compared with the transepicondylar axis defined by bony landmarks. The longitudinal rotation axis was found to pass through the medial joint compartment. The optimal flexion axis passed through the centers of the posterior femoral condyles. No significant difference was found between the optimal flexion and transepicondylar axes. To an average accuracy of better than 3.4 mm in translation, and 2.9 degrees in orientation, knee kinematics were represented successfully by simple rotations about the optimal flexion and longitudinal rotation axes. The optimal flexion axis is fixed in the femur and can be considered the true flexion axis of the knee. The transepicondylar axis axis, which is identified easily by palpation, closely approximates the optimal flexion axis.     

Paths across generations: academic competence and aggressive behaviors in young mothers and their children

This research compared the social and cognitive development of young mothers when they were children with the social and cognitive development of their offspring. Intergenerational development was investigated over a 17-year period for 57 women who had been studied longitudinally from childhood to adulthood and who became young mothers (R. B. Cairns & B. D. Cairns, 1994). The children of these women, in turn, were followed prospectively from 1 to 2 years old through the early school years. The academic competence of mothers when they were children was significantly linked to the academic competence of their children at school age. In contrast, the across-generation correlations between measures of aggressive behavior of the mothers when they were children and measures of aggressive behavior of their children in early school grades were modest and unreliable. Certain within-generation continuities were observed in both cognitive and aggressive development.     

Decompensation of pressure-overload hypertrophy in G alpha q-overexpressing mice

BACKGROUND: Receptor-mediated activation of myocardial Gq signaling is postulated as a biochemical mechanism transducing pressure-overload hypertrophy. The specific effects of Gq activation on the functional and morphological adaptations to pressure overload are not known. METHODS AND RESULTS: To determine the effects of intrinsic myocyte G alpha q signaling on the left ventricular hypertrophic response to experimental pressure overload, transgenic mice overexpressing G alpha q specifically in the heart (G alpha q-25) and nontransgenic siblings underwent microsurgical creation of transverse aortic coarctation and the morphometric, functional, and molecular characteristics of these pressure-overloaded hearts were compared at increasing times after surgery. Before aortic banding, isolated G alpha q-25 ventricular myocytes exhibited contractile depression (depressed +dl/dt and -dl/dt) and G alpha q-25 hearts showed a pattern of fetal gene expression similar to the known characteristics of nontransgenic pressure-overloaded mice. Three weeks after transverse aortic banding, G alpha q-25 left ventricles hypertrophied to a similar extent (approximately 30% increase) as nontransgenic mice. However, whereas nontransgenic mice exhibited concentric left ventricular remodeling with maintained ejection performance (compensated hypertrophy), G alpha q-25 left ventricles developed eccentric hypertrophy and ejection performance deteriorated, ultimately resulting in left heart failure (decompensated hypertrophy). The signature hypertrophy-associated progress of fetal cardiac gene expression observed at baseline in G alpha q-25 developed after aortic banding of nontransgenic mice but did not significantly change in aortic-banded G alpha q-25 mice. CONCLUSIONS: Intrinsic cardiac myocyte G alpha q activation stimulates fetal gene expression and depresses cardiac myocyte contractility. Superimposition of the hemodynamic stress of pressure overload on G alpha q overexpression stimulates a maladaptive form of eccentric hypertrophy that leads to rapid functional decompensation. Therefore G alpha q-stimulated cardiac hypertrophy is functionally deleterious and compromises the ability of the heart to adapt to increased mechanical load. This finding supports a reevaluation of accepted concepts regarding the mechanisms for compensation and decompensation in pressure-overload hypertrophy.