Optimizing High-Speed Railroad Timetable with Passenger and Station Service Demands: A Case Study in the Wuhan-Guangzhou Corridor

This paper aims to optimize high-speed railroad timetables for a corridor. We propose an integer programming model using a time-space network-based approach to consider passenger service demands, train scheduling, and station service demands simultaneously. A modified branch-and-price algorithm is used for the computation. This algorithm solves the linear relaxation of all nodes in a branch-and-bound tree using a column generation algorithm to derive a lower-bound value (LB) and derive an upper-bound value (UB) using a rapid branching strategy. The optimal solution is derived by iteratively updating the upper- and lower-bound values. Three acceleration strategies, namely, initial solution iteration, delayed constraints, and column removal, were designed to accelerate the computation. The effectiveness and efficiency of the proposed model and algorithm were tested using Wuhan-Guangzhou high-speed railroad data. The results show that the proposed model and algorithm can quickly reduce the defined cost function by 38.2% and improve the average travel speed by 10.7 km/h, which indicates that our proposed model and algorithm can effectively improve the quality of a constructed train timetable and the travel efficiency for passengers. Document type: Articl

Long-term high salt intake involves reduced SK Currents and Increased Excitability of PVN Neurons with projections to the rostral ventrolateral medulla in rats

Evidence indicates that high salt (HS) intake activates presympathetic paraventricular nucleus (PVN) neurons, which contributes to sympathoexcitation of salt-sensitive hypertension. The present study determined whether 5 weeks of HS (2% NaCl) intake alters the small conductance Ca2+-activated potassium channel (SK) current in presympathetic PVN neurons and whether this change affects the neuronal excitability. In whole-cell voltage-clamp recordings, HS-treated rats had significantly decreased SK currents compared to rats with normal salt (NS, 0.4% NaCl) intake in PVN neurons. The sensitivity of PVN neuronal excitability in response to current injections was greater in HS group compared to NS controls. The SK channel blocker apamin augmented the neuronal excitability in both groups but had less effect on the sensitivity of the neuronal excitability in HS group compared to NS controls. In the HS group, the interspike interval (ISI) was significantly shorter than that in NS controls. Apamin significantly shortened the ISI in NS controls but had less effect in the HS group. This data suggests that HS intake reduces SK currents, which contributes to increased PVN neuronal excitability at least in part through a decrease in spike frequency adaptation and may be a precursor to the development of salt-sensitive hypertension

Exogenous erythropoietin administration attenuates intermittent hypoxia-induced cognitive deficits in a murine model of sleep apnea

Background: In rodents, exposure to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Such findings are markedly attenuated in rodents exposed to sustained hypoxia 9SH) of similar magnitude. The hypoxia-sensitive gene erythropoietin (EPO) has emerged as a major endogenous neuroprotectant, and could be involved in IH-induced neuronal dysfunction. Methods and Results: IH induced only transiently increased expression of EPO mRNA in hippocampus, which was continued in (SH)-exposed mice. IH, but not SH, adversely affected two forms of spatial learning in the water maze, and increased markers of oxidative stress. However, on a standard place training task, mice treated with exogenously administered EPO displayed normal learning, and were protected from the spatial learning deficits observed in vehicle-treated (C) littermates exposed to IH. Moreover, anxiety levels were increased in IH as compared to normoxia, while no changes in anxiety emerged in EPO-treated mice. Additionally, C mice, but not EPO-treated IH-exposed mice had significantly elevated levels of NADPH oxidase expression, as well as increased MDA and 8-OHDG levels in cortical and hippocampal lysates. Conclusions: The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by imbalances between EPO expression and increased NADPH oxidase activity, and thus pharmacological agents targeting EPO expression in CNS may provide a therapeutic strategy in sleep-disordered breathing

3D fracture propagation simulation and pressure decline analysis research for I-shaped fracture of coalbed

After hydraulic fracturing, some treatments intended for production enhancement fail to yield predetermined effects. The main reason is the insufficient research about the fracture propagation mechanism. There is compelling evidence that I-shaped fracture, two horizontal fractures at the junction of coalbed and cover/bottom layer, and one vertical fracture in the coalbed have formed in part of the coalbed after hydraulic fracturing. Therefore, this paper aims at I-shaped fracture propagation simulation. A novel propagation model is derived on the basis of a three-dimensional (3D) model, and the coupling conditions of vertical fracture and horizontal fractures are established based on the flow rate distribution and the bottom-hole pressure equality, respectively. Moreover, an associated PDA (pressure decline analysis of post-fracturing) model is established. Both models complement with each other and work together to guide fracturing treatment. Finally, a field case is studied to show that the proposed models can effectively investigate and simulate fracture initiation/propagation and pressure decline

Leveraging Prototype Patient Representations with Feature-Missing-Aware Calibration to Mitigate EHR Data Sparsity

Electronic Health Record (EHR) data frequently exhibits sparse characteristics, posing challenges for predictive modeling. Current direct imputation such as matrix imputation approaches hinge on referencing analogous rows or columns to complete raw missing data and do not differentiate between imputed and actual values. As a result, models may inadvertently incorporate irrelevant or deceptive information with respect to the prediction objective, thereby compromising the efficacy of downstream performance. While some methods strive to recalibrate or augment EHR embeddings after direct imputation, they often mistakenly prioritize imputed features. This misprioritization can introduce biases or inaccuracies into the model. To tackle these issues, our work resorts to indirect imputation, where we leverage prototype representations from similar patients to obtain a denser embedding. Recognizing the limitation that missing features are typically treated the same as present ones when measuring similar patients, our approach designs a feature confidence learner module. This module is sensitive to the missing feature status, enabling the model to better judge the reliability of each feature. Moreover, we propose a novel patient similarity metric that takes feature confidence into account, ensuring that evaluations are not based merely on potentially inaccurate imputed values. Consequently, our work captures dense prototype patient representations with feature-missing-aware calibration process. Comprehensive experiments demonstrate that designed model surpasses established EHR-focused models with a statistically significant improvement on MIMIC-III and MIMIC-IV datasets in-hospital mortality outcome prediction task. The code is publicly available at \url{https://github.com/yhzhu99/SparseEHR} to assure the reproducibility

LH level on the antagonist administration day as a predictor of the reproductive outcomes in women with normal ovarian function

IntroductionThe addition of antagonists is mainly based on estrogen level and follicle size, while LH level has not received sufficient attention.In this study, LH Level on the antagonist administration day was used as the main research objective to explore its relationship with laboratory indicators and pregnancy outcomes.Methods and AnalysisWe enrolled 854 patients with normal ovarian function undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) between May 2021 to May 2022 at the Reproductive Center of Shandong University of Traditional Chinese Medicine.We used the quartile method to group LH levels on the antagonist administration day. There were four groups: Q1 (0.53IU/L≤LH ≤ 1.89IU/L); Q2 (1.89IU/L<LH ≤ 3.01IU/L); Q3 (3.01IU/L<LH≤ 5.29 IU/L); Q4 (5.29IU/L<LH ≤ 8.72IU/L). A total of 452 fresh embryo transplantation cycles and 1726 Frozen embryo transplantation cycles were carried out.ResultThere were significant differences among the four groups in terms of total Gn dosage, E2, P and LH on trigger day, number of retrieved oocytes, number of 2PN embryos, number of blastocysts, Number of ET and fresh ETR.There is a significant correlation between LH on antagonist administration day and Basal LH Level,LH on trigger day,number of oocytes retrieved,number of 2PN embryos,number of blastocysts, number of ET.Using Fresh ETR,Fresh CPR,OHSS and Cumulative CPR as the criterion respectively, the optimal cut-off value for evaluating LH on antagonist administration day was 4.18IU/L,3.99IU/L,4.63IU/L,4.66IU/L.ConclusionThere was a significant positive correlation between LH on the antagonist administration day and number of oocytes retrieved,number of 2PN embryos,number of blastocysts.LH on the antagonist administration day could predict Fresh CPR,OHSS and Cumulative CPR to some extent

Upregulated antimicrobial immune response mediated by neutrophils in the development from allergic rhinitis to asthma

BackgroundAllergic rhinitis (AR) and asthma are closely related, and AR is regarded as an important risk factor for the onset of asthma. However, the pathogenesis of the development of asthma from AR is still undefined.ObjectiveThe aim of this study was to investigate the mechanisms underlying the development of asthma from AR by comparing the transcriptome features of patients with AR with and without asthma.MethodsPatients with AR with or without asthma caused by weed pollen who presented to the Allergy Clinic of Peking Union Medical College Hospital were recruited for this study. Peripheral blood samples of all the patients were collected during the weed pollen season (September) when the patients had allergic symptoms and outside the pollen season (November) when the patients had no symptoms. Transcriptomic analysis was conducted, and the differentially expressed genes (DEGs) and enriched immune pathways between the patients with AR with asthma (AR-asthma group) and those without asthma (AR group) were identified. In addition, the expression levels of some pivotal differentially expressed RNAs were quantified using quantitative polymerase chain reaction (PCR).ResultsDuring the weed pollen season, the immune-related Gene Ontology (GO) terms with P value < 0.05, enriched by the upregulated genes in the AR-asthma group compared to the AR group included antifungal humoral response, neutrophil-mediated killing of bacterium, antibacterial humoral response, antimicrobial humoral immune response mediated by antimicrobial peptides, and regulation of the T cell receptor signaling pathway. The immune-related GO terms with P values <0.05 enriched by downregulated genes were positive regulation of natural killer cell-mediated cytotoxicity, microglial cell activation, natural killer cell activation, and leukocyte-mediated cytotoxicity. The GO term of antimicrobial humoral immune response mediated by antimicrobial peptides was upregulated both during and outside the pollen season, and the upregulated expression of three DEGs (LTF, PF4, and ELANE) included in this term was verified through quantitative PCR.ConclusionsThe activation of the antimicrobial immune response mediated by neutrophils and the depression of cytotoxicity mediated by natural killer cells may play roles in the progression from AR to asthma

Undiagnosed diabetic retinopathy in Northeast China: prevalence and determinants

ObjectiveTo report the prevalence and contributing factors of undiagnosed diabetic retinopathy (DR) in a population from Northeastern China.Subjects/MethodsA total of 800 subjects from the Fushun Diabetic Retinopathy Cohort Study were enrolled. A questionnaire assessing incentives and barriers to diagnosis of DR was administered. Logistic regression was used to identify clinical and sociodemographic factors associated with undiagnosed DR. In a prespecified subgroup analysis, we divided patients into vision-threatening diabetic retinopathy (VTDR) and non-VTDR (NVTDR) subgroups.ResultsAmong 800 participants with DR, 712 (89.0%) were undiagnosed. Among 601 with NVTDR, 566 (94.2%) were undiagnosed. Among 199 with VTDR, 146 (73.4%) were undiagnosed. The risk factors affecting the timely diagnosis of NVTDR and VTDR exhibit significant disparities. In multivariate models, factors associated with undiagnosed VTDR were age over 60 years (OR = 2.966; 95% CI = 1.205-7.299; P = 0.018), duration of diabetes over 10 years (OR = 0.299; 95% CI = 0.118-0753; P = 0.010), visual impairment or blindness (OR = 0.310; 95% CI = 0.117-0.820; P = 0.018), receiving a reminder to schedule an eye examination (OR = 0.380; 95% CI = 0.163-0.883; P = 0.025), and the belief that “people with diabetes are unlikely to develop an eye disease” (OR = 4.691; 95% CI = 1.116-19.724; P = 0.035). However, none of the factors were associated with undiagnosed NVTDR (all P ≥ 0.145).ConclusionOur research has uncovered a disconcerting trend of underdiagnosis in cases of DR within our population. Addressing determinants of undiagnosed DR may facilitate early detection

Transgenerational Epigenetic Inheritance Under Environmental Stress by Genome-Wide DNA Methylation Profiling in Cyanobacterium

Epigenetic modifications such as DNA methylation are well known as connected with many important biological processes. Rapid accumulating evidence shows environmental stress can generate particular defense epigenetic changes across generations in eukaryotes. This transgenerational epigenetic inheritance in animals and plants has gained interest over the last years. Cyanobacteria play very crucial role in the earth, and as the primary producer they can adapt to nearly all diverse environments. However, few knowledge about the genome wide epigenetic information such as methylome information in cyanobacteria, especially under any environment stress, was reported so far. In this study we profiled the genome-wide cytosine methylation from a model cyanobacterium Synechocystis sp. PCC 6803, and explored the possibility of transgenerational epigenetic process in this ancient single-celled prokaryote by comparing the DNA methylomes among normal nitrogen medium cultivation, nitrogen starvation for 72 h and nitrogen recovery for about 12 generations. Our results shows that DNA methylation patterns in nitrogen starvation and nitrogen recovery are much more similar with each other, significantly different from that of the normal nitrogen. This study reveals the difference in global DNA methylation pattern of cyanobacteria between normal and nutrient stress conditions and reports the evidence of transgenerational epigenetic process in cyanobacteria. The results of this study may contribute to a better understanding of epigenetic regulation in prokaryotic adaptation to and survive in the ever changing environment