817 research outputs found

    A note on "hierarchical models for multi-project planning and scheduling"

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    We consider the multi-mode resource-constrained project scheduling problem. The focus is on an algorithm which is supposed to find a makespan optimal solution. This algorithm has been presented in a recent paper by Speranza and Vercellis. The correctness of the algorithm is examined. Moreover, two counterexamples in which the algorithm does not lead to an existing optimal solution are presented

    Project scheduling with discrete time-resource and resource-resource tradeoffs

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    We consider an extension of the classical resource-constrained project scheduling problem (RCPSP), which covers discrete resource-resource and time-resource tradeoffs. As a result a project scheduler is permitted to identify several alternatives or modes of accomplishment for each activity of the project. The solution procedure we present is a considerable generalization of the branch-and-bound algorithm proposed by Demeulemeester and Herroelen, which is currently the most powerful method for optimally solving the RCPSP. More precisely, we extend their concept of delay alternatives by introducing mode alternatives. The basic enumeration scheme is then enhanced by dominance rules which highly increase the performance of the algorithm. The computational results obtained by solving the Standard ProGen instances indicate that the new method outperforms the most rapid procedure reported in the literature by a factor of four. Additionally and more important than the average reduction of the solution time is the substantial decrease of the variance of the solution times

    Interkulturelles Lehrforschungsprojekt – Untersuchungen zum Mathematikunterricht in Brasilien und Deutschland im Spiegel des Umweltschutzes

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    Im Rahmen der Lehramtsausbildung stellen Lehrforschungsprojekte eine Möglichkeit dar, Studierende an mathematik-didaktisches Forschen heranzuführen. Eine Definition für den Begriff „Lehrforschungsprojekt“ findet man bei Weidemann: „Allgemein gesagt ist ein Lehrforschungsprojekt eine Lehrveranstaltung, in der Studierende auf Basis ihres bereits erworbenen methodologischen und theoretischen Wissens und unter Anwendung bereits erlernter (bzw. im Rahmen der Lehrveranstaltung zu erwerbender) Methoden selbständig eine Forschungsfrage bearbeiten und ein kleines Forschungsprojekt durchführen, wobei sie sich forschend nicht nur inhaltlichthematisches Wissen erarbeiten, sondern auch Forschen lernen.“ (Weidemann, 2010). Neben einer soliden fachlichen und fachdidaktischen Grundbildung werden für die Lehramtsausbildung zudem zunehmend auch Forderungen nach Interdisziplinarität, Internationalität und Interkulturalität gestellt (vgl. Moll & Reiss 2013, Holzbrecher 2013). Derartige Forderungen umzusetzen, stellt eine große Herausforderung im Lehrbetrieb dar. Hier soll ein Versuch skizziert werden, im Rahmen eines Statistik- und Methodenseminars diesen Forderungen gerecht zu werden. Exemplarisch wird hier von der Erstellung und Auswertung von Teilen eines Fragebogens berichtet

    Asymmetric magnetic bubble expansion under in-plane field in Pt/Co/Pt: effect of interface engineering

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    We analyse the impact of growth conditions on asymmetric magnetic bubble expansion under in-plane field in ultrathin Pt / Co / Pt films. Specifically, using sputter deposition we vary the Ar pressure during the growth of the top Pt layer. This induces a large change in the interfacial structure as evidenced by a factor three change in the effective perpendicular magnetic anisotropy. Strikingly, a discrepancy between the current theory for domain-wall propagation based on a simple domain-wall energy density and our experimental results is found. This calls for further theoretical development of domain-wall creep under in-plane fields and varying structural asymmetry.Comment: 16 pages, 3 figure

    The bifunctional dihydrofolate reductase thymidylate synthase of Tetrahymena thermophila provides a tool for molecular and biotechnology applications

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    BACKGROUND: Dihydrofolate reductase (DHFR) and thymidylate synthase (TS) are crucial enzymes in DNA synthesis. In alveolata both enzymes are expressed as one bifunctional enzyme. RESULTS: Loss of this essential enzyme activities after successful allelic assortment of knock out alleles yields an auxotrophic marker in ciliates. Here the cloning, characterisation and functional analysis of Tetrahymena thermophila's DHFR-TS is presented. A first aspect of the presented work relates to destruction of DHFR-TS enzyme function in an alveolate thereby causing an auxotrophy for thymidine. A second aspect is to knock in an expression cassette encoding for a foreign gene with subsequent expression of the target protein. CONCLUSION: This system avoids the use of antibiotics or other drugs and therefore is of high interest for biotechnological applications

    Biochemical and molecular characterisation of Tetrahymena thermophila extracellular cysteine proteases

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    BACKGROUND: Over the last decades molecular biologic techniques have been developed to alter the genome and proteome of Tetrahymena thermophila thereby providing the basis for recombinant protein expression including functional human enzymes. The biotechnological potential of Tetrahymena has been proved in numerous publications, demonstrating fast growth, high biomass, fermentation in ordinary bacterial/yeast equipment, up-scalability, existence of cheap and chemical defined media. For these reasons Tetrahymena offers promising opportunities for the development of a high expression system. Yet optimised high yield strains with protease deficiency such as commonly used in yeast and bacterial systems are not available. RESULTS: This work presents the molecular identification of predominant proteases secreted into the medium by Tetrahymena thermophila. A one-step purification of the proteolytic enzymes is described. CONCLUSION: The information provided will allow silencing of protease activity by either knock out methods or by Tetrahymena specific antisense-ribosome-techniques. This will facilitate the next step in the advancement of this exciting organism for recombinant protein production

    Few-Particle Effects in Semiconductor Quantum Dots: Observation of Multi-Charged-Excitons

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    We investigate experimentally and theoretically few-particle effects in the optical spectra of single quantum dots (QDs). Photo-depletion of the QD together with the slow hopping transport of impurity-bound electrons back to the QD are employed to efficiently control the number of electrons present in the QD. By investigating structurally identical QDs, we show that the spectral evolutions observed can be attributed to intrinsic, multi-particle-related effects, as opposed to extrinsic QD-impurity environment-related interactions. From our theoretical calculations we identify the distinct transitions related to excitons and excitons charged with up to five additional electrons, as well as neutral and charged biexcitons.Comment: 4 pages, 4 figures, revtex. Accepted for publication in Physical Review Letter

    Targeted next-generation sequencing of cancer genes in poorly differentiated thyroid cancer

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    Poorly differentiated thyroid carcinoma (PDTC) is a rare malignancy with higher mortality than well-differentiated thyroid carcinoma. The histological diagnosis can be difficult as well as the therapy. Improved diagnosis and new targeted therapies require knowledge of DNA sequence changes in cancer-relevant genes. The TruSeq Amplicon Cancer Panel was used to screen cancer genomes from 25 PDTC patients for somatic single-nucleotide variants in 48 genes known to represent mutational hotspots. A total of 4490 variants were found in 23 tissue samples of PDTC. Ninety-eight percent (4392) of these variants did not meet the inclusion criteria, while 98 potentially pathogenic or pathogenic variants remained after filtering. These variants were distributed over 33 genes and were all present in a heterozygous state. Five tissue samples harboured not a single variant. Predominantly, variants in P53 (43% of tissue samples) were identified, while less frequently, variants in APC, ERBB4, FLT3, KIT, SMAD4 and BRAF (each in 17% of tissue samples) as well as ATM, EGFR and FBXW7 (each in 13% of tissue samples) were observed. This study identified new potential genetic targets for further research in PDTC. Of particular interest are four observed ERBB4 (alias HER4) variants, which have not been connected to this type of thyroid carcinoma so far. In addition, APC and SMAD4 mutations have not been reported in this subtype of cancer either. In contrast to other reports, we did not find CTNNB1 variants

    Secretion of functional human enzymes by Tetrahymena thermophila

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    BACKGROUND: The non-pathogenic ciliate Tetrahymena thermophila is one of the best-characterized unicellular eucaryotes used in various research fields. Previous work has shown that this unicellular organism provides many biological features to become a high-quality expression system, like multiplying to high cell densities with short generation times in bioreactors. In addition, the expression of surface antigens from the malaria parasite Plasmodium falciparum and the ciliate Ichthyophthirius multifiliis suggests that T. thermophila might play an important role in vaccine development. However, the expression of functional mammalian or human enzymes remains so far to be seen. RESULTS: We have been able to express a human enzyme in T. thermophila using expression modules that encode a fusion protein consisting of the endogenous phospholipase A(1 )precursor and mature human DNaseI. The recombinant human enzyme is active, indicating that also disulfide bridges are correctly formed. Furthermore, a detailed N-glycan structure of the recombinant enzyme is presented, illustrating a very consistent glycosylation pattern. CONCLUSION: The ciliate expression system has the potential to become an excellent expression system. However, additional optimisation steps including host strain improvement as wells as measures to increase the yield of expression are necessary to be able to provide an alternative to the common E. coli and yeast-based systems as well as to transformed mammalian cell lines
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