Biomedical subjects
Publications and source records attributed to P Engels.
Repulsive laser potential pulses applied to vortex lattices of rapidly rotating Bose-Einstein condensates create propagating density waves which we have observed experimentally and modeled computationally to high accuracy. We have observed a rich variety of dynamical phenomena ranging from interference effects and shock-wave formation to anisotropic sound propagation.
We observe interlaced square vortex lattices in rotating dilute-gas spinor Bose-Einstein condensates (BEC). After preparing a hexagonal vortex lattice in a one-component BEC in an internal atomic state |1, we coherently transfer a fraction of the superfluid to a different state |2. The subsequent evolution of this pseudo-spin-1/2 superfluid towards a state of offset square lattices involves an intriguing interplay of phase-separation and -mixing dynamics, both macroscopically and on the length scale of the vortex cores, and a stage of vortex turbulence. The stability of the square structure is proved by its response to applied shear perturbations. An interference technique shows the spatial offset between the two vortex lattices. Vortex cores in either component are filled by fluid of the other component, such that the spin-1/2 order parameter forms a Skyrmion lattice.
We create rapidly rotating Bose-Einstein condensates in the lowest Landau level by spinning up the condensates to rotation rates Omega > 99% of the centrifugal limit for a harmonically trapped gas, while reducing the number of atoms. As a consequence, the chemical potential drops below the cyclotron energy 2 variant Planck's over 2pi Omega. While in this mean-field quantum-Hall regime we still observe an ordered vortex lattice, its elastic shear strength is strongly reduced, as evidenced by the observed very low frequency of Tkachenko modes. Furthermore, the gas approaches the quasi-two-dimensional limit. The associated crossover from interacting- to ideal-gas behavior along the rotation axis results in a shift of the axial breathing mode frequency.
We directly image Tkachenko waves in a vortex lattice in a dilute-gas Bose-Einstein condensate. The low (sub-Hz) resonant frequencies are a consequence of the small but nonvanishing elastic shear modulus of the vortex-filled superfluid. The frequencies are measured for rotation rates as high as 98% of the centrifugal limit for the harmonically confined gas. Agreement with a hydrodynamic theory worsens with increasing rotation rate, perhaps due to the increasing fraction of the volume displaced by the vortex cores. We also observe two low-lying m=0 longitudinal modes at about 20 times higher frequency.
We study the formation of large vortex aggregates in a rapidly rotating dilute-gas Bose-Einstein condensate. When we remove atoms from the rotating condensate with a tightly focused, resonant laser, the density can be locally suppressed, while fast circulation of a ring-shaped superflow around the area of suppressed density is maintained. Thus a giant vortex core comprising 7 to 60 phase singularities is formed. The giant core is only metastable, and it will refill with distinguishable single vortices after many rotation cycles. The surprisingly long lifetime of the core can be attributed to the influence of strong Coriolis forces in the condensate. In addition we have been able to follow the precession of off-center giant vortices for more than 20 cycles.
We have studied the dynamics of large vortex lattices in a dilute-gas Bose-Einstein condensate. While undisturbed lattices have a regular hexagonal structure, large-amplitude quadrupolar shape oscillations of the condensate are shown to induce a wealth of nonequilibrium lattice dynamics. When exciting an m=-2 mode, we observe shifting of lattice planes, changes of lattice structure, and sheetlike structures in which individual vortices appear to have merged. Excitation of an m=+2 mode dissolves the regular lattice, leading to randomly arranged but still strictly parallel vortex lines.
We have developed an evaporative cooling technique that accelerates the rotation of an ultracold 87Rb gas, confined in a static harmonic potential. As a normal gas is evaporatively spun up and cooled below quantum degeneracy, it is found to nucleate vorticity in a Bose-Einstein condensate. Measurements of the condensate's aspect ratio and surface-wave excitations are consistent with effective rigid-body rotation. Rotation rates of up to 94% of the centrifugal limit are inferred. A threshold in the normal cloud's rotation is observed for the intrinsic nucleation of the first vortex. The threshold value lies below the prediction for a nucleation mechanism involving the excitation of surface waves of the condensate.
INTRODUCTION/PURPOSE: The complexity of cardiac surgery requires continuous training, education and information addressing different individuals: physicians (cardiac surgeons, residents, anaesthesiologists, cardiologists), medical students, perfusionists and patients. Efficacy and efficiency of education and training will likely be improved by the use of multimedia information systems. Nevertheless, computer-based education is facing some serious disadvantages: 1) multimedia productions require tremendous financial and time resources; 2) the obtained multimedia data are only usable for one specific target user group in one specific instructional context; 3) computer based learning programs often show deficiencies in the support of individual learning styles and in providing individual information adjusted to the learner's individual needs. In this paper we describe a computer-system, providing multiple re-use of multimedia-data in different instructional sceneries and providing flexible composition of content to different target user groups. TOOLS AND METHODS: The ZYX document model has been developed, allowing the modelling and flexible on-the-fly composition of multimedia fragments. It has been implemented as a DataBlade module into the object-relational database system Informix Dynamic Server and allows for presentation-neutral storage of multimedia content from the application domain, delivery and presentation of multimedia material, content based retrieval, re-use and composition of multimedia material for different instructional settings. Multimedia data stored in the repository, that can be processed and authored in terms of our identified needs is created by using a next generation authoring environment called CardioOP-Wizard. High-quality intra-operative video is recorded using a video-robot. Difficult surgical procedures are visualized with generic and CT-based 3D-animations. RESULTS: An on-line architecture for multiple re-use and flexible composition of media data has been established. The system contains the following instructional applications (prototypically implemented): a multimedia textbook on operative techniques, an interactive module for problem based-training, a module for creation and presentation of lectures and a module for patient information. Principles of cognitive psychology and knowledge management have been employed in the program. These instructional applications provide information ranging from basic knowledge at the beginner's level, procedural knowledge for the advanced level to implicit knowledge for the professional level. For media-annotation with meta-data a metainformation system, the CardioOP-Clas has been developed. The prototype focuses on aortocoronary bypass grafting and heart transplantation. CONCLUSION: The demonstrated system reflects an integrated approach in terms of information technology and teaching by means of multiple re-use and composition of stored media-items to the individual user and the chosen educational setting on different instructional levels.
Mutations in a protein designated Parkin were shown to be involved in the pathogenesis of autosomal recessive juvenile parkinsonism. Nothing is known about its regional and subcellular distribution in the mouse. In order to elucidate the Parkin mRNA and protein distribution in the adult mouse, the mouse cDNA was cloned and polyclonal antisera were generated against the N-terminal part of mouse Parkin. The antibodies were shown to be specific using Western blot analysis, immunostaining of cells transfected with mouse Parkin and pre-absorption tests. The Parkin protein expression profile was studied using immunohistochemistry and Western blot analysis and was compared with that of the mRNA yielded by in situ hybridization and RT-PCR analysis. Parkin protein was widely distributed in all subdivisions of the mouse brain. Low levels were found in the telencephalon and diencephalon, while the brainstem contained a large number of cells heavily expressing Parkin. Ultrastructural analysis and double immunohistochemistry revealed that the majority of Parkin-expressing cells were neurons, while only single glial cells exhibited immunostaining. The protein was distributed nonhomogeneously throughout the entire cytoplasm. A subpopulation of Parkin-immunopositive cells displayed speckled immunodeposits in the nucleus. Dopaminergic cells of the substantia nigra pars compacta exhibited high levels of Parkin mRNA but no Parkin protein, while the striatum contained immunopositive profiles but no mRNA signals. Our data indicate that Parkin is neither restricted to a single functional system nor associated with a particular transmitter system. The speckled nuclear distribution of Parkin immunoreactivity strongly suggests a role for Parkin in gene expression.
BACKGROUND: In the abdominal aorta, the use of knitted rather than woven dacron prostheses has shown an early and slow late dilation. The dilation of woven versus knitted dacron prostheses in the thoracic aortic position has not yet been investigated. METHOD: From 1992, 25 patients entered a prospective study: 13 Gelweave and 12 Gelseal prostheses (diameter 18-26 mm) were implanted in the descending thoracic aorta. Computed tomography (CT) scans without contrast-enhancement were performed 2 weeks, and 1 and 2 years postoperatively. The full length of the grafts was scanned and the diameter was measured in mm measured at a level outside the areas of intercostal artery reimplantation. Patient determinants analysed were age, hypertension and implantation diameter of the grafts. The Gelseal group had a mean age of 63.7 years and seven were males. The Gelweave group had a mean age of 67.8 years and seven were males. RESULTS: the mean implantation diameters were 19.6 +/- 1.7 mm and 22.0 +/- 2.7 mm (P = 0.02) for the Gelseal and Gelweave grafts, respectively. On the CT-scans at 2 weeks postoperatively, the diameter had increased by 18.8 +/- 4.8% (P = 0.0001) in the Gelseal and by 5.7 +/- 6.4% (P = 0.007) in the Gelweave grafts. This difference in diameter at 2 weeks between the two prostheses was significant (P < 0.0000 1). At 1 year the diameter had increased by 28.4 +/- 5.2% (P = 0.0001) and by 8.4 +/- 4.6% (P = 0.0003) for the Gelseal and Gelweave grafts, respectively, compared with the implantation diameter. The increase in diameter between the postoperative values at 2 weeks and those at 1 year was statistically significant in the Gelseal grafts (P = 0.0002) but not in the Gelweave grafts (P = 0.56). At 2 years an increase in diameter by 31.4 +/- 5.2% (P = 0.0001) and by 7.4 +/- 7.1% (P = 0.014) for the knitted and woven prosthetic grafts, respectively, was noted compared with the initial implantation diameter. The increase in diameter between the CT measurements at 2 weeks and those at 2 years was statistically significant in the Gelseal group (P = 0.001) but not in the Gelweave group (P = 0.86). The difference in this late increase in diameter between the two implanted grafts was also significant (P < 0.005). Age, hypertension and initial diameter did not appear to be significant determinants. CONCLUSION: In contrast to the Gelseal prosthesis in the descending aorta, the Gelweave prosthesis does not show any late dilation.
Ser-13 and Ser-54 were shown to provide the sole sites for the protein kinase A (PKA)-mediated phosphorylation of the human cAMP-specific phosphodiesterase isoform HSPDE4D3. The ability of PKA to phosphorylate and activate HSPDE4D3 was mimicked by replacing Ser-54 with either of the negatively charged amino acids, aspartate or glutamate, within the consensus motif of RRES54. The PDE4 selective inhibitor rolipram ¿4-[3-(cyclopentoxy)-4-methoxyphenyl]-2-pyrrolidone¿ inhibited both PKA-phosphorylated HSPDE4D3 and the Ser-54-->Asp mutant, with an IC50 value that was approximately 8-fold lower than that seen for the non-PKA-phosphorylated enzyme. Lower IC50 values for inhibition by rolipram were seen for a wide range of non-activated residue 54 mutants, except for those which had side-chains able to serve as hydrogen-bond donors, namely the Ser-54-->Thr, Ser-54-->Tyr and Ser-54-->Cys mutants. The Glu-53-->Ala mutant exhibited an activity comparable with that of the PKA phosphorylated native enzyme and the Ser-54-->Asp mutant but, in contrast to the native enzyme, was insensitive to activation by PKA, despite being more rapidly phosphorylated by this protein kinase. The activated Glu-53-->Ala mutant exhibited a sensitivity to inhibition by rolipram which was unchanged from that of the native enzyme. The double mutant, Arg-51-->Ala/Arg-52-->Ala, showed no change in either enzyme activity or rolipram inhibition from the native enzyme and was incapable of providing a substrate for PKA phosphorylation at Ser-54. No difference in inhibition by dipyridamole was seen for the native enzyme and the Ser-54-->Asp and Ser-54-->Ala mutants. A model is proposed which envisages that phosphorylation by PKA triggers at least two distinct conformational changes in HSPDE4D3; one of these gives rise to enzyme activation and another enhances sensitivity to inhibition by rolipram. Activation of HSPDE4D3 by PKA-mediated phosphorylation is suggested to involve disruption of an ion-pair interaction involving the negatively charged Glu-53. The increase in susceptibility to inhibition by rolipram upon PKA-mediated phosphorylation is suggested to involve the disruption of a hydrogen-bond involving the side-chain hydroxy group of Ser-54.
Currently not much is known about the distribution and function of the phosphodiesterase type 7 (PDE-7) enzyme. Therefore, we carried out an extensive distribution analysis of the rat and human PDE-7 by in situ hybridization as well as RT-PCR. We isolated a partial rat cDNA clone that is highly homologous to the sequence of the human PDE-7 gene. RT-PCR tissue distribution analyses revealed expression of the mRNA of the human and rat-enzymes in most of the examined tissues, like adult heart, lung, brain, and liver, as well as in several cell lines of the immune system. In situ hybridization with the rat PDE-7 showed a differential expression pattern during the late phases of the developing rat brain with higher levels of mRNA in cortical and telencephalic structures in d 16, 18, and 20 embryonic stages, whereas in adult rat brain, higher amounts of mRNA could only be detected in cerebellum and, to a lesser extent, in hippocampus and the olfactory system.
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Phospholipases A2 (PLA2) form an extended class of enzymes that play an important role in signal transduction. Phospholipase A2-like (PLA2L) belongs to the secreted forms of phospholipases A2, but constitutes a new subgroup. We have assigned the gene for this enzyme to human chromosome 8q24-qter using fluorescence in situ hybridization and radiation hybrid mapping techniques.
We have analyzed the brain distribution of the rat 5-HT4 receptor mRNA. A receptor specific probe was used for in situ hybridization of rat brain sections. Abundant expression of the 5-HT4 receptor mRNA was observed in the olfactory system, striatum, medial habenula and the hippocampal formation, while faint or no specific signals could be detected in most other areas of the brain. Several brain areas which display strong ligand binding do not contain mRNA, suggesting an axonal localization of the 5-HT4 receptor.
The 'famille nombreuse' of cyclic nucleotide phosphodiesterases, responsible for degrading the ubiquitous second messenger molecules, cAMP and cGMP, maintains its place as a major focus of interest for many research laboratories in both academia and industry. The increase in knowledge of the primary sequences, plus the availability of selective inhibitors, are rapidly improving our insight into the structure, regulation and function of these pivotal enzymes of cellular homeostasis. Here, Thomas Müller, Peter Engels and John Fozard focus on family 4 of the phosphodiesterases, which is of particular interest owing to both the number of genes (and splice variants) and the emergence of selective inhibitors, which are enabling the functional significance of these enzymes to be defined.
When replacing the thoracic aorta, gelatin-sealed triaxial knitted Dacron prostheses are used as they have zero porosity and are easy to handle. It is known that knitted prostheses (not triaxially constructed), when implanted in the abdominal aorta or in the peripheral vessels, show a dilatation of 10-20%. The initial in vivo expansion of this prosthesis in the thoracic aorta was assessed using computed tomography scanning in 18 patients. The graft sizes used were 18mm (n = 4). 20mm (n = 5). 22mm (n = 4), 26mm (n = 1), 28mm (n = 2) and 30mm (n = 2). All patients were kept normotensive postoperatively. Computed tomography scan measurement was performed within 4 weeks of operation. using standard computed tomography equipment and no contrast. Two radiologists checked and agreed upon the slice levels and measurements compared with the manufacturer's stated size referring to internal diameter of the crimped prosthesis. The mean(s.d.) 'in vivo' size was 16.2(6)% larger. This 'true size' should be taken as the reference measurement when considering further dilatation over the period of follow-up.