Mathematical modeling of the Drosophila neuromuscular junction

Poster presentation: An important challenge in neuroscience is understanding how networks of neurons go about processing information. Synapses are thought to play an essential role in cellular information processing however quantitative and mathematical models of the underlying physiologic processes that occur at synaptic active zones are lacking. We are generating mathematical models of synaptic vesicle dynamics at a well-characterized model synapse, the Drosophila larval neuromuscular junction. This synapse's simplicity, accessibility to various electrophysiological recording and imaging techniques, and the genetic malleability intrinsic to Drosophila system make it ideal for computational and mathematical studies. We have employed a reductionist approach and started by modeling single presynaptic boutons. Synaptic vesicles can be divided into different pools; however, a quantitative understanding of their dynamics at the Drosophila neuromuscular junction is lacking [4]. We performed biologically realistic simulations of high and low release probability boutons [3] using partial differential equations (PDE) taking into account not only the evolution in time but also the spatial structure in two dimensions (the extension to three dimensions will be implemented soon). PDEs are solved using UG, a program library for the calculation of multi-dimensional PDEs solved using a finite volume approach and implicit time stepping methods leading to extended linear equation systems be solvedwith multi-grid methods [3,4]. Numerical calculations are done on multi-processor computers for fast calculations using different parameters in order to asses the biological feasibility of different models. In preliminary simulations, we modeled vesicle dynamics as a diffusion process describing exocytosis as Neumann streams at synaptic active zones. The initial results obtained with these models are consistent with experimental data. However, this should be regarded as a work in progress. Further refinements will be implemented, including simulations using morphologically realistic geometries which were generated from confocal scans of the neuromuscular junction using NeuRA (a Neuron Reconstruction Algorithm). Other parameters such as glutamate diffusion and reuptake dynamics, as well as postsynaptic receptor kinetics will be incorporated as well

Reactive anion exchange processes of synthesis of gadolinium iron garnet powders powders

In the present study, we carried out the synthesis of gadolinium iron garnet by using the method of anion resin exchange precipitation. To obtain precursors with the most suitable Gd/Fe ratio, different types of anion exchange resins were used. Products of synthesis were investigated by chemical analysis, X-Ray diffraction, and electron microscopy. Garnet phase Gd[3]Fe[5]O[12] was obtained at 10000C with crystallite of size 19 nm

Temperature-driven refacetting phase transition in Pb chains on Si(557)

By using quantitative low energy electron diffraction, we have studied the temperature-driven phase transition of Pb chains grown on Si(557) substrates at a surface concentration of 1.3 ML. This concentration, which is still below one physical monolayer, exhibits a unique switching of electrical conductance from one dimensional to two dimensional above 78 K, which is coupled to this phase transition, and was investigated for this reason. Annealing to 640 K causes a concentration-driven refacetting of the whole surface into large (223) facets at low temperatures, while along the chains a so-called (1,5) linear phase is formed, causing a tenfold periodicity. At Tc=78 K, we analyze a temperature-driven order-order transition along the [¯1¯12] direction in detail, which again turns out to be a refacetting transition. The two-dimensional character of this transition was seen by corresponding structural changes along the [1¯10] direction as well. Refacetting causes a change in periodicity and destroys the conditions of Fermi nesting necessary for one-dimensional conductance. © 2008 The American Physical Society.DF

Is time running out? The urgent need for appropriate global health curricula in Germany

Recently, representatives of politics, health officials and academia in Germany have advocated a greater role for Germany in matters concerning global health. However, health professionals in Germany are rarely taught about global health topics and accordingly real expertise in this field is lacking. To advance knowledge and competencies at German universities and adequately equip health professionals to achieve Germany’s political goals, global health curricula must be developed at medical schools and other institutions. Such ambitions raise questions about the required content and dimensions of global health curricula as the field is currently highly heterogeneous and ill defined. To systematically identify strengths and shortcomings of current curricula, we scrutinised the global health curriculum at our institution, Charité—Universitätsmedizin Berlin, using an analytical framework that integrates the various approaches of global health. Our analysis identified that four (technical, social justice, security and humanitarian) of five approaches are present in our core global health curriculum. Local and global aspects of the field are equally represented. We propose that the use of such a structured analytical framework can support the development of GH curricula for all health professionals—in Germany and elsewhere. But it can also help to evaluate existing curricula like ours at Charité. This framework has the potential to support the design of comprehensive GH trainings, serving German aspirations in politics and academia to promote health worldwide

No-wait Job-Shop Scheduling: Komplexität und Local Search

This thesis deals with the structure of the no-wait job-shop problem as well as the derivation of fast approximation algorithms. These algorithms are based on a decomposition approach into a sequencing and a timetabling problem that was initially introduced by Macchiaroli et al. (1999). In the thesis the problems are derived from a mixed integer formulation of the original problem and proved to be NP-hard in the strong sense. After presenting a fast heuristic approach for the timetabling problem, the focus lies on the sequencing problem for which several local search algorithms are presented. The algorithms are tested on a wide variety of benchmark problems for the classical job-shop problem. Among the algorithms, the tabu search approach outperforms all other algorithms that can be found in the literature in objective value as well as computation time

Submap Matching for Stereo-Vision Based Indoor/Outdoor SLAM

Autonomous robots operating in semi- or unstructured environments, e.g. during search and rescue missions, require methods for online on-board creation of maps to support path planning and obstacle avoidance. Perception based on stereo cameras is well suited for mixed indoor/outdoor environments. The creation of full 3D maps in GPS-denied areas however is still a challenging task for current robot systems, in particular due to depth errors resulting from stereo reconstruction. State-of-the-art 6D SLAM approaches employ graph-based optimization on the relative transformations between keyframes or local submaps. To achieve loop closures, correct data association is crucial, in particular for sensor input received at different points in time. In order to approach this challenge, we propose a novel method for submap matching. It is based on robust keypoints, which we derive from local obstacle classification. By describing geometrical 3D features, we achieve invariance to changing viewpoints and varying light conditions. We performed experiments in indoor, outdoor and mixed environments. In all three scenarios we achieved a final 3D position error of less than 0.23% of the full trajectory. In addition, we compared our approach with a 3D RBPF SLAM from previous work, achieving an improvement of at least 27% in mean 2D localization accuracy in different scenarios

Synaptic boutons sizes are tuned to best fit their physiological performances

To truly appreciate the myriad of events which relate synaptic function and vesicle dynamics, simulations should be done in a spatially realistic environment. This holds true in particular in order to explain as well the rather astonishing motor patterns which we observed within in vivo recordings which underlie peristaltic contractionsas well as the shape of the EPSPs at different forms of long-term stimulation, presented both here, at a well characterized synapse, the neuromuscular junction (NMJ) of the Drosophila larva (c.f. Figure 1). To this end, we have employed a reductionist approach and generated three dimensional models of single presynaptic boutons at the Drosophila larval NMJ. Vesicle dynamics are described by diffusion-like partial differential equations which are solved numerically on unstructured grids using the uG platform. In our model we varied parameters such as bouton-size, vesicle output probability (Po), stimulation frequency and number of synapses, to observe how altering these parameters effected bouton function. Hence we demonstrate that the morphologic and physiologic specialization maybe a convergent evolutionary adaptation to regulate the trade off between sustained, low output, and short term, high output, synaptic signals. There seems to be a biologically meaningful explanation for the co-existence of the two different bouton types as previously observed at the NMJ (characterized especially by the relation between size and Po), the assigning of two different tasks with respect to short- and long-time behaviour could allow for an optimized interplay of different synapse types. We can present astonishing similar results of experimental and simulation data which could be gained in particular without any data fitting, however based only on biophysical values which could be taken from different experimental results. As a side product, we demonstrate how advanced methods from numerical mathematics could help in future to resolve also other difficult experimental neurobiological issues

Genetic Dissection of Structural and Functional Components of Synaptic Plasticity. III. CREB Is Necessary for Presynaptic Functional Plasticity

AbstractIncreased cAMP (in dunce mutants) leads to an increase in the structure and function of the Drosophila neuromuscular junction. Synaptic Fasciclin II (Fas II) controls this structural plasticity, but does not alter synaptic function. Here, we show that CREB, the cAMP response element–binding protein, acts in parallel with Fas II to cause an increase in synaptic strength. Expression of the CREB repressor (dCREB2-b) in the dunce mutant blocks functional but not structural plasticity. Expression of the CREB activator (dCREB2-a) increases synaptic strength only in FasII mutants that increase bouton number. This CREB-mediated increase in synaptic strength is due to increased presynaptic transmitter release. Expression of dCREB2-a in a FasII mutant background genetically reconstitutes this cAMP-dependent plasticity. Thus, cAMP initiates parallel changes in CREB and Fas II to achieve long-term synaptic enhancement