Robust Target Training for Multi-Source Domain Adaptation

Given multiple labeled source domains and a single target domain, most existing multi-source domain adaptation (MSDA) models are trained on data from all domains jointly in one step. Such an one-step approach limits their ability to adapt to the target domain. This is because the training set is dominated by the more numerous and labeled source domain data. The source-domain-bias can potentially be alleviated by introducing a second training step, where the model is fine-tuned with the unlabeled target domain data only using pseudo labels as supervision. However, the pseudo labels are inevitably noisy and when used unchecked can negatively impact the model performance. To address this problem, we propose a novel Bi-level Optimization based Robust Target Training (BORT$^2$) method for MSDA. Given any existing fully-trained one-step MSDA model, BORT$^2$ turns it to a labeling function to generate pseudo-labels for the target data and trains a target model using pseudo-labeled target data only. Crucially, the target model is a stochastic CNN which is designed to be intrinsically robust against label noise generated by the labeling function. Such a stochastic CNN models each target instance feature as a Gaussian distribution with an entropy maximization regularizer deployed to measure the label uncertainty, which is further exploited to alleviate the negative impact of noisy pseudo labels. Training the labeling function and the target model poses a nested bi-level optimization problem, for which we formulate an elegant solution based on implicit differentiation. Extensive experiments demonstrate that our proposed method achieves the state of the art performance on three MSDA benchmarks, including the large-scale DomainNet dataset. Our code will be available at \url{https://github.com/Zhongying-Deng/BORT2}Comment: Accepted to BMVC 202

Generative Model Based Noise Robust Training for Unsupervised Domain Adaptation

Target domain pseudo-labelling has shown effectiveness in unsupervised domain adaptation (UDA). However, pseudo-labels of unlabeled target domain data are inevitably noisy due to the distribution shift between source and target domains. This paper proposes a Generative model-based Noise-Robust Training method (GeNRT), which eliminates domain shift while mitigating label noise. GeNRT incorporates a Distribution-based Class-wise Feature Augmentation (D-CFA) and a Generative-Discriminative classifier Consistency (GDC), both based on the class-wise target distributions modelled by generative models. D-CFA minimizes the domain gap by augmenting the source data with distribution-sampled target features, and trains a noise-robust discriminative classifier by using target domain knowledge from the generative models. GDC regards all the class-wise generative models as generative classifiers and enforces a consistency regularization between the generative and discriminative classifiers. It exploits an ensemble of target knowledge from all the generative models to train a noise-robust discriminative classifier and eventually gets theoretically linked to the Ben-David domain adaptation theorem for reducing the domain gap. Extensive experiments on Office-Home, PACS, and Digit-Five show that our GeNRT achieves comparable performance to state-of-the-art methods under single-source and multi-source UDA settings

Hypolipidemic agent Z-guggulsterone: metabolism interplays with induction of carboxylesterase and bile salt export pump

Z-Guggulsterone is a major ingredient in the Indian traditional hypolipidemic remedy guggul. A study in mice has established that its hypolipidemic effect involves the farnesoid X receptor (FXR), presumably by acting as an antagonist of this receptor. It is generally assumed that the antagonism leads to induction of cytochrome P450 7A1 (CYP7A1), the rate-limiting enzyme converting free cholesterol to bile acids. In this study, we tested whether Z-guggulsterone indeed induces human CYP7A1. In addition, the expression of cholesteryl ester hydrolase CES1 and bile salt export pump (BSEP) was monitored. Contrary to the general assumption, Z-guggulsterone did not induce CYP7A1. Instead, this phytosterol significantly induced CES1 and BSEP through transactivation. Z-Guggulsterone underwent metabolism by CYP3A4, and the metabolites greatly increased the induction potency on BSEP but not on CES1. BSEP induction favors cholesterol elimination, whereas CES1 involves both elimination and retention (probably when excessively induced). Interestingly, clinical trials reported the hypolipidemic response rates from 18% to 80% and showed that higher dosages actually increased VLDL cholesterol. Our findings predict that better hypolipidemic outcomes likely occur in individuals who have a relatively higher capacity of metabolizing Z-guggulsterone with moderate CES1 induction, a scenario possibly achieved by lowering the dosing regimens

Evaluation of parameters affecting Agrobacterium-mediated transient expression in citrus

Abstract Agrobacterium-mediated transient expression assays are a convenient alternative to stable expression because they are simple, easy to perform, and achieve gene expression rapidly. This study investigated the factors affecting transient gene expression efficiency in citrus by observing the cryo-sectioning of leaf samples under a laser confocal microscope. These factors included the composition of the infiltration buffer, the Agrobacterium cell density, the leaf development stage, the incubation temperature, and plant genotype. The highest transient expression level of yellow fluorescent protein (YFP) was detected in Mexican lime (Citrus aurantifolia) on the third day after the intermediate-aged leaves were infiltrated with the improved infiltration buffer 1 (15 mmol L−1 2-(N-morpholino) ethanesulfonic acid, 10 mmol L−1 MgCI2, and 200 pmol L−1 acetosyringone), which had an optical density of 0.8 and was incubated at 22°C. Additionally, this transient expression assay was applied to other citrus genotypes. Of note, trifoliate orange (Poncirus trifoliata) and kumquat (Fortunella obovate) had higher expression efficiency than other six genotypes of the Citrus genus. Our study provides research basis for the selection of optimization strategies in transient gene expression and improves the method for available genome investigation in citrus

The Intrinsic Energy Resolution of LaBr3_3(Ce) Crystal for GECAM

The intrinsic resolution is the primary limitation on the total energy resolution of LaBr$_3$(Ce) crystal. This intrinsic resolution arises from two effects: fluctuations occurring in the process of energy transfer to luminescent centers within the LaBr$_3$(Ce) crystal and the LaBr$_3$(Ce) crystal's non-proportional luminescence. Presently, experimental measurements regarding the intrinsic resolution of LaBr$_3$(Ce) crystal are scarce, and the underlying physical mechanisms remain incompletely understood. In this paper, we aim to elucidate the concept of intrinsic resolution. We investigated the entire physical process of luminescence following energy deposition in the LaBr$_3$(Ce) crystal, quantifying the various components in the total energy resolution. We conducted a series of experimental measurements and Geant4 simulations, determining the intrinsic resolution of LaBr$_3$(Ce) crystal to 100 keV electrons as 2.12%. The non-proportionality contributes significantly at 1.43%, while fluctuations in the energy transfer process accounted for 0.27%. It is evident that non-proportionality in light output constitutes the primary source of intrinsic resolution. Horizontal and vertical unevenness in light collection contributed 0.25% and 0.07%, respectively. Statistical fluctuations showed the largest impact on the total energy resolution, at 2.86%. The contribution from fluctuations in single-photoelectron events was 0.77%. Furthermore, we reconstructed the photon response using Geant4, and the consistency between the simulated relative light yield and the experimentally measured one confirmed the reliability of the LaBr$_3$(Ce) detector mass model employed in the simulation.Comment: 11 pages, 16 figure

Long-term functional maintenance of primary human hepatocytes in vitro

The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.</p

Analysis of risk factors associated with pre-myopia among primary school students in the Mianyang Science City Area

Objectives To find out the prevalence rate of pre-myopia among primary school students in the Mianyang Science City Area, analyze its related risk factors, and thus provide a reference for local authorities to formulate policies on the prevention and control of myopia for primary school students. Methods　 October 2022, Cluster sampling was adopted by our research group to obtain the vision levels of 2278 primary school students employing a diopter test in the Science City Area. In addition, questionnaires were distributed to help us find the risk factors associated with pre-myopia. Results The prevalence rate of pre-myopia among primary school students in the Science  City Area was 45.27%, of which 43.82% were boys and 46.92% were girls, with no statistically significant difference in the prevalence rate of myopia between boys and girls (c2 =2.171, P=0.141). Multiple logistic regression analysis demonstrated that the main risk factors for pre-myopia were having at least one parent with severe myopia, spending less than 2 hours a day outdoors, lack of sleep looking at electronic screens for more than 1 hours, and having an improper reading and writing posture. Outdoor activity time less than 2 hours per day, lack of sleep, looking at the electronic screen for more than 1 hour per day, and incorrect reading and writing posture were all positively associated with the pre-myopia (P values < 0.05). Conclusion The Science City Area has a high prevalence rate of pre-myopia among primary school students. It is proposed that students, schools, families, and local authorities work together to increase the time spent outdoors, get adequate sleep, reduce the time spent staring at digital screens and develop scientific use of eye habits

Short Gamma-ray Bursts: the mass of the accretion disk and the initial radius of the outflow

In this work we estimate the accretion-disk mass in the specific scenario of binary-neutron-star-merger with current observational data. Assuming that the outflows of short Gamma-ray Bursts (GRBs) are driven via neutrino-antineutrino annihilation we estimate the disk mass of about half of short bursts in the sample to be $\sim 0.01-0.1 M_\odot$, in agreement with that obtained in the numerical simulations. Massive disks ($\sim {\rm several} 0.1 M_\odot$) found in some other short GRBs may point to the more efficient magnetic process of energy extraction or the neutron star and black hole binary progenitor. Our results suggest that some short bursts may be really due to the coalescence of double neutron stars and are promising gravitational wave radiation sources. For future short GRBs with simultaneous gravitational-wave detections, the disk mass may be reliably inferred and the validity of our approach will be tested. We also propose a method to constrain the initial radius of a baryonic outflow where it is launched ($R_0$) without the need of identifying an ideal thermal spectrum. We then apply it to GRB 090510 and get that $R_0 \lesssim 6.5\times 10^{6}(\Gamma_{\rm ph}/2000)^{-4}$ cm, suggesting that the central engine is a black hole with a mass $< 22 M_\odot(\Gamma_{\rm ph}/2000)^{-4}$, where $\Gamma_{\rm ph}$ is the bulk Lorentz factor of the outflow at the photospheric radius.Comment: 8 pages including 1 table, to appear in Ap

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis

Background: Excessive inflammation results in severe tissue damage as well as serious acute or chronic disorders, and extensive research has focused on finding new anti-inflammatory hit compounds with safety and efficacy profiles from natural products. As promising therapeutic entities for the treatment of inflammation-related diseases, fusaproliferin and its analogs have attracted great interest. However, the underlying anti-inflammatory mechanism is still poorly understood and deserves to be further investigated.Methods: For the estimation of the anti-inflammatory activity of fusaproliferin (1) and its analogs (2-4)in vitro and in vivo, lipopolysaccharide (LPS)-induced RAW264.7 macrophages and zebrafish embryos were employed. Then, transcriptome analysis was applied to guide subsequent western blot analysis of critical proteins in related signaling pathways. Surface plasmon resonance assays (SPR) combined with molecular docking analyses were finally applied to evaluate the affinity interactions between 1-4 and TLR4 and provide a possible interpretation of the downregulation of related signaling pathways.Results: 1-4 significantly attenuated the production of inflammatory messengers, including nitric oxide (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the ability of compound 1 to reverse LPS stimulation and the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPKs) signaling pathways contribute to the anti-inflammatory process. Experimental verification at the protein level revealed that 1 can inhibit the activation of inhibitor of NF-κB kinase (IKK), degradation of inhibitor of NF-κB (IκB), and phosphorylation of NF-κB and reduce nuclear translocation of NF-κB. 1 also decreased the phosphorylation of MAPKs, including p38, extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK). SPR assays and molecular docking results indicated that 1-4 exhibited affinity for the TLR4 protein with KD values of 23.5–29.3 μM.Conclusion: Fusaproliferin and its analogs can be hit compounds for the treatment of inflammation-associated diseases