Part feeding at high-variant mixed-model assembly lines

The part feeding problem at automotive assembly plants deals with the timely supply of parts to the designated stations at the assembly line. According to the just-in-time principle, buffer storages at the line are frequently refilled with parts retrieved from a central storage area. In the industrial application at hand, this is accomplished by means of an internal shuttle system which supplies the various stations with the needed parts based on a given assembly sequence. The main objective is to minimize the required number of shuttle drivers. To solve this in-house transportation problem, a heuristic solution procedure is developed which is based on the decomposition of the entire planning problem into two stages. First, transportation orders are derived from the given assembly sequence. In the second stage, these orders are assigned to tours of the shuttle system taking transportation capacity restrictions, due dates and tour scheduling constraints into account. Numerical results show that the proposed heuristic solves even large-sized problem instances in short computational time. Benchmark comparisons with Kanban systems reveal the superiority of the proposed predictive part feeding approach.     

Tardive dyskinesia risk with first‐ and second‐generation antipsychotics in comparative randomized controlled trials: a meta‐analysis

Tardive dyskinesia (TD) risk with D2/serotonin receptor antagonists or D2 receptor partial agonists (second‐generation antipsychotics, SGAs) is considered significantly lower than with D2 antagonists (first‐generation antipsychotics, FGAs). As some reports questioned this notion, we meta‐analyzed randomized controlled studies (RCTs) to estimate the risk ratio (RR) and annualized rate ratio (RaR) of TD comparing SGAs vs. FGAs and SGAs vs. SGAs. Additionally, we calculated raw and annualized pooled TD rates for each antipsychotic. Data from 57 head‐to‐head RCTs, including 32 FGA and 86 SGA arms, were meta‐analyzed, yielding 32 FGA‐SGA pairs and 35 SGA‐SGA pairs. The annualized TD incidence across FGA arms was 6.5% (95% CI: 5.3‐7.8%) vs. 2.6% (95% CI: 2.0‐3.1%) across SGA arms. TD risk and annualized rates were lower with SGAs vs. FGAs (RR=0.47, 95% CI: 0.39‐0.57, p<0.0001, k=28; RaR=0.35, 95% CI: 0.28‐0.45, p<0.0001, number‐needed‐to‐treat, NNT=20). Meta‐regression showed no FGA dose effect on FGA‐SGA comparisons (Z=?1.03, p=0.30). FGA‐SGA TD RaRs differed by SGA comparator (Q=21.8, df=7, p=0.003), with a significant advantage of olanzapine and aripiprazole over other non‐clozapine SGAs in exploratory pairwise comparisons. SGA‐SGA comparisons confirmed the olanzapine advantage vs. non‐clozapine SGAs (RaR=0.66, 95% CI: 0.49‐0.88, p=0.006, k=17, NNT=100). This meta‐analysis confirms a clinically meaningfully lower TD risk with SGAs vs. FGAs, which is not driven by high dose FGA comparators, and documents significant differences with respect to this risk between individual SGAs.     

Equality of average and steady-state levels in some nonlinear models of biological oscillations

Nonlinear oscillatory systems, playing a major role in biology, do not exhibit harmonic oscillations. Therefore, one might assume that the average value of any of their oscillating variables is unequal to the steady-state value. For a number of mathematical models of calcium oscillations (e.g. the Somogyi–Stucki model and several models developed by Goldbeter and co-workers), the average value of the cytosolic calcium concentration (not, however, of the concentration in the intracellular store) does equal its value at the corresponding unstable steady state at the same parameter values. The average value for parameter values in the unstable region is even equal to the level at the stable steady state for other parameter values, which allow stability. This holds for all parameters except those involved in the net flux across the cell membrane. We compare these properties with a similar property of the Higgins–Selkov model of glycolytic oscillations and two-dimensional Lotka–Volterra equations. Here, we show that this equality property is critically dependent on the following conditions: There must exist a net flux across the model boundaries that is linearly dependent on the concentration variable for which the equality property holds plus an additive constant, while being independent of all others. A number of models satisfy these conditions or can be transformed such that they do so. We discuss our results in view of the question which advantages oscillations may have in biology. For example, the implications of the findings for the decoding of calcium oscillations are outlined. Moreover, we elucidate interrelations with metabolic control analysis. This paper is dedicated to the memory of the late Reinhart Heinrich, who was the academic teacher of S.S. and, to a great extent, also of M.M.     

Reversibility and "pH-T phase diagrams" of Rapana venosa hemocyanin and its structural subunits

We have studied the stability and reassociation behaviour of native molecules of Rapana venosa hemocyanin and its two subunits, termed RvH1 and RvH2. In the presence of different concentrations of Ca(2+) and Mg(2+) ions and pH values, the subunits differ not only in their reassociation behaviour, but also in their formation of helical tubules and multidecamers. RvH1 revealed a greater stability at higher pH values compared to RvH2. Overall, the stability of reassociated RvH and its structural subunits was found to be pH-dependent. The increasing stability of native Hc and its subunits, shown by pH-induced CD transitions (acid and alkaline denaturation), can be explained with the formation of quaternary structure. The absence of a Cotton effect at temperatures 20-40 degrees C in the pH-transition curves of RvH2 indicates that this subunit is stabilized by additional "factors", e.g.: non-ionic/hydrophobic stabilization and interactions of carbohydrate moieties. A similar behaviour was observed for the T-transition curves in a wide pH interval for RvH and its structural subunits. At higher temperatures, many of the secondary structural elements are preserved especially at neutral pH, even at extreme high temperatures above 90 degrees C the protein structures resemble a "globule state".     

Genetic determinants for intramuscular fat content and water-holding capacity in mice selected for high muscle mass

Intramuscular fat content and water-holding capacity are important traits in livestock as they influence meat quality, nutritive value of the muscle, and animal health. As a model for livestock, two inbred lines of the Berlin Muscle Mouse population, which had been long-term selected for high muscle mass, were used to identify genomic regions affecting intramuscular fat content and water-holding capacity. The intramuscular fat content of the Musculus longissimus was on average 1.4 times higher in BMMI806 than in BMMI816 mice. This was accompanied by a 1.5 times lower water-holding capacity of the Musculus quadriceps in BMMI816 mice. Linkage analyses with 332 G₃ animals of reciprocal crosses between these two lines revealed quantitative trait loci for intramuscular fat content on chromosome 7 and for water-holding capacity on chromosome 2. In part, the identified loci coincide with syntenic regions in pigs in which genetic effects for the same traits were found. Therefore, these muscle-weight-selected mouse lines and the produced intercross populations are valuable genetic resources to identify genes that could also contribute to meat quality in other species.     

Sperm number trumps sperm size in mammalian ejaculate evolution

Postcopulatory sexual selection is widely accepted to underlie the extraordinary diversification of sperm morphology. However, why does it favour longer sperm in some taxa but shorter in others? Two recent hypotheses addressing this discrepancy offered contradictory explanations. Under the sperm dilution hypothesis, selection via sperm density in the female reproductive tract favours more but smaller sperm in large, but the reverse in small, species. Conversely, the metabolic constraint hypothesis maintains that ejaculates respond positively to selection in small endothermic animals with high metabolic rates, whereas low metabolic rates constrain their evolution in large species. Here, we resolve this debate by capitalizing on the substantial variation in mammalian body size and reproductive physiology. Evolutionary responses shifted from sperm length to number with increasing mammalian body size, thus supporting the sperm dilution hypothesis. Our findings demonstrate that body-size-mediated trade-offs between sperm size and number can explain the extreme diversification in sperm phenotypes.     

Drosophila p24 homologues eclair and baiser are necessary for the activity of the maternally expressed Tkv receptor during early embryogenesis

p24 proteins are assumed to play an important role in the transport of secreted and transmembrane proteins into membranes. However, only few cargo proteins are known that partially, but in no case completely require p24 proteins for membrane transport. Here, we show that two p24 proteins are essential for dorsoventral patterning of Drosophila melanogaster embryo. Mutations in the genes, eclair (eca) and baiser (bai), encoding two p24 proteins reduce signalling by the TGF-beta homologue, Dpp, in early embryos. This effect is strictly maternal and specific to early embryogenesis, as Dpp signalling in other contexts is not notably affected. We provide genetic evidence that in the absence of eca or bai function in the oocyte, the maternally expressed type I TGF-beta receptor Tkv is not active. We propose that during early embryogenesis eca and bai are specifically required for the activity of the maternal Tkv, while the zygotic Tkv is not affected in the mutant embryos. Mutations in either eca or bai are sufficient for the depletion of Tkv activity and no enhancement of the phenotypes was observed in embryos derived from oocytes mutant for both genes. The dependence of maternal Tkv protein on the products of p24 genes may serve as an in vivo model for studying p24 proteins.