Parton and Hadron Correlations in Jets

Correlation between shower partons is first studied in high $p_T$ jets. Then in the framework of parton recombination the correlation between pions in heavy-ion collisions is investigated. Since thermal partons play very different roles in central and peripheral collisions, it is found that the correlation functions of the produced hadrons behave very differently at different centralities, especially at intermediate $p_T$. The correlation function that can best exhibit the distinctive features is suggested. There is not a great deal of overlap between what we can calculate and what has been measured. Nevertheless, some aspects of our results compare favorably with experimental data.Comment: 28 pages in Latex + 13 figures. This is a revised version with extended discussions added without quantitative changes in the result

Learning to Search for Job Shop Scheduling via Deep Reinforcement Learning

Recent studies in using deep reinforcement learning (DRL) to solve Job-shop scheduling problems (JSSP) focus on construction heuristics. However, their performance is still far from optimality, mainly because the underlying graph representation scheme is unsuitable for modeling partial solutions at each construction step. This paper proposes a novel DRL-based method to learn improvement heuristics for JSSP, where graph representation is employed to encode complete solutions. We design a Graph Neural Network based representation scheme, consisting of two modules to effectively capture the information of dynamic topology and different types of nodes in graphs encountered during the improvement process. To speed up solution evaluation during improvement, we design a novel message-passing mechanism that can evaluate multiple solutions simultaneously. Extensive experiments on classic benchmarks show that the improvement policy learned by our method outperforms state-of-the-art DRL-based methods by a large margin

Identification of Long Non-coding and Messenger RNAs Differentially Expressed Between Primary and Metastatic Melanoma

Purpose: Melanoma is the most aggressive and life-threatening cutaneous cancer. To explore new treatment strategies, it is essential to identify the mechanisms underlying melanoma tumorigenesis and metastasis.Methods: In the current study, we demonstrated altered expression of long non-coding RNA (lncRNA) and messenger RNA (mRNA) in melanoma using data from the Cancer Genome Atlas (TCGA) database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein–protein interaction (PPI) analyses were conducted. We also constructed a functional lncRNA-mRNA regulatory network and Kaplan-Meier analysis.Results: We identified 246 differentially expressed (DE) lncRNAs and 856 DEmRNAs. A total of 184 DElncRNAs and 428 DEmRNAs were upregulated in metastatic melanoma, while all others were downregulated. Additionally, we investigated the co-expression pattern of 363 genes, among which 26 upregulated lncRNAs, 9 down- regulated lncRNAs, 49 upregulated mRNAs and 151 downregulated mRNAs were identified as being co-expressed with others. Survival analysis suggested high levels of 14 lncRNAs and 10 mRNAs may significantly increase or decrease overall survival. These differentially expressed genes are also potentially prognostic in melanoma.Conclusion: Our findings observe potential roles for lncRNAs and mRNAs during melanoma progression and provide candidate biomarkers for further studies

Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice

B cells play an important role in type 1 diabetes (T1D) development. However, the role of B cell activation-induced cytidine deaminase (AID) in diabetes development is not clear. We hypothesized that AID is important in the immunopathogenesis of T1D. To test this hypothesis, we generated AID-deficient (AID–/–) NOD mice. We found that AID–/–NOD mice developed accelerated T1D, with worse insulitis and high levels of anti-insulin autoantibody in the circulation. Interestingly, neither maternal IgG transferred through placenta, nor IgA transferred through milk affected the accelerated diabetes development. AID–/–NOD mice showed increased activation and proliferation of B and T cells. We found enhanced T-B cell interactions in AID–/–NOD mice, with increased T-bet and IFN-γ expression in CD4+ T cells in the presence of AID–/– B cells. Moreover, excessive lymphoid expansion was observed in AID–/–NOD mice. Importantly, antigen-specific BDC2.5 CD4+ T cells caused more rapid onset of diabetes when cotransferred with AID–/– B cells than when cotransferred with AID+/+ B cells. Thus, our study provides insights into the role of AID in T1D. Our data also suggest that AID is a negative regulator of immune tolerance and ablation of AID can lead to exacerbated islet autoimmunity and accelerated T1D development

IL-10 deficiency accelerates type 1 diabetes development via modulation of innate and adaptive immune cells and gut microbiota in BDC2.5 NOD mice

Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of insulin-producing β cells. BDC2.5 T cells in BDC2.5 CD4+ T cell receptor transgenic Non-Obese Diabetic (NOD) mice (BDC2.5+ NOD mice) can abruptly invade the pancreatic islets resulting in severe insulitis that progresses rapidly but rarely leads to spontaneous diabetes. This prevention of diabetes is mediated by T regulatory (Treg) cells in these mice. In this study, we investigated the role of interleukin 10 (IL-10) in the inhibition of diabetes in BDC2.5+ NOD mice by generating Il-10-deficient BDC2.5+ NOD mice (BDC2.5+Il-10-/- NOD mice). Our results showed that BDC2.5+Il-10-/- NOD mice displayed robust and accelerated diabetes development. Il-10 deficiency in BDC2.5+ NOD mice promoted the generation of neutrophils in the bone marrow and increased the proportions of neutrophils in the periphery (blood, spleen, and islets), accompanied by altered intestinal immunity and gut microbiota composition. In vitro studies showed that the gut microbiota from BDC2.5+Il-10-/- NOD mice can expand neutrophil populations. Moreover, in vivo studies demonstrated that the depletion of endogenous gut microbiota by antibiotic treatment decreased the proportion of neutrophils. Although Il-10 deficiency in BDC2.5+ NOD mice had no obvious effects on the proportion and function of Treg cells, it affected the immune response and activation of CD4+ T cells. Moreover, the pathogenicity of CD4+ T cells was much increased, and this significantly accelerated the development of diabetes when these CD4+ T cells were transferred into immune-deficient NOD mice. Our study provides novel insights into the role of IL-10 in the modulation of neutrophils and CD4+ T cells in BDC2.5+ NOD mice, and suggests important crosstalk between gut microbiota and neutrophils in type 1 diabetes development

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H