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The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.  相似文献   
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Tumor suppressor genes such as p53 contribute to the oncogenic process via loss-of-function mechanisms such as genetic mutation or complex formation with other cellular or viral proteins. p53 is mutated in approximately 50% of human tumors and has an important role in the genesis or progression of both colorectal and hepatocellular cancers. Colorectal cancer is leading cause of cancer mortality in the United States, whereas hepatocellular cancer is the leading worldwide cause of cancer death; the liver is a primary site of morbidity in both diseases. Because systemic tumor suppressor gene therapy is currently not feasible, we have chosen to develop a regional form of such therapy directed at primary or metastatic liver neoplasms. Gene replacement therapy with p53 is a promising new strategy to treat advanced human cancers.  相似文献   
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New IS technology is contributing to continuous quality improvement throughout the organization. Hypertext and hypermedia offer new ways for decision makers to gain easy and relevant access to information. By combining hypertext with total quality tools, decision makers are able to explore the richness of data bases in more creative and useful ways. This article describes how you can develop a hypertext system that can help employees improve their job performance through better problem solving.  相似文献   
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Several methodological and ethical issues are addressed in the context of 3 related school-based studies of the primary and targeted prevention of depressive symptoms and disorder in high school adolescents. These issues include obtaining S consent and the protection of confidentiality, minimizing attrition over long-term follow-up periods, the "unit of assignment" issue common to most school-based research, and ensuring therapist fidelity to the intervention protocol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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Steve Woolgar 《电信纪事》2002,57(3-4):159-179
The importance of rigorous research into the actual impact of the new Information and Communication Technologies (icts) on society in general cannot be overemphasised. The answer to questions concerning the precise effect ofiCTs on interpersonal relations, communication, social inclusion and exclusion, trust and identity are now central to discussion in both commercial and business fora. This paper examines the concept of the “virtual society“ in the light of the findings of the ESRC (Economic and Social Research Council) Virtual Society? Programme (1997–2002). The paper describes the need to rethink the actual approaches used in researching this area of social science at the same time as performing the analyses themselves. The author also highlights the requirement for future research to examine actual on the ground experiences. How are new technologies actually used and by whom? In addition, the author utilises his overview of this large body of research to put forward a useful guide for predicting the use of ICTs in practice. These “5 rules of virtuality” serve as pointers to the experiences that may be encountered in the development and implementation of new technologies.  相似文献   
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