Hemodynamic and inotropic effects of endothelin-1 in vivo

Endothelin-1 (ET-1) is known to have strong vasoactive properties. Contradictory results have been reported with regard to its inotropic effects. This study examined the dose-dependent (500, 1000, 2500, 5000 and 10,000 ng ET-1/kg vs. NaCl controls) hemodynamic and inotropic effects of ET-1 in 53 open-chest rats during and after a 7-min infusion. Besides measurements in the intact circulation the myocardial function was examined by isovolumic registrations independent of peripheral vascular effects. A transient ET-1 induced (500, 1000, 2500, 5000 ng ET-1/kg) decrease of the left ventricular systolic pressure (LVSP) and the mean aortic pressure (AoPmean) was followed by a dose-related rise of these pressures (LVSP: -1%, -1%, +8%, +16% vs. preinfusion values; AoPmean: -11%, +9%, +39%, +52%). Heart rate (HR) was not influenced by ET-1. Due to the dose-dependent decrease of the stroke volume (SV) the cardiac output (CO) was reduced (CO: -8%, -23%, -40%, -50%). After an initial vasodilatation ET-1 elevates the total peripheral resistance (TPR: -1%, +49%, +139%, +215%) dose-dependently. 10,000 ng ET-1/kg was a lethal dose resulting in cardiac failure within minutes (low output). Since the maximum of the isovolumic LVSP (peak LVSP) and the corresponding dP/dtmax (peak dP/dtmax) were unchanged under ET-1, the isovolumic measurements do not indicate a positive inotropic effect of ET-1 in vivo in contrast to published results of in vitro experiments. It may be possible that a direct positive inotropic effect of ET-1 observed in in vitro studies is counterbalanced in vivo by an indirect negative inotropic effect due to the coronary-constrictive effect of ET-1

Structural organization, expression, and functional characterization of the murine cytomegalovirus immediate-early gene 3.

We have previously defined ie3 as a coding region located downstream of the ie1 gene which gives rise to a 2.75-kb immediate-early (IE) transcript. Here we describe the structural organization of the ie3 gene, the amino acid sequence of the gene product, and some of the functional properties of the protein. The 2.75-kb ie3 mRNA is generated by splicing and is composed of four exons. The first three exons, of 300, 111, and 191 nucleotides (nt), are shared with the ie1 mRNA and are spliced to exon 5, which is located downstream of the fourth exon used by the ie1 mRNA. Exon 5 starts 28 nt downstream of the 3' end of the ie1 mRNA and has a length of 1,701 nt. The IE3 protein contains 611 amino acids, the first 99 of which are shared with the ie1 product pp89. The IE3 protein expressed at IE times has a relative mobility of 88 kDa in gels, and a mobility shift to 90 kDa during the early phase is indicative of posttranslational modification. Sequence comparison reveals significant homology of the exon 5-encoded amino acid sequence with the respective sequence of UL 122, a component of the IE1-IE2 complex of human cytomegalovirus (HCMV). This homology is also apparent at the functional level. The IE3 protein is a strong transcriptional activator of the murine cytomegalovirus (MCMV) e1 promoter and shows an autoregulatory function by repression of the MCMV ie1/ie3 promoter. The high degree of conservation between the MCMV ie3 and HCMV IE2 genes and their products with regard to gene structure, amino acid sequence, and protein functions suggests that these genes play a comparable role in the transcriptional control of the two cytomegaloviruses

Characterization of the murine cytomegalovirus early transcription unit e1 that is induced by immediate-early proteins

The regulation of murine cytomegalovirus early (E) gene expression was studied in the cell line B25, which is stably transfected with the immediate-early ie1/ie3 gene complex. Infection of B25 cells in the presence of the protein synthesis inhibitor cycloheximide resulted in the expression of some E genes, whereas for the expression of other E genes prior protein synthesis was still mandatory, thus showing differences in the expression requirements of individual E genes. Transcription unit e1, a member of the E genes induced by immediate-early products of the ie1/ie3 gene complex, was characterized. It is located between map units 0.709 and 0.721 of the genome of murine cytomegalovirus strain Smith. A 2.6-kilobase RNA specified in this region is spliced from three exons of 912, 177, and 1,007 or 1,020 nucleotides, which are separated by introns of 93 and 326 nucleotides. The second AUG located in the first exon 119 nucleotides downstream of the 5' cap site is followed by an open reading frame of 990 nucleotides. The predicted polypeptide of 330 amino acids has a calculated molecular mass of 36.4 kilodaltons. Transfection with e1 revealed three antigenically related proteins of 36, 37, and 38 kilodaltons; these proteins probably represent differently modified forms of the predicted protein. These three proteins are phosphorylated and are associated with intranuclear inclusion bodies. A 33-kilodalton protein also derived from e1 was identified as a product of nonspliced transcripts. Comparison of amino acid sequences revealed homology between the murine cytomegalovirus transcription unit e1 and a human cytomegalovirus E transcription unit

Inlets, ducts, and nozzles

The internal fluid mechanics research program in inlets, ducts, and nozzles consists of a balanced effort between the development of computational tools (both parabolized Navier-Stokes and full Navier-Stokes) and the conduct of experimental research. The experiments are designed to better understand the fluid flow physics, to develop new or improved flow models, and to provide benchmark quality data sets for validation of the computational methods. The inlet, duct, and nozzle research program is described according to three major classifications of flow phenomena: (1) highly 3-D flow fields; (2) shock-boundary-layer interactions; and (3) shear layer control. Specific examples of current and future elements of the research program are described for each of these phenomenon. In particular, the highly 3-D flow field phenomenon is highlighted by describing the computational and experimental research program in transition ducts having a round-to-rectangular area variation. In the case of shock-boundary-layer interactions, the specific details of research for normal shock-boundary-layer interactions are described. For shear layer control, research in vortex generators and the use of aerodynamic excitation for enhancement of the jet mixing process are described

Inlets, ducts and nozzles

The internal fluid mechanics research program in inlets, ducts, and nozzles is described. The program consists of a balanced effort between the development of computational tools and the conduct of experimental research. The experiments are designed to better understand the fluid flow physics, to develop new or improved flow models, and to provide benchmark quality data sets for validation of the computational methods. The inlet, duct, and nozzle research program is described according to three major classifications of flow phenomena: highly three-dimensional flow fields; shock-boundary layer interactions; and shear layer control. Specific examples of current and future elements of the research program are described for each of these phenomena. In particular, the highly three-dimensional flow field phenomena is highlighted by describing the computational and experiemental research program in transition ducts having a round-to-rectangular area variation. In the case of shock-boundary layer interactions, the specific details of research for normal shock-boundary layer interactions are described. For shear layer control research in vortex generators and the use of aerodynamic excitation for enhancement of the jet mixing process are described. Future research in inlets, ducts, and nozzles will include more emphasis on three-dimensional full Navier-Stokes methods and corresponding experiments designed to concentrate on the appropriate three-dimensional fluid flow physics

Classical Concepts in Quantum Programming

The rapid progress of computer technology has been accompanied by a corresponding evolution of software development, from hardwired components and binary machine code to high level programming languages, which allowed to master the increasing hardware complexity and fully exploit its potential. This paper investigates, how classical concepts like hardware abstraction, hierarchical programs, data types, memory management, flow of control and structured programming can be used in quantum computing. The experimental language QCL will be introduced as an example, how elements like irreversible functions, local variables and conditional branching, which have no direct quantum counterparts, can be implemented, and how non-classical features like the reversibility of unitary transformation or the non-observability of quantum states can be accounted for within the framework of a procedural programming language.Comment: 11 pages, 4 figures, software available from http://tph.tuwien.ac.at/~oemer/qcl.html, submitted for QS2002 proceeding

The state space for two qutrits has a phase space structure in its core

We investigate the state space of bipartite qutrits. For states which are locally maximally mixed we obtain an analog of the ``magic'' tetrahedron for bipartite qubits--a magic simplex W. This is obtained via the Weyl group which is a kind of ``quantization'' of classical phase space. We analyze how this simplex W is embedded in the whole state space of two qutrits and discuss symmetries and equivalences inside the simplex W. Because we are explicitly able to construct optimal entanglement witnesses we obtain the border between separable and entangled states. With our method we find also the total area of bound entangled states of the parameter subspace under intervestigation. Our considerations can also be applied to higher dimensions.Comment: 3 figure

Microscopic gauge-invariant theory of the c-axis infrared response of bilayer cuprate superconductors and the origin of the superconductivity induced absorption bands

We report on results of our theoretical study of the c-axis infrared conductivity of bilayer high-Tc cuprate superconductors using a microscopic model involving the bilayer-split (bonding and antibonding) bands. An emphasis is on the gauge-invariance of the theory, which turns out to be essential for the physical understanding of the electrodynamics of these compounds. The description of the optical response involves local (intra-bilayer and inter-bilayer) current densities and local conductivities. The local conductivities are obtained using a microscopic theory, where the quasiparticles of the two bands are coupled to spin fluctuations. The coupling leads to superconductivity and is described at the level of generalized Eliashberg theory. Also addressed is the simpler case of quasiparticles coupled by a separable and nonretarded interaction. The gauge invariance of the theory is achieved by including a suitable class of vertex corrections. The resulting response of the model is studied in detail and an interpretation of two superconductivity-induced peaks in the experimental data of the real part of the c-axis conductivity is proposed. The peak around 400/cm is attributed to a collective mode of the intra-bilayer regions, that is an analogue of the Bogolyubov-Anderson mode playing a crucial role in the theory of the longitudinal response of superconductors. For small values of the bilayer splitting, its nature is similar to that of the transverse plasmon of the phenomenological Josephson superlattice model. The peak around 1000/cm is interpreted as a pair breaking-feature that is related to the electronic coupling through the spacing layers separating the bilayers.Comment: 18 pages, 15 figures, submitted to Phys. Rev.