902 research outputs found

    Using recommendations to help novices to reuse design knowledge

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    This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-21530-8_35. Copyright @ Springer 2011.The use of pattern languages is not so straightforward since its users have to identify the patterns they need, browsing the language and understanding both the benefits and trade-offs of each pattern as well as the relations and interactions it has with other patterns. Novice designers might benefit from tools that assist them in this learning task. In this paper we describe a recommendation tool embedded in a visual environment for pattern-based design which aims at suggesting patterns to help novice designers to produce better designs and understand the language.Spanish Ministry of Science and Innovatio

    Member Value Optimierung in föderal strukturierten NPO

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    In föderal strukturierten Verbänden mit einem Dachverband und juristisch selbstständigen Mitgliedsorganisationen gehört das Spannungsfeld zwischen nationaler (zentraler) Steuerung und (dezentralem) Föderalismus zum Alltag. Dabei geht es um die Frage, wie sich die Teilorganisationen unter einem gemeinsamen Dach arrangieren, um ein gemeinsames Ziel zu erreichen. Ob und wie effizient das gelingt, hängt unter anderem davon ab, ob die Mitgliedsorganisationen einen Mehrwert und Nutzen durch ihre Dachorganisation wahrnehmen. Das zeigt die Studie am Beispiel der Marketing-Koordination in acht Dachverbänden und 86 Sektionen. Eine bessere Zusammenarbeit weisen jene Verbände auf, denen es gelingt, eine Organisationskultur zu schaffen, mit der sich die Mitgliedsorganisationen identifizieren können

    Untersuchungen zur Diagnose und Therapie der felinen infektiösen Peritonitis

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    Gene therapy of malignant gliomas with retroviral pseudotype vectors

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    In der retroviralen Gentherapie von Gliomen ist die effiziente und spezifische Transduktion von Gliomzellen ausschlaggebend für den Therapieerfolg. Als besonders schwierig erwies sich in diesem Zusammenhang [1]: (i) die ausreichende Distribution retroviraler Vektoren im Tumorgewebe (ii) die Transduktion einzelner, infiltrierender Tumorzellen und (iii) die Transduktion von Tumorbereichen mit geringer Zellzeilungsaktivität. In der vorliegenden Arbeit wurden verschiedene Strategien angewandt, um diese Ziele zu erreichen. Lentivirale Vektoren wurden mit Glykoproteinen des Lymphozytären Choriomeningitis Virus (LCMV-GP) und des Vesikulären Stomatitis Virus (VSV-G) pseudotypisiert. Lentivirale Vektoren vermitteln anders als gammaretrovirale Vektoren einen effizienten Gentransfer in ruhende Zellen [2]. Auf diese Weise können auch Tumoranteile mit geringer Zellteilungsaktivität transduziert werden. Allerdings sollte dabei die Transduktion des ebenfalls mitotisch inaktiven Hirngewebes vermieden werden. Vergleichende Tropismusstudien mit den oben genannten Pseudotypvektoren zeigten, dass LCMV-GP Pseudotypen einen effizienten und spezifischen Gentransfer in Gliomzellen in vitro und in vivo vermitteln. Auch einzelne, infiltrierende Tumorzellen wurden von LCMV-GP Pseudotypvektoren transduziert. Normale Hirnzellen, insbesondere Neurone, wurden von LCMV-GP Pseudotypen dagegen kaum infiziert. Im Gegensatz dazu transduzierten VSV-G Pseudotypen Neurone in vitro und in vivo mit hoher Effizienz, während Gliomzellen von VSVG Pseudotypen weniger stark transduziert wurden als von LCMV-GP Pseudotypen. Das Suizidgen hsv-tk (Herpes Simplex Virus Thymidinkinase) wurde anschließend durch lentivirale LCMV-GP Pseudotypvektoren in Gliome in vivo eingebracht werden. Diese Suizidgentherapie bewirkte einen starken Antitumoreffekt und führte zu einer kompletten Eliminierung des Tumors bei 90% der behandelten Ratten. Ergebnisse dieser Studien verdeutlichen, dass LCMV-GP-pseudotypisierte lentivirale Vektoren ein hoch effizientes und spezifisches Vektorsystem zum Gentransfer in maligne Gliomzellen darstellen

    Co-regulated expression of HAND2 and DEIN by a bidirectional promoter with asymmetrical activity in neuroblastoma

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    <p>Abstract</p> <p>Background</p> <p><it>HAND2</it>, a key regulator for the development of the sympathetic nervous system, is located on chromosome 4q33 in a head-to-head orientation with <it>DEIN</it>, a recently identified novel gene with stage specific expression in primary neuroblastoma (NB). Both genes are expressed in primary NB as well as most NB cell lines and are separated by a genomic sequence of 228 bp. The similar expression profile of both genes suggests a common transcriptional regulation mediated by a bidirectional promoter.</p> <p>Results</p> <p>Northern Blot analysis of <it>DEIN </it>and <it>HAND2 </it>in 20 primary NBs indicated concurrent expression levels of the two genes, which was confirmed by microarray analysis of 236 primary NBs (Pearson's correlation coefficient r = 0.65). While <it>DEIN </it>expression in the latter cohort was associated with stage 4S (p = 0.02), <it>HAND2 </it>expression was not associated with tumor stage. In contrast, both <it>HAND2 </it>and <it>DEIN </it>transcript levels were highly associated with age at diagnosis <12 months (p = 0.001). The intergenic region shows substantial homology in different species (89%, 72% and 53% identity between human and mouse, chicken and zebrafish, respectively) and contains many highly conserved putative transcription factor binding sites. Using luciferase reporter gene constructs, asymmetrical bidirectional promoter activity was found in four NB cell lines: In <it>DEIN </it>orientation, an average 3.4 fold increase in activity was observed as compared to the promoterless vector, whereas an average 15.4 fold activation was detected in <it>HAND2 </it>orientation. The presence of two highly conserved putative regulatory elements, one of which was shown to enhance <it>HAND2 </it>expression in branchial arches previously, displayed weak repressor activity for both genes.</p> <p>Conclusion</p> <p><it>HAND2 </it>and <it>DEIN </it>represent a gene pair that is tightly linked by a bidirectional promoter in an evolutionary highly conserved manner. Expression of both genes in NB is co-regulated by asymmetrical activity of this promoter and modulated by the activity of two cis-regulatory elements acting as weak repressors. The concurrent quantitative and tissue specific expression of <it>HAND2 </it>and <it>DEIN </it>suggests a functional link between both genes.</p

    Prevalence and genotyping of Trichomonas infections in wild birds in central Germany

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    Avian trichomonosis is a widespread disease in columbids and other birds, caused by ingestion of the unicellular flagellate Trichomonas gallinae which proliferate primarily in the upper respiratory tracts. Studies using genetic analyses have determined some highly pathogenic lineages in birds, but the prevalence and distribution of potentially pathogenic and non-pathogenic T. gallinae lineages in wild birds is still not well known. We examined 440 oral swab samples of 35 bird species collected between 2015 and 2017 in Hesse, central Germany, for Trichomonas spp. infection and for determining the genetic lineages. Of these birds, 152 individuals were caught in the wild and 288 individuals were admitted from the wild to a veterinary clinic. The overall Trichomonas spp. prevalence was 35.6%. We observed significant differences between bird orders, with the highest prevalence in owls (58%) and columbids (50%), while other orders had slightly lower prevalences, with 36% in Accipitriformes, 28% in Falconiformes and 28% in Passeriformes. Among 71 successfully sequenced samples, we found 13 different haplotypes, including two previously described common lineages A/B (20 samples) and C/V/N (36 samples). The lineage A/B has been described as pathogenic, causing lesions and mortality in columbids, raptors and finches. This lineage was found in 11 of the 35 species, including columbids (feral pigeon, woodpigeon, stock dove), passerines (greenfinch, chaffinch, blackbird) and raptors (common kestrel, sparrowhawk, red kite, peregrine falcon and common buzzard). One new lineage (R) was found in a sample of a chaffinch. In conclusion, we found that the prevalence of Trichomonas spp. infection in wild birds was high overall, and the potentially pathogenic lineage A/B was widespread. Our findings are worrying, as epidemic outbreaks of trichomonosis have already been observed in Germany in several years and can have severe negative effects on bird populations. This disease may add to the multiple pressures that birds face in areas under high land-use intensity

    Function and regulation of the glutathione peroxidase homologous gene GPXH

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    When exposed to strong sunlight, photosynthetic organisms encounter photooxidative stress by the increased production of reactive oxygen species causing harmful damages to proteins and membranes. Consequently, a fast and specific induction of defense mechanisms is required to protect the organism from cell death. In Chlamydomonas reinhardtii, the glutathione peroxidase homologous gene GPXH/GPX5 was shown to be specifically upregulated by singlet oxygen formed during high light conditions presumably to prevent the accumulation of lipid hydroperoxides and membrane damage. We now showed that the GPXH protein is a thioredoxin-dependent peroxidase catalyzing the reduction of hydrogen peroxide and organic hydroperoxides. Furthermore, the GPXH gene seems to encode a dual-targeted protein, predicted to be localized both in the chloroplast and the cytoplasm, which is active with either plastidic TRXy or cytosolic TRXh1. Putative dual-targeting is achieved by alternative transcription and translation start sites expressed independently from either a TATA-box or an Initiator core promoter. Expression of both transcripts was upregulated by photooxidative stress even though with different strengths. The induction required the presence of the core promoter sequences and multiple upstream regulatory elements including a Sp1-like element and an earlier identified CRE/AP-1 homologous sequence. This element was further characterized by mutation analysis but could not be confirmed to be a consensus CRE or AP1 element. Instead, it rather seems to be another member of the large group of TGAC-transcription factor binding sites found to be involved in the response of different genes to oxidative stres

    Bildkommunikation : Integration der Ergebnisse aus vier Jahrzehnten empirischer Forschung

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    In sämtlichen modernen Arten der Kommunikation nehmen Bilder eine zunehmend exponierte Stellung ein. Begründet wird dies vor allem mit ihrer besonderen Verhaltenswirksamkeit, welche durch die leichte Aufnahme, Verarbeitung und Speicherung von Informationen gestützt wird. Außerdem lassen sich Emotionen sehr viel leichter durch Bilder transportieren. Es ist somit nicht verwunderlich, daß häufig von einer Überlegenheitswirkung bildlicher Stimuli im Vergleich zu bspw. textlichen Stimuli ausgegangen wird. Die besondere Wirkung der Bildkommunikation ist seit den fühen 60er Jahren Gegenstand empirischer Forschung in den Sozialwissenschaften. Mittlerweile haben sich umfangreiche Erkenntnisse aus Studien mit unterschiedlichsten Zielsetzungen und Versuchsbedingungen angesammelt. Dieser Beitrag integriert erstmalig die vielfältigen empirischen Befunde zum Bildkommunikationseffekt und leistet damit einen Beitrag zu seiner empirischen Verallgemeinerung. In diesem Zusammenhang gelangen fortgeschrittene Methoden der Metaanalyse zur Anwendung. Aus den Ergebnissen der Metaanalyse lassen sich inferenzstatistisch abgesicherte Aussagen über die differenzierte Wirkung von Bildern unter unterschiedlichen Umweltbedingungen ableiten
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