121 research outputs found
Duocarmycin-based prodrugs for cancer prodrug monotherapy
No full textThe synthesis and biological evaluation of novel prodrugs based on the cytotoxic antibiotic duocarmycin SA (1) for a selective treatment of cancer using a prodrug monotherapy (PMT) are described. Transformation of the phenol 8 with the glucuronic acid benzyl ester trichloroacetimidate 9b followed by reaction with DMAI center dot HCl (10) gives the glucuronide 11b, which is deprotected to afford the desired prodrug 4a containing a glucuronic acid moiety. In addition, the prodrug 4b with a glucuronic methyl ester unit is prepared. The cytotoxicity of the glucuronides is determined using a HTCFA- assay with IC(50) values of 610 nM for 4a and 3300 nM for 4b. In the presence of beta-glucuronidase, 4a expresses an IC(50) value of 0.9 nM and 4b of 2.1 nM resulting in QIC(50) values of about 700 for 4a and 1600 for 4b. (c) 2008 Elsevier Ltd. All rights reserved
Synthesis of the first spacer containing prodrug of a duocarmycin analogue and determination of its biological activity
No full textThe synthesis of the first spacer containing, duocarmycin analogue prodrug 11 was realised, its biological properties evaluated and compared to its counterpart prodrug 2 without a spacer unit. The synthesis comprises the manufacture of the new acetylated derivatives 19 and 20b of two double spacer systems, their activation and coupling to the pharmacophoric seco-drug (+)-3. Unprecedented biological results were found as the new prodrug 11 showed a fairly low QIC(50) value of 20, but on the other hand a high stability and very low DNA alkylation efficiency. These findings indicate a changed cytostatic mode of action induced by the self-immolative spacer moiety which was employed
Asymmetric Synthesis and Biological Evaluation of Glycosidic Prodrugs for a Selective Cancer Therapy
No full textA severe limitation in cancer therapy is the often insufficient differentiation between malign and benign tissue using known chemotherapeutics. One approach to decrease side effects is antibody-directed enzyme prodrug therapy (ADEPT). We have developed new glycosidic prodrugs such as (-)-(1S)-26b based on the antibiotic (+)-duocarmycin SA ((+)-1) with a QIC(50) value of 3500 (QIC(50)=IC(50) of prodrug/IC(50) of prodrug+enzyme) and an IC(50) value for the corresponding drug (prodrug + enzyme) of 16pM. The asymmetric synthesis of the precursor (-)-(1S)-19 was performed by arylation of the enantiomerically pure epoxide (+)-(S)29 (>= 98% ee)
Author Commentary: Mobile Music Technology: From Innovation to Ubiquitous Use
No full textThis author commentary chapter accompanies the re-publication of my co-authored 2006 paper ‘Mobile Music Technology: Report on an Emerging Community’ - one of 30 papers selected from 1,200 NIME papers to be included in the book ‘A NIME Reader: Fifteen Years of New Interfaces for Musical Expression, published by Springer and edited by Alexander Refsum Jensenius and Michael J. Lyons
Author Correction: A shared neural basis underlying psychiatric comorbidity
No full textCorrection to: Nature Medicine. Published online 24 April 2023. In the version of this article initially published, the STRATIFY data also included cohort data from the ESTRA consortium, though this was not acknowledged in the author list and the section in Methods on the Stratify dataset. The Methods are now updated, and the author list is amended to combine the STRATIFY and ESTRA consortium names and to include the following authors: Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Hervé Lemaître, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris and Sylvane Desrivières. The STRATIFY and ESTRA consortia are now combined to list Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Gareth J. Barker, Arun L. W. Bokde, Hervé Lemaître, Frauke Nees, Dimitri Papadopoulos Orfanos, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris, Henrik Walter, Robert Whelan, Sylvane Desrivières and Gunter Schumann as members, and the IMAGEN consortium is updated to also include Sylvane Desrivières. Affiliations, author contributions and acknowledgements have been updated to reflect the new authorship, and all changes have been made in the HTML and PDF versions of the article
Author Correction: A shared neural basis underlying psychiatric comorbidity
No full textCorrection to: Nature Medicine https://doi.org/10.1038/s41591-023-02317-4. Published online 24 April 2023. In the version of this article initially published, the STRATIFY data also included cohort data from the ESTRA consortium, though this was not acknowledged in the author list and the section in Methods on the Stratify dataset. The Methods are now updated, and the author list is amended to combine the STRATIFY and ESTRA consortium names and to include the following authors: Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Hervé Lemaître, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris and Sylvane Desrivières. The STRATIFY and ESTRA consortia are now combined to list Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Gareth J. Barker, Arun L. W. Bokde, Hervé Lemaître, Frauke Nees, Dimitri Papadopoulos Orfanos, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris, Henrik Walter, Robert Whelan, Sylvane Desrivières and Gunter Schumann as members, and the IMAGEN consortium is updated to also include Sylvane Desrivières. Affiliations, author contributions and acknowledgements have been updated to reflect the new authorship, and all changes have been made in the HTML and PDF versions of the article.</p
Possibilities and limitations of forensic linguistics : multidisciplinarity at the studies of forensic-linguistic texts with special regards to the topics of criminalistic, jurisprudence and forensic handwriting analysis
No full textDie Arbeit ist in vier Themengebiete gegliedert, welche anhand von interdisziplinär vernetzten Beispielen am Schluss veranschaulicht werden, um das breite Spektrum der Anwendungsmöglichkeiten aufzuzeigen.
Der erste Teil, welcher auch den Schwerpunkt und den umfangreichsten Teil dieser Arbeit darstellt, ist das Themengebiet der forensischen Linguistik. Dabei werden im Speziellen die Hypothesen, Analysemethoden und im Besonderen die Autorenerkennung als Herzstück beleuchtet und anschließend die Möglichkeiten und Grenzen dieser wissenschaftlichen Methode aufgezeigt.
Der zweite Teil „Der kriminalistische Ansatz“ beschäftigt sich mit der Arbeitsweise der Kriminalisten und der Spurensicherung, wobei zunächst ein paar Grundbegriffe erläutert werden, um das Thema besser zu veranschaulichen. Hier werden auch die wissenschaftlichen Methoden und modernen Analysegeräte für verschiedene kriminalistische Spuren beschrieben und erklärt, unter anderem die zur Schriftvergleichung verwendeten Gerätschaften, welche für den anschließenden dritten Teil, die forensische Schriftvergleichung, von Bedeutung sind. Bei der forensischen Schriftvergleichung geht es im Besonderen um die Analysemethoden und die graphisch relevanten Aspekte von Schriften.
Anschließend wird im vierten Teil kurz auf das in dieser Arbeit auch relevante Thema der Rechtswissenschaften eingegangen.
Diese vier Themengebiete werden im letzten Teil mit wahren und themenmäßig sehr unterschiedlichen Beispielen verbunden, um die Aspekte aller bei den Ermittlungen und Analysen von (kriminalistischen) Fällen zu verdeutlichen.This paper is structured in four topics, which are illustrated in form of multidisciplinary examples at the last chapter of this work to demonstrate the possibilities of the application spectrum.
The first part, which represents the main part of this work, gives the attention to the subject of forensic linguistics. In this case the hypotheses, the multivariate methods of analysis and the identification of the author, as the special part, are demonstrated and afterwards the possibilities and the limitations of these subjects are illustrated.
The second part of this work is about criminalistic analysis methods, which includes the work of a criminalist and the securing of evidence. At the beginning some special terms will be defined to be able to retrace this art of working. Whatsoever the scientific methods and modern analysis equipment for criminalistic evidence are described and avowed, including also the ones, which are needed for the following third part, the forensic handwriting analysis. The forensic handwriting analysis deals with the methods of the analysis of handwritings and the relevant graphic aspects of handwritings.
Afterwards it’ll be payed regards to jurisprudence, which also plays a part in this work.
In the last part all these four themes are brought together and are manifested with the help of true and various examples to demonstrate the whole range of variations in crime scene investigations and analysis methods.vorgelegt von Frauke ObermoserAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersInnsbruck, Univ., Diss., 201
Possibilities and limitations of forensic linguistics : multidisciplinarity at the studies of forensic-linguistic texts with special regards to the topics of criminalistic, jurisprudence and forensic handwriting analysis
No full textDie Arbeit ist in vier Themengebiete gegliedert, welche anhand von interdisziplinär vernetzten Beispielen am Schluss veranschaulicht werden, um das breite Spektrum der Anwendungsmöglichkeiten aufzuzeigen.
Der erste Teil, welcher auch den Schwerpunkt und den umfangreichsten Teil dieser Arbeit darstellt, ist das Themengebiet der forensischen Linguistik. Dabei werden im Speziellen die Hypothesen, Analysemethoden und im Besonderen die Autorenerkennung als Herzstück beleuchtet und anschließend die Möglichkeiten und Grenzen dieser wissenschaftlichen Methode aufgezeigt.
Der zweite Teil „Der kriminalistische Ansatz“ beschäftigt sich mit der Arbeitsweise der Kriminalisten und der Spurensicherung, wobei zunächst ein paar Grundbegriffe erläutert werden, um das Thema besser zu veranschaulichen. Hier werden auch die wissenschaftlichen Methoden und modernen Analysegeräte für verschiedene kriminalistische Spuren beschrieben und erklärt, unter anderem die zur Schriftvergleichung verwendeten Gerätschaften, welche für den anschließenden dritten Teil, die forensische Schriftvergleichung, von Bedeutung sind. Bei der forensischen Schriftvergleichung geht es im Besonderen um die Analysemethoden und die graphisch relevanten Aspekte von Schriften.
Anschließend wird im vierten Teil kurz auf das in dieser Arbeit auch relevante Thema der Rechtswissenschaften eingegangen.
Diese vier Themengebiete werden im letzten Teil mit wahren und themenmäßig sehr unterschiedlichen Beispielen verbunden, um die Aspekte aller bei den Ermittlungen und Analysen von (kriminalistischen) Fällen zu verdeutlichen.This paper is structured in four topics, which are illustrated in form of multidisciplinary examples at the last chapter of this work to demonstrate the possibilities of the application spectrum.
The first part, which represents the main part of this work, gives the attention to the subject of forensic linguistics. In this case the hypotheses, the multivariate methods of analysis and the identification of the author, as the special part, are demonstrated and afterwards the possibilities and the limitations of these subjects are illustrated.
The second part of this work is about criminalistic analysis methods, which includes the work of a criminalist and the securing of evidence. At the beginning some special terms will be defined to be able to retrace this art of working. Whatsoever the scientific methods and modern analysis equipment for criminalistic evidence are described and avowed, including also the ones, which are needed for the following third part, the forensic handwriting analysis. The forensic handwriting analysis deals with the methods of the analysis of handwritings and the relevant graphic aspects of handwritings.
Afterwards it’ll be payed regards to jurisprudence, which also plays a part in this work.
In the last part all these four themes are brought together and are manifested with the help of true and various examples to demonstrate the whole range of variations in crime scene investigations and analysis methods.vorgelegt von Frauke ObermoserAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersInnsbruck, Univ., Diss., 201
Dynamics and heterogeneity of environmental attitude, willingness and behavior in Germany from 1993 to 2021
No full textfirst_pagesettingsOrder Article ReprintsOpen AccessArticleDynamics and Heterogeneity of Environmental Attitude, Willingness and Behavior in Germany from 1993 to 2021by Frauke Meyer, Hawal Shamon* [ORCID] and Stefan Vögele[ORCID]Forschungszentrum Jülich GmbH, Institut für Energie- und Klimaforschung, Systemforschung und Technologische Entwicklung (IEK-STE), 52425 Jülich, Germany*Author to whom correspondence should be addressed.Sustainability 2022, 14(23), 16207; https://doi.org/10.3390/su142316207Received: 26 October 2022 / Revised: 23 November 2022 / Accepted: 24 November 2022 / Published: 5 December 2022(This article belongs to the Section Social Ecology and Sustainability)Download Browse FiguresVersions NotesAbstractThis paper analyzes environmental attitude, willingness, and behavior using a relatively broad range of survey items from the four Environment Modules of the International Social Survey Programme (ISSP) in Germany. The ISSP Environment Module is a repeated cross-sectional large-scale survey in Germany covering a period of nearly 30 years with four survey waves (1993, 2000, 2010, and 2020). We find that environmental attitude, willingness, and behavior are relatively stable between 1993 and 2010 in Germany. However, in the fourth wave, we find a significant upward trend in attitude and willingness compared to 2010—even though the COVID-19 pandemic was omnipresent at the time of the survey. This could indicate that climate change and environmental issues have gained such significance that they cannot easily be fully displaced by other major events, such as a pandemic. Moreover, we detect systematic heterogeneity in environmental attitude, willingness, and behavior predominantly with respect to respondents’ education, residential region, and political orientation but also some heterogeneity regarding gender, age, and income. Finally, we reveal that the dynamic of environmental attitude, willingness, and behavior also depends on certain socio-demographic characteristics, such as residential region, or political orientation. Our findings are essential for a better understanding of the social feasibility of transformation pathways towards a sustainable energy system
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