Closed-loop control of product properties in metal forming

Metal forming processes operate in conditions of uncertainty due to parameter variation and imperfect understanding. This uncertainty leads to a degradation of product properties from customer specifications, which can be reduced by the use of closed-loop control. A framework of analysis is presented for understanding closed-loop control in metal forming, allowing an assessment of current and future developments in actuators, sensors and models. This leads to a survey of current and emerging applications across a broad spectrum of metal forming processes, and a discussion of likely developments.Engineering and Physical Sciences Research Council (Grant ID: EP/K018108/1)This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.cirp.2016.06.00

Histone Chaperone CHAF1A Inhibits Differentiation and Promotes Aggressive Neuroblastoma

Neuroblastoma arises from the embryonal neural crest secondary to a block in differentiation. Long-term patient survival correlates inversely with the extent of differentiation, and treatment with retinoic acid or other prodifferentiation agents improves survival modestly. In this study, we show the histone chaperone and epigenetic regulator CHAF1A functions in maintaining the highly dedifferentiated state of this aggressive malignancy. CHAF1A is a subunit of the chromatin modifier chromatin assembly factor 1 and it regulates H3K9 trimethylation of key target genes regulating proliferation, survival, and differentiation. Elevated CHAF1A expression strongly correlated with poor prognosis. Conversely, CHAF1A loss-of-function was sufficient to drive neuronal differentiation in vitro and in vivo. Transcriptome analysis of cells lacking CHAF1A revealed repression of oncogenic signaling pathways and a normalization of glycolytic metabolism. Our findings demonstrate that CHAF1A restricts neural crest differentiation and contributes to the pathogenesis of high-risk neuroblastoma. Cancer Res; 74(3); 765-74. ©2013 AACR

Genetic studies of body mass index yield new insights for obesity biology

Note: A full list of authors and affiliations appears at the end of the article. Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p