Manufacturing-error-based maintenance for high-precision machine tools

Nowadays, the condition-based maintenance (CBM), in which repairs are triggered by the heuristic symptoms of the component faults, is finding increasing applications in the industrial fields. However, for the high-precision machine tools, the conventional CBM might not be the optimal option, which is uneconomic and incapable of ensuring their machining accuracy. In order to overcome these shortcomings, this paper propose the manufacturing-error-based maintenance (MEBM), where the repairs are initiated based on the manufacturing errors instead of the heuristic symptoms. In MEBM, repairs are taken properly at the occurrence of the excessive machining errors, and therefore, the premature and redundant maintenance can be avoided and the maintenance cost can be minimized; what is more, the machining errors are controlled in the closed loops, and therefore, the machining accuracy can be guaranteed. Based on the principles of the MEBM, a prototype maintenance system—the transient backlash error (TBE)-based maintenance system—is established. To achieve this aim, first, the width of the backlash in the mechanical chain is measured by utilizing the built-in encoders and the analytical mapping relationship between the backlash width and the TBE is derived. Relying on these foundations, the TBE can be indirectly estimated. Then, the warning threshold of the TBE is customized according to the permissible roundness error of the workpiece. Thus, the maintenance actions can be precisely implemented: when the monitored TBE exceeds its warning threshold, maintenance workers will be notified to lessen the backlash width, and meanwhile, the permissible maximal size for the backlash will also be informed

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours.

G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition. Exposure to CX-5461, and its related drug CX-3543, blocks replication forks and induces ssDNA gaps or breaks. The BRCA and NHEJ pathways are required for the repair of CX-5461 and CX-3543-induced DNA damage and failure to do so leads to lethality. These data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016).This work was supported by the Canadian Breast Cancer Foundation BC/Yukon, BC Cancer Foundation, Stand Up to Cancer Canada (SU2C-AACR-DT-18-15), TFRI Grant 1021, CCSRI Grant 701584, CIHR Grant MOP-126119, Canada Foundation for Innovation and Cancer Research UK. Grant Brown lab is supported by CCSRI Impact Grant 702310 (to G.W.B.) and Ontario Government Scholarship (to B.H.). S.A. is supported by a Canada Research Chair in Molecular Oncology. The Balasubramanian lab is supported by a programme grant (C14303/A17197) and core funding (C14303/A17197) from Cancer Research UK

Quantifying Appetite and Satiety

The scientific study of human appetite and eating behavior has become increasingly important in recent years due to the rise of body fat dysregulation and the conditions of obesity, diabetes and eating disorders. In addition, changes in appetite occur in several other disease states and physical conditions affecting general health. For these reasons a strong methodology is required to ensure objective and quantifiable measures of appetite behavior and associated psychological sensations. The use of a multi-level research platform can help the alignment of psychological, behavioral and physiological variables. The Satiety Cascade provides a graphic formulation for clarifying distinct measurable variables such as hunger, satiation and satiety. An agreed methodology allows outcomes from different studies to be compared. Specific experimental designs, measurement instruments, and standard operating procedures have been developed to ensure good conduct. Several study designs are widely used and can be deployed to answer specific research questions. Specific procedures have been developed for the measurement of homeostatic and hedonic processes involved in appetite. A case study of the comprehensive assessment of a potential anti-obesity drug is described as a model procedure. Good Laboratory Practice applies in this field as in other areas of biomedical research