We evaluated the normal Raman (NR) and the surface-enhanced Raman scattering (SERS) of three sympathomimetic amines: phenethylamine, ephedrine, and 3,4-methylenedioxymethamphetamine (MDMA). In ...addition, quantum mechanical calculations–geometry optimization and calculations of the harmonic vibrational frequencies–were performed using the density functional theory (DFT) approach. Vibrational assignments were made by comparing the experimental and calculated spectra. The study found that both NR and SERS provided excellent spectra for the drugs tested. Certain conditions, such as response to various laser wavelengths and background fluorescence of the analyte, could be easily managed using SERS techniques. The DFT-calculated spectra could be correlated with the experimental spectra without the aid of a scaling factor. We also present a set of discriminant bands, useful for distinguishing the three compounds, despite their structural similarities.
A series of N-hydroxy-3-phenyl-2-propenamides were prepared as novel inhibitors of human histone deacetylase (HDAC). These compounds were potent enzyme inhibitors, having IC50s < 400 nM in a ...partially purified enzyme assay. However, potency in cell growth inhibition assays ranged over 2 orders of magnitude in two human carcinoma cell lines. Selected compounds having cellular IC50 < 750 nM were tested for maximum tolerated dose (MTD) and for efficacy in the HCT116 human colon tumor xenograft assay. Four compounds having an MTD ≥ 100 mg/kg were selected for dose−response studies in the HCT116 xenograft model. One compound, 9 (NVP-LAQ824), had significant dose-related activity in the HCT116 colon and A549 lung tumor models, high MTD, and low gross toxicity. On the basis, in part, of these properties, 9 has entered human clinical trials in 2002.
The Synthesis of a Novel Inhibitor of B-Raf Kinase Denni-Dischert, Donatienne; Marterer, Wolfgang; Bänziger, Markus ...
Organic process research & development,
01/2006, Letnik:
10, Številka:
1
Journal Article
Recenzirano
A scaleable synthetic route to 4,7‘bis-isoquinolinyl-1-yl-(2-tert-butyl-pyrimidine-5-yl)amine (1), an inhibitor of B-Raf kinase is described. The key step in the synthesis is the Pd-catalyzed Negishi ...coupling of 4-bromo-1-chloroisoquinoline with trifluoromethanesulfonic acid isoquinoline-7-yl ester to yield 1-chloro4,7‘bis-isoquinolinyl. This intermediate is transformed to the desired drug substance in one additional step, by reaction with 2-tert-butyl-5-aminopyrimidine in the presence of NaH. A special focus was put on the finally successful removal of traces of Zn and Pd in the drug substance, which came from the Negishi coupling.
Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to ...characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs. We validated our process in two patients with prostate cancer, including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were present in matched tissue. Moreover, we identified 10 early trunk and 56 metastatic trunk mutations in the non-CTC tumor samples and found 90% and 73% of these mutations, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We evaluated the use of abiraterone acetate (1,000 mg) plus prednisone (5 mg) in patients with high risk, nonmetastatic, castration resistant prostate cancer.
Patients considered at high risk for ...progression to metastatic disease (prostate specific antigen 10 ng/ml or greater, or prostate specific antigen doubling time 10 months or less) received abiraterone acetate plus prednisone daily in 28-day cycles. The primary study end point was the proportion of patients in whom a 50% or greater prostate specific antigen reduction was achieved during cycles 1 to 6. Secondary end points included time to prostate specific antigen progression, time to radiographic evidence of disease progression and safety.
Of the 131 enrolled patients 44 (34%) remained on treatment with a median followup of 40.0 months. Median age was 72 years (range 48 to 90). Of the patients 82.4% were white and 14.5% were black. Median screening prostate specific antigen was 11.9 ng/dl and median prostate specific antigen doubling time was 3.4 months. Prostate specific antigen was significantly reduced (p <0.0001) with a 50% or greater prostate specific antigen reduction in 86.9% of cases and a 90% or greater reduction in 59.8%. Median time to prostate specific antigen progression was 28.7 months (95% CI 21.2–38.2). Median time to radiographic evidence of disease progression was not reached but on sensitivity analysis in 15 patients it was estimated to be 41.4 months (95% CI 27.6–not estimable). Baseline testosterone 12.5 ng/dl or greater and a 90% or greater prostate specific antigen reduction at cycle 3 were associated with longer time to prostate specific antigen progression and radiographic evidence of disease progression. Outcomes in black patients were similar to those in other patients. Adverse events, grade 3 or greater adverse events and serious adverse events were reported in 96.2%, 61.1% and 43.5% of patients, respectively.
In patients with high risk, nonmetastatic, castration resistant prostate cancer treatment with abiraterone acetate plus prednisone demonstrated a significant 50% or greater prostate specific antigen reduction with encouraging results for the secondary end points, including the safety of 5 mg prednisone.
This book argues that intellectual property (IP) management development and innovation are fundamental to economic development , especially in newly emerging economies which often hold vast reserves ...of natural resources and human knowledge that remain unprotected. It sheds light on countries that are gradually realising this situation, with examples from many parts of the world, including Eastern Europe, Africa and especially Asia including India, where a great deal is being made of innovation and intellectual property to stimulate economic growth. These case studies are seen within the theoretical context of the future of cross-border IP which is slowly becoming a reality. Specific examples go beyond the patent prosecution highway, to which China has also recently signed up, and India’s development of generic drugs at lower costs. Experts in the field including practising IP lawyers explain and criticise current and new models being tested in emerging economies concerning IPR. Original case studies of hitherto little understood breaches of African trademarks by the US and Japan, and patenting mistakes in relation to little known Indian forest plants all damage emerging economies and their native people's lives. While proper implementation of IP laws by emerging economies themselves can lead to positive outcomes for all involved, the key is an independent judiciary coupled by thoughtful and thoroughly understood implementation of IP laws within the context of cross border IP. The book shows through models how different emerging economies are at various levels of developing their IPR and what paths they are taking to do this. Finally, it provides a comprehensive assessment of the ways in which innovation, protection and enforcement of IP laws can help newly emerging economies achieve economic growth without destroying natural and human resources, while moving ahead from the current global financial crisis.
Ruth Taplin is Director of the Centre for Japanese and East Asian Studies, UK. She is the author/editor of over 200 articles and 14 books, including most recently Intellectual Property and the New Global Japanese Economy , also published by Routledge. She is the editor of the Journal of Interdisciplinary Economics .
Alojzy Z. Nowak is Dean of the School of Management, University of Warsaw, Poland.
"In Japan and South Korea, intellectual property rights are widely taught at schools, in higher education, to senior citizens and on company training courses. Too many people in the West are struggling with the concept, so this book will provide solid groundwork for anyone seeking to understand how protection of intellectual property rights is a key stimulant to investment." – James Brewer, Insurance Day, Issue 2, 233, 2010
"This thought-provoking book argues that a country’s development of a robust intellectual property rights (IPRs) framework is fundamental to long-term economic success in today’s globalized world... Packed full of fascinating case studies, this absorbing book graphically illustrates how an underdeveloped IPR framework can be a significant economic disadvantage... The editors, Professors Ruth Taplin and Alojzy Nowak, must be commended for having gathered together an impressive line-up of experts in the field and practicing IP lawyers… This work is essential reading for anyone wanting to properly understand the emerging global and regional trends in intellectual property rights management." - Sean Curtin, Japan Society Review, Volume 31; www.japansociety.org.uk
"The book shows how different emerging economies are at various levels of developing their IPRs through various paths. It provides a comprehensive assessment of the ways in which innovation, protection and enforcement of IP laws can help newly emerging economies achieve economic growth without destroying natural and human resources, while moving ahead from the current global financial crisis... The book should be useful to all researchers and practitioners of IPRs, policy makers, etc. who wishes to keep themselves update with overall perspective and various IPRs related issues." Dr T K Mukherjee, Indian Journal of Traditional Knowledge Vol. 10(1), January 2011, pp. 213
"The book explains different types of innovation models, highlights success stories and explains some of the barriers to developing an innovation culture that understands IP and how to use it. The Africa chapter is written by Dario Tanziani and Nthabisheng Phaswana who illustrate, quite effectively, countries whose GDP and IP filing statistics reflect one another suggesting that IP infrastructure and GDP growth are linked... There are several other excellent chapters that highlight how certain developing countries have embraced innovation and effectively created models that are driving growth. The emerging theme is that an "independent judiciary coupled with thoughtful and thoroughly understood implementation of IP laws within the context of cross border IP" is key." - Afro-IP; Monday, 18 June 2012
List of illustrations Notes on contributors Acknowledgements List of abbreviations 1. Cross border Intellectual Property and theoretical models - Ruth Taplin 2. Innovation and Intellectual Property Rights in China and India: Prospects and Strategies - Bernard Arogyaswamy and Lisa Dolak 3. African Intellectual Property Law and the Newly Emerging African Economies with an Emphasis on South Africa - Nthabisheng Phaswana and Dario Tanziani 4. Two types of University Technology Transfer Intermediaries: TLO and TMC the Case of Thailand and the United States - Akio Nishizawa 5. The Financial Crisis, Intellectual Property and Prospects for Recovery: the Case of Poland, Central and Eastern Europe - Alojzy Z Nowak 6. Socio Economic changes Effected by Intellectual Property Rights - the Indian perspective - Mohan Dewan 7. Development of Intellectual Property Rights in Turkey: its Implications for the Turkish Economy - Erhun Kula and Selin Ozoguz 8. Cluster development, Intellectual Property and Global Competitiveness: Prospects of the Nano Sector in Hsinchu Science Park - Chyi Yih- Luan Index
The Japanese economy is the second largest in the world and is becoming once more one of the most competitive. Despite the stagnation and deflation experienced during the 1990s, Japan has ...progressively become more aware of the need to be a global player, in particular under the radical administration of former Prime Minister Koizumi. A vigorous approach to intellectual property borrowed from the US and Europe, stressing the importance of innovation, assisted in kick-starting the Japanese economy again and has sustained its increasingly high performance. This book examines how Japan has used this new approach to intellectual property (IP) to revitalise its economy. It explains how IP has traditionally been used in Japan, and goes on to identify the ways in which this has changed in recent years, identifying the different facets of IP utilised to propel the Japanese economy to new heights: Firstly, by promoting IP through Technical Licensing Organisations (TLO) laws and uniting the universities with the needs of industry. Secondly, via radical changes to employees’ rights to compensation through the landmark decisions made by the Tokyo District Court. Thirdly, by the streamlining of patenting applications and procedures through the Tokyo and Osaka District IP Courts, and the Japanese Patent Office. Fourthly, by internationalising its capital markets, as displayed by the cooperation between the Tokyo Stock Exchange and the London Stock Exchange (LSE) and other bourses. Overall, this book is essential reading for all those interested in understanding the modern Japanese economy, and how it is adapting to exploit the opportunities and challenges of an increasingly globalised world.
Ruth Taplin is the author/editor of over 200 articles and 14 books. The most recent are: Exploiting Patent Rights and a New Climate for Innovation in Japan ; Valuing Intellectual Property in Japan, Britain and the United States ; Risk Management and Innovation in Japan, Britain and the United States ; Japanese Telecommunications: Market and Policy in Transition ; Outsourcing and Human Resource Management: An International Survey ; and Innovation and Business Partnering in Japan, Europe and the United States (the last five also published by Routledge). Professor Taplin has been Editor of the Journal of Interdisciplinary Economics for 14 years. She is Director of the Center for Japanese and East Asian Studies, which won Exporter of the Year in Trading/Pathfinder in 2000 for the UK. Currently she is a Research Fellow at Birkbeck College, University of London and the University of Leicester, and has been a Visiting Professor and Research Fellow at a number of universities in the UK and abroad.
'The book is recommended reading for those interested in understanding how the Japanese economy is changing, the evolving role of IP in revitalizing the economy, and how Japan is attempting to adapt to the opportunities and challenges of an increasingly globalised world.' - Sean Curtin, Japan Society Book Reviews,December 2008
"Overall this book is essential reading for all those interested in understanding the modern Japanese economy and how it is adapting to exploit the opportunities and challenges of an increasingly globalised world" - YouTube Review of Favourite Book, December 2014
1. Roots of IP Drive and Economic Globalization 2. Japan as an IP Nation 3. Historical Perspective of the Economy and IP 4. Cross-border IP and Fast Tracking of Patent Applications 5. Changes to the Patent Court and Employee’s Rights to Compensation 6. Changes in Japanese Corporate Governance 7. Future Developments in the Japanese Exchanges 8. Conclusion
With the recent global economic crisis, attitudes and practices in relation to intellectual property valuation are changing as exemplified by the dichotomy explained in this book, which makes it ...unique. While there has been a move towards global harmonisation in terms of valuation of both tangible and intangible assets that are based on innovation, there is also a tendency against global harmonisation because of cultural attitudes and practices of different countries. This can be seen most acutely in relation to intellectual property valuation in Asia, especially East Asia, which often differs from the West's perception of valuation. The book is written by experts in intellectual property, valuation and innovation who are mainly practitioners covering innovators, marketers, accountants, social innovators and business and management academics. The breadth and practitioner background of most of the contributors make the material relevant to those involved in valuation, economics, business, management, accounting and finance, law and maritime insurance. This book takes an interdisciplinary approach that cross-cuts all the above-mentioned disciplines and takes the understanding of intellectual property valuation to a new level.
Oliver Taplin's seminal study was revolutionary in drawing out the significance of stage action in Greek tragedy at a time when plays were often read purely as texts, rather than understood as ...performances. Professor Taplin explores nine plays, including Aeschylus' agamemnon and Sophocles' Oedipus the King . The details of theatrical techniques and stage directions, used by playwrights to highlight key moments, are drawn out and related to the meaning of each play as a whole. With extensive translated quotations, the essential unity of action and speech in Greek tragedy is demonstrated. Now firmly established as a classic text, Greek Tragedy in Action is even more relevant today, when performances of Greek tragedies and plays inspired by them have had such an extraordinary revival around the world.
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