Real-Time Bidding by Reinforcement Learning in Display Advertising

The majority of online display ads are served through real-time bidding (RTB) --- each ad display impression is auctioned off in real-time when it is just being generated from a user visit. To place an ad automatically and optimally, it is critical for advertisers to devise a learning algorithm to cleverly bid an ad impression in real-time. Most previous works consider the bid decision as a static optimization problem of either treating the value of each impression independently or setting a bid price to each segment of ad volume. However, the bidding for a given ad campaign would repeatedly happen during its life span before the budget runs out. As such, each bid is strategically correlated by the constrained budget and the overall effectiveness of the campaign (e.g., the rewards from generated clicks), which is only observed after the campaign has completed. Thus, it is of great interest to devise an optimal bidding strategy sequentially so that the campaign budget can be dynamically allocated across all the available impressions on the basis of both the immediate and future rewards. In this paper, we formulate the bid decision process as a reinforcement learning problem, where the state space is represented by the auction information and the campaign's real-time parameters, while an action is the bid price to set. By modeling the state transition via auction competition, we build a Markov Decision Process framework for learning the optimal bidding policy to optimize the advertising performance in the dynamic real-time bidding environment. Furthermore, the scalability problem from the large real-world auction volume and campaign budget is well handled by state value approximation using neural networks.Comment: WSDM 201

Study on Gut Microbiota in Children with Cerebral Palsy and Epilepsy

Compared to children with cerebral palsy (CP), children with both CP and concurrent epilepsy (CPE) have more severe gastrointestinal symptoms, such as functional constipation (FC), and are more prone to recurrent infections. Our previous study found that these children have gut microbiota (GM) disorders, which are significantly related to the gastrointestinal symptoms and immune functions. The children with CPE also has altered oral microbiota (OM), which is consistent with the change of GM. In addition, the change of OM and GM has potential impact on the occurrence of clinical diseases such as periodontitis, dental caries and malnutrition. In our previous study, it was also found that the abundance of butyric acid- and lactic acid-producing bacteria in the GM of children who have CPE with liquid food in their diet decreased significantly, while the abundance of opportunistic pathogenic bacteria increased significantly. After the butyric acid-, lactic acid-producing probiotics and dietary fibers were administered by us to treat the FC in children with CPE, the FC improved significantly, and the abundance of butyric acid- and lactic acid-producing bacteria in the intestine increased

Multiplexed detection of eight respiratory viruses based on nanozyme colorimetric microfluidic immunoassay

Pandemics caused by respiratory viruses, such as the SARS-CoV-1/2, influenza virus, and respiratory syncytial virus, have resulted in serious consequences to humans and a large number of deaths. The detection of such respiratory viruses in the early stages of infection can help control diseases by preventing the spread of viruses. However, the diversity of respiratory virus species and subtypes, their rapid antigenic mutations, and the limited viral release during the early stages of infection pose challenges to their detection. This work reports a multiplexed microfluidic immunoassay chip for simultaneous detection of eight respiratory viruses with noticeable infection population, namely, influenza A virus, influenza B virus, respiratory syncytial virus, SARS-CoV-2, human bocavirus, human metapneumovirus, adenovirus, and human parainfluenza viruses. The nanomaterial of the nanozyme (Au@Pt nanoparticles) was optimized to improve labeling efficiency and enhance the detection sensitivity significantly. Nanozyme-binding antibodies were used to detect viral proteins with a limit of detection of 0.1 pg/mL with the naked eye and a microplate reader within 40 min. Furthermore, specific antibodies were screened against the conserved proteins of each virus in the immunoassay, and the clinical sample detection showed high specificity without cross reactivity among the eight pathogens. In addition, the microfluidic chip immunoassay showed high accuracy, as compared with the RT-PCR assay for clinical sample detection, with 97.2%/94.3% positive/negative coincidence rates. This proposed approach thus provides a convenient, rapid, and sensitive method for simultaneous detection of eight respiratory viruses, which is meaningful for the early diagnosis of viral infections. Significantly, it can be widely used to detect pathogens and biomarkers by replacing only the antigen-specific antibodies

Fatty Acid Desaturase 1 Influences Hepatic Lipid Homeostasis by Modulating the PPARα‐FGF21 Axis

The fatty acid desaturase 1 (FADS1), also known as delta-5 desaturase (D5D), is one of the rate-limiting enzymes involved in the desaturation and elongation cascade of polyunsaturated fatty acids (PUFAs) to generate long-chain PUFAs (LC-PUFAs). Reduced function of D5D and decreased hepatic FADS1 expression, as well as low levels of LC-PUFAs, were associated with nonalcoholic fatty liver disease. However, the causal role of D5D in hepatic lipid homeostasis remains unclear. In this study, we hypothesized that down-regulation of FADS1 increases susceptibility to hepatic lipid accumulation. We used in vitro and in vivo models to test this hypothesis and to delineate the molecular mechanisms mediating the effect of reduced FADS1 function. Our study demonstrated that FADS1 knockdown significantly reduced cellular levels of LC-PUFAs and increased lipid accumulation and lipid droplet formation in HepG2 cells. The lipid accumulation was associated with significant alterations in multiple pathways involved in lipid homeostasis, especially fatty acid oxidation. These effects were demonstrated to be mediated by the reduced function of the peroxisome proliferator-activated receptor alpha (PPARα)-fibroblast growth factor 21 (FGF21) axis, which can be reversed by treatment with docosahexaenoic acid, PPARα agonist, or FGF21. In vivo, FADS1-knockout mice fed with high-fat diet developed increased hepatic steatosis as compared with their wild-type littermates. Molecular analyses of the mouse liver tissue largely corroborated the observations in vitro, especially along with reduced protein expression of PPARα and FGF21. Conclusion: Collectively, these results suggest that dysregulation in FADS1 alters liver lipid homeostasis in the liver by down-regulating the PPARα-FGF21 signaling axis

Causal relationships between NAFLD, T2D and obesity have implications for disease subphenotyping

Background & aims: Non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and obesity are epidemiologically correlated with each other but the causal inter-relationships between them remain incompletely understood. We aimed to explore the causal relationships between the 3 diseases. Methods: Using both UK Biobank and publicly available genome-wide association study data, we performed a 2-sample bidirectional Mendelian randomization analysis to test the causal inter-relationships between NAFLD, T2D, and obesity. Transgenic mice expressing the human PNPLA3-I148M isoforms (TghPNPLA3-I148M) were used as an example to validate causal effects and explore underlying mechanisms. Results: Genetically driven NAFLD significantly increased the risk of T2D and central obesity but not insulin resistance or generalized obesity, while genetically driven T2D, body mass index and WHRadjBMI causally increased NAFLD risk. The animal study focusing on PNPLA3 corroborated these causal effects: compared to the TghPNPLA3-I148I controls, the TghPNPLA3-I148M mice developed glucose intolerance and increased visceral fat, but maintained normal insulin sensitivity, reduced body weight, and decreased circulating total cholesterol. Mechanistically, the TghPNPLA3-I148M mice demonstrated decreased pancreatic insulin but increased glucagon secretion, which was associated with increased pancreatic inflammation. In addition, transcription of hepatic cholesterol biosynthesis pathway genes was significantly suppressed, while transcription of thermogenic pathway genes was activated in subcutaneous and brown adipose tissues but not in visceral fat in TghPNPLA3-I148M mice. Conclusions: Our study suggests that lifelong, genetically driven NAFLD causally promotes T2D with a late-onset type 1-like diabetic subphenotype and central obesity; while genetically driven T2D, obesity, and central obesity all causally increase the risk of NAFLD. This causal relationship revealed new insights into how nature and nurture drive these diseases, providing novel hypotheses for disease subphenotyping. Lay summary: Non-alcoholic fatty liver disease, type 2 diabetes and obesity are epidemiologically correlated with each other, but their causal relationships were incompletely understood. Herein, we identified causal relationships between these conditions, which suggest that each of these closely related diseases should be further stratified into subtypes. This is important for accurate diagnosis, prevention and treatment of these diseases

Higher serum Lp-PLA2 is associated with cognitive impairment in Parkinson’s disease patients

ObjectiveTo explore the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cognitive impairment in Parkinson’s disease (PD-CI).MethodsA case–control study involving 100 hospitalized PD patients and 60 healthy controls was carried out. Serum Lp-PLA2 level was detected by automatic biochemical analyzer. Based on whether Parkinson’s patients have cognitive impairment, PD patients were subdivided to analyze the clinical value of Lp-PLA2. Relationship between Lp-PLA2 and PD-CI risk was analyzed by logistic regression. Diagnostic value of Lp-PLA2 in PD-CI patients was investigated using receiver’s operator characteristic curves.ResultsThe levels of serum Lp-PLA2 activity in Parkinson’s disease with normal cognition (PD-NC) and PD-CI patients were significantly higher than those in healthy controls (HCs), respectively. Furthermore, compared to the PD-NC group, the serum Lp-PLA2 activity level was significantly higher in PD-CI patients. Multivariable logistic regression analysis indicated that higher Lp-PLA2 level was an independent risk factor for PD patients with cognitive impairment. Moreover, the area under the efficacy curve of Lp-PLA2 for predicting PD-CI is 0.659.ConclusionOur study shows that higher levels of Lp-PLA2 activity in PD patients are associated with the risk of developing cognitive impairment. Therefore, given the wide availability, safety, and convenience of monitoring serum Lp-PLA2 activity, it may serve as an early biomarker for cognitive impairment in PD patients

Tsinghua Scientific Satellite Precise Orbit Determination Using Onboard GNSS Observations with Antenna Center Modeling

The Tsinghua scientific satellite is a Chinese spherical micro satellite for Earth gravity and atmospheric scientific measurements. The accurate orbits of this satellite are the prerequisites to satisfy the mission objectives. A commercial off-the-shelf dual-frequency GNSS receiver is equipped on the satellite for precise orbit determination (POD). The in-flight performances of the receiver are assessed. Regular long-duration gaps up to 50 min are observed in GNSS data, and the typical data availability is about 60–70% each day. The RMS of code noises is 0.24 m and 0.30 m for C1 and P2 codes, respectively. The RMS of fitting residuals of the carrier phase geometry-free L1–L2 combination is 2.4 mm. The GNSS receiver antenna center offsets (ACOs) and antenna center variations (ACVs) maps are estimated using in-flight data for both dual-frequency and single-frequency POD. Significant improvements in POD performances are obtained when the measurement models are updated by using the ACO and ACV maps’ corrections. With the updated measurement model, the RMS of the orbit overlap differences is 1.23 cm in three dimensions for dual-frequency POD, which is reduced by 27%. Meanwhile, two different empirical acceleration types are employed and compared for dual-frequency POD, and the results show that consistency on the 5 cm level is demonstrated for orbit solutions obtained with the updated measurement model. After correcting the ACO and ACV maps, the precision of single-frequency orbit solutions is better than 10 cm, which is improved by 32%. The results indicate that the antenna center modeling can significantly improve the consistency of Tsinghua scientific satellite precise orbits, which will be conducive to the realization of the mission objectives

The application of indocyanine green in guiding prostate cancer treatment

Objective: Indocyanine green (ICG) with near-infrared fluorescence absorption is approved by the United States Food and Drug Administration for clinical applications in angiography, blood flow evaluation, and liver function assessment. It has strong optical absorption in the near-infrared region, where light can penetrate deepest into biological tissue. We sought to review its value in guiding prostate cancer treatment. Methods: All related literature at PubMed from January 2000 to December 2020 were reviewed. Results: Multiple preclinical studies have demonstrated the usefulness of ICG in identifying prostate cancer by using different engineering techniques. Clinical studies have demonstrated the usefulness of ICG in guiding sentinel node dissection during radical prostatectomy, and possible better preservation of neurovascular bundle by identifying landmark prostatic arteries. New techniques such as adding fluorescein in additional to ICG were tested in a limited number of patients with encouraging result. In addition, the use of the ICG was shown to be safe. Even though there are encouraging results, it does not carry sufficient sensitivity and specificity in replacing extended pelvic lymph node dissection during radical prostatectomy. Conclusion: Multiple preclinical and clinical studies have shown the usefulness of ICG in identifying and guiding treatment for prostate cancer. Larger randomized prospective studies are warranted to further test its usefulness and find new modified approaches