A Robust Reactive Scheduling System with Application to Parallel Machine Scheduling

In this turbulent world, scheduling role has become crucial in most manufacturing production, and service systems. It allows the allocation of limited resources to activities with the objective of optimizing one performance measure or more. Resources may be machines in a factory, operating rooms in a hospital, or employees in a company, while activities can be jobs in a manufacturing plant, surgeries in a hospital, or paper work in a company. The goal of each schedule is to optimize some performance measures, which could be the minimization of the schedule makespan, the jobs\u27 completion times, jobs\u27 earliness and tardiness, among others. Until very recently, research has concentrated on scenarios that assume a predefined schedule that is failure free. Initial schedules produced in advance are being followed hoping no delays will occur, because once they do, the whole schedule may be compromised as it is not designed to adapt to change. Researchers focused on the generation of good schedules in the presence of complex constraints while assuming fixed processing times, known job arrival times, unbreakable machines, and immune employees. However, this is not the case in the real world, where processing times are stochastic, job arrival times could be unknown, machines do break down, and employees get sick. In fact, most environments including manufacturing are dynamic by nature and not static, vulnerable to many unpredictable events, which leads the initial schedule to become obsolete once it is executed. The reason these deterministic schedules fail is because they do not account for variability, scheduling the activities directly after each other, so when a certain activity is delayed, all its successors will be delayed too. In this dissertation, new repair and rescheduling algorithms, and robust systems equipped with learning capability are developed for the unrelated parallel machine environment, a known NP-hard problem. The introduced rules and algorithms were subjected to different stochastic rates of breakdowns and delays and were judged based on several performance measures to ensure the optimization of both the schedule quality and stability. Schedule quality is assessed based on the schedule Makespan (time to finish all jobs) and CPU, while schedule stability is based on the number of shifted jobs from one machine to another and the time to match up with the original schedule after the occurrence of a breakdown. The extensive computational tests and analyses show the superiority of the proposed algorithms and systems compared to existing methods in the literature, especially when implemented with the learning capability. Moreover, the rules were ranked based on their performance for different performance measure combinations, allowing the decision maker to easily determine the most appropriate repair/rescheduling rule depending on the performance measure(s) desired

Simulation and Optimization Of Ant Colony Optimization Algorithm For The Stochiastic Uncapacitated Location-Allocation Problem

This study proposes a novel methodology towards using ant colony optimization (ACO) with stochastic demand. In particular, an optimizationsimulation-optimization approach is used to solve the Stochastic uncapacitated location-allocation problem with an unknown number of facilities, and an objective of minimizing the fixed and transportation costs. ACO is modeled using discrete event simulation to capture the randomness of customers’ demand, and its objective is to optimize the costs. On the other hand, the simulated ACO’s parameters are also optimized to guarantee superior solutions. This approach’s performance is evaluated by comparing its solutions to the ones obtained using deterministic data. The results show that simulation was able to identify better facility allocations where the deterministic solutions would have been inadequate due to the real randomness of customers’ demands

A Dynamic Heuristic for the Stochastic Unrelated Parallel Machine Scheduling Problem

This paper addresses the problem of batch scheduling in an unrelated parallel machine environment with sequence dependent setup times and an objective of minimizing the total weighted mean completion time. The jobs\u27 processing times and setup times are stochastic for better depiction of the real world. This is a NP-hard problem and in this paper, new heuristics are developed and compared to existing ones using simulation. The results and analysis obtained from the computational experiments proved the superiority of the proposed algorithm PMWP over the other algorithms presented

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

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings