Rabbit models of heart disease.

Human heart disease is a major cause of death and disability. A variety of animal models of cardiac disease have been developed to better understand the etiology, cellular and molecular mechanisms of cardiac dysfunction and novel therapeutic strategies. The animal models have included large animals (e.g. pig and dog) and small rodents (e.g. mouse and rat) and the advantages of genetic manipulation in mice have appropriately encouraged the development of novel mouse models of cardiac disease. However, there are major differences between rodent and human hearts that raise cautions about the extrapolation of results from mouse to human. The rabbit is a medium-sized animal that has many cellular and molecular characteristics very much like human, and is a practical alternative to larger mammals. Numerous rabbit models of cardiac disease are discussed, including pressure or volume overload, ischemia, rapid-pacing, doxorubicin, drug-induced arrhythmias, transgenesis and infection. These models also lead to the assessment of therapeutic strategies which may become beneficial in human cardiac disease

Economies of Scale for Real Estate Investment Trusts

Using the translog cost function to estimate economies of scale for a sample of Real Estate Investment Trusts for the years 1992-1994, we find significant evidence that economies of scale exist for REITs for all years examined. The results show that measurement of scale economies is sensitive to the model used for the measurement. Individual characteristics of the REIT, such as type of management and degree of leverage, affect the magnitude of the scale economy. Additional variables accounting for property type diversification and geographic influences have little additional impact on the measured scale economies. Finally, the measured economies of scale for REITs vary considerably over time.

Vlasov Simulations of Trapping and Inhomogeneity in Raman Scattering

We study stimulated Raman scattering (SRS) in laser-fusion conditions with the Eulerian Vlasov code ELVIS. Back SRS from homogeneous plasmas occurs in sub-picosecond bursts and far exceeds linear theory. Forward SRS and re-scatter of back SRS are also observed. The plasma wave frequency downshifts from the linear dispersion curve, and the electron distribution shows flattening. This is consistent with trapping and reduces the Landau damping. There is some acoustic ($\omega\propto k$) activity and possibly electron acoustic scatter. Kinetic ions do not affect SRS for early times but suppress it later on. SRS from inhomogeneous plasmas exhibits a kinetic enhancement for long density scale lengths. More scattering results when the pump propagates to higher as opposed to lower density.Comment: 4 pages, 6 figures. Submitted to "Journal of Plasmas Physics" for the conference proceedings of the 19th International Conference on Numerical Simulation of Plasma

Simultaneous Measurements of Mitochondrial NADH and Ca2+ during Increased Work in Intact Rat Heart Trabeculae

AbstractThe main goal of this study is to investigate the role of mitochondrial [Ca2+], [Ca2+]m, in the possible up-regulation of the NADH production rate during increased workload. Such up-regulation is necessary to support increased flux through the electron transport chain and increased ATP synthesis rates. Intact cardiac trabeculae were loaded with Rhod-2(AM), and [Ca2+]m and mitochondrial [NADH] ([NADH]m) were simultaneously measured during increased pacing frequency. It was found that 53% of Rhod-2 was localized in mitochondria. Increased pacing frequency caused a fast, followed by a slow rise of the Rhod-2 signal, which could be attributed to an abrupt increase in resting cytosolic [Ca2+], and a more gradual rise of [Ca2+]m, respectively. When the pacing frequency was increased from 0.25 to 2Hz, the slow Rhod-2 component and the NADH signal increased by 18 and 11%, respectively. Based on a new calibration method, the 18% increase of the Rhod-2 signal was calculated to correspond to a 43% increase of [Ca2+]m. There was also a close temporal relationship between the rise (time constant ∼25s) and fall (time constant ∼65s) of [Ca2+]m and [NADH]m when the pacing frequency was increased and decreased, respectively, suggesting that increased workload and [Ca2+]c cause increased [Ca2+]m and consequently up-regulation of the NADH production rate

Calmodulin Mediates Differential Sensitivity of CaMKII and Calcineurin to Local Ca2+ in Cardiac Myocytes

AbstractCalmodulin (CaM) mediates Ca-dependent regulation of numerous pathways in the heart, including CaM-dependent kinase (CaMKII) and calcineurin (CaN), yet the local Ca2+ signals responsible for their selective activation are unclear. To assess when and where CaM, CaMKII, and CaN may be activated in the cardiac myocyte, we integrated new mechanistic computational models of CaM, CaMKII, and CaN with the Shannon-Bers model of excitation-contraction coupling in the rabbit ventricular myocyte. These models are validated with independent in vitro data. In the intact myocyte, model simulations predict that CaM is highly activated in the dyadic cleft during each beat, but not appreciably in the cytosol. CaMKII-δC was almost insensitive to cytosolic Ca due to relatively low CaM affinity. Dyadic cleft CaMKII exhibits dynamic frequency-dependent responses to Ca, yet autophosphorylates only when local phosphatases are suppressed. In contrast, dyadic cleft CaN in beating myocytes is predicted to be constitutively active, whereas the extremely high affinity of CaN for CaM allows gradual integration of small cytosolic CaM signals. Reversing CaM affinities for CaMKII and CaN also reverses their characteristic local responses. Deactivation of both CaMKII and CaN seems dominated by Ca dissociation from the complex (versus Ca-CaM dissociation from the target). In summary, the different affinities of CaM for CaMKII and CaN determine their sensitivity to local Ca signals in cardiac myocytes

Self-modulation instability of a long proton bunch in plasmas

An analytical model for the self-modulation instability of a long relativistic proton bunch propagating in uniform plasmas is developed. The self-modulated proton bunch resonantly excites a large amplitude plasma wave (wake field), which can be used for acceleration of plasma electrons. Analytical expressions for the linear growth rate and the number of exponentiations are given. We use the full three-dimensional particle-in-cell (PIC) simulations to study the beam self-modulation and the transition to the nonlinear stage. It is shown that the self-modulation of the proton bunch competes with the hosing instability which tends to destroy the plasma wave. A method is proposed and studied through PIC simulations to circumvent this problem which relies on the seeding of the self-modulation instability in the bunch

Plasmas and Controlled Nuclear Fusion

Contains report on one research project.U.S. Atomic Energy Commission (Contract AT(30-1)-3980

Microwave Electronics

Contains reports on three research projects