Design of a five-axis ultra-precision micro-milling machine—UltraMill. Part 1: Holistic design approach, design considerations and specifications

High-accuracy three-dimensional miniature components and microstructures are increasingly in demand in the sector of electro-optics, automotive, biotechnology, aerospace and information-technology industries. A rational approach to mechanical micro machining is to develop ultra-precision machines with small footprints. In part 1 of this two-part paper, the-state-of-the-art of ultra-precision machines with micro-machining capability is critically reviewed. The design considerations and specifications of a five-axis ultra-precision micro-milling machine—UltraMill—are discussed. Three prioritised design issues: motion accuracy, dynamic stiffness and thermal stability, formulate the holistic design approach for UltraMill. This approach has been applied to the development of key machine components and their integration so as to achieve high accuracy and nanometer surface finish

Micro-manufacturing : research, technology outcomes and development issues

Besides continuing effort in developing MEMS-based manufacturing techniques, latest effort in Micro-manufacturing is also in Non-MEMS-based manufacturing. Research and technological development (RTD) in this field is encouraged by the increased demand on micro-components as well as promised development in the scaling down of the traditional macro-manufacturing processes for micro-length-scale manufacturing. This paper highlights some EU funded research activities in micro/nano-manufacturing, and gives examples of the latest development in micro-manufacturing methods/techniques, process chains, hybrid-processes, manufacturing equipment and supporting technologies/device, etc., which is followed by a summary of the achievements of the EU MASMICRO project. Finally, concluding remarks are given, which raise several issues concerning further development in micro-manufacturing

Clinicopathologic characteristics and treatment outcomes of hepatoid adenocarcinoma of the stomach, a rare but unique subtype of gastric cancer

<p>Abstract</p> <p>Background</p> <p>Gastric hepatoid adenocarcinoma (HAC) is a special type of gastric cancer that morphologically mimics hepatocellular carcinoma. In this study, we performed an evaluation of clinicopathologic characteristics, treatment outcome, and prognosis in patients with gastric HAC.</p> <p>Methods</p> <p>We consecutively enrolled patients with pathologically proven gastric HAC at Seoul National University Hospital between January 1996 and December 2008 and conducted a retrospective review. Among 15,253 patients with gastric cancer, 26 patients (0.17%) were diagnosed as gastric HAC.</p> <p>Results</p> <p>Among 26 patients, 22 were male and the median age was 63. Stage at diagnosis was stage IB in 3 patients, stage II in 6 patients, stage III in 7 patients, and stage IV in 10 patients. Eight patients out of 18 patients with stage IB, II, III, and IV relapsed after curative surgery. Relapse-free survival for these patients was 16.67 months. The most common metastatic site was intraabdominal lymph nodes (n = 9), followed by the liver (n = 8). Thirteen patients received palliative chemotherapy. The most commonly used regimen was a combination of fluoropyrimidine and platinum. Partial response was observed in one patient and stable disease in 5 patients. Median overall survival and progression free survival of these patients were 8.03 (95% CI: 6.59-9.47) and 3.47 months (95% CI: 0.65-6.29), respectively.</p> <p>Conclusions</p> <p>Gastric HAC is a very rare but unique type of stomach cancer. Early detection of this type of cancer is of critical importance to patient prognosis. Additional studies to reveal the biology of this tumor are warranted.</p

Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.Whole-genome sequencing of esophageal adenocarcinoma samples was performed as part of the International Cancer Genome Consortium (ICGC) through the oEsophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium and was funded by Cancer Research UK. We thank the ICGC members for their input on verification standards as part of the benchmarking exercise. We thank the Human Research Tissue Bank, which is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, from Addenbrooke’s Hospital and UCL. Also the University Hospital of Southampton Trust and the Southampton, Birmingham, Edinburgh and UCL Experimental Cancer Medicine Centres and the QEHB charities. This study was partly funded by a project grant from Cancer Research UK. R.C.F. is funded by an NIHR Professorship and receives core funding from the Medical Research Council and infrastructure support from the Biomedical Research Centre and the Experimental Cancer Medicine Centre. We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited. We would like to thank Dr. Peter Van Loo for providing the NGS version of ASCAT for copy number calling. We are grateful to all the patients who provided written consent for participation in this study and the staff at all participating centres. Some of the work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The work at UCLH/UCL was also supported by the CRUK UCL Early Cancer Medicine Centre.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.365