Gene therapy of malignant glioma with retroviral vectors and tumor-infiltrating progenitor cells

Gene therapy as a therapeutic strategy in the treatment of human gliomas is limited by the efficacy of gene transfer and intratumoral distribution of viral vectors. The major goals of this study were to enhance the gene transfer to glioma cells in vivo by using lentiviral vectors and to improve intratumoral distribution by selecting migratory progenitor cells that could function as packaging cells for the viral vectors. Therefore, the final goal was to establish tumor infiltrating packaging cells that release viral vectors within glioma in vivo. Lentiviral vectors were chosen to deliver genes into glioma cells. In contrast to currently used retroviral vectors, they transduce quiescent as well as mitotic cells. This is of major importance as within a defined treatment window, the majority of tumor cells are not mitotically active. However, lentiviral vectors can also infect normal brain cells. To define vectors with a specific tropism for glioma cells, lentiviral vectors pseudotyped with two different glycoproteins were used. Vectors pseudotyped with glycoproteins of the lymphocytic choriomeningitis virus (LCMV-GP) mediated efficient and specific transduction of rat glioma cells in vitro and in vivo, whereas vectors pseudotyped with the glycoproteins of the vesicular stomatatitis virus (VSV-G) preferentially transduced normal brain cells [Miletic et al., 2004]. Bone marrow derived progenitor cells were isolated to establish the tumor-infiltrating cells (BM-TICs) that could also serve as packaging cells. BM-TICs have a high passaging capacity in vitro, which is necessary for genetic modification and large scale production in the clinic. They were also found to show specific migration towards and into malignant glioma in vivo. In a therapeutic approach using BM-TICs stably expressing a suicide gene, an efficient therapeutic effect was demonstrated. The modified cells were also detected in vivo by non-invasive positron emission tomography (PET) and therapeutic outcome was followed-up by imaging methods and correlated with histopathology [Miletic et al., 2007]. To test packaging capabilities of BMTICs, the cells were modified with packaging constructs for retroviral LCMV-GP pseudotypes (BM-TIPCs). BM-TIPCs continuously produced retroviral vector particles for several weeks. Upon injection into experimental rat glioma, these cells migrated and were widely distributed within the tumor. Furthermore, released vector particles transduced glioma cells in solid as well as border areas [Fischer, Miletic et al., 2007]. In conclusion, the presented packaging system is highly attractive for future therapeutic applications in human glioblastoma especially in conjunction with an imaging-guided approach

Compressive sensing based velocity estimation in video data

This paper considers the use of compressive sensing based algorithms for velocity estimation of moving vehicles. The procedure is based on sparse reconstruction algorithms combined with time-frequency analysis applied to video data. This algorithm provides an accurate estimation of object's velocity even in the case of a very reduced number of available video frames. The influence of crucial parameters is analysed for different types of moving vehicles.Comment: 4 pages, 5 figure

Plagiarism frenzy in Serbia: In deep mud

A spate of plagiarism scandals has been shaking Serbia’s political and university life, with issues being raised about political parties’ and public officials’ malpractices in obtaining PhD degrees, and about the integrity of Serbian higher education in general

The impact of the financial crisis on the Gross Domestic Product: Technical Analysis

According to the existing literature in macroeconomics, a recession reduces output and employment in the short run; after an adjustment process, however, the output is expected to return to its long-term equilibrium and employment to come back to its natural level. Theory notwithstanding, many economists shed doubts on this idea; according to them, a recession may permanently reduce potential output by destroying capital, human capital, and knowledge. This thesis seeks to evaluate the impact of the European financial crisis on the potential output of different European countries. To answer the research question – For the so-defined “PIIGS” countries: how did the differential between potential GDP and observed GDP develop after the financial crisis of 2008? – the Box-Jenkins technique is implemented to shape an autoregressive integrated moving average model, which can forecast the development of the potential Gross Domestic Product. Additionally, an application of the Long Short-Term Memory Networks based on an Artificial Recurrent Neural Network architecture is proposed as a starting point on which to develop a more in-depth analysis. The outcomes resulting from the empirical analysis are mainly uniform across countries: a small impact is detected in the proximity of the financial crisis, which, however, expands over time. The only circumstance where it is possible to report a complete economic recovery is in Ireland. All the other economies reflect a situation in which the potential GDP forecasted is significantly above the observed GDP

What Kind of Ontologies Do We Need in the Biomedical Domain?

We tackle the question as to what sort of ontologies we primarily need in the biomedical domain. For this purpose, we will first provide a simple categorization of ontologies and describe an important use case related to modeling and documenting events. Then, the impact of using upper-level ontologies as a basis to address our use case will be shown in order to derive an answer to our research question. Although formal ontologies can serve as a starting point to understand conceptualization in a domain and facilitate interesting inferences, it is even more important to account for the dynamic and changing nature of knowledge. Being unconstrained by pre-defined categories and relationships can facilitate timely enrichment of a conceptual scheme and provide links and dependency structures in an informal manner. Semantic enrichment can be achieved by other mechanisms such as tagging or the creation of synsets as, for example, provided in WordNet

Computational study of structure formation and dynamic properties of organic molecules in hybrid inorganic/organic interfaces

Hybridstrukturen aus organischen und anorganischen Halbleitern (HIOS) vereinen die besten Eigenschaften beider Materialklassen zu Konjugaten mit großem Anwendungspotential. Ihre engen Struktur-Eigenschafts-Beziehungen, eröffnen viele interessante wissenschaftliche Herausforderungen. Um z.B. ihre optoelektronischen Eigenschaften vorherzusagen, müssen die früher Stadien des Dünnschichtwachstums erforscht werden. Das erste Ziel dieser Arbeit ist es, den Einfluss der Entropie auf die Oberflächendiffusion von kurzen Polyphenyl Molekülen auf amorphem Siliziumdioxid, a-SiO2 zu untersuchen. Das zweite Ziel ist es, den Einfluss partieller Fluorierung auf para-Sexiphenyls (p-6P) zu untersuchen. Des Weiteren untersuchen wir Selbstdiffusion von p-6P auf einer Zinkoxid (ZnO) Oberfläche und Selbstorganisation bzw. Schichtwachstum auf a-SiO2. Hierfür verwenden wir klassische atomistische Molekular- und Langevin-Dynamik-Simulationen, kombiniert mit klassischer Diffusionstheorie. In Bezug auf das erste Ziel quantifizieren wir die entropischen Beiträge zu den Freie-Energie-Barrieren für die Oberflächendiffusion von Polyphenylen unterschiedlicher Länge und zeigen, dass die Entropie zum dominierenden Teil der freien Energie für längere Moleküle wird. Zweitens demonstrieren wir, dass die Erhöhung der Anzahl fluorierter Gruppen im p-6P die Diffusion in der apolaren Richtung der ZnO-Oberfläche verringert, aber die Diffusion in der polaren Richtung erhöht. Drittens untersuchen wir den Einfluss der Fluorierung auf die Nukleation und das Wachstum von p-6P auf a-SiO2 mit einem Simulationsmodell, das experimentelle Gasphasenepitaxie nachahmt. Wir reproduzieren korrekte Einheitszellen bei Raumtemperatur und zeigen, dass die Erhöhung der Anzahl fluorierter Gruppen zu einem Schicht-für-Schicht-Wachstum auf der Oberfläche führt. Diese Arbeit ebnet den Weg für zukünftige Simulationen von Dünnschichtwachstum kleiner organischer Moleküle auf anorganischen Oberflächen.Hybrid structures of organic molecules and inorganic semiconductors (HIOS) combine favorable properties of each material into conjugates with great application potential. The optoelectronic properties of hybrid materials depend on the structure of individual molecules and their alignment relative to the inorganic surface. It is an interesting scientific challenge to predict the optoelectronic properties of HIOS based on studying the early stages of thin film growth and interface formation. The aim of this thesis is to investigate the effect of entropy in surface diffusion of short polyphenyl molecules on an amorphous silicon dioxide, a-SiO2. Second objective is to study the influence of partial fluorination of the organic para-sexiphenyl molecule (p-6P) on self-diffusion on an inorganic zinc oxide (ZnO) surface and on self-assembly and growth on the a-SiO2. For this we employ all-atom molecular dynamics and Langevin dynamics simulations, combined with classical diffusion theory. In respect to the first aim, we quantify entropic contributions to the free energy barrier of surface diffusion for short oligophenyls of varying length and demonstrate that entropy becomes even the dominant part of the free energy for longer molecules. For the second aim, we demonstrate that the increase in the number of fluorinated groups inside of the p-6P decreases the diffusivity in the apolar direction of the ZnO surface but increases the diffusivity in the polar direction. Thirdly, we study the influence of fluorination on nucleation and growth on a-SiO2 with a simulation model that mimics experimental deposition from the vapor. We reproduce the structures with correct room-temperature unit-cell parameters and demonstrate that the increase in the number of fluorinated groups leads to a layer-by-layer growth on the surface. This work can stimulate ideas for future simulations of nucleation and growth of small organic molecules with high tuning potential, on inorganic surfaces