Ranking tournaments with no errors II: Minimax relation

A tournament T=(V,A) is called cycle Mengerian (CM) if it satisfies the minimax relation on packing and covering cycles, for every nonnegative integral weight function defined on A. The purpose of this series of two papers is to show that a tournament is CM iff it contains none of four Möbius ladders as a subgraph; such a tournament is referred to as Möbius-free. In the first paper we have given a structural description of all Möbius-free tournaments, and have proved that every CM tournament is Möbius-free. In this second paper we establish the converse by using our structural theorems and linear programming approach

Ranking tournaments with no errors I: Structural description

In this series of two papers we examine the classical problem of ranking a set of players on the basis of a set of pairwise comparisons arising from a sports tournament, with the objective of minimizing the total number of upsets, where an upset occurs if a higher ranked player was actually defeated by a lower ranked player. This problem can be rephrased as the so-called minimum feedback arc set problem on tournaments, which arises in a rich variety of applications and has been a subject of extensive research. In this series we study this NP-hard problem using structure-driven and linear programming approaches. Let T=(V,A) be a tournament with a nonnegative integral weight w(e) on each arc e. A subset F of arcs is called a feedback arc set if T\F contains no cycles (directed). A collection C of cycles (with repetition allowed) is called a cycle packing if each arc e is used at most w(e) times by members of C. We call T cycle Mengerian (CM) if, for every nonnegative integral function w defined on A, the minimum total weight of a feedback arc set is equal to the maximum size of a cycle packing. The purpose of these two papers is to show that a tournament is CM iff it contains none of four Möbius ladders as a subgraph; such a tournament is referred to as Möbius-free. In this first paper we present a structural description of all Möbius-free tournaments, which relies heavily on a chain theorem concerning internally 2-strong tournaments

Epidemic characteristics, high-risk townships and space-time clusters of human brucellosis in Shanxi Province of China, 2005–2014

BACKGROUND: Brucellosis, one of the world's most important zoonosis, has been re-emerging in China. Shanxi Province, located in northern China, where husbandry development has been accelerated in recent years, has a rather high incidence of human brucellosis but drew little attention from the researchers. This study aimed to describe the changing epidemiology of human brucellosis in Shanxi Province from 2005 to 2014 and explore high-risk towns and space-time clusters for elucidating the necessity of decentralizing disease control resource to township level in epidemic regions, particularly in hotspot areas.METHODS: We extracted data from the Chinese National Notifiable Infectious Disease Reporting System to describe the incidence and spatiotemporal distribution of human brucellosis in Shanxi Province. Geographic information system was used to identify townships at high risk for the disease. Space-Time Scan Statistic was applied to detect the space-time clusters of human brucellosis during the past decade.RESULTS: From 2005 to 2014, a total of 50,002 cases of human brucellosis were recorded in Shanxi, with a male-to-female ratio of 3.9:1. The reported incidence rate increased dramatically from 7.0/100,000 in 2005 to 23.5/100,000 in 2014, with an average annual increase of 14.5%. There were still 33.8% cases delaying diagnosis in 2014. The proportion of the affected towns increased from 31.5% in 2005 to 82.5% in 2014. High-risk towns spread from the north to the center and then south of Shanxi Province, which were basins and adjacent highlands suitable for livestock cultivation. During the past decade, there were 55 space-time clusters of human brucellosis detected in high risk towns; the clusters could happen in any season. Some clusters' location maintained stable over time.CONCLUSIONS: During the last decade, Shanxi province's human brucellosis epidemic had been aggravated and high-risk areas concentrated in some towns located in basins and adjacent highlands. Space-time clusters existed and some located steadily over time. Quite a few cases still missed timely diagnosis. Greater resources should be allocated and decentralized to mitigate the momentum of rise and improve the accessibility of prompt diagnosis treatment in the high-risk townships

Comprehensive analysis of lncRNA-associated competing endogenous RNA network in tongue squamous cell carcinoma

Background Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play an important role in the competitive endogenous RNA (ceRNA) networks in that they regulate protein-coding gene expression by sponging microRNAs (miRNAs). However, the understanding of the ceRNA network in tongue squamous cell carcinoma (TSCC) remains limited. Methods Expression profile data regarding mRNAs, miRNAs and lncRNAs as well as clinical information on 122 TSCC tissues and 15 normal controls from The Cancer Genome Atlas (TCGA) database were collected. We used the edgR package to identify differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs) and miRNAs (DEmiRNAs) between TSCC samples and normal samples. In order to explore the functions of DEmRNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed. Subsequently, a ceRNA network was established based on the identified DElncRNAs–DEmiRNAs and DEmiRNAs–DEmRNAs interactions. The RNAs within the ceRNA network were analyzed for their correlation with overall disease survival. Finally, lncRNAs were specifically analyzed for their correlation with clinical features in the included TSCC patient samples. Results A total of 1867 mRNAs, 828 lncRNAs and 81 miRNAs were identified as differentially expressed in TSCC tissues (—log 2fold change— ≥ 2; adjusted P value <0.01). The resulting ceRNA network included 16 mRNAs, 56 lncRNAs and 6 miRNAs. Ten out of the 56 lncRNAs were found to be associated with the overall survival in TSCC patients (P < 0.05); 10 lncRNAs were correlated with TSCC progression (P < 0.05). Conclusion Our study deepens the understanding of ceRNA network regulatory mechanisms in TSCC. Furthermore, we identified ten lncRNAs (PART1, LINC00261, AL163952.1, C2orf48, FAM87A, LINC00052, LINC00472, STEAP3-AS1, TSPEAR-AS1 and ERVH48-1) as novel, potential prognostic biomarkers and therapeutic targets for TSCC

Epidemiology of human anthrax in China, 1955-2014

Using national surveillance data for 120,111 human anthrax cases recorded during 1955-2014, we analyzed the temporal, seasonal, geographic, and demographic distribution of this disease in China. After 1978, incidence decreased until 2013, when it reached a low of 0.014 cases/100,000 population. The case-fatality rate, cumulatively 3.6% during the study period, has also decreased since 1990. Cases occurred throughout the year, peaking in August. Geographic distribution decreased overall from west to east, but the cumulative number of affected counties increased during 2005-2014. The disease has shifted from industrial to agricultural workers; 86.7% of cases occurred in farmers and herdsmen. Most (97.7%) reported cases were the cutaneous form. Although progress has been made in reducing incidence, this study highlights areas that need improvement. Adequate laboratory diagnosis is lacking; only 7.6% of cases received laboratory confirmation. Geographic expansion of the disease indicates that livestock control programs will be essential in eradicating anthrax

Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation

The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and aberrant functions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV

Epidemiology of Human Anthrax in China, 1955−2014

Using national surveillance data for 120,111 human anthrax cases recorded during 1955-2014, we analyzed the temporal, seasonal, geographic, and demographic distribution of this disease in China. After 1978, incidence decreased until 2013, when it reached a low of 0.014 cases/100,000 population. The case-fatality rate, cumulatively 3.6% during the study period, has also decreased since 1990. Cases occurred throughout the year, peaking in August. Geographic distribution decreased overall from west to east, but the cumulative number of affected counties increased during 2005-2014. The disease has shifted from industrial to agricultural workers; 86.7% of cases occurred in farmers and herdsmen. Most (97.7%) reported cases were the cutaneous form. Although progress has been made in reducing incidence, this study highlights areas that need improvement. Adequate laboratory diagnosis is lacking; only 7.6% of cases received laboratory confirmation. Geographic expansion of the disease indicates that livestock control programs will be essential in eradicating anthrax

The Enhancing Effects of the Light Chain on Heavy Chain Secretion in Split Delivery of Factor VIII Gene

Coagulation factor VIII (FVIII) is secreted as a heterodimer consisting of a heavy chain (HC) and a light chain (LC), which can be expressed independently and reassociate with recovery of biological activity. Because of the size limitation of adeno-associated virus (AAV) vectors, a strategy for delivering the HC and LC separately has been developed. However, the FVIII HC is secreted 10–100-fold less efficiently than the LC. In this study, we demonstrated that the F309S mutation and enhanced B-domain glycosylations alone are not sufficient to improve FVIII HC secretion, which suggested a role of the FVIII LC in regulating HC secretion. To characterize this role of the FVIII LC, we compared FVIII HC secretion with and without the LC via post-translational protein trans-splicing. As demonstrated in vitro, ligation of the LC to the HC significantly increased HC secretion. Such HC secretion increases were also confirmed in vivo by hydrodynamic injection of FVIII intein plasmids into hemophilia A mice. Moreover, similar enhancement of HC secretion can also be observed when the LC is supplied in trans, which is probably due to the spontaneous association of the HC and the LC in the secretion pathway. In sum, enhancing the secretion of the FVIII HC polypeptide may require the proper association of the FVIII LC polypeptide in cis or in trans. These results may be helpful in designing new strategies to improve FVIII gene delivery