Mechanisms contributing to the cardiac inotropic effect of Na pump inhibition and reduction of extracellular Na.

Reduction of the transsarcolemmal [Na] gradient in rabbit cardiac muscle leads to an increase in the force of contraction. This has frequently been attributed to alteration of Ca movements via the sarcolemmal Na/Ca exchange system. However, the specific mechanisms that mediate the increased force at individual contractions have not been clearly established. In the present study, the [Na] gradient was decreased by reduction of extracellular [Na] or inhibition of the Na pump by either the cardioactive steroid acetylstrophanthidin or by reduction of extracellular [K]. Contractile performance and changes in extracellular Ca (sensed by double-barreled Ca-selective microelectrodes) were studied in order to elucidate the underlying basis for the increase in force. In the presence of agents that inhibit sarcoplasmic reticulum (SR) function (10 mM caffeine, 100-500 nM ryanodine), reduction of the [Na] gradient produced increases in contractile force similar to that observed in the absence of caffeine or ryanodine. It is concluded that an intact, functioning SR is not required for the inotropic effect of [Na] gradient reduction (at least in rabbit ventricle). However, this does not exclude a possible contribution of enhanced SR Ca release in the inotropic response to [Na] gradient reduction in the absence of caffeine or ryanodine. Acetylstrophanthidin (3-5 microM) usually leads to an increase in the magnitude of extracellular Ca depletions associated with individual contractions. However, acetylstrophanthidin can also increase extracellular Ca accumulation during the contraction, especially at potentiated contractions. This extracellular Ca accumulation can be suppressed by ryanodine and it is suggested that this apparent enhancement of Ca efflux is secondary to an enhanced release of Ca from the SR. Under conditions where Ca efflux during contractions is minimized (after a rest interval in the presence of ryanodine), acetylstrophanthidin increased both the rate and the extent of extracellular Ca depletions. Thus, acetylstrophanthidin can increase both Ca influx and Ca efflux during the cardiac muscle contraction. These results can be explained by a simple model where the direction of net Ca flux via Na/Ca exchange during the action potential is determined by the changes in reversal potential of the Na/Ca exchange. Reduction of the [Na] gradient may well lead to net cellular Ca uptake (via Na/Ca exchange) and may also elevate the resting intracellular [Ca].(ABSTRACT TRUNCATED AT 400 WORDS

Civic Identities, Online Technologies: From Designing Civics Curriculum to Supporting Civic Experiences

Part of the Volume on Civic Life Online: Learning How Digital Media Can Engage Youth.Youth today are often criticized for their lack of civic participation and involvement in political life. Technology has been blamed, amongst many other causes, for fostering social isolation and youth's retreat into a private world disconnected from their communities. However, current research is beginning to indicate that these might be inaccurate perceptions. The Internet has provided new opportunities to create communities that extend beyond geographic boundaries, to engage in civic and volunteering activities across local and national frontiers, to learn about political life, and to experience the challenges of democratic participation. How do we leverage youth's interest in new technologies by developing technology-based educational programs to promote civic engagement? This chapter explores this question by proposing socio-technical design elements to be considered when developing technology-rich experiences. It presents a typology to guide the design of Internet-based interventions, taking into account both the affordances of the technology and the educational approach to the use of the technology. It also presents a pilot experience in a northeastern university that offered a pre-orientation program in which incoming freshman designed a three-dimensional virtual campus of the future and developed new policies and programs to strengthen the relationship between college campus and neighbor communities

Zakharov-Shabat system and hyperbolic pseudoanalytic function theory

In [1] a hyperbolic analogue of pseudoanalytic function theory was developed. In the present contribution we show that one of the central objects of the inverse problem method the Zakharov-Shabat system is closely related to a hyperbolic Vekua equation for which among other results a generating sequence and hence a complete system of formal powers can be constructed explicitly.Comment: 9 page

Influence of temperature on the calcium sensitivity of the myofilaments of skinned ventricular muscle from the rabbit.

The steady-state myofilament Ca sensitivity was determined in skinned cardiac trabeculae from the rabbit right ventricle (diameter, 0.13-0.34 mm) at 36, 29, 22, 15, 8, and 1 degree C. Muscles were stimulated to 0.5 Hz and stretched to a length at which maximum twitch tension was generated. The preparation was then skinned with 1% vol/vol Triton X-100 in a relaxing medium (10 mM EGTA, pCa 9.0). Each preparation was exposed to a series of Ca-containing solutions (pCa 6.3-4.0) at two of the six temperatures studied (temperature was regulated to +/- 0.1 degree C). The pCa values (mean +/- SD, n = 6) corresponding to half maximal tension at 36, 29, 22, 15, 8, and 1 degree C were 5.47 +/- 0.07, 5.49 +/- 0.07, 5.34 +/- 0.05, 5.26 +/- 0.09, 4.93 +/- 0.06, and 4.73 +/- 0.04, respectively. Mean (+/- SD) maximum tension (Cmax) developed by the preparation as a percentage of that at 22 degrees C was 118 +/- 10, 108 +/- 5, 74 +/- 6, 57 +/- 7, and 29 +/- 5% at 36, 29, 15, 8, and 1 degree C, respectively. As cooling led to a shift of Ca sensitivity towards higher [Ca2+] and a reduction of Cmax, the Ca sensitivity curves over this range of temperatures do not cross over as has been described for canine Purkinje fibers (Fabiato 1985). Since tension is decreased by cooling at all levels of [Ca2+] it is unlikely that changes in myofilament Ca sensitivity play a role in the large hypothermic inotropy seen in rabbit ventricular muscle. The increase in sensitivity of the myofilaments to Ca on warming from 1 to 29 degrees C might be related to the increase in force seen on rewarming from a rapid cooling contracture in intact rabbit ventricular muscle

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.

Strong unique continuation for general elliptic equations in 2D

We prove that solutions to elliptic equations in two variables in divergence form, possibly non-selfadjoint and with lower order terms, satisfy the strong unique continuation property.Comment: 10 page

Factorization Rules in Quantum Teichm\"uller Theory

We study the representation theory of the quantum Teichmueller space when going to infinity in the classical Teichmueller space. The geometric ingredients are the extension of Thurston's shear coordinates to the augmented Teichmueller space and the study of the Weil-Petersson Poisson structure for this extension. The result is analogous to the factorization rule found in conformal field theory.Comment: 28 pages, 7 figures. Version 2: corrected misprints, added Figure 3, corrected the proof of Proposition 9 and Lemma 1

Impact of climate induced glacial melting on coastal marine systems in the Western Antarctic Peninsula region

IMCOAST is an international research program that features a multidisciplinary approach involving geo and biological sciences, field investigations, remote sensing and modeling and knowledge into the hydrographical and biological history of the marine coastal ecosystems of the Western Antarctic Peninsula region