Dynamic Budget Throttling in Repeated Second-Price Auctions

Throttling is one of the most popular budget control methods in today's online advertising markets. When a budget-constrained advertiser employs throttling, she can choose whether or not to participate in an auction after the advertising platform recommends a bid. This paper focuses on the dynamic budget throttling process in repeated second-price auctions from a theoretical view. An essential feature of the underlying problem is that the advertiser does not know the distribution of the highest competing bid upon entering the market. To model the difficulty of eliminating such uncertainty, we consider two different information structures. The advertiser could obtain the highest competing bid in each round with full-information feedback. Meanwhile, with partial information feedback, the advertiser could only have access to the highest competing bid in the auctions she participates in. We propose the OGD-CB algorithm, which involves simultaneous distribution learning and revenue optimization. In both settings, we demonstrate that this algorithm guarantees an $O(\sqrt{T\log T})$ regret with probability $1 - O(1/T)$ relative to the fluid adaptive throttling benchmark. By proving a lower bound of $\Omega(\sqrt{T})$ on the minimal regret for even the hindsight optimum, we establish the near optimality of our algorithm. Finally, we compare the fluid optimum of throttling to that of pacing, another widely adopted budget control method. The numerical relationship of these benchmarks sheds new light on the understanding of different online algorithms for revenue maximization under budget constraints.Comment: 29 pages, 1 tabl

Alcohol drinking alters oral microbiota to modulate the progression of alcohol-related liver disease

Summary: Alcohol-related liver disease (ALD) is one of the leading causes of liver-related death worldwide. However, roles of oral microbiota in regulating the progression of ALD remain unknown. Here, we fed mice with control or ethanol diet to establish chronic-plus-binge ALD model. 16S ribosomal DNA sequencing was performed on oral and cecum samples. We demonstrated that alcohol drinking influenced bacterial richness, microbial structure, and composition in oral samples of ethanol-fed mice compared with control mice. Alcohol consumption also remodeled relationships among oral microbes and altered functions of oral microbiota. Furthermore, oral microbiota, such as Streptococcus, Helicobacter, Alloprevotella, and Psychrobacter were closely associated with ALD parameters. Finally, we observed Sutterellaceae_uncultured, Dyella, and Gemmatimonas possibly translocated along with oral-gut axis and positively correlated with the severity of ALD. Altogether, alcohol consumption reprogramed composition and functions of oral microbiota to promote ALD progression, suggesting that oral microbes might become a new target for ALD therapy

A combined amplicon approach to nematode polyparasitism occurring in captive wild animals in southern China

Abstract Background Gastrointestinal tract (GIT) nematodes prefer to live in the intestines of wild animals, causing damage and even death, and posing a zoonotic risk. The polyparasitism of GIT nematodes results in the complex dynamics of the nematode communities that occur naturally in wild animals. However, the nematode community in captive wild animals is poorly understood. Methods We combined  microscopic examination and amplicon sequencing for community diversity. Results We characterized GIT nematode assemblages to one order, one family, four genera, and ten species, in 512 fecal samples of 121 species from captive wild animals in southern China. The positive rate of GIT nematodes was 20.7% (106/512), including 42.3% (11/26) in reptiles, 26.5% (39/147) in herbivores, 25.0% (25/100) in non-human primates, 20.0% (5/25) in omnivores, 12.2% (9/74) in carnivores, and 12.1% (17/140) in avians. The dominant nematodes were Haemonchus contortus in herbivores and Trichuris species in primates. The nematode communities of arboreal primates differed from their terrestrial counterparts, reflecting both host phylogeny and ecological constraints. Soil-transmitted Strongyloides species were widespread throughout the herbivore, primate, avian, and carnivore communities, and tended to infect omnivorous primates and terrestrial herbivores. In addition, new Trichuris and Heterakis species were found in the nematode communities of captive porcupines and peafowls. Conclusion This study highlights the variation in the composition of the GIT nematode community and strengthens the attention to the harms induced by zoonotic nematodes and co-infective nematodes with low species richness. Graphical Abstrac

Integrative single-cell RNA and ATAC sequencing reveals that the FOXO1-PRDX2-TNF axis regulates tendinopathy

IntroductionTendinopathy, the most common form of chronic tendon disorder, leads to persistent tendon pain and loss of function. Profiling the heterogeneous cellular composition in the tendon microenvironment helps to elucidate rational molecular mechanisms of tendinopathy.Methods and resultsIn this study, through a multi-modal analysis, a single-cell RNA- and ATAC-seq integrated tendinopathy landscape was generated for the first time. We found that a specific cell subpopulation with low PRDX2 expression exhibited a higher level of inflammation, lower proliferation and migration ability, which not only promoted tendon injury but also led to microenvironment deterioration. Mechanistically, a motif enrichment analysis of chromatin accessibility showed that FOXO1 was an upstream regulator of PRDX2 transcription, and we confirmed that functional blockade of FOXO1 activity induced PRDX2 silencing. The TNF signaling pathway was significantly activated in the PRDX2-low group, and TNF inhibition effectively restored diseased cell degradation.DiscussionWe revealed an essential role of diseased cells in tendinopathy and proposed the FOXO1-PRDX2-TNF axis is a potential regulatory mechanism for the treatment of tendinopathy

Additional file 1 of A combined amplicon approach to nematode polyparasitism occurring in captive wild animals in southern China

Additional file 1: Figure S1. Standard curve of egg shedding, SSU rRNA, and ITS2 effective sequence analyses. (A) Analysis of egg shedding of N. brasiliensis from SD rats. (B) SSU rRNA effective sequence analysis curve of N. brasiliensis from SD rats. (C) ITS2 effective sequence analysis curve of N. brasiliensis from SD rats. Table S1. Description of 512 fecal samples collected from 121 species of captive wild animals at three sampling sites in southern China. Table S2. PCR primers for all loci. Table S3. Six categories of representative sequences of SSU rRNA and ITS2. Table S4. Evaluation of the classification effect of the amplicon

YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates glucose, lipid, and energy homeostasis. While gene expression of FGF21 is regulated by the nuclear hormone receptor peroxisome proliferator-activated receptor alpha in the fasted state, little is known about the regulation of trafficking and secretion of FGF21. We show that mice with a mutation in the Yip1 domain family, member 6 gene (Klein-Zschocher [KLZ]; Yipf6 KLZ/Y ) on a high-fat diet (HFD) have higher plasma levels of FGF21 than mice that do not carry this mutation (controls) and hepatocytes from Yipf6 KLZ/Y mice secrete more FGF21 than hepatocytes from wild-type mice. Consequently, Yipf6 KLZ/Y mice are resistant to HFD-induced features of the metabolic syndrome and have increased lipolysis, energy expenditure, and thermogenesis, with an increase in core body temperature. Yipf6 KLZ/Y mice with hepatocyte-specific deletion of FGF21 were no longer protected from diet-induced obesity. We show that YIPF6 binds FGF21 in the endoplasmic reticulum to limit its secretion and specifies packaging of FGF21 into coat protein complex II (COPII) vesicles during development of obesity in mice. Levels of YIPF6 protein in human liver correlate with hepatic steatosis and correlate inversely with levels of FGF21 in serum from patients with nonalcoholic fatty liver disease (NAFLD). YIPF6 is therefore a newly identified regulator of FGF21 secretion during development of obesity and could be a target for treatment of obesity and NAFLD

Intestinal α1-2-Fucosylation Contributes to Obesity and Steatohepatitis in Mice.

Background & aimsFucosyltransferase 2 (Fut2)-mediated intestinal α1- 2-fucosylation is important for host-microbe interactions and has been associated with several diseases, but its role in obesity and hepatic steatohepatitis is not known. The aim of this study was to investigate the role of Fut2 in a Western-style diet-induced mouse model of obesity and steatohepatitis.MethodsWild-type (WT) and Fut2-deficient littermate mice were used and features of the metabolic syndrome and steatohepatitis were assessed after 20 weeks of Western diet feeding.ResultsIntestinal α1-2-fucosylation was suppressed in WT mice after Western diet feeding, and supplementation of α1-2-fucosylated glycans exacerbated obesity and steatohepatitis in these mice. Fut2-deficient mice were protected from Western diet-induced features of obesity and steatohepatitis despite an increased caloric intake. These mice have increased energy expenditure and thermogenesis, as evidenced by a higher core body temperature. Protection from obesity and steatohepatitis associated with Fut2 deficiency is transmissible to WT mice via microbiota exchange; phenotypic differences between Western diet-fed WT and Fut2-deficient mice were reduced with antibiotic treatment. Fut2 deficiency attenuated diet-induced bile acid accumulation by altered relative abundance of bacterial enzyme 7-α-hydroxysteroid dehydrogenases metabolizing bile acids and by increased fecal excretion of secondary bile acids. This also was associated with increased intestinal farnesoid X receptor/fibroblast growth factor 15 signaling, which inhibits hepatic synthesis of bile acids. Dietary supplementation of α1-2-fucosylated glycans abrogates the protective effects of Fut2 deficiency.Conclusionsα1-2-fucosylation is an important host-derived regulator of intestinal microbiota and plays an important role for the pathogenesis of obesity and steatohepatitis in mice