The Worldwide Triumph of the Research University and Globalizing Science

This chapter provides an overview of the findings and chapters of volume 33 in the International Perspectives on Education and Society (IPES) series. It describes the common dataset and methods used by an international research team. The chapter synthesizes the results of a series of country-level case studies and cross-national and regional comparisons on the growth of scientific research from 1900 until 2011. Additionally, the chapter provides a quantitative analysis of global trends in scientific, peer-reviewed publishing over the same period. The introduction identifies common themes that emerged across the case studies examined in-depth during the multi-year research project Science Productivity, Higher Education, Research Development and the Knowledge Society (SPHERE). First, universities have long been and increasingly are the primary organizations in science production around the globe. Second, the chapters describe in-country and cross-country patterns of competition and collaboration in scientific publications. Third, the chapters describe the national policy environments and institutionalized organizational forms that fostered scientific research. The introduction reviews selected findings and limitations of previous bibliometric studies and explains that the chapters in the volume overcome these limitations by applying neo-institutional theoretical frameworks to analyze bibliometric data over an extensive period

mTORC1/autophagy-regulated MerTK in mutant BRAFV600 melanoma with acquired resistance to BRAF inhibition

BRAF inhibitors (BRAFi) and the combination therapy of BRAF and MEK inhibitors (MEKi) were recently approved for therapy of metastatic melanomas harbouring the oncogenic BRAFV600 mutation. Although these therapies have shown pronounced therapeutic efficacy, the limited durability of the response indicates an acquired drug resistance that still remains mechanistically poorly understood at the molecular level. We conducted transcriptome gene profiling in BRAFi-treated melanoma cells and identified that Mer tyrosine kinase (MerTK) is specifically upregulated. MerTK overexpression was demonstrated not only in melanomas resistant to BRAFi monotherapy (5 out of 10 samples from melanoma patients) but also in melanoma resistant to BRAFi+MEKi (1 out of 3), although MEKi alone does not affect MerTK. Mechanistically, BRAFi-induced activation of Zeb2 stimulates MerTK in BRAFV600 melanoma through mTORC1-triggered activation of autophagy. Co-targeting MerTK and BRAFV600 significantly reduced tumour burden in xenografted mice, which was pheno-copied by co-inhibition of autophagy and mutant BRAFV600

Synthesis of [F-18]RGD-K5 by catalyzed [3+2] cycloaddition for imaging integrin alpha(v)beta(3) expression in vivo

<p>In the last few years click chemistry reactions, and in particular copper-catalyzed cycloadditions have been used extensively for the preparation of new bioconjugated molecules such as F-18-radiolabeled radiopharmaceuticals for positron emission tomography (PET). This study is focused on the synthesis of the Siemens imaging biomarker [F-18]RGD-K5. This cyclic peptide contains an amino acid sequence which is a well known binding motif for integrin alpha(v)beta(3) involved in cellular-adhesion to the extracellular matrix. We developed an improved "click" chemistry method using Cu(I)-Monophos as catalyst to conjugate [F-18]fluoropentyne to the RGD-azide precursor yielding [F-18]RGD-K5. A comparison is made with the registered Siemens method with respect to synthesis, purification and quality control. [F-18]RGD-K5 was obtained after 75 min overall synthesis time with an overall radiochemical yield of 35% (EOB). The radiochemical purity was >98% and the specific radioactivity was 100-200 GBq/mu mol at the EOS. (C) 2013 Elsevier Inc. All rights reserved.</p>