Generisches Simulationsmodell für Stückgutspeditionsanlagen auf Basis der Anforderungen von KMUs

Simulation can be used to plan and optimize less-than-truckload (LTL) terminals. To develop simulation models, specific expertise in this field is needed, which often requires high financial investments for acquisition of this knowledge. Due to limited financial resources, SMEs are often incapable to get to this expertise. The objective of the paper is to develop a generic model for LTL terminal planning that can be used without simulation expertise and that can be adapted to individual SME layouts. Therefore, based on focus group interviews with SMEs, a catalog of requirements is developed, including input variables and design criteria. Key performance indicators (KPIs) are defined to evaluate the results. A feasibility study for implementing a generic model based on the identified requirements is then performed. The implementation is done by modeling the I-layout of an LTL terminal

A biased-randomized simheuristic for a hybrid flow shop with stochastic processing times in the semiconductor industry

© 2022 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other worksCompared to other industries, production systems in semiconductor manufacturing have an above-average level of complexity. Developments in recent decades document increasing product diversity, smaller batch sizes, and a rapidly changing product range. At the same time, the interconnections between equipment groups increase due to rising automation, thus making production planning and control more difficult. This paper discusses a hybrid flow shop problem with realistic constraints, such as stochastic processing times and priority constraints. The primary goal of this paper is to find a solution set (permutation of jobs) that minimizes the production makespan. The proposed algorithm extends our previous work by combining biased-randomization techniques with a discrete-event simulation heuristic. This simulation-optimization approach allows us to efficiently model dependencies caused by batching and by the existence of different flow paths. As shown in a series of numerical experiments, our methodology can achieve promising results even when stochastic processing times are considered.Peer ReviewedPostprint (author's final draft

A biased-randomized discrete-event algorithm for the hybrid flow shop problem with time dependencies and priority constraints

Based on a real-world application in the semiconductor industry, this article models and discusses a hybrid flow shop problem with time dependencies and priority constraints. The analyzed problem considers a production where a large number of heterogeneous jobs are processed by a number of machines. The route that each job has to follow depends upon its type, and, in addition, some machines require that a number of jobs are combined in batches before starting their processing. The hybrid flow model is also subject to a global priority rule and a “same setup” rule. The primary goal of this study was to find a solution set (permutation of jobs) that minimizes the production makespan. While simulation models are frequently employed to model these time-dependent flow shop systems, an optimization component is needed in order to generate high-quality solution sets. In this study, a novel algorithm is proposed to deal with the complexity of the underlying system. Our algorithm combines biased-randomization techniques with a discrete-event heuristic, which allows us to model dependencies caused by batching and different paths of jobs efficiently in a near-natural way. As shown in a series of numerical experiments, the proposed simulation-optimization algorithm can find solutions that significantly outperform those provided by employing state-of-the-art simulation software.Peer ReviewedPostprint (published version

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation