Models and methods for operational planning in freight railroads

textRailroads are facing increasing demand for freight transportation. Effective planning and scheduling are crucial to improve the utilization of expensive resources (such as crew and track), reduce operational costs, and provide on-time service. This dissertation focuses on problem modeling and solution method development for real planning problems faced by railroads. It consists of three chapters that study two important planning problems in the daily operations of U.S. freight railroads: crew assignment and train movement planning. Chapter 2 proposes an optimization model to decide crew-to-train assignments and deadheads for double-ended crew districts. We develop an effective solution approach, combining optimization and a standalone heuristic, that generates optimal solutions in minutes. The excellent performance of this solution approach makes it well-suited for implementation within a real-time decision support tool for crew dispatchers. Chapter 3 discusses crew repositioning given the uncertainty in trains’ arrival and departure times. We propose models that minimize the expected crew holding, train delay, and deadheading cost, and develop both exact and heuristic solution methods to provide insights for crew planning under train schedule uncertainty. The last chapter studies the movement planning problem for trains traveling in a territory with multiple through tracks (mainlines) and various junctions. We explore a number of heuristic algorithms to obtain good solutions within a reasonable amount of time. The contributions of this dissertation include modeling enhancements, algorithmic development, implementation and computational testing, and validation using real data.Operations Research and Industrial Engineerin

Loop-mediated isothermal amplification for detection of porcine circovirus type 2

<p>Abstract</p> <p>Background</p> <p>Porcine circovirus type 2 (PCV2) is the primary causative agent of the emerging swine disease known as postweaning multisystemic wasting syndrome (PMWS). Nowadays, polymerase chain reaction (PCR) is still the most widespread technique in pathogen detection. Loop-mediated isothermal amplification (LAMP), a novel nucleic acid amplification method developed in 2000, will possibly replace PCR in the field of detection. To establish a LAMP method for rapid detection of PCV2, two pairs of primers were designed specially from the open reading frame 2 (ORF2) sequences of PCV2. A LAMP method for rapid detection of PCV2 was established. To compare with PCR, sensitivity and specificity of LAMP were evaluated using the optimized reaction system. The LAMP products could be determined by agarose gel electrophoresis or adding SYBR Green I dye.</p> <p>Results</p> <p>The amplification of LAMP could be obtained at 63°C for 60 min. The detection limit was nearly 1 copy of DNA plasmid, more sensitive than PCR. There was no cross-reaction with porcine circovirus type 1 (PCV1), porcine pseudorabies virus (PRV) and porcine parvovirus (PPV) under the same conditions.</p> <p>Conclusions</p> <p>LAMP is an useful rapid detection method with high sensitivity and specificity for PCV2.</p

Universal factorial Schur P,QP,Q-functions and their duals

We define universal factorial Schur $P,Q$-functions and their duals, which specialize to generalized (co)-homology "Schubert basis" for loop spaces of the classical groups. We also investigate some of their properties.Comment: 10 pages, old paper written in 2012.1

Association between ultra-processed food consumption and risk of breast cancer: a systematic review and dose-response meta-analysis of observational studies

BackgroundSome epidemiological studies have examined the association between consumption of ultra-processed food (UPF) and the risk of breast cancer. However, the results were inconsistent. Therefore, we carried out a systematic review and dose-response meta-analysis to examine whether an association exists between high consumption of UPF and breast cancer risk.MethodsPubMed/MEDLINE, ISI Web of Science, EBSCO and CNKI databases were systematically searched from inception to May 2023. The summary relative risks (RRs) and 95% confidence intervals (CIs) associated with UPF consumption and breast cancer were calculated using a random-effects model (DerSimonian-Laird method). Heterogeneity between included studies was examined using the Cochran’s Q test and I-square (I2) statistics. Publication bias was studied by visual inspection of funnel plot asymmetry and Begg’s and Egger’s tests.ResultsOverall, six articles involving 462,292 participants, were eligible to be included in this study. Compared to the lowest consumption, highest consumption of UPF was related to a higher risk of breast cancer (RR = 1.10; 95%CI: 1.00–1.22, p = 0.056). Besides, the linear dose–response analysis showed that each 10% increment in UPF consumption was related to a 5% higher risk of breast cancer (RR = 1.05; 95%CI: 1.00–1.10, p = 0.048). Subgroup analyses suggested that UPF consumption was positively associated with breast cancer risk in case-control studies (RR = 1.13; 95%CI: 1.01–1.26, p = 0.028). Additionally, there was also a significant positive association between UPF consumption and breast cancer risk in the subgroup with sample size&lt;5,000(RR = 1.17; 95%CI: 1.02–1.35, p = 0.028).ConclusionOur results indicate that higher consumption of UPF is slightly related to a higher risk of breast cancer. Further studies in particular of large prospective cohort studies are warranted to confirm these results

Salidroside Stimulates Mitochondrial Biogenesis and Protects against H 2

Salidroside (SAL) is an active component of Rhodiola rosea with documented antioxidative properties. The purpose of this study is to explore the mechanism of the protective effect of SAL on hydrogen peroxide- (H2O2-) induced endothelial dysfunction. Pretreatment of the human umbilical vein endothelial cells (HUVECs) with SAL significantly reduced the cytotoxicity brought by H2O2. Functional studies on the rat aortas found that SAL rescued the endothelium-dependent relaxation and reduced superoxide anion (O2∙-) production induced by H2O2. Meanwhile, SAL pretreatment inhibited H2O2-induced nitric oxide (NO) production. The underlying mechanisms involve the inhibition of H2O2-induced activation of endothelial nitric oxide synthase (eNOS), adenosine monophosphate-activated protein kinase (AMPK), and Akt, as well as the redox sensitive transcription factor, NF-kappa B (NF-κB). SAL also increased mitochondrial mass and upregulated the mitochondrial biogenesis factors, peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1α), and mitochondrial transcription factor A (TFAM) in the endothelial cells. H2O2-induced mitochondrial dysfunction, as demonstrated by reduced mitochondrial membrane potential (Δψm) and ATP production, was rescued by SAL pretreatment. Taken together, these findings implicate that SAL could protect endothelium against H2O2-induced injury via promoting mitochondrial biogenesis and function, thus preventing the overactivation of oxidative stress-related downstream signaling pathways

Peripheral Blood Lymphocyte Subsets Predict the Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer

BackgroundNon–small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients’ response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy.MethodsTo explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs.ResultsThe two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4+CD45RA− T cell (HR = 0.644, P = 0.047) and CD8+ T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4+CD45RA− T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4+CD45RA− T cell &gt;311.3 × 106/L as the threshold. In contrast, CD8+ T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4+ T cell and its subsets were significantly higher in patients with mild (grades 1–2) immune-related adverse events (irAEs) than those without irAEs. CD8+CD38+ T cell was associated with total irAEs and severe (grades 3–4) irAEs but was not suitable to be a predictive biomarker.ConclusionPeripheral blood CD4+CD45RA− T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8+CD38+ T cell was associated with irAEs and severe irAEs

Histopathological Features and Composition of Gut Microbiota in Rhesus Monkey of Alcoholic Liver Disease

Alcohol-induced chronic liver disease (ALD) is becoming the most common liver disease in the world. However, there are no effective, universally accepted therapies for ALD. The etiology of ALD remains blurry so far. Historical evidence has demonstrated a link between the liver and gut microbiota. But it is difficult to distinguish the effect of gut microbiota changes caused by alcohol consumption in humans since the microbiota change detected in humans is complicated by diet and environmental factors. Due to the genetic, physiological, metabolic, and behavioral similarities to humans, the rhesus monkey provides excellent translational validity in preclinical studies, and the diet and environmental conditions can be controlled well in rhesus monkey. In our study, we explored the relationship between ALD and the gut microbiome in the rhesus monkeys with alcoholic liver steatosis. Our results showed that there was a change of the bacterial community structure in monkeys with ALD. Differences of the relative abundances of gut microbiota at phylum, order, family, genus, and species levels were observed between control monkeys and monkeys with ALD, and different pathways enriched in the monkeys with ALD were identified by metagenomic function analysis. Firmicutes, Proteobacteria, Verrucomicrobia tended to increase whereas Bacteroidetes and Actinobacteria decreased in the fecal microbiota of ALD group compared to the control group. Lactobacillales and Lactobacillus significantly decreased in ALD monkeys compared with normal monkeys, Streptococcus was lower in the ALD group compared with the control group. The non-human primate model of ALD will be useful for exploration of the microbiome markers as diagnosis and potentially prognosis for ALD. The ALD model will benefit the development of new therapeutic procedures for treating ALD and provide safety and efficacy evaluation for clinical application