To Live or to Die: Prosurvival Activity of PPARγ in Cancers

The role of PPARγ in tumorigenesis is controversial. In this article, we review and analyze literature from the past decade that highlights the potential proneoplastic activity of PPARγ. We discuss the following five aspects of the nuclear hormone receptor and its agonists: (1) relative expression of PPARγ in human tumor versus normal tissues; (2) receptor-dependent proneoplastic effects; (3) impact of PPARγ and its agonists on tumors in animal models; (4) clinical trials of thiazolidinediones (TZDs) in human malignancies; (5) TZDs as chemopreventive agents in epidemiology studies. The focus is placed on the most relevant in vivo animal models and human data. In vitro cell line studies are included only when the effects are shown to be dependent on the PPARγ receptor

Shared Information-Based Safe And Efficient Behavior Planning For Connected Autonomous Vehicles

The recent advancements in wireless technology enable connected autonomous vehicles (CAVs) to gather data via vehicle-to-vehicle (V2V) communication, such as processed LIDAR and camera data from other vehicles. In this work, we design an integrated information sharing and safe multi-agent reinforcement learning (MARL) framework for CAVs, to take advantage of the extra information when making decisions to improve traffic efficiency and safety. We first use weight pruned convolutional neural networks (CNN) to process the raw image and point cloud LIDAR data locally at each autonomous vehicle, and share CNN-output data with neighboring CAVs. We then design a safe actor-critic algorithm that utilizes both a vehicle's local observation and the information received via V2V communication to explore an efficient behavior planning policy with safety guarantees. Using the CARLA simulator for experiments, we show that our approach improves the CAV system's efficiency in terms of average velocity and comfort under different CAV ratios and different traffic densities. We also show that our approach avoids the execution of unsafe actions and always maintains a safe distance from other vehicles. We construct an obstacle-at-corner scenario to show that the shared vision can help CAVs to observe obstacles earlier and take action to avoid traffic jams.Comment: This paper gets the Best Paper Award in the DCAA workshop of AAAI 202

Surrogate Lagrangian Relaxation: A Path To Retrain-free Deep Neural Network Pruning

Network pruning is a widely used technique to reduce computation cost and model size for deep neural networks. However, the typical three-stage pipeline significantly increases the overall training time. In this paper, we develop a systematic weight-pruning optimization approach based on Surrogate Lagrangian relaxation, which is tailored to overcome difficulties caused by the discrete nature of the weight-pruning problem. We prove that our method ensures fast convergence of the model compression problem, and the convergence of the SLR is accelerated by using quadratic penalties. Model parameters obtained by SLR during the training phase are much closer to their optimal values as compared to those obtained by other state-of-the-art methods. We evaluate our method on image classification tasks using CIFAR-10 and ImageNet with state-of-the-art MLP-Mixer, Swin Transformer, and VGG-16, ResNet-18, ResNet-50 and ResNet-110, MobileNetV2. We also evaluate object detection and segmentation tasks on COCO, KITTI benchmark, and TuSimple lane detection dataset using a variety of models. Experimental results demonstrate that our SLR-based weight-pruning optimization approach achieves a higher compression rate than state-of-the-art methods under the same accuracy requirement and also can achieve higher accuracy under the same compression rate requirement. Under classification tasks, our SLR approach converges to the desired accuracy $3\times$ faster on both of the datasets. Under object detection and segmentation tasks, SLR also converges $2\times$ faster to the desired accuracy. Further, our SLR achieves high model accuracy even at the hard-pruning stage without retraining, which reduces the traditional three-stage pruning into a two-stage process. Given a limited budget of retraining epochs, our approach quickly recovers the model's accuracy.Comment: arXiv admin note: text overlap with arXiv:2012.1007

Data-Driven Distributionally Robust Electric Vehicle Balancing for Autonomous Mobility-on-Demand Systems under Demand and Supply Uncertainties

Electric vehicles (EVs) are being rapidly adopted due to their economic and societal benefits. Autonomous mobility-on-demand (AMoD) systems also embrace this trend. However, the long charging time and high recharging frequency of EVs pose challenges to efficiently managing EV AMoD systems. The complicated dynamic charging and mobility process of EV AMoD systems makes the demand and supply uncertainties significant when designing vehicle balancing algorithms. In this work, we design a data-driven distributionally robust optimization (DRO) approach to balance EVs for both the mobility service and the charging process. The optimization goal is to minimize the worst-case expected cost under both passenger mobility demand uncertainties and EV supply uncertainties. We then propose a novel distributional uncertainty sets construction algorithm that guarantees the produced parameters are contained in desired confidence regions with a given probability. To solve the proposed DRO AMoD EV balancing problem, we derive an equivalent computationally tractable convex optimization problem. Based on real-world EV data of a taxi system, we show that with our solution the average total balancing cost is reduced by 14.49%, and the average mobility fairness and charging fairness are improved by 15.78% and 34.51%, respectively, compared to solutions that do not consider uncertainties.Comment: 16 page

FUsed in Sarcoma is a Novel Regulator of Manganese Superoxide Dismutase Gene Transcription

AIMS: FUsed in sarcoma (FUS) is a multifunctional DNA/RNA-binding protein that possesses diverse roles, such as RNA splicing, RNA transport, DNA repair, translation, and transcription. The network of enzymes and processes regulated by FUS is far from being fully described. In this study, we have focused on the mechanisms of FUS-regulated manganese superoxide dismutase (MnSOD) gene transcription. RESULTS: Here we demonstrate that FUS is a component of the transcription complex that regulates the expression of MnSOD. Overexpression of FUS increased MnSOD expression in a dose-dependent manner and knockdown of FUS by siRNA led to the inhibition of MnSOD gene transcription. Reporter analyses, chromatin immunoprecipitation assay, electrophoretic mobility shift assay, affinity chromatography, and surface plasmon resonance analyses revealed the far upstream region of MnSOD promoter as an important target of FUS-mediated MnSOD transcription and confirmed that FUS binds to the MnSOD promoter and interacts with specificity protein 1 (Sp1). Importantly, overexpression of familial amyotropic lateral sclerosis (fALS)-linked R521G mutant FUS resulted in a significantly reduced level of MnSOD expression and activity, which is consistent with the decline in MnSOD activity observed in fibroblasts from fALS patients with the R521G mutation. R521G-mutant FUS abrogates MnSOD promoter-binding activity and interaction with Sp1. INNOVATION AND CONCLUSION: This study identifies FUS as playing a critical role in MnSOD gene transcription and reveals a previously unrecognized relationship between MnSOD and mutant FUS in fALS

The All-Data-Based Evolutionary Hypothesis of Ciliated Protists with a Revised Classification of the Phylum Ciliophora (Eukaryota, Alveolata)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ The file attached is the published version of the article

Quantitative assessment of the upper airway in infants and children with subglottic stenosis

OBJECTIVES/HYPOTHESIS: Determine whether quantitative geometric measures and a computational fluid dynamic (CFD) model derived from medical imaging of children with subglottic stenosis (SGS) can be effective diagnostic and treatment planning tools. STUDY DESIGN: Retrospective chart and imaging review in a tertiary care hospital. METHODS: Computed tomography scans (n = 17) of children with SGS were analyzed by geometric and CFD methods. Polysomnograms (n = 15) were also analyzed. Radiographic data were age/weight flow normalized and were compared to an atlas created from radiographically normal airways. Five geometric, seven CFD, and five polysomnography measures were analyzed. Statistical analysis utilized a two-sample t test with Bonferroni correction and area under the curve analysis. RESULTS: Two geometric indices (the ratio of the subglottic to midtracheal airway, the percent relative reduction of the subglottic airway) and one CFD measure (the percent relative reduction of the hydraulic diameter of the subglottic airway) were significant for determining which children with SGS received surgical intervention. Optimal cutoffs for these values were determined. Polysomnography, the respiratory effort-related arousals index, was significant only prior to Bonferroni correction for determining which children received surgical intervention. CONCLUSIONS: Geometric and CFD variables were sensitive at determining which patients with SGS received surgical intervention. Discrete quantitative assessment of the pediatric airway was performed, yielding preliminary data regarding possible objective thresholds for surgical versus nonsurgical treatment of disease. This study is limited by its small, retrospective, single-institution nature. Further studies to validate these findings and possibly optimize treatment threshold recommendations are warranted

Interactions of Several Lipid-Related Gene Polymorphisms and Cigarette Smoking on Blood Pressure Levels

The interactions of single nucleotide polymorphisms (SNPs) and cigarette smoking on blood pressure levels are limited. The present study was undertaken to detect nine lipid-related SNPs and their interactions with cigarette smoking on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaⅡ, hepatic lipase gene (LIPC) -250G>A, endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase (MTHFR) 677C>T, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 935 nonsmokers and 845 smokers. The interactions were detected by factorial regression analysis. The frequencies of genotypes (ACAT-1 and LIPG), alleles (ABCA-1), and both genotypes and alleles (LDL-R, LIPC, PPARD and SCARB1) were different between nonsmokers and smokers (P < 0.05-0.001). The levels of pulse pressure (PP, ABCA-1), and systolic, diastolic blood pressure (SBP, DBP) and PP (LIPC) in nonsmokers were different among the genotypes (P < 0.01-0.001). The levels of SBP (ABCA-1, ACAT-1, LIPG and PCSK9), DBP (ACAT-1, LDL-R, LIPC, PCSK9 and PPARD), and PP (LIPC, LIPG, MTHFR and PCSK9) in smokers were different among the genotypes (P < 0.01-0.001). The SNPs of ABCA-1, ACAT-1 and PCSK9; ACAT-1, LDL-R, MTHFR and PCSK9; and ABCA-1, LIPC, PCSK9 and PPARD were shown interactions with cigarette smoking to influence SBP, DBP and PP levels (P < 0.05-0.001); respectively. The differences in blood pressure levels between the nonsmokers and smokers might partly result from different interactions of several SNPs and cigarette smoking

Polymorphism of rs1044925 in the acyl-CoA:cholesterol acyltransferase-1 gene and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

<p>Abstract</p> <p>Background</p> <p>The association of rs1044925 polymorphism in the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) gene and serum lipid profiles is not well known in different ethnic groups. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was carried out to clarify the association of rs1044925 polymorphism in the ACAT-1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.</p> <p>Methods</p> <p>A total of 626 subjects of Bai Ku Yao and 624 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of rs1044925 polymorphism in the ACAT-1 gene was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.</p> <p>Results</p> <p>The levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (<it>P </it>< 0.01 for all). The frequency of A and C alleles was 79.0% and 21.0% in Bai Ku Yao, and 87.3% and 12.7% in Han (<it>P </it>< 0.001); respectively. The frequency of AA, AC and CC genotypes was 63.2%, 31.4% and 5.2% in Bai Ku Yao, and 75.6%, 23.2% and 1.1% in Han (<it>P </it>< 0.001); respectively. The levels of TC, LDL-C and ApoB in Bai Ku Yao but not in Han were different between the AA and AC/CC genotypes in females but not in males (<it>P </it>< 0.05 for all). The C allele carriers had lower serum TC, LDL-C and ApoB levels as compared with the C allele noncarriers. The levels of TC, LDL-C and ApoB in Bai Ku Yao but not in Han were correlated with genotypes in females but not in males (<it>P </it>< 0.05 for all). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, and blood pressure in both ethnic groups (<it>P </it>< 0.05-0.001).</p> <p>Conclusions</p> <p>These results suggest that the polymorphism of rs1044925 in the ACAT-1 gene is mainly associated with female serum TC, LDL-C and ApoB levels in the Bai Ku Yao population. The C allele carriers had lower serum TC, LDL-C and ApoB levels than the C allele noncarriers.</p