Plug-and-Work Material Handling Systems

One disadvantage of automated material handling systems is their relative Inflexibility: once racks are installed and conveyors are laid, making even mi-nor changes to a system can be cumbersome and expensive. However, recent progress in the capabilities and cost of basic system components, such as controllers, drives, and sensors, has made possible a new class of material handling systems having a much higher degree of flexibility. We propose underlying de- sign principles for such systems and describe several prototype plug-and-work systems, which feature decentralized control and ease of reconfiguration

RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML