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Dissertations / Theses on the topic 'Neu3'

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Published: 9 October 2021

Last updated: 10 March 2023

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1

MOZZI, ALESSANDRA. "Sialidases and cancer: human sialidase neu3 enhances egfr activation in colorectal cancer." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2014. http://hdl.handle.net/10281/50237.

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Abnormal glycosylation is known to be associated with cancer malignancy. In the cell, this process is finely regulated by many enzymes, including sialidases or neuraminidases; these are glycohydrolases widely distributed in nature that remove sialic acid residues from glycoproteins and glycolipids. In mammals, four sialidases with different subcellular localizations and biochemical features have been described: a lysosomal sialidase (NEU1), a cytosolic sialidase (NEU2), a plasma membrane-associated sialidase (NEU3) and a mitochondrial sialidase (NEU4). Studies performed over the last decade have focused on the involvement of sialylation in the progression of cancer and moreover on the association of sialidase deregulation to the tumorigenic transformation. In particular, recent studies on the Japanese population have shown that sialidase NEU3 is often deregulated in colorectal cancer and also that it co-immunoprecipitates with the epidermal growth factor receptor (EGFR), the molecular target of the most recent therapies based on monoclonal antibodies. In collaboration with the Istituto Nazionale dei Tumori of Milan (Italy) (IRCCS) and with the Istituto Cantonale di Patologia of Locarno (Switzerland) we recruited a cohort of 85 Caucasian patients resected for a colorectal cancer. By real-time PCR experiments we observed a deregulation of the mitochondrial sialidase transcripts and, on the contrary, an up regulation of NEU3 mRNA in tumor tissues compared to paired normal mucosa. Moreover, by comparing NEU3 and EGFR mRNA levels, we observed a statistically significant correlation, suggesting that the increase in EGFR expression could be associated with NEU3 increment. Vice versa, no correlation was observed between the overexpression of NEU3 sialidase and mutations in KRAS, BRAF, PIK3CA and PTEN diagnostic markers. Experiments performed on colorectal cancer cell lines have demonstrated that overexpression of wild type NEU3 enhanced EGFR activation, compared to colon normal mucosa CCD841 cell line, irrespectively of mRNA and protein levels, mutational and gene status of the receptor in all the cell lines tested. The only exception was represented by SW620 cells, that are commonly used as EGFR negative control. Moreover, Western Blots of wild type NEU3 overexpressing cells revealed increased EGFR and ERK1/2 phosphorylation in SW480 colorectal cell line and also in DIFI cells, which represents the best cellular model to study the EGFR pathway, while mRNA and total EGFR protein contents remained constant. On the contrary, we could not detect any EGFR activation in cells overexpressing a totally inactive mutant of NEU3. In addition we performed MTT based test in transfected cells. Western blot analyses showed a significant increase of cell viability, only upon overexpression of wild type NEU3, the inactive mutant being completely ineffective in this respect. Having demonstrated that the human NEU3 sialidase is more strongly anchored to the membrane its murine counterpart, we proved, not only by the lectin binding assay but also by mass spectrometry, that this sialidase directly modified the sialylation level of EGFR extracellular domain. Moreover we also showed that NEU3 overexpression modulated the response to the pharmacological treatment with Cetuximab. The overexpression of the active form of NEU3 sialidase lead to a significant increase in cell viability in all tested cell lines, also under pharmacological treatment with Cetuximab, with the exception of SW48 cells that presented a hyperactivating mutation in the tyrosine kinase domain of EGFR, causing the receptor to act independently from the dimerization. Our data suggest that, in the cell lines in which EGFR acts correctly as a dimer, sialidase overexpression caused an increment of viability even in those presenting hyperactivating mutations in the downstream pathways, that influence the efficacy of the therapy. We decided to extend the analysis of the deregulation of human sialidases to other types of cancer, in order to identify and deepen the knowledge of common variations of these enzymes also in the Western population. On the whole, by demonstrating the role of sialidase NEU3 in CRC, our work strongly suggests that this enzyme might be taken into consideration as a new effective molecular marker for CRC diagnosis and treatment. Furthermore, these data confirm the need of further studies concerning the role played by sialidases as a defining factor in cancer progression, opening up potential applications in diagnosis and therapy.

2

Jeyaseelan, B. R. J. "PLASMA MEMBRANE SIALIDASE NEU3 SILENCING EFFECTS ON THE MOLECULAR PHENOTYPE OF MELANOMA CELLS." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/480824.

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Human melanoma has been shown to be marked by an atypical cellular ganglioside profile and by the upregulation of plasma membrane sialidase NEU3. In this PhD thesis, I analyzed NEU3 silencing effects on the two human primary melanoma cell lines, named L3 and L6. These cell lines were stably transfected with a lentiviral vector. Previous results already demonstrated that NEU3 silenced melanoma cells reduced their migration potential and their growth in soft agar medium. Based on these data, my PhD work was focused towards the molecular features and signaling pathways alterations induced by NEU3 silencing in primary melanoma cell lines. Whole genome microarray analysis revealed the presence of differentially expressed genes above all associated with migration, motility, and control of cell death (G0 biological processes enrichment analysis). Some of these genes were validated by Real Time PCR: MAL, SEMA 3B, SEMA 3C and SEMA 5A. NEU3 silenced clones of both cell lines, 3C, 6A and 6B underwent to the upregulation of MAL, SEMA 3B and 3C. In contrast, SEMA 5A was downregulated. Different expression of markers related to epithelial mesenchymal transitions (N and E cadherin, MITF, vimentin, claudin 1, zo 1) was also revealed in NEU3 silenced clones. This proved the acquisition of a different molecular phenotype after NEU3 silencing that could explain the less motile properties. Moreover, we analyzed the activation of signaling pathways involved in these processes and we found a less activation of PI3K/AKT/PRAS40 axis and p38 kinases. Significantly, both these signaling pathways are involved in melanoma migration and differentiation control. All these results suggest that NEU3 upregulation could enhance melanoma malignancy by altering specific signaling pathways that are involved in cell motility and cell differentiation and thus NEU3 could be a novel target for treating melanoma.

3

Dileo, L. "CELLULAR DYNAMICS OF SIALIDASE NEU3 IN A MODEL OF STABLE INDUCIBLE OVEREXPRESSION IN HELA CELLS." Doctoral thesis, Università degli Studi di Milano, 2010. http://hdl.handle.net/2434/148877.

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Sialidases are glycohydrolytic enzymes that remove sialic acid residues from gangliosides and sialoglycoproteins. In mammals there are four isoenzymes, Neu1, Neu2, Neu3, Neu4, which differ in their subcellular localization and substrate specificity. Neu3 in particular is a peripheral membrane protein localized on the extracellular leaflet of cellular plasma membrane and it is present also in the early and recycling endosome (1). Neu3 shows an high specificity toward gangliosides, moreover it is able to modify the ganglioside composition of cell plasma membrane of adjacent cells (2). Modulating ganglioside content, Neu3 appears to be involved in important cellular processes such as proliferation, differentiation and transmembrane signalling. At the moment, cellular dynamics of Neu3 are still little known, in particular the rate of Neu3 protein attended on plasma membrane and in endosome compartment, like as the possibility of Neu3 recruitment on plasma membrane in response to EGF or FBS stimuli. To investigate these aspects, we have employed a model of MmNeu3 overexpression in HeLa cells using an inducible mammalian expression system (Tet-Off Gene Expression System). In this approach a tetracycline- controlled transactivator (tTA) activates transcription of sialidase in absence of doxycycline (dox); when dox is added to the culture medium MmNeu3 gene promoter is turned off. Experimental Procedures 1. HeLa cells were cultured in Dulbecco’s Modified Eagle Medium with high glucose supplemented with 10% (v/v) fetal bovine serum (FBS), and 4mM glutamine. To obtain a cell line with a stable inducible expression of murine sialidase Neu3, cells were subjectd to a double consecutive transfection. At first HeLa cells were transfected with regulator plasmid pTet-Off, encoding the tetracycline-controlled transactivator (tTA) doxycycline-dependent, and resistant clones were selected in presence of G418. Then, HeLa tTA cells were stable transfected with response plasmid which contained Neu3 gene under control of the tetracycline-response element (TRE). Resistant clones were selected in presence of puromycin. To follow MmNEU3 expression the enzyme has an HA (hemagglutinin) epitope tag and is expressed as GFP fusion protein. Mock cells (HeLa tTA2 pac) were transfected with response plasmid carrying only puromycin resistance. HeLa tTA2 pac were cultured in Dulbecco’s Modified Eagle Medium with high glucose supplemented with 10% (v/v) fetal bovine serum (FBS), 4mM glutamine, 0.5 µg/ml puromycin and 0.25 mg/ml G418. HeLa tTA2 MmNeu3-HA-GFP were cultured in the same medium but with the addition of 1 ng/ml Doxycycline (dox) to keep down the expression of MmNeu3. MmNEU3 gene promoter was turned on removing dox from culture medium. 2. The enzymatic activity of Neu3 was determined using 4-MU-Neu5Ac as substrate. Assays were performed in triplicate with 0.1 mM 4-MU-Neu5Ac, 30 µg of total protein of HeLa tTA2 pac and HeLa tTA2 MmNeu3-HA-GFP cells treated or not with dox (1 ng/ml), in the presence of 12.5 mM sodium-citrate/phosphate buffer pH 3.8 for 30 min at 37°C. 3. To analyze sphingolipid pattern HeLa tTA2 pac and HeLa tTA2 MmNeu3-HA-GFP cells treated or not with dox were labelled with [3-3H] sphingosine (2.5 × 10-9M) with 2 h pulse followed by a 48 h chase. Following total lipid extraction and partitioning, gangliosides and neutral sphingolipids were separated by HPTLC and analysed by radiochromatoscanning. 4. Western Blot analyses were performed on HeLa tTA2 pac and HeLa tTA2 MmNeu3-HA-GFP cells. Primary antibodies were used as follows: anti-EGFR (Cell Signalling), anti-phospho-EGFR (Tyr 1148) (Calbiochem), anti-HA (Sigma), anti-caveolin 1 (Santa Cruz Biotechnology), anti-Transferrin Receptor (TfR, Invitrogen), anti-AKT 1/2/3 (Santa Cruz Biotechnology). 5. HeLa tTA2 MmNeu3-HA-GFP cells at confluence were stained overnight in serum-free medium and then stimulated for 10 minutes with 100 ng/ml of epidermal growth factor (EGF) (Sigma), or for 2-4 hours with 10% (v/v) FBS, in presence or absence of dox in culture medium at difference time (6, 14, 24 h). 6. After or during dox removal, HeLa tTA2 MmNeu3-HA-GFP cells were treated with 0.1 µg/ml Brefeldin A (BFA) at different time (18, 24, 26 h). Then, cells were harvested by scraping and subjected to ultracentrifugation on OptiPrep density gradient. 7. Lipid rafts of HeLa tTA2 MmNeu3-HA-GFP cell lysates were separated by a discontinued OptiPrep density gradient. Briefly cell lysates were adjusted to a final density of 40% of OptiPrep Density Gradient Medium (Sigma), placed in a centrifuge tube and overload with a discontinuous OptiPrep density gradient from 30% to 5%. Samples were then centrifuged at 170000 ×g for 4 h, after which eight fractions of 1.5 ml (except for the first fraction that was of 1.2 ml) were collected from the top to the bottom of the gradient. Aliquots of the OptiPrep gradient fractions were analysed for their protein concentration, sialidase content and activity and subjected to Western-blot analysis. Results and Discussion First, we have characterized the cellular model, in particular we have assessed the time course of expression and enzymatic activity of Neu3 after promoter turning off/on. Furthermore, we have analyzed sphingolipid pattern and cell signalling modification during variation of Neu3 expression. When promoter was turning on by removal of dox, sphingolipid pattern analysis showed a significative decrease of GM3 (-60%) and GD1a (-75%) compared to mock cells, whereas we observed an increase of GM1 and lactosylceramide. To analyze MmNeu3 localization and cellular dynamics we have employed a discontinuous OptiPrep density gradient. The fractions were tested for Neu3 sialidase activity, and for HA, caveolin-1, TfR proteins by immunoblot analysis. At the beginning of expression (6h) the enzyme was only associated with no-DRM regions of cell membranes, whereas after 24h, when Neu3 expression was at the 50 % of maximum level, about 50 % of MmNeu3 protein resided in DRM, and 50 % in no-DRM. When MmNeu3 promoter was turned on after FBS withdrawal, sialidase distribution was modified, also 100 ng/ml EGF stimulation for 10 minutes of HeLa N3 cells determined an increased of MmNeu3 protein in DRM regions, consequently sialidase activity and protein rate increased in DRM region after EGF stimulus. BFA action determines the disassembly of the Golgi apparatus, in this way it blocks the transport of many proteins from Golgi to plasma membrane. BFA treatment during 24 h MmNeu3 expression changed sialidase distribution in DRM regions. 1. Zanchetti G. et al., Biochem. J. 2007, 408, 211-219. 2. Papini N. et al., J. Biol. Chem. 2004, 279, 16989-16995.

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CANALI, MARIA ELENA. "THE ROLE OF SIALIDASE NEU3 IN THE CARDIAC RESPONSE TO ISCHEMIA AND REPERFUSION INJURY." Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/690293.

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THE ROLE OF SIALIDASE NEU3 IN THE CARDIAC RESPONSE TO ISCHEMIA AND REPERFUSION INJURY Maria Elena Canalia,b, Marco Piccolia, Andrea Ghiroldia, Federica Cirilloa, and Luigi Anastasiaa,b a Laboratorio delle cellule staminali e ingegneria tissutale, IRCCS Policlinico San Donato, piazza Malan 2, 20097 San Donato Milanese, Milano, Italia; email: maria.canali@unimi.it b Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, via Luigi Mangiagalli 31, 20133, Milano, Italia; L'infarto miocardico acuto (AMI) è una delle cause più comuni di morte in tutto il mondo. Le strategie di riperfusione sono le procedure salvavita più utilizzate per il trattamento dell'AMI, ma inducono anche l’insorgenza del cosiddetto danno da ischemia e riperfusione (IRI), con conseguente sviluppo di insufficienza cardiaca. Molti sforzi sono stati fatti per chiarire i meccanismi molecolari coinvolti nell'IRI e, in questo contesto, l'attivazione delle chinasi pro-sopravvivenza, nonché il fattore inducibile dell'ipossia (HIF-1α), sono stati riconosciuti come regolatori chiave della risposta cellulare all'IRI. Al riguardo, abbiamo recentemente identificato un nuovo meccanismo di attivazione dei HIF-1α mediato dalla sialidasi NEU3, che è stato in grado di aumentare la resistenza delle cellule muscolari allo stress ipossico. Pertanto, lo scopo di questo studio è stato quello di valutare se NEU3 potesse avere un ruolo anche nel contrastare il danno da ischemia e riperfusione. A tal fine, NEU3 è stato sovraespresso nei cardiomioblasti di ratto H9C2, i quali sono stati trasfettati con un plasmide contenete la sequenza di NEU3 per sovraesprimere l'enzima. Sorprendentemente, le cellule NEU3 overesprimenti hanno mostrato un tasso di proliferazione e sopravvivenza, così come un tasso di attivazione di HIF-1α e delle chinasi pro-sopravvivenza Akt ed Erk significativamente maggiore rispetto ai controlli a seguito dell'IRI. È interessante notare che il trattamento con gli inibitori di Akt ed Erk, nonché con gli inibitori di NEU3 (DANA e LR332) ha completamente annullato gli effetti benefici mediati dall'enzima, supportando il possibile coinvolgimento della sialidasi nel contrastare l'IRI attraverso l'attivazione delle chinasi pro-sopravvivenza. Inoltre, abbiamo studiato anche il possibile coinvolgimento di NEU3 nella regolazione del processo di fibrosi cardiaca, una risposta fisiologica alla lesione del tessuto cardiaco, caratterizzata dalla deposizione di proteine della matrice extracellulare da parte di miofibroblasti attivati. I nostri studi hanno dimostrato che la sovraespressione della sialidasi NEU3 è sufficiente per ridurre il transdifferenziamento dei fibroblasti a miofibroblasti attraverso la diminuzione del contenuto cellulare di GM3.
THE ROLE OF SIALIDASE NEU3 IN THE CARDIAC RESPONSE TO ISCHEMIA AND REPERFUSION INJURY Maria Elena Canalia,b, Marco Piccolia, Andrea Ghiroldia, Federica Cirilloa, and Luigi Anastasiaa,b a Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, piazza Malan 2, 20097 San Donato Milanese, Milan, Italy; email: maria.canali@unimi.it b Department of Biomedical Sciences for Health, University of Milan, via Luigi Mangiagalli 31, 20133, Milan, Italy; Acute myocardial infarction (AMI) is one of the most common causes of death worldwide. Reperfusion strategies are the most used life-saving procedures for AMI treatment but they also induce ischemia/reperfusion injury (IRI), ultimately resulting in development of heart failure. Many efforts have been made to clarify the molecular mechanisms involved in IRI. In this context, the activation of pro-survival kinases, as well as the hypoxia inducible factor (HIF-1α), have been recognized as key steps in the cellular response to IRI. Along this line, we recently identified a novel mechanism of HIF-1α activation mediated by sialidase NEU3, which ultimately increased muscular cells resistance to hypoxic stress. Thus, aim of this study was to assess whether NEU3 could play a role in reducing IRI. To this purpose, NEU3 was overexpressed in H9C2 rat cardiomyocytes and were transfected with NEU3 plasmid to overexpress the enzyme. Remarkably, NEU3 overexpressing cells showed a significantly increased proliferation rate and survival, as well as the activation of HIF-1α and pro-survival kinases Akt and Erk after IRI, as compared to controls. Interestingly, treatment with Akt and Erk inhibitors, as well as with NEU3 inhibitors (DANA and LR332) reverted the beneficial effects mediated by the enzyme, supporting the possible involvement of NEU3 in counteracting IRI through the activation of pro-survival kinases. Moreover, we investigated also the possible involvement of NEU3 in regulating the process of cardiac fibrosis, a physiological response to cardiac tissue injury, characterized by the deposition of extracellular matrix proteins by activated myofibroblasts. Interestingly, we demonstrated that the overexpression of the sialidase NEU3 is sufficient to reduce the fibroblasts-myofibroblasts conversion by reducing the cellular content of GM3.

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RIVA, ALICE. "Investigation of the role of NEU3 in colorectal carcinogenesis and in the prediction of efficacy of EGFR targeted therapies." Doctoral thesis, Università del Piemonte Orientale, 2015. http://hdl.handle.net/11579/81672.

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Garatti, A. "SIALIDASE NEU3 EXPRESSION IN A HUMAN MODEL OF CARDIAC ISCHEMIA AND ITS INTERPLAY WITH THE HYPOXIA-INDUCIBLE FACTOR (HIF-1) SIGNALING PATHWAY." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/338131.

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The hypoxic condition determines several functional consequences that ultimately lead to cellular death and irreversible damage to cardiac myocytes. Under hypoxic condition, cells activate several protective pathways; among them, HIF-1α plays a key role in controlling cellular response to hypoxia at molecular level. However, HIF-1α regulatory mechanisms are extremely complex. On these premises, the present work was based on the hypothesis that NEU3 sialidase, a glycolytic enzyme ubiquitously expressed over the plasmatic membrane, can have a regulatory activity on HIF-1α expression in hypoxic/ischemic cardiac myocytes. The experiments performed in this in-vitro model allowed us to draw the following conclusions: 1) Endogenous NEU3 sialidase expression and activity are up-regulated in murine skeletal muscle cells (C2C12) upon oxygen starvation, leading to a signaling cascade resulting in the activation of HIF-1α. 2) Moreover, induced overexpression of NEU3 significantly increases HIF-1α expression and cell resistance to hypoxic stress, whereas NEU3 silencing causes the opposite effects and renders myoblasts more susceptible to apoptosis. 3) The hypoxia-driven activation of NEU3 sialidase can activate the EGFR prosurvival signaling pathway by controlling the content of ganglioside GM3. Furthermore, we demonstrated that NEU3 overexpression causes a reduction of ganglioside GM3, which is known to block EGFR autophosphorylation. Then resulted were extended from skeletal muscle to cardiac myocytes, particularly aiming to ascertain the role of NEU3 in activating the human cardiomyocyte response to hypoxia. Particularly, we evaluated if NEU3 activation occurred in human cardiomyocytes using two different models: 1) A model of acute cardiac ischemia achieved during aortic cross-clamp time and extracorporeal circulation in adult patient submitted to cardiac surgical procedures. 2) A model of chronic hypoxia in neonates and young patients operated for cyanogen congenital cardiac defects. In the acute model of cardiac ischemia, we harvested a sample of right atrial appendage just before and after aortic cross-clamping, during routine adult cardiac surgery procedure. However, no significant activation of NEU3 and HIF-1α was evident in cardiac sample harvested before and after aortic cross-clamping. In our opinion there are several possible explanations for the lack of NEU3 and HIF-1α increased expression in the cardiac surgery model. First, it is possible that in the in-vivo setting the mean aortic cross-clamp time was too short (mean time = 79 minutes) to elucidate the same response that we observed in the in vitro model, where the cells were incubated under hypoxic conditions for at least 12 hours. Secondly, and most important in our opinion, the technique of myocardial protection, especially cardioplegic arrest and hypothermia, by protecting the myocardium from the ischemic injury could have limited NEU3 and HIF-1α expression in our samples. To overcome these limitation, in the final part of my PhD program we evaluated HIF-1α and NEU3 expression in a human in-vivo model of chronic cardiac hypoxia, studying patients affected by cyanotic cardiac defects submitted to surgical correction. In this model of chronic hypoxia, we observed a significant increase in NEU3 expression and activity in cyanotic patients. Furthermore, a significant increase of EGFR was observed, supporting the hypothesis that this signaling pathway is upregulated by the sialidase NEU3. Indeed we observed an increase in expression of genes downstream of EGFR, both related to cellular proliferation (ERK and p38) and to apoptosis resistance (AKT and p70S6K). Finally we observed a significant activation of HIF-1α and of its downstream genes. Another important aspect of cellular adaptation to hypoxia is the metabolic switch between oxidative and glycolytic metabolism, the so-called “Pasteur effect”. In the present study we found that the glycolytic enzymes Glucose transporter Glut1, the Aldolase and the GAPDH were significantly enhanced in the cyanotic group which in turn demonstrates that the myocardium of patients affected by cyanogen cardiac defects is metabolic adapted to chronic hypoxia. In conclusion, the results of this PhD project support the hypothesis of a physiological role of NEU3 in mediating cellular response to hypoxic stress. It is interesting to underline that NEU3 activation is mediated by ganglioside GM3 on cellular membrane. Indeed, an increase in NEU3 level determines a reduction of GM3, which is a well know inhibitor of EGF receptor. On these premises, to mimic the effects of NEU3 activation, it could be possible to inhibit GM3 synthesis, in example by the selective inhibition of the sialyltransferase involved in the last passage of its synthesis. In this direction, our laboratory is performing some experiments with small chemical molecules, designed for blocking selectively the GM3 synthesis with the aim of activating the endogenous response to hypoxic stress.

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Pabst, Rebekka. "Neue Bilder, neue Möglichkeiten." Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-201713.

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In der heutigen Filmindustrie bietet das 3D-Design ein anerkanntes Mittel, um virtuelle Welten oder Charaktere zu erschaffen. Doch das 3D-Design dringt mittlerweile auch in andere Bereiche vor, so etwa der Medizin und der Architektur. Dabei bietet die virtuelle Rekonstruktion auch vielfältige Möglichkeiten für die Archäologie/Ägyptologie. Beispielsweise können von kleineren Objekten oder Papyri virtuelle 3D-Modelle erstellt werden. Der große Vorteil dabei ist, dass die Originale nicht beschädigt werden und mehrere Wissenschaftler zur gleichen Zeit an ein und demselben Objekt forschen können. Selbst für die Bauforschung dürfte das 3D-Design immer bedeutender werden. Gebäude, die sich heute nur in ihren Grundrissen erhalten haben, können mithilfe des 3D-Designs nahezu vollständig rekonstruiert werden. Nicht zu unterschätzen ist dabei auch die Wirkung, die virtuelle Rekonstruktionen von ägyptischen Tempeln, Gräbern, Gebäuden auf die Gesellschaft erzielen. Durch die 3DRekonstruktionen kann nicht nur Wissenschaftlern, sondern auch Interessierten ein anschaulicher Eindruck von der Lebenswelt des Alten Ägypten vermittelt werden. Bislang steht das 3D-Design allerdings in dem Ruf, besonders schwer erlernbar und sehr kostenintensiv zu sein. Doch gibt es neben einigen aufwendigen 3D-Design-Programmen auch nahezu kostenfreie Alternativen, die man sowohl privat wie beruflich nutzen kann. Diese Programme sind dabei sehr anwenderfreundlich gestaltet und relativ leicht zu erlernen. Ziel des Vortrages ist es, diese Programme und ihre Möglichkeiten für die Ägyptologie vorzustellen.

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Hoyer, Walter, Frank Richter, Werner A. Goedel, Eberhard Köhler, Bernhard Wielage, Stefan Spange, Michael Hietschold, et al. "Profillinie 1: Neue Materialien und neue Werkstoffe." Universitätsbibliothek Chemnitz, 2005. http://nbn-resolving.de/urn:nbn:de:swb:ch1-200501492.

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Die Entwicklung neuer Materialien und neuer Werkstoffe wird heute international als Schlüsseltechnologie mit Querschnittscharakter und Schrittmacherfunktion für viele industrielle Bereiche eingestuft. Die Wirtschaftskraft der hoch entwickelten Industriegesellschaften hängt zunehmend von Erfolgen in der Materialwissenschaft und der Werkstofftechnologie ab. Die Forschungsaktivitäten in der Profillinie 1 sind gekennzeichnet durch Interdisziplinarität und Vernetzung von Forschungsvorhaben. Von besonderer Bedeutung ist darüber hinaus die zusätzliche Verzahnung mit der Profillinie 6 der TU Chemnitz “Modellierung, Simulation, Hochleistungsrechnen“, um die Material- und Werkstoffforschung durch den intelligenten Einsatz leistungsstarker Rechentechnik weniger kostenintensiv gestalten zu können.

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Walker, Steve Pache Veronica Bühler Jonas Heiniger Markus. "Neue Filme." Zürich : Hochschule für Gestaltung und Kunst, 2006. http://sfv.zhdk.ch/diplomfilme/index.php?show=4.

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Gallert, Ute. "Neue Fahrbibliothek." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-63392.

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Auf den Straßen des Vogtlandkreises ist ein neuer Bibliotheksbus unterwegs. Die zur Zeit noch „graue Maus“ löst den in die Jahre gekommenen lila Bus ab. Nach 18 Jahren Dienst und über 186.000 zurückgelegten Kilometern häuften sich bei diesem Reparaturen und damit verbundene Ausfallzeiten. Auch tropisch anmutende 40 Grad im Sommer oder Eiseskälte im vogtländischen Winter können den Mann hinter dem Lenkrad künftig nicht mehr schrecken.

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Doms, Annette. "Neue Wege." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-56751.

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Stimpfl-Abele, Bernhard. "Das Neue." Thesis, Konstfack, Ädellab/Metallformgivning, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:konstfack:diva-3229.

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The new is probably the most powerful and natural fact which influences us since we are borne. It is such an undefined and incredible word we use so often for „simple facts in our daily life but we are not aware of its power and the power of use. We need this word to explain a progress. It seems like the result of a magic trick. The new is so strong that it automatically takes away the light from the already known. Everything has its opposite and the new has the old; booth can only exist together, responsible for the process in the evolution. My essay examines the problematic around the new in a philosophical and critical way. It contains a large research about our relationship to the new and how it can appear in life. With Boris Groys article “on the new” I bring a problem between museum and art. Peter Dittmars article “the fascination of the new” shows also my point of view within art. “art shouldn´t be just beautiful, it should be creative, innovative and contemporary. Transformation “when the old passes to the new” shows the difference between 2 standing points of the new “the new as repetition in form of a copy” and “the new between the living and the dead” – a repetition in form of a mirror picture which is not just a repetition or copy, it is a another view of the new”. This difference is playing an important role in my practical work. My research is based on facts which appear in books and articles I collected around the contemporary art world. These facts will be put in contrast to each other, so it can automatically flow in a bride discussion which will be the most interesting and main part of my essay „the new“. My intention from the beginning to the final conclusion of this essay is clearly not to define „the new“ in any sense, it is more about an investigation of arguments which will help me to find theories about „the new“ in my practical work. Michel Foucaults questions about an author in the interpretation of the new structure my essay and will also be described in pictures which open a completely new dimension for the essay.What is the new?Do we have proofs of its authenticity and originality?What are the modes of the existence?From where does it come from, how is it distributed, from which controlled?

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Lorenz, Anja. "NEUE LEBENS:WELT:KRISEN." Universitätsbibliothek Chemnitz, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-qucosa-114781.

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Es heißt nicht grundlos New Media oder mittlerweile Social Media: Die derzeitigen Möglichkeiten, die vor allem das Social Web mit sich bringt, eröffnen es nahezu jedem, sich an der Verbreitung von Informationen – passiv wie aktiv – zu beteiligen. Diese Partizipationsmöglichkeiten bringen fraglos positive Effekte, aber auch negative Phänomene zum Vorschein.

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Becker, Sabina. "Neue Sachlichkeit /." Köln : Böhlau, 2000. http://catalogue.bnf.fr/ark:/12148/cb388695370.

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Lattemann, Christoph. "Neue Technologien – Neue Anforderungen an die Forschungsmethoden im Bildungswesen." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-125660.

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Die GENEME stellt auf ihrer diesjährigen Konferenz „innovative Technologien und Prozesse zur Organisation, Kooperation und Kommunikation in virtuellen Gemeinschaften“ in ihren thematischen Mittelpunkt. Virtuelle Gemeinschaften werden schon seit Mitte der 1990er Jahre beforscht. Gab es aber im frühen Web 1.0 kaum Applikationen und Konzepte zur Förderung der Interaktivität und der Kollaboration, werden die Internetnutzer seit etwa 2003 im Web 2.0 zu sogenannten Prosumern. Sie konsumieren nicht nur Inhalte sondern produzieren sie auch. Katalysatoren hierfür sind virtuelle Gemeinschaften, die sich zu thematischen Gemeinschaften, so genannten Communities of Practice, formieren. Die Möglichkeiten und der Aktionsradius zur Interaktion und Kollaboration in Virtuellen Gemeinschaften werden aktuell im Internet neu definiert. Dies erklärt sich durch die Entwicklung neuer Technologien und Internetdienste. (...)

16

Cachelin, Joël-Luc. "Management in der Multioptionsgesellschaft neue Manager für neue Zeiten." Wiesbaden Gabler, 2009. http://d-nb.info/994758464/04.

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Thrun, Martin. "Eigensinn und soziales Verhängnis Erfahrung und Kultur "anderer Musik" im 20. Jahrhundert." Leipzig Schröder, 2009. http://d-nb.info/997350202/04.

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Machner, Bodo. "Neue Produkte, neue Märkte, effizientere Prozesse – Herausforderungen an das Produktdatenmanagement." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-228070.

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Die immer schnellere Veränderung des Umfelds stellt auch die internationale Automobilindustrie vor große Herausforderungen. Vor den Experten der Branche wurden diese beispielsweise auf dem 12. Internationalen CAR-Symposium der Universität auch vom Vorstandsvorsitzenden der BMW Group Dr. Norbert Reithofer diskutiert (Car 2010). Aus dem Spannungsfeld zwischen profitablem Wachstum und Globalisierung erwachsen nicht nur größere Absatzzahlen sondern auch die Zunahme an Varianz aufgrund länderspezifischer Gesetzgebung und unterschiedlichen Kundenbedürfnissen in den Hauptmärkten Europa, Nordamerika und Asien. Ein »historisches« Beispiel für diese unterschiedlichen Kundenanforderungen war die Anforderung der amerikanischen Kunden an den »Cupholder«. Das Thema ist inzwischen gelöst. Komplexer ist der Widerspruch zwischen der Ausrichtung unserer Fahrzeuge auf das Fahrerlebnis des Fahrers in den klassischen Märkten und dem Trend zum Chauffeur in vielen neuen Märkten (v.a. China).

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Eder, Alexandra. "Integration digitaler Medien an berufsbildenden Schulen aus der Sicht von Lehrkräften : eine allgemeine empirische Standortbestimmung und qualitative Studie zur Verwendung einer Computerneuausstattung an berufsbildenden Schulen /." Göttingen : Sierke, 2009. http://d-nb.info/994958676/04.

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20

Gemperle, Claudius. "Neue Elektronenspinecho-Experimente /." [S.l.] : [s.n.], 1990. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=9192.

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21

Derenthal, Gabriele. "Neue komplexe Chloronitrosylruthenate." [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=96830737X.

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22

Grammetbauer, Maren. "Das neue Verbraucherleitbild." [S.l. : s.n.], 2004. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB11195174.

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Schönefeld, Frank. "Digitale Transformation - Beispiele aus der Praxis. Neue Wege zum Kunden. Neue Geschäftsmodelle. Neue Wege in Produktion und Kollaboration." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2018. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-232814.

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Schönefeld, Frank. "Digitale Transformation - Beispiele aus der Praxis. Neue Wege zum Kunden. Neue Geschäftsmodelle. Neue Wege in Produktion und Kollaboration." TUDpress, 2017. https://tud.qucosa.de/id/qucosa%3A30772.

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25

Rasche, Julia. "Alltagsoffene Medienpädagogik in der Schule : Untersuchung zu regionalen Bedingungen und praktischer Realisierung /." Kassel : Kassel Univ. Press, 2009. http://d-nb.info/997724323/04.

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26

Schneider, Anita. "Neue Frau und Neue Sachlichkeit, Weibliche Existenzproblematik am ende der Weimarer Republik." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0019/MQ49439.pdf.

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27

Binderheim, Stefan Jürgen. "Neue Strategien im Anlagefondsvertrieb /." Zürich, 2001. http://aleph.unisg.ch/hsgscan/hm00033269.pdf.

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Inderbitzin, Claudia. "Microfinance eine neue Anlageklasse? /." St. Gallen, 2007. http://www.biblio.unisg.ch/org/biblio/edoc.nsf/wwwDisplayIdentifier/00711218002/$FILE/00711218002.pdf.

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Bracht, Kathrin. "Neue Inhibitoren zellmembranständiger Proteinkinasen /." Konstanz, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000252796.

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Kratz, Harald. "Neue Studien zu Ringumlagerungsmetathesen." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968797989.

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31

Mitterpleininger, Josef. "Neue Synthesewege zu Organorheniumoxiden." kostenfrei, 2008. http://mediatum2.ub.tum.de/node?id=682210.

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Tücks, Petra. "Das Darmstädter Neue Palais." Darmstadt [u.a.] Selbstverl. der Hess. Hist. Komm. [u.a.], 2005. http://bvbm1.bib-bvb.de/webclient/DeliveryManager?pid=214687&customa̲tt2̲=simplev̲iewer.

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Brunner, Martin F. "Neue Plattformen für Publikumszeitschriftenmarken /." Lohmar : Eul, 2008. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=017176816&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.

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34

Ruppel, Raimund. "Neue Heterokumulene und Carbene." [S.l. : s.n.], 1999. http://deposit.ddb.de/cgi-bin/dokserv?idn=957650612.

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35

Brasse, Gregor. "Neue Naturstoffe aus Collembolen." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=976583879.

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Nika, Wassiliki. "Neue Carboxylate des Erbiums." [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=967363888.

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Schütte, Mike. "Neue Wege zu Metallsiliciden." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972359095.

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38

Steege, Jens. "Neue Antithrombotika mit Imidazolpartialstruktur." [S.l.] : [s.n.], 2005. http://www.diss.fu-berlin.de/2005/21/index.html.

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39

Nitzschke, Katrin. "Neue Öffnungszeiten des Buchmuseums." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2006. http://nbn-resolving.de/urn:nbn:de:swb:14-1160130685023-99440.

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40

Roelofsen, Heike. "Neuer Ort - neue Perspektiven." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-39108.

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Abstract:

Im April 2010 feierte die Umweltbibliothek Dresden ihre Wiedereröffnung nach dem Umbau. Sie ist eine Spezialbibliothek, die der Öffentlichkeit Bücher und andere Medien zum Thema Umwelt anbietet. Der Bestand umfasst rund 7.000 Medien, darunter 60 laufende Zeitschriften, Spiele, Karten, CDs und DVDs. Vor allem sind die zahlreichen Veröffentlichungen hervorzuheben, die nicht über den Buchhandel, sondern von wissenschaftlichen Einrichtungen oder Behörden bezogen werden.

41

Richter, Frank. "Neue Anti-Spam-Techniken." Universitätsbibliothek Chemnitz, 2004. http://nbn-resolving.de/urn:nbn:de:swb:ch1-200400379.

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Workshop "Netz- und Service-Infrastrukturen" Dieser Beitrag zum Workshop "Netz- und Service-Infrastrukturen" 2004 analysiert den Stand der Anti-Spam-Maßnahmen an der TU Chemnitz und zeigt neue Techniken auf.

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Piehler, Robert. "Neues Radio, neue Möglichkeiten." Bachelor's thesis, Universitätsbibliothek Chemnitz, 2007. http://nbn-resolving.de/urn:nbn:de:swb:ch1-200700084.

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Durch seinen veränderten Distributionskanal im Vergleich zum terrestrischen Rundfunk kann Webradio als die neue Form des Radios bezeichnet werden. Exakter muss jedoch von einer unter vielen neuen Formen des Radios die Rede sein. Denn neben den Radioangeboten im WWW gibt es, besonders im Bereich des Digitalradios, mehrere neue Ausprägungen des Mediums Hörfunk, die sich größtenteils schon lange nicht mehr nur auf einen monomodal auditiven Content-Mix aus Service und Musik beschränken. Technologien werden zusammengeführt und vernetzt, woraus sich neue Rezeptionsmöglichkeiten ergeben. Am Beispiel des Webradios sollen diese nachfolgend für die Mutter aller Technologie- und Datennetze, dem Internet, aufgezeigt und auf die aktuelle Akzeptanz in der Bevölkerung untersucht werden. Wer nutzt überhaupt das Webradio? Warum wählt man gerade dieses Medium und wozu wird es vorrangig genutzt? Zu diesen Fragen wird in der vorliegenden Arbeit eine fragebogen-basierte Studie entworfen, deren Umsetzung jedoch den Rahmen sprengen würde und die daher hier nicht Gegenstand der Betrachtung sein soll. Ziel ist es, zunächst kommunikationswissenschaftliche Grundlagen des Webradios zu klären, um auf dieser Basis einen aussagekräftigen Fragebogen über Rezeption und Rezeptionsmotive zu erhalten.

43

Timmermann, Heinz. "Neue Akzente statt Neubeginn." Universität Potsdam, 2006. http://opus.kobv.de/ubp/volltexte/2008/2311/.

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Inhalt: Anti-amerikanisch oder Amerika-kritisch? Spannung zwischen Interessen und Werten Offene und stille Diplomatie gegenüber Russland Neue Bewegung im Dreieck Deutschland-Russland-Polen Großeuropa in fließendem Zustand

44

Heimerdinger, Julia. "Neue Musik im Spielfilm." Saarbrücken Pfau, 2003.

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45

Schütz, Alexander. "Das neue argentinische Scheckrecht /." Berlin : Duncker und Humblot, 1997. http://www.gbv.de/dms/spk/sbb/recht/toc/273757520.pdf.

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46

Mc, Leod Shirley. "Der neue Bibliotheksindex BIX." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-107246.

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Entwickelt 1999 von der Bertelsmann Stiftung und dem Deutschen Bibliotheksverband ist der Bibliotheksindex BIX eines der ältesten Leistungsmessungsinstrumente in der bibliothekarischen Welt. Jedes Jahr beteiligen sich rund 250 Bibliotheken am BIX. Sie nutzen die Ergebnisse, um ihre Dienstleistungen zu vergleichen und sich der Öffentlichkeit zu präsentieren. Der BIX ist ein Steuerungsinstrument und dient als Grundlage für Managemententscheidungen und trägt so zur Leistungssteigerung bei, die wiederum allen Bürgerinnen und Bürgern zugutekommt.

47

Rachkov, Ilia. "Das neue russische Devisenrecht." WU Vienna University of Economics and Business, 2002. http://epub.wu.ac.at/3367/1/ap088.pdf.

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Bonte, Achim, and Michael Golsch. "Neue Berufe in Bibliotheken." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-136800.

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Wie auch in anderen Bibliotheksregionen ist die Ausleihe von gedruckten Medien in Sachsen insgesamt rückläufig. In den Universitätsbibliotheken beträgt das Minus im Fünfjahresvergleich rund 14 %. Dass öffentliche Bibliotheken im Zeitalter von Google, Wikipedia, Amazon & Co. Servicemonopole verlieren und zügig ihre Produkte und Angebotsprofile verändern müssen, ist inzwischen schon häufig beschrieben worden. Welche immensen Herausforderungen und Gefährdungen objektiv bestehen, zeigen die Bereiche der Medien- und Informationsbranche besonders gut, die privatwirtschaftlich organisiert sind. Videotheken, Musikhäuser, Buchhandlungen oder Verlage – sie alle leiden bereits deutlich unter dem massiven Innovations- und Wettbewerbsdruck der Digitalen Revolution, suchen fieberhaft alternative Geschäftsmodelle, erhalten neue Eigentümer oder verschwinden gar vom Markt.

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Herrmann, Ines. "Neue Medien im Fremdsprachenunterricht." Master's thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-203297.

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Die Arbeit bildet die fachwissenschaftlich gestützte Erziehung von Deutsch-als-Fremdsprachelehrkräften zur Medienmündigkeit ab. Dafür werden Vorstudien zu einem umfassenden Konzept zusammengefügt. Es werden drei Fachbereiche vernetzt: Lehrerbildung, Medienpädagogik und Deutsch als Fremdsprache. Der Konzeption abgeleitet ist eine mögliche Didaktik für neuere Technologien, die mit einem von der Autorin selbst erstellten Kursbaustein veranschaulicht wird.

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Doralt, Peter, Andrea Kaminek, Maria Füzy, Gerlinde Schwahofer, and Christoph Diregger. "Das neue ungarische Aktienrecht." WU Vienna University of Economics and Business, 1998. http://epub.wu.ac.at/3397/1/ap054.pdf.

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