527 research outputs found

    Conceptualisation of family farms’ flexibility

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    Agricultural enterprises in transition countries face dynamic changes in the prevailing economic, legal and political conditions. The success of an enterprise depends on its ability to adjust its farming system in response to these changing conditions. To meet this challenge, flexible and adaptable production technology is required. Thus, the farm’s choice of technology is an important decision which determines its future performance. Although the concept of a firm’s flexibility is widely analysed in microeconomics literature, there is no comprehensive framework to facilitate the analysis of family farms’ flexibility, especially considering market imperfections and other obstacles associated with the transition process. In this paper we formulate the theoretical framework for flexibility analysis in order to investigate the impact of farm-specific characteristics on optimal flexibility design and to explain the differences between farms using different production technologies. In a simplified formal model, a competitive risk-averse firm producing one product is assumed to face fluctuating demand under uncertainty. By choosing the level of flexibility, the decision-maker determines the technology of the firm, expressed by the cost function. The optimal level of flexibility will be found by backward induction in the two-stage decision-making process, including ex ante technology decision and ex post output level decision. Using comparative statics and existing theoretical literature, some hypothesis about the relationship between flexibility and other firm characteristics will be formalised. Some possible model extensions that account for specific characteristics of the family farm business in transition countries, as well as future empirical analysis are discussed.flexibility, output price risk, family farms, Farm Management,

    Historical word-formation in Slavic

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    Slavic languages have a unique feature in word-formation that sets them apart from other Indo-European languages. This feature is the high degree of productivity of affixation, where derivation is more significant than compounding. Affixes, especially suffixes in noun formation, offer a wide range of possibilities. This phenomenon is a result of changes that occurred over time in the structure of Proto-Slavonic, leading to a gradual shift of morpheme boundaries in the word. As a result, the number and formal complexity of suffixes increased, which helped to solidify the semantic categories of word-formation. Additionally, the word-formation systems of the written standard languages in the Slavia Orthodoxa were also influenced by the peculiarities of word-formation in Old Church Slavonic

    Untersuchung der Struktur und Interaktion mit allosterischen Modulatoren der Familie C GPCRs mit Hilfe von Sequenz-, Struktur- und Ligand-basierten Verfahren

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    This study focuses on structural features of a particular GPCR type, the family C GPCRs. Structure- and ligand-based approaches were adopted for prediction of novel mGluR5 binding ligand and their binding modes. The objectives of this study were: 1. An analysis of function and structural implication of amino acids in the TM region of family C GPCRs. 2. The prediction of the TM domain structure of mGluR5. 3. The discovery of novel selective allosteric modulators of mGluR5 by virtual screening. 4. The prediction of a ligand binding mode for the allosteric binding site in mGluR5. GPCRs are a super-family of structurally related proteins although their primary amino acid sequence can be diverse. Using sequence information a conservation analysis of family C GPCRs should be applied to reveal characteristic differences and similarities with respect function, folding and ligand binding. Using experimental data and conservation analysis the allosteric binding site of mGluR5 should be characterized regarding NAM and PAM and selective ligand binding. For further evaluation experimental knowledge about family A GPCRs as well as conservation between vertebrate rhodopsins was planned to be compared to results obtained for family C GPCRs (Section 4.1 Conservation analysis of family C GPCRs). Since no receptor structure is available for any family C GPCR, discussion of conserved sequence positions between family A and C GPCRs requires the prediction of a receptor structure for mGluR5 using a family A receptor as template. In order to predict the mGluR5 structure a sequence alignment to a GPCR template protein will have to be proposed and GPCR specific features considered in structure calculation (Section 4.1.4 Structure prediction of mGluR5). The obtained structure was intended to be involved in ligand binding mode prediction of newly discovered active molecules. For discovery of novel selective mGluR modulators several ligand-based virtual screening protocols were adapted and evaluated. Prediction models were derived for selection of possibly active molecules using a diverse collection of known mGluR binding ligands. For that purpose a data collection of known mGluR binding ligands should be established and this reference collection analyzed with respect to different ligand activity classes, NAM or PAM and selective modulators. The prediction of novel NAMs and PAMs using several combinations of 2D-, 3D-, pharmacophore or molecule shape encoding methods with machine learning techniques and similarity determining methods should be tested in a prospective manner (Section 4.2 Virtual screening for novel mGluR modulators). In collaboration with Merz Pharmaceuticals (Merz GmbH & Co. KGaA, Frankfurt am Main, Germany) the modulating effect of a few hundred molecules should be approved in a functional cell-based assay. With the objective to predict a binding mode of the discovered active molecules, molecule docking should be applied using the allosteric binding site of the modeled mGluR5 structure (Section 4.2.4 Modeling of binding modes). Predicted ligand binding modes are to be correlated to conservation profiles that had resulted from the sequence-based entropy analysis and information from mutation experiments, and shall be compared to known ligand binding poses from crystal structures of family A GPCRs.Im Rahmen dieser Arbeit wurden Konzepte zur Aufklärung struktureller und funktioneller Eigenschaften von G-Protein gekoppelten Rezeptoren (GPCR) der Familie C entwickelt und angewendet. Mit unterschiedlichen Methodiken der Bio- und Chemieinformatik orientiert an experimentellen Ergebnissen wurden Fragestellungen bezĂĽglich des Funktionsmechanismus von GPCRs untersucht. In Verlauf wurde anhand verfĂĽgbarer experimenteller Daten aus Mutations- und Ligandenbindungsstudien ein Vergleich konservierter Bereiche der Rezeptor-Familien A und C angefertigt. Die Konserviertheitsanalyse stĂĽtzte sich auf die Berechnung der Shannon-Entropie und wurde fĂĽr ein multiples Sequenzalignment von Transmembrandomänen unterschiedlicher 96 Familie C GPCRs ermittelt. Konservierte Bereiche wurden mit Hilfe experimenteller Daten interpretiert und insbesondere zur Definition von Regionen in der allosterischen Bindetasche hinsichtlich Selektivität verwendet. Mit dem Ziel, neue selektive allosterische Modulatoren fĂĽr den metabotropen Glutamatrezeptor des Typs fĂĽnf (mGluR5) zu finden, wurden mehrere Liganden-basierte Ansätze zur virtuellen Vorhersage der Aktivität von MolekĂĽlen entwickelt und getestet. Die dabei angewendete Strategie basierte auf der Kenntnis bereits bekannter Liganden, deren Strukturen und Aktivitätswerte fĂĽr das Erstellen von Vorhersagemodelle genutzt werden konnten. Die prospektive Vorhersage stĂĽtzte sich auf unterschiedliche Methoden zur Ă„hnlichkeitsberechnung und Arten der MolekĂĽlkodierung. Die Testung der MolekĂĽle erfolgte hinsichtlich ihrer modulatorischen Wirkung am mGluR5. Die Art der Messung erfasste die Ă„nderungen des Ca2+-Levels in der Zelle. mGluR5-bindende Modulatoren wurden zur Selektivitätsbestimmung einer Testung am mGluR1 unterzogen. Insgesamt konnten 8 von 228 getesteten MolekĂĽlen im Aktivitätsbereich unter 10μM ermittelt werden, darunter befand sich ein positiver allosterischer Modulator. Von den restlichen sieben negativen Modulatoren (NAM) waren fĂĽnf selektiv fĂĽr mGluR5. Alle identifizierten NAMs wurden mittels molekularem Dockings auf mögliche Interaktion mit der Transmembrandomäne von mGluR5 untersucht. Die Bindungshypothese entsprach einer Ăśberlagerung der gefundenen MolekĂĽle und ihrer möglicher Interaktionspunkte. Exemplarisch am mGluR5 konnte somit die Eignung einer modellierten GPCR-Struktur fĂĽr eine Hypothesengenerierung bezĂĽglich Ligandenbindung und struktureller Zusammenhänge untersucht werden

    Identification and analysis of patterns in DNA sequences, the genetic code and transcriptional gene regulation

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    The present cumulative work consists of six articles linked by the topic ”Identification and Analysis of Patterns in DNA sequences, the Genetic Code and Transcriptional Gene Regulation”. We have applied a binary coding, to efficiently findpatterns within nucleotide sequences. In the first and second part of my work one single bit to encode all four nucleotides is used. The three possibilities of a one - bit coding are: keto (G,U) - amino (A,C) bases, strong (G,C) - weak (A,U) bases, and purines (G,A) - pyrimidines (C,U). We found out that the best pattern could be observed using the purine - pyrimidine coding. Applying this coding we have succeeded in finding a new representation of the genetic code which has been published under the title ”A New Classification Scheme of the Genetic Code” in ”Journal of Molecular Biology” and ”A Purine-Pyrimidine Classification Scheme of the Genetic Code” in ”BIOForum Europe”. This new representation enables to reduce the common table of the genetic code from 64 to 32 fields maintaining the same information content. It turned out that all known and even new patterns of the genetic code can easily be recognized in this new scheme. Furthermore, our new representation allows us for speculations about the origin and evolution of the translation machinery and the genetic code. Thus, we found a possible explanation for the contemporary codon - amino acid assignment and wide support for an early doublet code. Those explanations have been published in ”Journal of Bioinformatics and Computational Biology” under the title ”The New Classification Scheme of the Genetic Code, its Early Evolution, and tRNA Usage”. Assuming to find these purine - pyrimidine patterns at the DNA level itself, we examined DNA binding sites for the occurrence of binary patterns. A comprehensive statistic about the largest class of restriction enzymes (type II) has shown a very distinctive purine - pyrimidine pattern. Moreover, we have observed a higher G+C content for the protein binding sequences. For both observations we have provided and discussed several explanations published under the title ”Common Patterns in Type II Restriction Enzyme Binding Sites” in ”Nucleic Acid Research”. The identified patterns may help to understand how a protein finds its binding site. In the last part of my work two submitted articles about the analysis of Boolean functions are presented. Boolean functions are used for the description and analysis of complex dynamic processes and make it easier to find binary patterns within biochemical interaction networks. It is well known that not all functions are necessary to describe biologically relevant gene interaction networks. In the article entitled ”Boolean Networks with Biologically Relevant Rules Show Ordered Behavior”, submitted to ”BioSystems”, we have shown, that the class of required Boolean functions can strongly be restricted. Furthermore, we calculated the exact number of hierarchically canalizing functions which are known to be biologically relevant. In our work ”The Decomposition Tree for Analysis of Boolean Functions” submitted to ”Journal of Complexity”, we introduced an efficient data structure for the classification and analysis of Boolean functions. This permits the recognition of biologically relevant Boolean functions in polynomial time

    Chapter-spanning Review: Teaching Method for Networking in Math Lessons

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    Central to this article is networking in math lessons, whereby concentration is placed on the construction of a student-focused teaching method for the networking of mathematical knowledge in the lower secondary. Firstly, normative standards and descriptive results will be compared. Secondly, several already existing teaching methods for networking in math lessons will be added to the method of „chapter-spanning task variation“. Using this method, attention is be placed on the integration of mathematical content and specific social netowrk-form (e.g. teacher led classes, group-work etc.). This paper will be concluded with the presentation of the testing of the method in the school context)

    Scale effects on genomic modelling and prediction

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    In dieser Arbeit wird eine neue Methode für den skalenunabhängigen Vergleich von LD-Strukturen in unterschiedlichen genomischen Regionen vorgeschlagen. Verschiedene Aspekte durch Skalen verursachter Probleme – von der Präzision der Schätzung der Marke-reffekte bis zur Genauigkeit der Vorhersage für neue Individuen - wurden untersucht. Darüber hinaus, basierend auf den Leistungsvergleichen von unterschiedlichen statistischen Methoden, wurden Empfehlungen für die Verwendungen der untersuchten Methoden gege-ben.In dieser Arbeit wird eine neue Methode für den skalenunabhängigen Vergleich von LD-Strukturen in unterschiedlichen genomischen Regionen vorgeschlagen. Verschiedene Aspekte durch Skalen verursachter Probleme – von der Präzision der Schätzung der Marke-reffekte bis zur Genauigkeit der Vorhersage für neue Individuen - wurden untersucht. Darüber hinaus, basierend auf den Leistungsvergleichen von unterschiedlichen statistischen Methoden, wurden Empfehlungen für die Verwendungen der untersuchten Methoden gegebenIn this thesis, a novel method for scale corrected comparisons of LD structure in different genomic regions is suggested. Several aspects of scale-caused problems – from precision of marker effect estimates to accuracy of predictions for new individuals - are investigated. Furthermore, based on a comparison of the performance of different approaches, recommendations on the application of examined methods are given
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