145 research outputs found
Introduction in "Embedding New Technologies into Society A Regulatory, Ethical and Societal Perspective"
Governing Nanomedicine: Lessons from within, and for the EU medical technology regulatory framework.
Rapidly emerging technologies, such as nanotechnologies, are posing significant\ud
challenges to regulatory governance due to the uncertainties of development\ud
trajectories, product properties, and potential risk problems (Davies\ud
2009). While nanotechnology-based products and processes fall within the\ud
scope of current regulatory instruments (European Commission 2008a;\ud
Ludlow, Bowman, and Hodge 2007; van Calster 2006), there is increasing\ud
concern that such frameworks may not be appropriate for adequately or\ud
effectively regulating all dimensions of the technology (see, for example,\ud
House of Lords Science and Technology Committee 2010; European Parliament\ud
2009a; Chaudhry et al. 2006; Taylor 2008, 2006; Royal Society and\ud
Royal Academy of Engineering 2004). The traditional approach of evidencebased\ud
regulation is not equipped to cope with myriad uncertainties surrounding\ud
the development and commercialisation of nanotechnologies. This does\ud
not mean that public policy can wait and see, however. Even in the case of\ud
evidence deficiencies, public responsibility goes beyond a laissez-faire\ud
approach to risk regulation. In the European Union and some other countries,\ud
precautionary regulatory action is required when basic values like\ud
human dignity, health, safety, environment, property, and privacy are at risk\ud
(Fisher 2007; European Commission 2000)
A Critical Analysis of the Environmental Dossiers from the OECD Sponsorship Programme for the Testing of Manufactured Nanomaterials
In 2015, the OECD finally published the findings of its seven year testing programme for manufactured nanomaterials.</p
Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor
The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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