Refine
Year of publication
- 2011 (82) (remove)
Document Type
- Doctoral Thesis (82) (remove)
Language
- English (82) (remove)
Has Fulltext
- yes (82)
Is part of the Bibliography
- no (82)
Keywords
- Geldpolitik (2)
- AIDS (1)
- Ackerbau (1)
- Analog Circuits (1)
- Analoges System (1)
- Analogschaltungen (1)
- Anbauflächen (1)
- Angiogenese (1)
- Anstrengung (1)
- Aufwandsschätzung (1)
Institute
- Biochemie und Chemie (18)
- Biowissenschaften (17)
- Physik (15)
- Geowissenschaften (6)
- Medizin (5)
- Psychologie (5)
- Wirtschaftswissenschaften (5)
- Informatik (4)
- Pharmazie (3)
- Institut für Ökologie, Evolution und Diversität (2)
Almost two decades ago, microRNAs were discovered as novel posttranscriptional regulators of gene expression. Since then, research efforts have uncovered their involvement in the control of various cellular processes including migration, proliferation and cell survival. Even more complex events, such as the formation of new blood vessels or organ development, have been shown to be tightly regulated and orchestrated by microRNAs. Due to their crucial regulatory role in tissue homeostasis in vertebrates, it does not come as a big surprise that dysregulated microRNA ex-pression is associated with pathology of diverse diseases. In this regard, the miR-17-92 cluster is a prime example since it has become famous for its amplified expression in tumours and its on-cogenic potential. Our lab demonstrated the expression of the members of the miR-17-92 cluster, namely miR-17, -18a, -19a, -20a, -19b and -92a, in endothelial cells and provided evidence for the anti-angiogenic activity of miR-92a in ECs as well as its important regulatory role in tissue re-covery after ischemia. In this work we addressed the function of the remaining members of the miR-17-92 cluster, i.e. miR-17, miR-18a, miR-19a and miR-20a, in endothelial cells and angiogenesis. Surprisingly, the individual members all displayed anti-angiogenic properties in endothelial cells in vitro, although overexpression of the whole cluster in transformed colonocytes was shown to promote tumour angiogenesis in a mouse model. In this context, we provide evidence that the individual miRs differentially affect the paracrine angiogenic activity of endothelial and tumour cells. Moreover, Antagomir-mediated inhibition of miR-17/20 in a mouse tumour model did not affect tumour angi-ogenesis, although miR-17/20 inhibition profoundly increased vascularization of Matrigel plugs. Thus, our research efforts suggest a differential involvement of the members of the miR-17-92 cluster in physiological and tumour angiogenesis. Additionally, we identified Janus kinase (JAK) 1 as a novel miR-17 target in endothelial cells and demonstrated the involvement of JAK1 in angio-genesis and in the phosphorylation of STAT3 in response to different cytokines in vitro. Overall, inhibition of specific members of the miR-17-92 cluster might represent an attractive therapeutic strategy to enhance angiogenesis in ischemic diseases. In the second part of the present work we investigated the therapeutic value of Antagomir-mediated microRNA inhibition in animal models of pulmonary arterial hypertension. Collectively, inhibition of miR-17 by the respective Antagomir revealed a significant improvement of pulmonary hemodynamics and cardiac function in both the chronic hypoxia mouse model and the mono-crotaline-induced lung injury rat model. Histomorphometric analysis of the lungs of the pulmonary hypertensive mice and rats uncovered a significant reduction of disease associated musculariza-tion of pulmonary arteries in Antagomir-17 treated animals compared to the control animals indicating interference with smooth muscle cell proliferation or survival. Probing of lung tissue of the pulmonary hypertensive rats for selected miR-17 targets uncovered a profound increase in the expression of the cyclin dependent kinase inhibitor p21 in the Antagomir-17 treated rats suggest-ing that inhibition of miR-17 impairs proliferation by impeding cell cycle progression. Analysis of miR-17 function in human smooth muscle cells in vitro corroborated the results from the animal experiments by demonstrating pro-proliferative activity of miR-17 and decreased levels of p21 in these cells. Collectively, our results indicate that Antagomir-17 improves pulmonary hemodyna-mics and cardiac function by interfering with vascular remodelling within the lung. Hence, inhibi-tion of miR-17 might be of therapeutic value to ameliorate the disease pattern in pulmonary arte-rial hypertension. In summary, the present work provides insights into the regulatory functions of members of the miR-17-92 cluster, especially miR-17, in blood vessels and suggests that specific inhibition of members of the miR-17-92 cluster might be a novel option to treat vascular diseases.
Purpose: The aim of this retrospective study is to evaluate the long term implant survival at 5 years, periimplantary conditions and prosthetic maintenance requirements for implant supported mandibular removable dentures retained on only 2 Ankylos® implants placed interforaminally in the mandible and using only conical double crown attachments. Materials and methods: Using the database at the Faculty of Dentistry, University of Frankfurt a selection process was performed to choose patients receiving only 2 Ankylos® implants placed interforaminally in the mandible and using only conical double crown attachments. Implant survival, periimplant condition (periodontal bleeding, plaque index and probing depth), bone loss (from panoramic radiographs) and mobility (using Periotest®) were monitored annually following implant loading. In addition a detailed prosthetic maintenance list was created for each patient based on their yearly checkups and emergency appointments. 37 patients with edentulous mandibles (34 with complete dentures in the upper jaw and 3 with tissue-tooth borne coverdentures) received 2 interforaminal Ankylos® implants (67 in the canine region, 7 in 2nd incisor region). Results: Mean Periotest® values at 5 years (-1.97 ±2.24) were lower than at loading (-1.47 ±2.33). A drop was seen in the Periotest® readings after the first year of loading. The decrease in mean Periotest® values between PTV5 and PTV 1 were not statistically significant (Tukey-Kramer test: p>0.05)
14 patients (37.8%) displayed no resorption at all with an average of 0.801 mm mesially and 0.807mm distally after 5 years. The most increase in bone loss was seen after the first year of loading. There was a gradual increase in bone resorption after the first year of loading. The differences between both distal and mesial bone resorption level at five years and at one year after loading are not significant (Tukey-Kramer test: p<0.05) Plaque and bleeding index values were low at a mean of 0.97 ±0.86 and 0.59 ±0.77 respectively after 5 years of loading. The increase from the first year of loading till the 5th year of loading was significantly higher for plaque measurements but not for bleeding measurements (Tukey-Kramer Test: p<0.05 and p>0.05 respectively). Mean probing depth values were higher after 5 years (2.61 ±0.92 mm) in comparison to the values at loading (2.15 ±0.75 mm). The difference between average values at year 5 and year 1 was statistically significant (Tukey-Kramer test: p<0.05). The most occurring form of maintenance was minor adjustments such as pressure point (15 patient or 40,5%) and relining 11 patients or 29.7%). Teeth breaking off the denture were less common (4 patients or 10.8%). 5 decementations of primary crowns occurred in 4 patients (10.8%) within the 5 year observation time. Other major complications were 4 loose abutments in 3 patients (8.1%), 3 decementations of secondary copings in 3 patients (8.1%) and 1 case (2.7%) in which the prosthetic metal framework fractured. No fracture of abutments or primary crowns occurred during the investigation. Implant survival was 100% percent after 5 years ,1 implants did not fulfil Albrektsson’s success criteria and showed more than 0.2 mm of bone loss per year after the first year of loading with the first year giving a success rate of 98.8%. Conclusion: In conclusion this study has demonstrated that patients have a wider variety of options when it comes to choosing a reliable prosthesis in the lower jaw. Patients with financial limitations can be provided with a reliable prosthetic option using removable dentures retained by conical double crown attachments on 2 implants. The requirements for such a construction are a mechanically stable implant system and a mechanically stable framework. When these prerequirments are fulfilled, the patient can be satisfied with a prosthesis of superior quality to other attachment types and the dentist can rely on the fact that frequent maintenance which costs time and money can be eliminated or at least reduced. Through further innovation this type of construction can also reach patients who are lower down on the economic scale such as elderly patients and retirees.
Protein translocation across the chloroplast membrane is mediated by molecular machinery composed of protein complexes termed the TOC/TIC (the outer/inner envelope chloroplasts translocases). This translocation process is regulated by metabolic energy in form of GTP and ATP and is influenced by the lipid composition of the membrane. The ability to study the function of a single complex “TOC” in vitro using purified protein or purified chloroplast outer envelope vesicles has been instrumental for our understanding of the mechanism underlying this process.
Indeed, the TOC complex has been purified by previously established procedures. However its functional and structural analyses are impaired by the limited yield of purified protein. Therefore, protocols for native TOC complex purification are described here. The complex isolation is achieved by direct biochemical treatment of biological membrane hosting this complex or by tandem affinity purification of modified protein complex components from generated transgenic plants.
Furthermore, in this thesis, radioactive based in vitro import assays are described, namely those that allow monitoring translocation activity across the outer envelope of chloroplast. Based on the analysis of knock-out plants and isolated complexes it was previously suggested that lipid dependence of protein translocation might exist. Thus, the question was raised whether the lipid composition of the membrane has a direct influence on the behavior and functionality of the TOC translocon, or whether additional components of the chloroplast membrane account for the observed effect in vivo. To answer this question, a technique for vesicle fusion was developed. The principal aim was to explore the effect of an exchange of the lipid environment surrounding the complex translocon. This method helped to demonstrate that the SQDG and PI act stimulatory on the translocation across the outer envelope of chloroplast, whereas DGDG exhibits an inhibitory effect on TOC complex functionality.
Within the present work, photodissociation reactions on 100Mo, 93Mo and 92Mo isotopes were studied by means of the Coulomb dissociation method at the LAND setup at GSI. Experimental data on these isotopes are important to explain the problem of the underproduction of the lighter p-nuclei - 92; 94Mo - within the models of the p-process nucleosynthesis. The reaction rates used in the nucleosynthesis calculations are usually obtained within the framework of the statistical model. In order to verify the model predictions and reduce the uncertainties, experimental measurements of the reaction cross sections are required. In particular, the data on (γ,n) reactions are of interest, since these reactions were shown to dominate the p-process flow in the molybdenum mass region.
As a result of the analysis of the present experiment, integrated Coulomb excitation cross sections of the 100Mo(γ,n), 100Mo(γ,2n), 93Mo(γ,n) and 92Mo(γ,n) reactions were determined. The measurement of the 93Mo isotope is particularly important, since this nucleus is unstable, and the corresponding cross section has not been measured before.
It should be emphasized that Coulomb dissociation is a unique tool to study photoninduced reactions on unstable nuclei, which is especially relevant in the context of nucleosynthesis network calculations. However, because of to the complexity of the data analysis procedure and a number of model assumptions that are required in order to extract the Coulomb excitation cross section from the data, one of the main aspects of this thesis was to verify the method by comparing the results with the previously published data obtained with real photon beams. Integrated cross sections of the 100Mo(γ,n) and 100Mo(γ,2n) reactions were directly compared to the data by Beil et al., obtained at Saclay with photons from positron annihilation, while an indirect comparison could be performed with a recent photoactivation measurement by Erhard and co-workers. A reasonable agreement was observed for the 1n channel: a scaling factor of 0.8 ± 0.1 between our result and Beil et al. data is consistent with the scaling factor of 0.89±0.09 reported by Erhard et al. between their data and Beil et al. data. Both results are in agreement with the scaling factor of 0.85 ± 0.03 recommended by Berman et al. for the data measured at Saclay on nuclei in the respective mass region. A somewhat lower factor of 0.61 ± 0.09 between the present data and Beil et al. data was obtained for the 2n channel. The discrepancy might be explained by both the substantial efficiency correction that has to be applied to the LAND data in the two-neutron case, as well as by an insufficiently accurate assumption that the Saclay neutron detector efficiency is energy- and multiplicity- independent.
A second important topic of the present thesis is the investigation of the efficiency of the CsI gamma detector. The calorimetric information that it delivers is essential to reconstruct the energy-differential cross section from the present measurement. The data taken with the gamma calibration sources shortly after the experiment were used for the investigation. In addition, a test experiment in refined conditions was conducted within the framework of this thesis. Numerous GEANT3 simulations of the detector were performed in order to understand various aspects of its performance. As a result, the efficiency of the detector was determined to be approximately a factor of 2 lower than the efficiency expected from the simulation. This result is consistent with several independent investigations, which were performed using different methods. At the same time, a remarkable agreement between the simulated and experimental data was achieved under assumption that the inefficiency of the detector is explained by the loss of data from a number of crystals, which are randomly chosen in each event according to their averaged performance ratio (the ”on-off” effect). The reasons for the observed malfunction are yet not fully clear. Regardless of the exact reason, in the present conditions a deconvolution of the measured data from the CsI response is not possible. Consequently, within the framework of this thesis, the results are presented in terms of integrated cross sections. A search for alternative methods of data interpretation, allowing to extract energy-differential information out of the available data, in currently ongoing.
In the more recent experiments at the LAND setup, where the Crystal Ball gamma detector was used as a calorimeter, the reconstruction of the energy-differential cross section with a reasonable resolution was already shown to be feasible. It means that, even considering the uncertainties of the present experiment of the order of 10%, the uncertainties of the statistical model predictions, which are on average estimated to be within a factor of 1.5-2, can already be constrained.
The analysis of the present experiment is still in progress. As a next step, Coulomb excitation cross section for 94Mo will be obtained. The 94Mo(γ,n) reaction cannot be studied by photoactivation, since the life time of the daughter nucleus is too long (4000 y). At the same time, this reaction plays a key role in the p-process nucleosynthesis.
The future of the LAND setup - the R3B setup1 at FAIR2 - will take advantage of a three orders of magnitude higher intensity of the radioactive beams [85], as well as of a completely new detector system. High-resolution measurements of the energy-differential cross sections will be possible for exotic nuclei, which were never accessible in the laboratory before. Such measurements will open great opportunities for nuclear astrophysics, allowing to obtain high-quality experimental data even for regions of the nuclear chart where the statistical model calculations are not applicable.
Stem cells are often referred to as potential candidates for the treatment of different pathologies. Their ability to differentiate into various tissue specific cell types offers the possibility to engineer cell systems or organs for replacement. One of the main questions in stem cell biology is how stemness properties are regulated and to what extend this regulation is intrinsic or conveyed by the direct microenvironment (‘niche’). In order to elucidate such regulatory processes, it is informative to analyze processes or molecules that are shared between different stem cell populations.
One such molecule that is expressed on a wide range of different embryonic and adult as well as tumor stem cells is the ABC transporter Abcg2. ABC transporters in general are transmembrane proteins that actively extrude endo- and exotoxins as well as xenobiotics, thereby protecting cells and organs. Additionally, ABC transporters are responsible for drug resistance in many cancers. A well-described characteristic of stem cells expressing Abcg2 is the formation of the ‘side population’ (SP) phenotype: An active Abcg2 transporter mediates the efflux of a particular fluorescent dye that is taken up by all cells, thus leading to a less brightly stained population. This phenomenon is widely used to characterize and isolate the most primitive stem cell subpopulation from embryonic and adult tissues, including tumors. Besides its role as toxin transporter little is known about the function of Abcg2 in stem cells. This is mainly due to the fact that its physiological substrate in stem cells remains unknown. The identification of such substrates is therefore of high interest because it would directly link the activity of ABC transporters to regulatory mechanisms in stem cell biology.
In the present study we wanted to test the hypothesis that the sphingolipid ceramide is a physiological substrate of the ABC transporter Abcg2. Sphingolipids are potent second messengers and are known to have regulatory functions in stem cells. In particular, the sphingolipid ceramide is described as a mediator of controlled cell death and inducer of differentiation. It is suggested that stem cells need to keep their intracellular ceramide content at low levels in order to prevent apoptosis or differentiation. We propose that Abcg2 and ceramide interact and that this interaction leads to changes in the absolute or relative amounts of ceramide. This in turn influences basic stem cell functions such as self renewal and differentiation.
We show that Abcg2 prevents cells from accumulating fluorescence labeled ceramide. Furthermore, exogenously applied ceramides inhibit the transport activity of Abcg2, measured by a decrease of the side population phenotype. This inhibitory effect is consistent with a competitive inhibition mechanism. Additionally, we show that active Abcg2 can increase the ceramide concentration in cell culture supernatant. Finally we demonstrate that Abcg2 protects from ceramide induced cytotoxicity in human cell lines. In summary, these in vitro results strongly suggest that Abcg2 has the ability to regulate ceramide levels.
Murine hematopoietic stem cells (HSCs) are the best characterized adult stem cell system so far. By using 7-colour fluorescence-activated cell sorting (FACS) we established the purification of the most primitive HSCs, reflected by their high engraftment capability when transplanted to lethally irradiated mice. By using this sorted cell populations it was in addition possible to establish a system to reproducibly manipulate HSCs ex vivo. This experimental system will serve in further elucidating the physiological consequences of Abcg2 mediated changes in ceramide levels on stem cells in vivo.
Taken together, this study shows that Abcg2 has the ability to regulate ceramide levels in cells. This in turn can lead to cellular protection from ceramide induced apoptosis. Additionally, the experimental techniques to further analyze the role of Abcg2 and ceramide in the most primitive hematopoietic stem cells were successfully established, enabling more detailed analysis in the future.
In the work presented herein the microscopic transport model BAMPS (Boltzmann Approach to Multi-Parton Scatterings) is applied to simulate the time evolution of the hot partonic medium that is created in Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC) and in Pb+Pb collisions at the recently started Large Hadron Collider (LHC). The study is especially focused on the investigation of the nuclear modification factor R_{AA}, that quantifies the suppression of particle yields at large transverse momentum with respect to a scaled proton+proton reference, and the simultaneous description of the collective properties of the medium in terms of the elliptic flow v_{2} within a common framework.
In this thesis, laboratory investigations have been conducted to investigate several processes occurring during the melt segregation (crystal settling and compaction processes), as well as during emplacement of plutons. With the help of three different sets of centrifuge experiments rates of these three magmatic processes have been evaluated. In the first series of the centrifuge experiments, the diapiric ascent of buoyant material from two source layers at different depths was studied. Through five models, the hypothesis of ascending diapirs was tested and it was demonstrated whether a rising diapir ascends straight upward or if its ascent might be deviated by another buoyant, softer – and consequently easier to travel through – layer which is located within the overburden strata. We were interested under which conditions they can be formed. For this purpose we placed perturbations on top of both the buoyant layers; either with a set-off of both the protrusions (for three of these experiments), or with both protrusion sitting directly on top of each other (for one of the experiments). In the first experiment, we omitted the perturbations, to test which pathways diapirs take which grow from natural Rayleigh-Taylor instabilities. Three others experiments differed in the viscosity contrast between the overburden and the buoyant material. Through the experimental runs, the effects of different overburden viscosities and perturbation positions on the number of the diapirs were observed. The modeling results show that two diapirs rising from the offset perturbations do not take the same pathway through the overburden layer. Rather, each diapir takes a different pathway, with the deeper diapir piercing through its overburden while rising, regardless if it was a buoyant layer or denser overburden layers. However, when the two perturbations were situated directly above each other in the different PDMS layers, this resulted in the formation of one big diapir rather than several smaller ones, and the overburden layer was less deformed than with offset perturbations. Diapiric structures as those derived from the models without perturbation and where the perturbation are offset occur within Great Kavir Basin (Iran), where numerous salt diapirs grew from several salt horizons, which show a similar spatial distribution. The resulting structure observed in the model where the two perturbations situated directly above each other, is close to what is observed in composite batholiths such as the Flasergranitoid Zone within the Bergsträßer Odenwald Crystalline Complex (Germany). The second series of models were aimed to study crystal settling within a magma. For this purpose experiments with an artificial magma of 30 vol% olivine in 70 vol% basaltic melt were conducted to elucidate the formation mechanisms and time scales of gravitational cumulates. Through the experiments, two physical processes have been observed: (i) purely mechanical compaction, and (ii) chemical compaction induced by dissolution and re-precipitation of settled crystals. The results reveals that the mechanical settling of the dense olivine suspension occurs at about 1/6 the speed of simple Stokes settling, and a sedimentation exponent n of 4.1 is found. Evidences of chemical compaction induced by dissolution and re-precipitation of settled crystals have been highlighted by a detailed analysis of the fine structure of olivine grain boundaries. This last has revealed (1) the presence of Ca, which is characteristic only for MORB-melt, at the interface of two adjacent Ol-grains even when no melt is present; (2) a not fully crystallized boundary layer between two adjacent olivine grains. The crystal size distribution curves and the grain size growth exponent n ~3.6 indicate that diffusion controlled Ostwald ripening is the dominant crystal growth mechanism in concentrated magmatic suspensions. Finally, the formation times in natural olivine adcumulates have been calculated. The last series of centrifuge experiments deals with the crystal-melt settling-floating mechanism in a system composed of natural two pyroxene gabbro. The results have revealed a vertical evolution of the major and trace elements in the melt phase. Then, a numerical modelling of the sedimentation process of the crystals has been made in order to describe the compaction evolution with time. In comparing the numerical simulation with the centrifuge modelling, the stratification of the compacted layer in the runs is reproduced in numerical models. Moreover, on the base of the numerical and centrifuge modelling, a sedimentation exponent describing a deviation of settling in concentrated suspensions from Stokes sedimentation has been evaluated. Finally, the numerical simulation is applied to the Muskox intrusion to estimate the formation time and the melt fraction evolution in using the hindered sedimentation model calculations.
A pattern is a word that consists of variables and terminal symbols. The pattern language that is generated by a pattern A is the set of all terminal words that can be obtained from A by uniform replacement of variables with terminal words. For example, the pattern A = a x y a x (where x and y are variables, and the letter a is a terminal symbol) generates the set of all words that have some word a x both as prefix and suffix (where these two occurrences of a x do not overlap). Due to their simple definition, pattern languages have various connections to a wide range of other areas in theoretical computer science and mathematics. Among these areas are combinatorics on words, logic, and the theory of free semigroups. On the other hand, many of the canonical questions in formal language theory are surprisingly difficult. The present thesis discusses various aspects of the inclusion problem of pattern languages. It can be divide in two parts. The first one examines the decidability of pattern languages with a limited number of variables and fixed terminal alphabets. In addition to this, the minimizability of regular expressions with repetition operators is studied. The second part deals with descriptive patterns, the smallest generalizations of arbitrary languages through pattern languages ("smallest" with respect to the inclusion relation). Main questions are the existence and the discoverability of descriptive patterns for arbitrary languages.
Visual perception has increasingly grown important during the last decades in the robotics domain. Mobile robots have to localize themselves in known environments and carry out complex navigation tasks. This thesis presents an appearance-based or view-based approach to robot self-localization and robot navigation using holistic, spherical views obtained by cameras with large fields of view. For view-based methods, it is crucial to have a compressed image representation where different views can be stored and compared efficiently. Our approach relies on the spherical Fourier transform, which transforms a signal defined on the sphere to a small set of coefficients, approximating the original signal by a weighted sum of orthonormal basis functions, the so-called spherical harmonics. The truncated low order expansion of the image signal allows to compare input images efficiently, and the mathematical properties of spherical harmonics also allow for estimating rotation between two views, even in 3D. Since no geometrical measurements need to be done, modest quality of the vision system is sufficient. All experiments shown in this thesis are purely based on visual information to show the applicability of the approach. The research presented on robot self localization was focused on demonstrating the usability of the compressed spherical harmonics representation to solve the well-known kidnapped robot problem. To address this problem, the basic idea is to compare the current view to a set of images from a known environment to obtain a likelihood of robot positions. To localize the robot, one could choose the most probable position from the likelihood map; however, it is more beneficial to apply standard methods to integrate information over time while the robot moves, that is, particle or Kalman filters. The first step was to design a fast expansion method to obtain coefficient vectors directly in image space. This was achieved by back-projecting basis functions on the input image. The next steps were to develop a dissimilarity measure, an estimator for rotations between coefficient vectors, and a rotation-invariant dissimilarity measure, all of them purely based on the compact signal representation. With all these techniques at hand, generating likelihood maps is straightforward, but first experiments indicated strong dependence on illumination conditions. This is obviously a challenge for all holistic methods, in particular for a spherical harmonics approach, since local changes usually affect each single element of the coefficient vector. To cope with illumination changes, we investigated preprocessing steps leading to feature images (e.g. edge images, depth images), which bring together our holistic approach and classical feature-based methods. Furthermore, we concentrated on building a statistical model for typical changes of the coefficient vectors in presence of changes in illumination. This task is more demanding but leads to even better results. The second major topic of this thesis is appearance-based robot navigation. I present a view-based approach called Optical Rails (ORails), which leads a robot along a prerecorded track. The robot navigates in a network of known locations which are denoted as waypoints. At each waypoint, we store a compressed view representation. A visual servoing method is used to reach a current target waypoint based on the appearance and the current camera image. Navigating in a network of views is achieved by reaching a sequence of stopover locations, one after another. The main contribution of this work is a model which allows to deduce the best driving direction of the robot based purely on the coefficient vectors of the current and the target image. It is based on image registration as the classical method by Lucas-Kanade, but has been transferred to the spectral domain, which allows for great speedup. ORails also includes a waypoint selection strategy and a module for steering our nonholonomic robot. As for our self-localization algorithm, dependance on illumination changes is also problematic in ORails. Furthermore, occlusions have to be handled for ORails to work properly. I present a solution based on the optimal expansion, which is able to deal with incomplete image signals. To handle dynamic occlusions, i.e. objects appearing in an arbitrary region of the image, we use the linearity of the expansion process and cut the image into segments. These segments can be treated separately, and finally we merge the results. At this point, we can decide to disregard certain segments. Slicing the view allows for local illumination compensation, which is inherently non-robust if applied to the whole view. In conclusion, this approach allows to handle the most important criticism to holistic view-based approaches, that is, occlusions and illumination changes, and consequently improves the performance of Optical Rails.
Clathrin-mediated endocytosis (CME) involves spatially and temporally restricted molecular dynamics.
Although protein kinases and the actin cytoskeleton contribute to the process, whether and how
functions of kinases and actin are integrated remains unknown. Here, we demonstrate that neural
Wiskott-Aldrich syndrome protein (N-WASP) and protein kinase CK2 form a complex and localize on
clathrin-coated vesicles (CCVs). N-WASP binds to and is phosphorylated by CK2, thereby reducing the
kinase activity of CK2. By contrast, N-WASP-promoted actin polymerization is decreased upon both
phosphorylation and binding of CK2. Knockdown of N-WASP and CK2, alone or in combination, results
in impaired endocytosis of epidermal growth factor (EGF) and increased cell-surface levels of EGF
receptor (EGFR). In order to rescue the phenotype of N-WASP-CK2 knockdown cells, both N-WASP and
CK2 activities and abilities to assemble in a complex are required. In summary, this study shows that the
N-WASP-CK2 complex integrates in a single circuit different activities contributing to CME of EGFR and
that the interplay between the two proteins optimizes this process.