The avian tectobulbar tract: development, explant culture, and effects of antibodies on the pattern of neurite outgrowth

The tectobulbar tract is the first long-distance projecting fiber pathway to appear during the development of the avian optic tectum (dorsal half of the mesencephalon). Immunologically stained wholemounts of the E3 mesencephalon reveal that the early tectobulbar axons course in a dorsal-to-ventral direction and abruptly turn in a caudal direction shortly before reaching the ventral midline. During subsequent development, more tectobulbar axons are generated that form a parallel array of thick fascicles coursing ventrally within the mesencephalon. At this later stage of development, the tectobulbar tract bifurcates into an ipsilateral and contralateral pathway, both growing in a caudal direction near the mesencephalic ventral midline. Bifurcation and change in direction of growth is accompanied by a complete loss of the fasciculated growth pattern. Each tectobulbar axon is thus divided into a proximal fasciculated and a distal unfasciculated segment. Tectobulbar fascicles occupy the most superficial surface layer of the mesencephalon at early stages and are displaced deeper into the tissue beginning at embryonic day 5. In both of these locations, tectobulbar axons express molecules involved in axon-axon and axon-substrate interactions like the G4 antigen, neural cell adhesion molecule (N-CAM), neurofascin, and T61 antigen as revealed by immunohistochemistry and immunoblotting. Stripes of the mesencephalon explanted onto a basal lamina substratum show vigorous outgrowth of neurites. These processes grow in fascicles at a growth rate of 40 microns/h. Staining of the neurites with specific antibodies, as well as the position of the retrogradely labeled cell bodies, is in agreement with these processes being tectobulbar axons. This in vitro explant system was used to investigate the expression and possible functional involvement of N-CAM, neurofascin, G4 protein, and T61 antigen in the growth of these axons. The presence of antigen- binding fragments of polyclonal anti-G4 antibodies completely blocks fasciculation of the neurites but has no influence on their rate of elongation. Antibodies against N-CAM and neurofascin have no detectable effects. The number and length of the in vitro growing axons are reduced by the monoclonal T61 antibody. This effect is reversible. The elucidation of the exact course in vivo and the accessibility to the axons growing in vitro make the tectobulbar tract an excellent model system for the investigation of the role of these and other proteins in axonal growth and guidance during the development of the CNS

An immersed boundary method for particles and bubbles in magnetohydrodynamic flows

This thesis presents a numerical method for the phase-resolving simulation of rigid particles and deformable bubbles in viscous, magnetohydrodynamic flows. The presented approach features solid robustness and high numerical efficiency. The implementation is three-dimensional and fully parallel suiting the needs of modern high-performance computing. In addition to the steps towards magnetohydrodynamics, the thesis covers method development with respect to the immersed boundary method which can be summarized in simple words by From rigid spherical particles to deformable bubbles. The development comprises the extension of an existing immersed boundary method to non-spherical particles and very low particle-to-fluid density ratios. A detailed study is dedicated to the complex interaction of particle shape, wake and particle dynamics. Furthermore, the representation of deformable bubble shapes, i.e. the coupling of the bubble shape to the fluid loads, is accounted for. The topic of bubble interaction is surveyed including bubble collision and coalescence and a new coalescence model is introduced. The thesis contains applications of the method to simulations of the rise of a single bubble and a bubble chain in liquid metal with and without magnetic field highlighting the major effects of the field on the bubble dynamics and the flow field. The effect of bubble coalescence is quantified for two closely adjacent bubble chains. A framework for large-scale simulations with many bubbles is provided to study complex multiphase phenomena like bubble-turbulence interaction in an efficient manner

Prostaglandin E Positively Modulates Endothelial Progenitor Cell Homeostasis: An Advanced Treatment Modality for Autologous Cell Therapy

Aims: The mobilization of endothelial progenitor cells (EPC) and their functioning in postnatal neovascularization are tightly regulated. To identify new modulators of EPC homeostasis, we screened biologically active prostaglandin E compounds for their effects on EPC production, trafficking and function. Methods and Results: We found that EPC are a rich source for prostaglandin E 2 (PGE 2), stimulating their number and function in an auto- and paracrine manner. In vivo blockade of PGE 2 production by selective cyclooxygenase-2 inhibition virtually abrogated ischemia-induced EPC mobilization demonstrating its crucial role in EPC homeostasis following tissue ischemia. Conversely, ex vivo treatment of isolated EPC with the clinically approved PGE 1 analogue alprostadil enhanced EPC number and function. These effects were mediated by increased expression of the chemokine receptor CXCR4 and were dependent on nitric oxide synthase activity. Most importantly, ex vivo PGE 1 pretreatment of isolated EPC significantly enhanced their neovascularization capacity in a murine model of hind limb ischemia as assessed by laser Doppler analysis, exercise stress test and immunohistochemistry. Conclusions: The conserved role for PGE in the regulation of EPC homeostasis suggests that ex vivo modulation of the prostaglandin pathway in isolated progenitor cells may represent a novel and safe strategy to facilitate cell-based therapies. Copyright (C) 2009 S. Karger AG, Base

Optimized supernova constraints on dark energy evolution

A model-independent method to study the possible evolution of dark energy is presented. Optimal estimates of the dark energy equation of state w are obtained from current supernovae data from Riess et al. (2004) following a principal components approach. We assess the impact of varying the number of piecewise constant estimates of w using a model selection method, the Bayesian information criterion, and compare the most favored models with some parametrizations commonly used in the literature. Although data seem to prefer a cosmological constant, some models are only moderately disfavored by our selection criterion: a constant w, w linear in the scale factor, w linear in redshift and the two-parameter models introduced here. Among these, the models we find by optimization are slightly preferred. However, current data do not allow us to draw a conclusion on the possible evolution of dark energy. Interestingly, the best fits for all varying-w models exhibit a w<-1 at low redshifts.Comment: 6 pages, 4 figures; typos removed and reference added to match published versio

Improving system of objectives maturity through systematic reuse of knowledge using ontology-based knowledge representations

Technical products are developed to meet the needs of different stakeholders. In addition, various constraints from all phases of the product life cycle have to be considered. In existing work, this information and its dependencies are systematically represented in the so-called system of objectives. A major challenge in modeling the system of objectives is that the necessary information in the system of objectives is often incomplete and uncertain. In addition, this uncertainty and the maturity of the system of objectives cannot be directly quantified because the target state of the system of objectives often cannot be unambiguously described. This research investigates a methodical approach to assess and improve the maturity of the system of objectives. Two means to reduce uncertainty and thus increase the maturity of the system of objectives are the systematic reuse of knowledge and the systematic building of knowledge through verification and validation activities

Perceived stress and team performance during a simulated resuscitation

Purpose: Barriers to optimal performance of cardiopulmonary resuscitation may partly relate to human factors, such as stress and specific emotions. The aim of this study was to investigate whether mental stress and different perceived emotions have a negative impact on the performance of rescuers. Methods: This prospective, observational study was conducted at the Simulator Center of the University Hospital Basel, Switzerland. A total of 120 medical students (70% female) participated in teams of three. They reported levels of perceived stress, feeling overwhelmed, motivation and specific emotions before, during, and after a simulated resuscitation. The association of stress/overload (index of stress and feeling overwhelmed), motivation, and specific emotions with resuscitation performance defined as hands-on time during the first 180s after cardiac arrest was investigated. Results: During resuscitation, levels of stress/overload, motivation, and negative emotions were significantly higher as compared to the periods before and after resuscitation. In contrast, positive emotions were highest before and after resuscitation and significantly lower during resuscitation. In general, females reported higher stress/overload and negative emotions, whereas males reported more positive emotions. A multivariate linear regression model showed negative associations of stress/overload (regression coefficient −18.12, 95% CI −30.73, −5.51, p=0.006) and positive associations of motivation (regression coefficient 13.45, 95% CI 0.95, 25.95, p=0.036) with resuscitation performance. Conclusion: A simulated cardiac arrest caused substantial perceived stress/overload and negative emotions, particularly in female students, which adversely impacted resuscitation performance. Further studies are required to expand our findings to more experienced medical professionals and investigate whether stress coping strategies improve resuscitation performanc