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Stem cell research is one of the most promising fields of modern biomedical research and regenerative medicine. Limited availability and ethical concerns suggest the renouncement of embryonic stem cells (ESCs), thus raising the need for more efficient procedures for the generation of stem cells, ideally through reprogramming of mammalian cells. The small molecule N-benzyl-2-(pyrimidin-4′-ylamino)-thiazole-4-carboxamide (thiazovivin) is known to improve the generation of human induced pluripotent stem cells (iPSCs) from human fibroblasts. We herein describe a highly efficient procedure for the synthesis of thiazovivin over just five steps, which should be suitable for a large-scale application, and the first x-ray crystal structure of the target compound. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.] 相似文献
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The authors offer a mathematical model for adverse selection by individual borrowers based on preferences for offers and the default (Bad) or non-default (Good) status of booked accounts. We define the condition for borrower risk and response when there is no adverse selection (NAS). This definition provides us with a direct comparison between the prior and posterior conditional probabilities of default by an individual borrower who Takes an offer; this allows us to obtain estimates of differential response rates for individual borrowers and the Good/Bad odds for Take, Non-Take and Accept sub-populations. Performance of different response-risk segments allows us to compare price-driven risk elasticity and price-driven response elasticity in the presence of Good or Bad adverse selections; a special case applies when the borrower's capacity to repay is not an issue. We offer limited experimental results for selected price-risk segments where action-based risk and response scores are used to estimate borrower preferences. The critical role of Non-Take inference is described. 相似文献
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Alexander J. Nichols Emmanuel Roussakis Oliver J. Klein Conor L. Evans 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2014,126(14):3745-3748
Hypoxia is an important contributing factor to the development of drug‐resistant cancer, yet few nonperturbative tools exist for studying oxygenation in tissues. While progress has been made in the development of chemical probes for optical oxygen mapping, penetration of such molecules into poorly perfused or avascular tumor regions remains problematic. A click‐assembled oxygen‐sensing (CAOS) nanoconjugate is reported and its properties demonstrated in an in vitro 3D spheroid cancer model. The synthesis relies on the sequential click‐based ligation of poly(amidoamine)‐like subunits for rapid assembly. Near‐infrared confocal phosphorescence microscopy was used to demonstrate the ability of the CAOS nanoconjugates to penetrate hundreds of micrometers into spheroids within hours and to show their sensitivity to oxygen changes throughout the nodule. This proof‐of‐concept study demonstrates a modular approach that is readily extensible to a wide variety of oxygen and cellular sensors for depth‐resolved imaging in tissue and tissue models. 相似文献
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Dr. Alexander Hoffmann Cooper Citek Dr. Stephan Binder Arne Goos Prof. Dr. Michael Rübhausen Oliver Troeppner Prof. Dr. Ivana Ivanović‐Burmazović Prof. Dr. Erik C. Wasinger Prof. Dr. T. Daniel P. Stack Prof. Dr. Sonja Herres‐Pawlis 《Angewandte Chemie (International ed. in English)》2013,52(20):5398-5401