SALBPGen - A systematic data generator for (simple) assembly line balancing

Assembly line balancing is a well-known and extensively researched decision problem which arises when assembly line production systems are designed and operated. A large variety of real-world problem variations and elaborate solution methods were developed and presented in the academic literature in the past 60 years. Nevertheless, computational experiments examining and comparing the performance of solution procedures were mostly based on very limited data sets unsystematically collected from the literature and from some real-world cases. In particular, the precedence graphs used as the basis of former tests are limited in number and characteristics. As a consequence, former performance analyses suffer from a lack of systematics and statistical evidence. In this article, we propose SALPBGen, a new instance generator for the simple assembly line balancing problem (SALBP) which can be applied to any other assembly line balancing problem, too. It is able to systematically create instances with very diverse structures under full control of the experiment's designer. In particular, based on our analysis of real-world problems from automotive and related industries, typical substructures of the precedence graph like chains, bottlenecks and modules can be generated and combined as required based on a detailed analysis of graph structures and structure measures like the order strength. We also present a collection of new challenging benchmark data sets which are suited for comprehensive statistical tests in comparative studies of solution methods for SALBP and generalized problems as well. Researchers are invited to participate in a challenge to solve these new problem instances.manufacturing, benchmark data set, assembly line balancing, precedence graph, structure analysis, complexity measures

Reducing physical ergonomic risks at assembly lines by line balancing and job rotation: A survey

Factors such as repetitiveness of work, required application of forces, handling of heavy loads, and awkward, static postures expose assembly line workers to risks of musculoskeletal disorders. As a rule, companies perform a post hoc analysis of ergonomic risks and examine ways to modify workplaces with high ergonomic risks. However, it is possible to lower ergonomic risks by taking ergonomics aspects into account right from the planning stage. In this survey, we provide an overview of the existing optimization approaches to assembly line balancing and job rotation scheduling that consider physical ergonomic risks. We summarize major findings to provide helpful insights for practitioners and identify research directions

preventing ergonomic risks with integrated planning on assembly line balancing and parts feeding

In this paper, we advise to perform assembly line balancing simultaneously with decision-making on parts feeding. Such integrated planning may open additional potential to reduce labour costs. Additional planning flexibility gained with the integrated planning may be used to mitigate ergonomic risks at workplaces. We formulate the integrated assembly line balancing and parts feeding planning problem, propose a mixed-integer model and compare integrated planning to a common hierarchical planning approach in a detailed case study on the assembly of a self-priming pump. Our case study illustrates that workplaces with high ergonomic risks may emerge even in productions that involve handling parts and workpieces of low weights and avoid static and awkward postures. We also show that the proposed integrated planning approach may eliminate excessive ergonomic risks and improve productivity indicators simultaneously

Future trends in management and operation of assembly systems: from customized assembly systems to cyber-physical systems

Future trends in management and operation of assembly systems: from customized assembly systems to cyber-physical systems

In Vitro

Epigallocatechin-3-gallate (EGCG) is the main compound of green tea with well-described antioxidant, anti-inflammatory, and tumor-suppressing properties. However, EGCG at high doses was reported to cause liver injury. In this study, we evaluated the effect of EGCG on primary culture of rat hepatocytes and on rat liver mitochondria in permeabilized hepatocytes. The 24-hour incubation with EGCG in concentrations of 10 μmol/L and higher led to signs of cellular injury and to a decrease in hepatocyte functions. The effect of EGCG on the formation of reactive oxygen species (ROS) was biphasic. While low doses of EGCG decreased ROS production, the highest tested dose induced a significant increase in ROS formation. Furthermore, we observed a decline in mitochondrial membrane potential in cells exposed to EGCG when compared to control cells. In permeabilized hepatocytes, EGCG caused damage of the outer mitochondrial membrane and an uncoupling of oxidative phosphorylation. EGCG in concentrations lower than 10 μmol/L was recognized as safe for hepatocytes in vitro

Shunting operations at flat yards : retrieving freight railcars from storage tracks

In this paper, we study the railcar retrieval problem (RRT) where specified numbers of certain types of railcars have to be withdrawn from the storage tracks of a flat yard. This task arises in the daily operations of workshop yards for railcar maintenance. The objective is to minimize the total cost of shunting via methods such as minimizing the usage of shunting engines. We describe the RRT formally, present a mixed-integer program formulation, and prove the general case to be NP-hard. For some special cases, exact algorithms with polynomial runtimes are proposed. We also analyze several intuitive heuristic solution approaches motivated by observed real-world planning routines. We evaluate their average performances in simulations with different scenarios and provide their worst-case performance guarantee. We show that although the analyzed heuristics result in much better solutions than the naive planning approach, they are still on average 30%-50% from the optimal objective value and may result in up to 14 times higher costs in the worst case. Therefore, we conclude that optimization should be implemented in practice in order to save valuable resources. Furthermore, we analyze the impacts of yard layout and the widespread organizational routine of presorting on the railcar retrieval cost

Cellular senescence is immunogenic and promotes anti-tumor immunity

Cellular senescence is a stress response that activates innate immune cells, but little is known about its interplay with the adaptive immune system. Here, we show that senescent cells combine several features that render them highly efficient in activating dendritic cells (DCs) and antigen-specific CD8 T cells. This includes the release of alarmins, activation of interferon signaling, enhanced MHC class I machinery, and presentation of senescence-specific self-peptides that can activate CD8 T cells. In the context of cancer, immunization with senescent cancer cells elicits strong anti-tumor protection mediated by DCs and CD8 T cells. Interestingly, this protection is superior to immunization with cancer cells undergoing immunogenic cell death. Finally, the induction of senescence in human primary cancer cells also augments their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. Our study indicates that senescent cancer cells can be exploited to develop efficient and protective CD8-dependent anti-tumor immune responses

Intestinal BMP-9 locally upregulates FGF19 and is down-regulated in obese patients with diabetes

believed to be mainly produced in the liver. The serum levels of BMP-9 were reported to be reduced in newly diagnosed diabetic patients and BMP-9 overexpression ameliorated steatosis in the high fat diet-induced obesity mouse model. Furthermore, injection of BMP-9 in mice enhanced expression of fibroblast growth factor (FGF)21. However, whether BMP-9 also regulates the expression of the related FGF19 is not clear. Because both FGF21 and 19 were described to protect the liver from steatosis, we have further investigated the role of BMP-9 in this context. We first analyzed BMP-9 levels in the serum of streptozotocin (STZ)-induced diabetic rats (a model of type I diabetes) and confirmed that BMP-9 serum levels decrease during diabetes. Microarray analyses of RNA samples from hepatic and intestinal tissue from BMP-9 KO- and wild-type mice (C57/Bl6 background) pointed to basal expression of BMP-9 in both organs and revealed a down-regulation of hepatic Fgf21 and intestinal Fgf19 in the KO mice. Next, we analyzed BMP-9 levels in a cohort of obese patients with or without diabetes. Serum BMP-9 levels did not correlate with diabetes, but hepatic BMP-9 mRNA expression negatively correlated with steatosis in those patients that did not yet develop diabetes. Likewise, hepatic BMP-9 expression also negatively correlated with serum LPS levels. In situ hybridization analyses confirmed intestinal BMP-9 expression. Intestinal (but not hepatic) BMP-9 mRNA levels were decreased with diabetes and positively correlated with intestinal E-Cadherin expression. In vitro studies using organoids demonstrated that BMP-9 directly induces FGF19 in gut but not hepatocyte organoids, whereas no evidence of a direct induction of hepatic FGF21 by BMP-9 was found. Consistent with the in vitro data, a correlation between intestinal BMP-9 and FGF19 mRNA expression was seen in the patients’ samples. In summary, our data confirm that BMP-9 is involved in diabetes development in humans and in the control of the FGF-axis. More importantly, our data imply that not only hepatic but also intestinal BMP-9 associates with diabetes and steatosis development and controls FGF19 expression. The data support the conclusion that increased levels of BMP-9 would most likely be beneficial under pre-steatotic conditions, making supplementation of BMP-9 an interesting new approach for future therapies aiming at prevention of the development of a metabolic syndrome and liver steatosis

A forward genetic screen reveals a primary role for Plasmodium falciparum Reticulocyte Binding Protein Homologue 2a and 2b in determining alternative erythrocyte invasion pathways.

Invasion of human erythrocytes is essential for Plasmodium falciparum parasite survival and pathogenesis, and is also a complex phenotype. While some later steps in invasion appear to be invariant and essential, the earlier steps of recognition are controlled by a series of redundant, and only partially understood, receptor-ligand interactions. Reverse genetic analysis of laboratory adapted strains has identified multiple genes that when deleted can alter invasion, but how the relative contributions of each gene translate to the phenotypes of clinical isolates is far from clear. We used a forward genetic approach to identify genes responsible for variable erythrocyte invasion by phenotyping the parents and progeny of previously generated experimental genetic crosses. Linkage analysis using whole genome sequencing data revealed a single major locus was responsible for the majority of phenotypic variation in two invasion pathways. This locus contained the PfRh2a and PfRh2b genes, members of one of the major invasion ligand gene families, but not widely thought to play such a prominent role in specifying invasion phenotypes. Variation in invasion pathways was linked to significant differences in PfRh2a and PfRh2b expression between parasite lines, and their role in specifying alternative invasion was confirmed by CRISPR-Cas9-mediated genome editing. Expansion of the analysis to a large set of clinical P. falciparum isolates revealed common deletions, suggesting that variation at this locus is a major cause of invasion phenotypic variation in the endemic setting. This work has implications for blood-stage vaccine development and will help inform the design and location of future large-scale studies of invasion in clinical isolates