The automotive industry is facing the fluctuation in demand regarding the variation and amount. Therefore the flexibility and changeability of an assembly line has to be calculable as well as the ...interaction between the assembly and logistics processes have to be considered in order to keep competitiveness.
This paper proposes a generic method, how to make a strategic decision between flexibility/changeability, economic efficiency as well as assembly and logistics processes.
In the last few years the number of offered vehicle derivatives in the multi variant serial production of the automotive industry increased. The existing assembly lines have to manage many ramp ups. ...It is necessary to increase the product and order flexibility of existing assembly lines to manage these challenges. This paper details the preconditions to learn, which assembly configurations fulfill the requirements of existing, further and future products. Therefore the developed method uses degrees of freedom in the assembly order.
The product development process within the automotive industry is subject to changing and varying demands due to external influences and internal strategic decisions. Influences and decisions, such ...as a shift from hybrid vehicles to fully electric architectures, turn into explicit requirements. For a manufacturer to remain competitive, these requirements need to be fulfilled within the early design phases of the development process. The car body substructure and body shop in particular have the highest interdependence with the automotive product development process. To reduce the resulting complexity of managing various requirements for each car body type, car manufacturers use modular design to create partitioned subassemblies. Although there is a wide range of strategies for the modularization of individual requirements, none of them offers the possibility of considering multiple influences and identifying interdependencies between formed modules. To solve this problem, we provide a structured approach for the early planning and design phases as means of achieving this multi-criteria modularization. We transform results from the requirement elicitation into dependency matrices to weight, compare and synchronize critical and relevant requirements. Thus, it is possible to analyze interdependencies to gain knowledge for the design of new product and production modules. In cooperation with the Mercedes-Benz Cars division, we validate our approach and create a domain-specific blueprint for car body substructures. Therefore, we are able to deepen the understanding, give part-specific recommendations and provide a new decomposition of modules of future vehicle architectures.
The genetics underlying heterosis, the difference in performance of crosses compared with midparents, is hypothesized to vary with relatedness between parents. We established a unique germplasm ...comprising three hybrid wheat sets differing in the degree of divergence between parents and devised a genetic distance measure giving weight to heterotic loci. Heterosis increased steadily with heterotic genetic distance for all 1903 hybrids. Midparent heterosis, however, was significantly lower in the hybrids including crosses between elite and exotic lines than in crosses among elite lines. The analysis of the genetic architecture of heterosis revealed this to be caused by a higher portion of negative dominance and dominance-by-dominance epistatic effects. Collectively, these results expand our understanding of heterosis in crops, an important pillar toward global food security.
Diabetic nephropathy is the leading cause of end-stage renal disease in European countries and is associated with an enhanced renal synthesis of endothelin (ET)-1. ETs are - beside their potent ...vasoconstrictor properties - very potent profibrotic acting paracrine hormones especially in the kidney.
We analyzed in rats with streptozotocin-induced diabetes the effects of an ETA-type (ETA) receptor antagonist (LU 135252) in comparison to a combined ETA/ETB receptor antagonist (LU 224332) on the expression of interstitial and glomerular collagen type I, III and IV as well as on fibronectin and laminin by quantitative immunohistochemistry using a computer-aided image analysis system. Global glomerular matrix deposition was analyzed after PAS staining. In addition to the morphometric examination of the kidneys, we also investigated GFR, urinary albumin and total protein excretion. The diabetic rats were treated for 36 weeks.
Treatment with either LU 135252 or LU 224332 normalized the amount of PAS-positive material within the glomeruli. The expression of glomerular fibronectin and type IV collagen was increased 36 weeks after induction of diabetes. The overexpression of these two matrix proteins within the glomeruli of diabetic rats was completely abolished by both ET receptor antagonists, whereas protein excretion was only reduced by about 50% as compared to diabetic rats without treatment.
The present study indicates that ETA receptor antagonists as well as combined ETA/ETB receptor antagonists reduce proteinuria and completely normalize the renal matrix protein expression in hyperglycemic rats with streptozotocin-induced diabetes. The antifibrotic effect seems to be mediated via the ETA receptor. ET receptor antagonists might be a new approach in the treatment of diabetic nephropathy.
Clinical course, diagnostic and therapeutic management, and neurodevelopmental outcome were evaluated in 11 patients with glutaryl-coenzyme A dehydrogenase deficiency. In 9 patients macrocephalus was ...present at or shortly after birth and preceded the neurological disease. In 7 children an acute illness resembling encephalitis appeared after a period of normal development; 2 had developmental delay and progressive "dystonic cerebral palsy." Later, all 9 displayed typical signs of a disorder of the basal ganglia. In 1 patient with macrocephalus the disorder was diagnosed before the onset of neurological disease; in another it was diagnosed prenatally. Computed tomography and magnetic resonance imaging scans revealed severe generalized cerebral atrophy, most striking in the frontal and temporal lobes in 10 patients. Further deterioration was halted after initiation of treatment consisting of low-protein diets, special formulas low in lysine and tryptophan, and supplements of riboflavin and L-carnitine. Only 1 patient showed a slight clinical improvement. Later, dietary therapy was discontinued in 2 older patients and relaxed in a third without observed adverse effects. Two patients in whom treatment could be initiated before the onset of neurological symptoms have developed normally. However, duration of follow-up (6 and 29 months) does not yet allow classification of glutaryl-coenzyme A dehydrogenase deficiency as a treatable disorder. Total body production of glutaric acid, reflected in the daily urinary output, was efficiently reduced by therapeutic measures. Levels of glutaric acid in plasma and cerebrospinal fluid remained unchanged, which may in part explain the overall unsatisfactory outcome. All patients presented with a severe secondary deficiency of carnitine.
PDF
