713 research outputs found
What fails and when? A process view of innovation failure
No full textResearch on innovation failure has proliferated lately but with little theoretical attention given to the diversity of the concept. Using process theorizing, we present a model and propositions to understand how a firm's anticipation and value toward failure depends on the type of failure (task versus outcome) and the phase (divergent versus convergent) and point (early versus later) ‘within’ the process that the failure occurs. Using the anticipation-value stances, we then present a typology of four modes of innovation failure that can arise ‘from’ task and outcomes failure in the innovation process. The four modes (and associated learning response) are unsolicited failures (prevent-alert-eliminate); hazardous failures (predict-modify-mitigate); fortuitous failures (probe-expose-extrapolate); and excursive failures (facilitate-analyze-harness). To help explain the ideas in our process model and typology, we use the well-known IDEO shopping cart innovation project as an illustrative example. Together, these contributions provide contingency oriented insights on how failure varies and journeys within and from the innovation process, which helps researchers and managers to better understand the related causes, effects and learning responses
Four new cases of lethal Osteogenesis Imperfecta due to glycine substitutions in the COL1A1 and COL1A2 genes
No full textAquileia und die Slavenmission: Zu Apotage und Symbolon im III. Freisinger Denkmal
No full textDer Aufsatz „Aquileia und die Slavenmission“ von Hartmut Trunte untersucht die historische Bedeutung von Aquileia in der Christianisierung der Slawen sowie die sprachlichen und theologischen Verbindungen, die durch die Missionsarbeit entstanden sind. Er analysiert dabei insbesondere die sogenannten Freisinger Denkmäler (FD I, II und III), die als bedeutende Zeugnisse der altslawischen Literatur und der slawischen Mission betrachtet werden. Trunte beginnt mit einer Diskussion über die Entdeckung und die frühere Forschungsgeschichte der Freisinger Denkmäler. Diese Texte, die zwischen 972 und 1039 datiert werden, sind in altkirchenslawischer Sprache verfasst und repräsentieren eine Verbindung zu den kirchenslawischen Texten der kyrillomethodianischen Mission. Der Autor beleuchtet die bisherigen Forschungsergebnisse und stellt fest, dass viele Fragen bezüglich der Herkunft, der genauen Datierung und der sprachlichen Besonderheiten dieser Texte nach wie vor ungeklärt sind. Ein zentraler Teil der Analyse widmet sich der Rolle von Aquileia als einem bedeutenden religiösen und kulturellen Zentrum, das lange Zeit unter byzantinischem Einfluss stand und somit eine wichtige Rolle in der Verbreitung des Christentums unter den slawischen Völkern spielte. Trunte argumentiert, dass die Nähe von Aquileia zu den griechisch-orthodoxen Traditionen die slawische Mission entscheidend geprägt hat. Er verweist auf mögliche griechische Einflüsse in den Texten der Freisinger Denkmäler, insbesondere auf die theologischen und liturgischen Konzepte, die in diesen Texten reflektiert werden. Ein besonderer Fokus liegt auf FD II, das als „Adhortatio ad poenitentiam“ bekannt ist und stark mit den Texten der kyrillomethodianischen Mission verbunden zu sein scheint. Die Diskussion um die Autorschaft und die möglichen Vorlagen für diese Texte wird vertieft, wobei Trunte auf verschiedene Theorien eingeht, die von einer direkten Verbindung zu griechischen Vorlagen bis hin zu althochdeutschen Einflüssen reichen. Die Frage der genauen Herkunft und der sprachlichen Charakteristika der Texte bleibt dabei umstritten, doch wird eine griechische Vorlage für wahrscheinlich gehalten. Trunte schließt mit der These, dass Aquileia als kulturelles und religiöses Zentrum einen wichtigen Beitrag zur Slawenmission leistete. Die Freisinger Denkmäler, insbesondere FD II, spiegeln diese Verbindung wider und zeigen, wie tief die slawische Kirche in den griechisch-orthodoxen Traditionen verwurzelt ist. Diese Analyse trägt zu einem besseren Verständnis der komplexen historischen und kulturellen Prozesse bei, die die Christianisierung der Slawen prägten.The essay ‘Aquileia and the Slavic Mission’ by Hartmut Trunte examines the historical significance of Aquileia in the Christianisation of the Slavs as well as the linguistic and theological connections that arose from the missionary work. In particular, he analyses the so-called Freising monuments (FD I, II and III), which are regarded as important testimonies to Old Slavic literature and the Slavic mission. Trunte begins with a discussion of the discovery and earlier research history of the Freising Monuments. These texts, dated between 972 and 1039, are written in Old Church Slavonic and represent a link to the Church Slavonic texts of the Cyrillomethodian mission. The author analyses the results of research to date and notes that many questions regarding the origin, exact dating and linguistic peculiarities of these texts remain unresolved. A central part of the analysis is devoted to the role of Aquileia as an important religious and cultural centre, which was under Byzantine influence for a long time and thus played an important role in the spread of Christianity among the Slavic peoples. Trunte argues that Aquileia's proximity to the Greek Orthodox traditions had a decisive influence on the Slavic mission. He points to possible Greek influences in the texts of the Freising monuments, in particular the theological and liturgical concepts reflected in these texts. A particular focus is on FD II, known as the ‘Adhortatio ad poenitentiam’, which seems to be strongly connected to the texts of the Cyrillomethodian mission. The discussion about the authorship and possible models for these texts is explored in depth, with Trunte discussing various theories ranging from a direct link to Greek models to Old High German influences. The question of the exact origin and linguistic characteristics of the texts remains controversial, but a Greek model is considered probable. Trunte concludes with the thesis that Aquileia, as a cultural and religious centre, made an important contribution to the Slavic mission. The Freising monuments, especially FD II, reflect this connection and show how deeply rooted the Slavic church is in the Greek Orthodox traditions. This analysis contributes to a better understanding of the complex historical and cultural processes that shaped the Christianisation of the Slavs
Metallo-drugs: development and action of anticancer agents/ edited by Astrid Sigel, Helmut Sigel, Eva Freisinger, and Roland K.O. Sigel.
No full textIn English.Includes bibliographical references and index.Volume 18 centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that it also provides excellent information for teaching.About the editors -- Historical development and perspectives of the series / Preface to volume 18 / Contributors to volume 18. -- 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. Subject index. Astrid Sigel, Helmut Sigel, Roland K.O. Sigel -- Astrid Sigel, Helmut Sigel, Eva Freisinger, Roland K.O. Sigel -- Imogen A. Riddell, Stephen J. Lippard -- Viktor Brabec, Jana Kasparkova, Vijay Menon, Nicholas P. Farrell -- V. Venkatesh, Peter J. Sadler -- Nicholas P. Farrell, Anil K. Gorle, Erica J. Peterson, Susan J. Berners-Price -- Enzo Alessio, Luigi Messori -- Maria V. Babak, Wee Han Ang -- Angela Casini, Raymond Wai-Yin Sun, Ingo Ott -- Edit Y. Tshuva, Maya Miller -- Debbie C. Crans, Lining Yang, Allison Haase, Xiaogai Yang -- Christopher R. Chitambar -- Lucia Cardo, Michael J. Lucia -- Ramon Vilar -- Matthew P. Sullivan, Hannah U. Holtkamp, Christian G. Hartinger -- Ulrich Schatzschneider -- Frank Thévenod -- Delphine Denoyer, Sharnel A.S. Clatworthy, Michael A. Cater -- Silvia Ziliotto, Olivia Ogle,Kathryn M. Taylor -- Cisplatin and oxaliplatin : our current understanding of their actions / Polynuclear platinum complexes : structural diversity and DNA binding / Platinum(IV) prodrugs / Metalloglycomics / The deceptively similar ruthenium(III) drug candidates KP1019 and NAMI-A have different actions : what did we learn in the past 30 years? / Multinuclear organometallic ruthenium-arene complexes for cancer therapy / Medicinal chemistry of gold anticancer metallodrugs / Coordination complexes of titanium(IV) for anticancer therapy / Health benefits of vanadium and its potential as an anticancer agent / Gallium complexes as anticancer drugs / Non-covalent metallo-drugs : using shape to target DNA and RNA junctions and other nucleic acid structures / Nucleic acid quadruplexes and metallo-drugs / Antitumor metallodrugs that target proteins / Metallointercalators and metalloinsertors : structural requirements for DNA recognition and anticancer activity / Iron and its role in cancer defense : a double-edged sword / Copper complexes in cancer therapy / Targeting zinc(II) signalling to prevent cancer /1 online resource (588 pages
Results of NMR metabolomics investigation
No full textBackground: Phenylketonuria (PKU; OMIM#261600) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in high phenylalanine (Phe) in blood and brain. If not treated early this results in intellectual disability, behavioral and psychiatric problems, microcephaly, motor deficits, eczematous rash, autism, seizures, and developmental problems. There is a controversial discussion of whether patients with PKU have an additional risk for atherosclerosis due to interference of Phe with cholesterol synthesis and LDL-cholesterol regulation. Since cholesterol also plays a role in membrane structure and myelination, better insight into the clinical significance of the impact of Phe on lipoprotein metabolism is desirable. In 22 treated PKU patients (mean age 38.7 years) and 14 healthy controls (mean age 35.2 years), we investigated plasma with NMR spectroscopy and quantified 105 lipoprotein parameters (including lipoprotein subclasses) and 24 low molecular weight parameters. Analysis was performed on a 600 MHz Bruker AVANCE IVDr spectrometer as previously described. Results: Concurrent plasma Phe in PKU patients showed a wide range with a mean of 899 μmol/L (50-1318 μmol/L). Total cholesterol and LDL-cholesterol were significantly lower in PKU patients versus controls: 179.4 versus 200.9 mg/dL (p < 0.02) and 79.5 versus 104.1 mg/dL (p < 0.0038), respectively. PKU patients also had lower levels of 22 LDL subclasses with the greatest differences in LDL2 Apo-B, LDL2 Particle Number, LDL2-phospholipids, and LDL2-cholesterol (p < 0.0001). There was a slight negative correlation of total cholesterol and LDL-cholesterol with concurrent Phe level. VLDL5-free cholesterol, VLDL5-cholesterol, VLDL5-phospholipids, and VLDL4-free cholesterol showed a significant (p < 0.05) negative correlation with concurrent Phe level. There was no difference in HDL and their subclasses between PKU patients and controls. Tyrosine, glutamine, and creatinine were significantly lower in PKU patients compared to controls, while citric and glutamic acids were significantly higher. Conclusions: Using NMR spectroscopy, a unique lipoprotein profile in PKU patients can be demonstrated which mimics a non-atherogenic profile as seen in patients treated by statins.publishersversionpublishe
O původu Kijevských listů a pražských zlomků a o bohemismech v starších cirkevně-slovanských památkách vůbec
No full textMit dem Nachdruck von Vondráks 1904 erschienenem Werk wird ein auf dem antiquarischen Buchmarkt praktisch nicht zu erwerbendes Desideratum wieder zugänglich, das in der langen und auch schwierigen Diskussion zur Thematik bis heute immer noch einen besonderen Stellenwert hat. Insbesondere gilt das für die aus dem Lateinischen ins Altslawische übersetzten glagolitischen Kiewer Blätter, die ein Sacramentarium (katholisches Kirchenbuch) beinhalten und in vielen Gesichtspunkten den Freisinger Denkmälern analoge Probleme zeigen. Vondrák hatte sehr deutlich die These ausgesprochen, daß Kiewer Blätter wie Freisinger Denkmäler in dem gleichen Gebiet (...) entstanden seien. Durchsuchbare elektronische Faksimileausgabe als PDF. Digitalisiert im Rahmen des DFG-Projektes Digi20 in Kooperation mit der BSB München. OCR-Bearbeitung durch den Verlag Otto Sagner.</P
Loss-of-function mutations of SURF-1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency
No full textMutations of SURF-1, a gene located on chromosome 9q34, have recently been identified in patients affected by Leigh syndrome (LS), associated with deficiency of cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain. To investigate to what extent SURF-1 is responsible for human disorders because of COX deficiency, we undertook sequence analysis of the SURF-1 gene in 46 unrelated patients. We analyzed 24 COX-defective patients classified as having typical Leigh syndrome (LSC(COX)), 6 patients classified as Leigh-like (LL(COX)) cases, and 16 patients classified as non-LS(COX) cases. Frameshift, stop, and splice mutations of SURF-1 were detected in 18 of 24 (75%) of the LS(COX) cases. No mutations were found in the LL(COX) and non-LS(COX) group of patients. Rescue of the COX phenotype was observed in transfected cells from patients harboring SURF-1 mutations, but not in transfected cell lines from 2 patients in whom no mutations were detected by sequence analysis. Loss of function of SURF-1 protein is specifically associated with LS(COX), although a proportion of LS(COX) cases must be the result of abnormalities in genes other than SURF-1. SURF-1 is the first nuclear gene to be consistently mutated in a major category of respiratory chain defects. DNA analysis can now be used to accurately diagnose LS(COX), a common subtype of Leigh syndrome
O původu Kijevských listů a pražských zlomků a o bohemismech v starších cirkevně-slovanských památkách vůbec
No full textMit dem Nachdruck von Vondráks 1904 erschienenem Werk wird ein auf dem antiquarischen Buchmarkt praktisch nicht zu erwerbendes Desideratum wieder zugänglich, das in der langen und auch schwierigen Diskussion zur Thematik bis heute immer noch einen besonderen Stellenwert hat. Insbesondere gilt das für die aus dem Lateinischen ins Altslawische übersetzten glagolitischen Kiewer Blätter, die ein Sacramentarium (katholisches Kirchenbuch) beinhalten und in vielen Gesichtspunkten den Freisinger Denkmälern analoge Probleme zeigen. Vondrák hatte sehr deutlich die These ausgesprochen, daß Kiewer Blätter wie Freisinger Denkmäler in dem gleichen Gebiet (...) entstanden seien. Durchsuchbare elektronische Faksimileausgabe als PDF. Digitalisiert im Rahmen des DFG-Projektes Digi20 in Kooperation mit der BSB München. OCR-Bearbeitung durch den Verlag Otto Sagner.</P
- …
