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Local order scheduling for mixed-model assembly lines in the aircraft manufacturing industry
Multi-variant products to be assembled on mixed-model assembly lines at locations within a production network need to be scheduled locally. Scheduling is a highly complex task especially if it simultaneously covers the assignment of orders, which are product variants to be assembled within a production period, to assembly lines as well as their sequencing on the lines. However, this is required if workers can flexibly fulfill tasks across stations of several lines and, thus, capacity of workers is shared among the lines. As this is the case for final assembly of the Airbus A320 Family, this paper introduces an optimization model for local order scheduling for mixed-model assembly lines covering both assignment to lines as well as sequencing. The model integrates the planning approaches mixed-model sequencing and level scheduling in order to minimize work overload in final assembly and to level material demand with regard to suppliers. The presented model is validated in the industrial application of the final assembly of the Airbus A320 Family. The results demonstrate significant improvement in terms of less work overload and a more even material demand compared to current planning
Natural history of periodontitis: Disease progression and tooth loss over 40years
ObjectivesTo assess long-term attachment and periodontitis-related tooth loss (PTL) in untreated periodontal disease over 40years
Stanniocalcin: a novel protein regulating calcium and phosphate transport across mammalian intestine
Clinical trial considerations on male contraception and collection of pregnancy information from female partners
<p>Abstract</p> <p>Background</p> <p>There is little guidance regarding the risk of exposure of pregnant women/ women of childbearing potential to genotoxic or teratogenic compounds via vaginal dose delivered through seminal fluid during sexual intercourse.</p> <p>Method</p> <p>We summarize current thinking and provide clinical trial considerations for a consistent approach to contraception for males exposed to genotoxic and/or teratogenic compounds or to compounds of unknown teratogenicity, and for collection of pregnancy data from their female partners.</p> <p>Results</p> <p>Where toxicity testing demonstrates genotoxic potential, condom use is required during exposure and for 5 terminal plasma half-lives plus 74 days (one human spermatogenesis cycle) to avoid conception.</p> <p>For non-genotoxic small molecules and immunoglobulins with unknown teratogenic potential or without a no observed adverse effect level (NOAEL) from embryo-fetal development (EFD) studies and no minimal anticipated biological effect level (MABEL), condom use is recommended for males with pregnant partner/female partner of childbearing potential. For teratogenic small molecules with estimated seminal fluid concentration and a margin between projected maternal area under the curve (AUC) and NOAEL AUC from EFD studies of ≥300 (≥100 for immunoglobulins) or in the absence of a NOAEL with a margin between MABEL plasma concentration and maternal C<sub>max</sub> of ≥300 (≥10 for immunoglobulins), condom use is not required. However, condom use is required for margins below the thresholds previously indicated. For small molecules with available seminal fluid concentrations, condom use is required if margins are <100 instead of <300. Condom use should continue for as long as the projected margin is at or above the defined thresholds.</p> <p>Pregnancy data should be proactively collected if pregnancy occurs during the condom use period required for males exposed to first-in-class molecules or to molecules with a target/class shown to be teratogenic, embryotoxic or fetotoxic in human or preclinical experiments.</p> <p>Conclusion</p> <p>These recommendations, based on a precaution principle, provide a consistent approach for minimizing the risk of embryo-fetal exposure to potentially harmful drugs during pregnancy of female partners of males in clinical trials. Proactive targeted collection of pregnancy information from female partners should help determine the teratogenic potential of a drug and minimize background noise and ethical/logistical issues.</p