De-confounding Representation Learning for Counterfactual Inference on Continuous Treatment via Generative Adversarial Network

Counterfactual inference for continuous rather than binary treatment variables is more common in real-world causal inference tasks. While there are already some sample reweighting methods based on Marginal Structural Model for eliminating the confounding bias, they generally focus on removing the treatment's linear dependence on confounders and rely on the accuracy of the assumed parametric models, which are usually unverifiable. In this paper, we propose a de-confounding representation learning (DRL) framework for counterfactual outcome estimation of continuous treatment by generating the representations of covariates disentangled with the treatment variables. The DRL is a non-parametric model that eliminates both linear and nonlinear dependence between treatment and covariates. Specifically, we train the correlations between the de-confounded representations and the treatment variables against the correlations between the covariate representations and the treatment variables to eliminate confounding bias. Further, a counterfactual inference network is embedded into the framework to make the learned representations serve both de-confounding and trusted inference. Extensive experiments on synthetic datasets show that the DRL model performs superiorly in learning de-confounding representations and outperforms state-of-the-art counterfactual inference models for continuous treatment variables. In addition, we apply the DRL model to a real-world medical dataset MIMIC and demonstrate a detailed causal relationship between red cell width distribution and mortality.Comment: 15 pages,4 figure

Performance of several simple, noninvasive models for assessing significant liver fibrosis in patients with chronic hepatitis B

Aim To compare the performance of several simple, noninvasive models comprising various serum markers in diagnosing significant liver fibrosis in the same sample of patients with chronic hepatitis B (CHB) with the same judgment standard. Methods A total of 308 patients with CHB who had undergone liver biopsy, laboratory tests, and liver stiffness measurement (LSM) at the Southwest Hospital, Chongqing, China between March 2010 and April 2014 were retrospectively studied. Receiver operating characteristic (ROC) curves and area under ROC curves (AUROCs) were used to analyze the results of the models, which incorporated ageplatelet (PLT) index (API model), aspartate transaminase (AST) to alanine aminotransferase (ALT) ratio (AAR model), AST to PLT ratio index (APRI model), γ-glutamyl transpeptidase (GGT) to PLT ratio index (GPRI model), GGT-PLT-albumin index (S index model), age-AST-PLT-ALT index (FIB-4 model), and age-AST-PLT-ALT-international normalized ratio index (Fibro-Q model). Results The AUROCs of the S index, GPRI, FIB-4, APRI, API, Fibro-Q, AAR, and LSM for predicting significant liver fibrosis were 0.726 (P < 0.001), 0.726 (P < 0.001), 0.621 (P = 0.001), 0.619 (P = 0.001), 0.580 (P = 0.033), 0.569 (P = 0.066), 0.495 (P = 0.886), and 0.757 (P < 0.001), respectively. The S index and GPRI had the highest correlation with histopathological scores (r = 0.373, P < 0.001; r = 0.372, P < 0.001, respectively) and LSM values (r = 0.516, P < 0.001; r = 0.513, P < 0.001, respectively). When LSM was combined with S index and GPRI, the AUROCs were 0.753 (P < 0.001) and 0.746 (P < 0.001), respectively. Conclusion S index and GPRI had the best diagnostic performance for significant liver fibrosis and were robust predictors of significant liver fibrosis in patients with CHB for whom transient elastography was unavailable

The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex

In vitro delivery of the diphtheria toxin catalytic (C) domain from the lumen of purified early endosomes to the external milieu requires the addition of both ATP and a cytosolic translocation factor (CTF) complex. Using the translocation of C-domain ADP-ribosyltransferase activity across the endosomal membrane as an assay, the CTF complex activity was 650–800-fold purified from human T cell and yeast extracts, respectively. The chaperonin heat shock protein (Hsp) 90 and thioredoxin reductase were identified by mass spectrometry sequencing in CTF complexes purified from both human T cell and yeast. Further analysis of the role played by these two proteins with specific inhibitors, both in the in vitro translocation assay and in intact cell toxicity assays, has demonstrated their essential role in the productive delivery of the C-domain from the lumen of early endosomes to the external milieu. These results confirm and extend earlier observations of diphtheria toxin C-domain unfolding and refolding that must occur before and after vesicle membrane translocation. In addition, results presented here demonstrate that thioredoxin reductase activity plays an essential role in the cytosolic release of the C-domain. Because analogous CTF complexes have been partially purified from mammalian and yeast cell extracts, results presented here suggest a common and fundamental mechanism for C-domain translocation across early endosomal membranes

Probiotic Yeast Inhibits VEGFR Signaling and Angiogenesis in Intestinal Inflammation

Background and Aims Saccharomyces boulardii (Sb) can protect against intestinal injury and tumor formation, but how this probiotic yeast controls protective mucosal host responses is unclear. Angiogenesis is an integral process of inflammatory responses in inflammatory bowel diseases (IBD) and required for mucosal remodeling during restitution. The aim of this study was to determine whether Sb alters VEGFR (vascular endothelial growth factor receptor) signaling, a central regulator of angiogenesis. Methods: HUVEC were used to examine the effects of Sb on signaling and on capillary tube formation (using the ECMatrix™ system). The effects of Sb on VEGF-mediated angiogenesis were examined in vivo using an adenovirus expressing VEGF-A(164) in the ears of adult nude mice (NuNu). The effects of Sb on blood vessel volume branching and density in DSS-induced colitis was quantified using VESsel GENeration (VESGEN) software. Results: 1) Sb treatment attenuated weight-loss (p<0.01) and histological damage (p<0.01) in DSS colitis. VESGEN analysis of angiogenesis showed significantly increased blood vessel density and volume in DSS-treated mice compared to control. Sb treatment significantly reduced the neo-vascularization associated with acute DSS colitis and accelerated mucosal recovery restoration of the lamina propria capillary network to a normal morphology. 2) Sb inhibited VEGF-induced angiogenesis in vivo in the mouse ear model. 3) Sb also significantly inhibited angiogenesis in vitro in the capillary tube assay in a dose-dependent manner (p<0.01). 4) In HUVEC, Sb reduced basal VEGFR-2 phosphorylation, VEGFR-2 phosphorylation in response to VEGF as well as activation of the downstream kinases PLCγ and Erk1/2. Conclusions: Our findings indicate that the probiotic yeast S boulardii can modulate angiogenesis to limit intestinal inflammation and promote mucosal tissue repair by regulating VEGFR signaling

Vascular permeability, vascular hyperpermeability and angiogenesis

The vascular system has the critical function of supplying tissues with nutrients and clearing waste products. To accomplish these goals, the vasculature must be sufficiently permeable to allow the free, bidirectional passage of small molecules and gases and, to a lesser extent, of plasma proteins. Physiologists and many vascular biologists differ as to the definition of vascular permeability and the proper methodology for its measurement. We review these conflicting views, finding that both provide useful but complementary information. Vascular permeability by any measure is dramatically increased in acute and chronic inflammation, cancer, and wound healing. This hyperpermeability is mediated by acute or chronic exposure to vascular permeabilizing agents, particularly vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A). We demonstrate that three distinctly different types of vascular permeability can be distinguished, based on the different types of microvessels involved, the composition of the extravasate, and the anatomic pathways by which molecules of different size cross-vascular endothelium. These are the basal vascular permeability (BVP) of normal tissues, the acute vascular hyperpermeability (AVH) that occurs in response to a single, brief exposure to VEGF-A or other vascular permeabilizing agents, and the chronic vascular hyperpermeability (CVH) that characterizes pathological angiogenesis. Finally, we list the numerous (at least 25) gene products that different authors have found to affect vascular permeability in variously engineered mice and classify them with respect to their participation, as far as possible, in BVP, AVH and CVH. Further work will be required to elucidate the signaling pathways by which each of these molecules, and others likely to be discovered, mediate the different types of vascular permeability

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Research on air-conditioning usage behaviour in offices with different occupancy

Occupant behaviours in the buildings are not only random and uncertain but also related to each occupant’s habitual preference. This leads to the performance gap between actual and expected energy consumption in buildings. Therefore, accurate information and modelling with regard to occupant behaviour are important for reliable energy simulation and energy-saving optimization design. Existing studies on occupant behaviour models in office space usually focus on single-person offices or full-floor buildings, without considering the behavioural differences among offices with different occupancy. Therefore, this study established the air-conditioning usage behaviour models in offices with different occupancy based on questionnaires and measured data. The results show that occupant compromise and clustering effect will increase with the increase of occupancy. Using the established models as input, this study compared the simulation results with that under the standard schedule. The difference rate is as high as 32.19% in winter and 13.07% in the whole year. And for areas with high energy consumption in winter, the gap may be bigger

Optimum design on impeller blade of mixed-flow pump based on CFD

AbstractThe three-dimensional flow field of the whole flow passage of a mixed-flow pump was numerically simulated by using CFD software on the basis of Spalart-Allmaras turbulent model according to the original design of the plant. Through analyzing the calculation results, the reason why the flow rate of this pump can not reach to the design requirements was found out. After replacing the impeller, a new pump impeller was optimally designed. The numerically simulation results show that the hydraulic performance of the newly designed impeller of the mixed-flow pump were obviously improved, and the engineering requirements of the owner were satisfied

A Novel Channel Calibration Method for Bistatic ISAR Imaging System

In practical bistatic inverse synthetic aperture radar (ISAR) imaging systems, the echo signals are modulated by non-ideal amplitude and phase characteristics of the transmitting and receiving channels, which seriously distorts image quality. However, the conventional channel calibration method based on a transponder is not applicable to bistatic ISAR imaging systems, since the baseline of the system is up to hundreds of kilometers. A channel calibration method only using calibration satellite echo information is proposed for the system, with a linear frequency modulation (LFM) waveform. Firstly, echoes of the calibration satellite are collected by tracking the satellite and multi-period echoes are aligned in the time domain, according to the pulse compression result. Then, the signal to noise ratio (SNR) is improved by accumulating multi-period echoes coherently in the time domain and the calibration coefficient is constructed based on the accumulated signal. Finally, spectrum of the echo signal is multiplied with the calibration coefficient to compensate the influence of channel characteristics. The effectiveness of the proposed method is verified by the simulation experiment with real satellite echoes