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Start Over Author "Chen, Yin" Publication Type Electronic Resources
198 results on '"Chen, Yin"'

1. Small signal impedance modelling and stability assessment of HVDC systems

Author

Chen, Yin and Xu, Lie

Subjects
621.31
Abstract

With high penetration of converter interfaced renewable energy and distributed generation, and increased use of HVDC interconnections, the characteristics of power systems is undergoing significantly changes. Interaction between grid-connected converters and networks is likely to increase, which may lead to stability and resonance problems, and in particular, when the grid is “weak” as the relatively high system impedance. Therefore, that is important adequate method is developed for assessing system stability. This thesis presents the small signal impedance modelling of grid-connected 2-level voltage source converters (VSC) and modular multilevel converter (MMC) for system stability assessment. In the case of 2-level VSC connected to weak grid system, the VSC impedance is mapped into the positive-negative (pn) sequence-frame for ease of analysis, and the stability problem associated with the coupling admittance is studied. It is found that traditional outer-loop controllers (e.g., active/reactive power and AC voltage controllers) create high coupling admittance that has negative impact on system stability. Improved outer-loop controllers are proposed and to improve the system stability which add compensation terms into the d and q-axis at the potential resonance frequency range. Small signal analysis and time domain simulation confirm the effectiveness of the proposed method. Large number of MMC based HVDC systems for interconnection or offshore wind farm integration are already in operation and many more will be installed in the coming years. MMC has multiple internal harmonics, which causes complex internal dynamics and multifrequency response. To accurately model the multiple frequency response and include all internal harmonics dynamics with MMC, the harmonic state-space (HSS) modeling approach is adopted. A detailed procedure for deriving the small-signal model of single-phase MMC system using HSS modelling approach is presented first. To address the issues related to single-phase MMC modelling including the existence of zero-sequence current and the use of controllers in abc frame, which are not in accordance with practical 3-phase system, impedance modelling and validation of the three-phase MMC based on HSS are conducted. In order to simplify the analysis on the coupling characteristics between different frequencies in MMCs, the proposed model is developed in pn frame, where the zero-sequence current in three-phase three wire system is modelled in a simple way. A simplified 2 by 2 admittance matrix in pn frame is extracted from the MMC small-signal model for ease of system stability analysis. Different outer-loop controllers, operating points and working mode are adopted and compared in the analysis to illustrate the effects system stability. It is found that for AC grid with single MMC, high PLL bandwidth leads to a less stable system. Compared with inverter mode, MMC in rectifier mode is more likely to induce system instability. Using the developed impedance model, the multi-infeed interaction factor (MIIF) measure is adopted to analyze the interactions for multi-infeed converter systems. Detailed studied are carried out for an AC network with two MMCs considering different MIIIF. Analytical studies and time-domain simulation results show that system with high MIIF where strong couplings between the two MMCs exist may lead to instability.

Published
2020
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2. Shape enumerators of self-dual NRT codes over finite fields

Author

Chen, Yin, Zhang, Runxuan, Chen, Yin, and Zhang, Runxuan

Abstract

We use invariant theory of finite groups to study shape enumerators of self-dual linear codes in a finite NRT metric space. We provide a new approach that avoids applying Molien's formula to compute all possible shape enumerators. Enhancing existing methods, we describe the shape enumerators of all self-dual NRT codes over an arbitrary finite field., Comment: 11 pages

Published
2024

3. Regression for matrix-valued data via Kronecker products factorization

Author

Chen, Yin-Jen, Tang, Minh, Chen, Yin-Jen, and Tang, Minh

Abstract

We study the matrix-variate regression problem $Y_i = \sum_{k} \beta_{1k} X_i \beta_{2k}^{\top} + E_i$ for $i=1,2\dots,n$ in the high dimensional regime wherein the response $Y_i$ are matrices whose dimensions $p_{1}\times p_{2}$ outgrow both the sample size $n$ and the dimensions $q_{1}\times q_{2}$ of the predictor variables $X_i$ i.e., $q_{1},q_{2} \ll n \ll p_{1},p_{2}$. We propose an estimation algorithm, termed KRO-PRO-FAC, for estimating the parameters $\{\beta_{1k}\} \subset \Re^{p_1 \times q_1}$ and $\{\beta_{2k}\} \subset \Re^{p_2 \times q_2}$ that utilizes the Kronecker product factorization and rearrangement operations from Van Loan and Pitsianis (1993). The KRO-PRO-FAC algorithm is computationally efficient as it does not require estimating the covariance between the entries of the $\{Y_i\}$. We establish perturbation bounds between $\hat{\beta}_{1k} -\beta_{1k}$ and $\hat{\beta}_{2k} - \beta_{2k}$ in spectral norm for the setting where either the rows of $E_i$ or the columns of $E_i$ are independent sub-Gaussian random vectors. Numerical studies on simulated and real data indicate that our procedure is competitive, in terms of both estimation error and predictive accuracy, compared to other existing methods.

Published
2024

4. Investigating the immunomodulatory roles of vitamin D and alpha-1 antitrypsin in human lung diseases

Author

Chen, Yin-Huai, Hawrylowicz, Catherine Martha, and Sethi, Tariq Jabbar

Abstract

Alpha-1 antitrypsin (AAT) is the most abundant serine protease inhibitor in the circulation, and is crucially protective in controlling pulmonary proteases including neutrophil elastase. AAT deficiency (AATD) is strongly associated with chronic obstructive pulmonary disease (COPD), primarily due to protease-antiprotease imbalance. However, recent studies also suggest immunomodulatory properties of AAT including the induction of IL-10 by dendritic cells and monocytes. Our group recently demonstrated that SERPINA1, the gene encoding AAT, is one of the most highly upregulated genes in vitamin D treated CD4+ T cells, and that AAT also upregulates IL-10 synthesis by these cells, in a complement C3a dependent manner. CD8+ T cells are implicated in the pathogenesis of COPD. Therefore the initial aim was to assess whether vitamin D increases AAT synthesis in CD8+ T cells. Vitamin D significantly upregulated SERPINA1/AAT in CD4+ T cells, with a much smaller effect in CD8+ T cells. Addition of exogenous TGF-β, previously shown to increase AAT secretion by other cell types, dose-dependently enhanced vitamin D induction of AAT in CD8+, but not CD4+, T cells. TGF-β with vitamin D increased VDR and RXRα in CD8+ T cells, whilst neutralization of TGF-β reduced the capacity of vitamin D to enhance both SERPINA1 and VDR in CD4+ T cells. These data imply that TGF-β modifies the response of vitamin D to human T cells. Data from a TGF-β bioassay suggested no difference in baseline secretion of bioactive TGF-β between the 2 cell types, but increased secretion by CD4+ T cells following vitamin D exposure, providing a potential explanation for the requirement of exogenous TGF-β in CD8+ T cell cultures. The next aim was to study AAT functions in T cells. Firstly, effects of wild-type (MM) and mutant (ZZ) AAT on CD8+ T cell immuno-regulatory function were assessed. However, little effect on cytokine responses including IL-10 induction was observed. As a result, gene expression microarrays were performed to further investigate AAT functions. These highlighted a low number of genes/pathways regulated by wild-type AAT, suggesting that AAT synthesised by CD8+ T cells may act on accessory cells, and/or that effects on CD8+ T cells may be indirect, requiring the presence of accessory cells in culture. The potential of vitamin D to increase AAT levels in AATD patients carrying the PiZZ mutation was next evaluated. The capacity of vitamin D +/- TGF-β to induce SERPINA1/AAT was compared in T cells from PiZZ patients, healthy control subjects and non-AATD COPD patients. The previously observed SERPINA1 induction by vitamin D +/- TGF-β in healthy individuals was reduced in PiZZ CD8+ but not CD4+ T cells. However, this response was significantly impaired at the protein level in both PiZZ CD4+ and CD8+ T cells, suggesting that T cells from AATD patients may exhibit a secretion defect. The IL-17 family cytokines are over-produced in severe and chronic respiratory disease. Since AAT may reduce IL-17A in animal models, evidence of dysregulated cytokine responses in PBMC cultures, following T cell receptor ligation, from AATD patients was investigated. Strikingly, an increased frequency of cells co-expressing IL-17A, with IL-17F and IL-22 was observed in PBMC cultures from PiZZ patients, in comparison to healthy individuals or older COPD patients. There was no difference in Th1 or Th2 cytokines including IFN-γ and IL-13 or IL-10 between the groups. Vitamin D increased IL-13 and decreased IFN-γ, IL-17A, IL-17F and IL-22. This enhanced Th17 response may be explained by the lack of AAT, although direct suppression by vitamin D is also possible, and this warrants further study. These findings suggest an interaction between vitamin D and AAT and support the concept that both are important mediators in the maintenance of respiratory health. Understanding how those mediators exert protective effects in the airways is critical in optimizing therapeutic strategies for AATD, where the only approved therapy has many limitations.

Published
2016

7. The Role of Environmental Chlorination Stress and Solar Ultraviolet Radiation in Skin Inflammation and Carcinogenesis

Author

Chen, Yin, Wang, Wei, Wilson, Amanda M., Snell, Jeremy Andrew, Chen, Yin, Wang, Wei, Wilson, Amanda M., and Snell, Jeremy Andrew

Abstract

A multitude of extrinsic environmental factors (referred to in their entirety as the ‘skin exposome’)impact structure and function of skin and its corresponding cellular components. The complex (i.e. additive, antagonistic, or synergistic) interactions between multiple extrinsic (exposome) and intrinsic (biological) factors are important determinants of skin health outcomes. Here, we have investigated the role of hypochlorous acid (HOCl) as an emerging component of the skin exposome serving molecular functions as an innate immune factor, environmental toxicant, and topical chemopreventive agent targeting solar UV-induced skin cancer. Our studies have explored the interaction between solar UV and HOCl-related environmental co-exposures identifying a heretofore unrecognized photo-chemopreventive activity of topical HOCl and chlorination stress that blocks inflammation and tumorigenic progression in UV-induced high-risk SKH-1 mouse skin, a finding in contrast with the pro-inflammatory and UV-enhancing effects of topical trichloroisocyanuric acid (TCIC), a common chloramine-type freshwater disinfectant. These observations on epithelial health and chlorination stress, explored for the first time in the context of skin exposure to chlorinated fresh water used for swimming pool disinfection, indicate a heretofore unrecognized role of chlorination stress as an environmental determinant of human epithelial health. We also demonstrate that reconstructed human gingiva (EpiGingivalTM), a gastrointestinal tissue with remarkable histological similarity to stratified skin, is subject to topical HOCl/TCIC-induced chlorination stress as a result of exposure to environmentally relevant dose regimens. Given the daily exposure of billions of people to chlorinated fresh water, our findings deserve future examinations that define cutaneous and gastrointestinal epithelial effects of freshwater chlorination relevant to human populations on a global scale.

Published
2023

8. Radiomics-based survival risk stratification of glioblastoma is associated with different genome alteration

Author

Xu, Pengfei, Li, Cong, Chen, Yin-Sheng, Li, De-Pei, Xi, Shao-Yan, Chen, Fu-Rong, Li, Xin, Chen, Zhong-Ping, Xu, Pengfei, Li, Cong, Chen, Yin-Sheng, Li, De-Pei, Xi, Shao-Yan, Chen, Fu-Rong, Li, Xin, and Chen, Zhong-Ping

Abstract

Background: Glioblastoma (GBM) is a remarkable heterogeneous tumor with few non-invasive, repeatable, and cost-effective prognostic biomarkers reported. In this study, we aim to explore the association between radiomic features and prognosis and genomic alterations in GBM. Methods: A total of 180 GBM patients (training cohort: n = 119; validation cohort 1: n = 37; validation cohort 2: n = 24) were enrolled and underwent preoperative MRI scans. From the multiparametric (T1, T1-Gd, T2, and T2-FLAIR) MR images, the radscore was developed to predict overall survival (OS) in a multistep postprocessing workflow and validated in two external validation cohorts. The prognostic accuracy of the radscore was assessed with concordance index (C-index) and Brier scores. Furthermore, we used hierarchical clustering and enrichment analysis to explore the association between image features and genomic alterations. Results: The MRI-based radscore was significantly correlated with OS in the training cohort (C-index: 0.70), validation cohort 1 (C-index: 0.66), and validation cohort 2 (C-index: 0.74). Multivariate analysis revealed that the radscore was an independent prognostic factor. Cluster analysis and enrichment analysis revealed that two distinct phenotypic clusters involved in distinct biological processes and pathways, including the VEGFA−VEGFR2 signaling pathway (q-value = 0.033), JAK−STAT signaling pathway (q-value = 0.049), and regulation of MAPK cascade (q-value = 0.0015/0.025). Conclusions: Radiomic features and radiomics-derived radscores provided important phenotypic and prognostic information with great potential for risk stratification in GBM. © 2023

Published
2023

9. Functional Peptide-Loaded Gelatin Nanoparticles as Eyedrops for Cornea Neovascularization Treatment

Author

Chu,Ya-Chun, Fang,Hsu-Wei, Wu,Yu-Yi, Tang,Yu-Jun, Hsieh,Erh-Hsuan, She,YiZhou, Chang,Che-Yi, Lin,I-Chan, Chen,Yin-Ju, Liu,Guei-Sheung, Tseng,Ching-Li, Chu,Ya-Chun, Fang,Hsu-Wei, Wu,Yu-Yi, Tang,Yu-Jun, Hsieh,Erh-Hsuan, She,YiZhou, Chang,Che-Yi, Lin,I-Chan, Chen,Yin-Ju, Liu,Guei-Sheung, and Tseng,Ching-Li

Abstract

Ya-Chun Chu,1,2,* Hsu-Wei Fang,2,3,* Yu-Yi Wu,1 Yu-Jun Tang,1 Erh-Hsuan Hsieh,1 YiZhou She,4 Che-Yi Chang,1 I-Chan Lin,5,6 Yin-Ju Chen,1,7– 9 Guei-Sheung Liu,1,10– 12 Ching-Li Tseng1,8,9,13 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 2Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei City, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County, Taiwan; 4School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 5Department of Ophthalmology, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan; 6Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; 7Department of Radiation Oncology, Taipei Medical University Hospital, Taipei City, Taiwan; 8International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 9Center for Precision Medicine and Translational Cancer Research, Taipei Medical University Hospital, Taipei City, Taiwan; 10Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia; 11Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia; 12Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia; 13Research Center of Biomedical Device, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan*These authors contributed equally to this workCorrespondence: Ching-Li Tseng, Tel +886 2 2736 1661 (ext. 5214), Email chingli@tmu.edu.twBackground: Corneal neovascularization (NV) is a process of abnormal vessel growth into the transparent cornea from the limbus and can disturb the light passing throu

Published
2023

10. Multimodal Feature Extraction and Fusion for Emotional Reaction Intensity Estimation and Expression Classification in Videos with Transformers

Author

Li, Jia, Chen, Yin, Zhang, Xuesong, Nie, Jiantao, Li, Ziqiang, Yu, Yangchen, Zhang, Yan, Hong, Richang, Wang, Meng, Li, Jia, Chen, Yin, Zhang, Xuesong, Nie, Jiantao, Li, Ziqiang, Yu, Yangchen, Zhang, Yan, Hong, Richang, and Wang, Meng

Abstract

In this paper, we present our advanced solutions to the two sub-challenges of Affective Behavior Analysis in the wild (ABAW) 2023: the Emotional Reaction Intensity (ERI) Estimation Challenge and Expression (Expr) Classification Challenge. ABAW 2023 aims to tackle the challenge of affective behavior analysis in natural contexts, with the ultimate goal of creating intelligent machines and robots that possess the ability to comprehend human emotions, feelings, and behaviors. For the Expression Classification Challenge, we propose a streamlined approach that handles the challenges of classification effectively. However, our main contribution lies in our use of diverse models and tools to extract multimodal features such as audio and video cues from the Hume-Reaction dataset. By studying, analyzing, and combining these features, we significantly enhance the model's accuracy for sentiment prediction in a multimodal context. Furthermore, our method achieves outstanding results on the Emotional Reaction Intensity (ERI) Estimation Challenge, surpassing the baseline method by an impressive 84\% increase, as measured by the Pearson Coefficient, on the validation dataset., Comment: Solutions of HFUT-CVers Team at the 5th ABAW Competition (CVPR 2023 workshop)

Published
2023

11. Comparison of Waymo Rider-Only Crash Data to Human Benchmarks at 7.1 Million Miles

Author

Kusano, Kristofer D., Scanlon, John M., Chen, Yin-Hsiu, McMurry, Timothy L., Chen, Ruoshu, Gode, Tilia, Victor, Trent, Kusano, Kristofer D., Scanlon, John M., Chen, Yin-Hsiu, McMurry, Timothy L., Chen, Ruoshu, Gode, Tilia, and Victor, Trent

Abstract

This paper examines the safety performance of the Waymo Driver, an SAE level 4 automated driving system (ADS) used in a rider-only (RO) ride-hailing application without a human driver, either in the vehicle or remotely. ADS crash data was derived from NHTSA's Standing General Order (SGO) reporting over 7.14 million RO miles through the end of October 2023 in Phoenix, AZ, San Francisco, CA, and Los Angeles, CA. This study is one of the first to compare overall crashed vehicle rates using only RO data (as opposed to ADS testing with a human behind the wheel) to a human benchmark that also corrects for biases caused by underreporting and unequal reporting thresholds reported in the literature. When considering all locations together, the any-injury-reported crashed vehicle rate was 0.41 incidents per million miles (IPMM) for the ADS vs 2.78 IPMM for the human benchmark, an 85% reduction or a 6.8 times lower rate. Police-reported crashed vehicle rates for all locations together were 2.1 IPMM for the ADS vs. 4.85 IPMM for the human benchmark, a 57% reduction or 2.3 times lower rate. Police-reported and any-injury-reported crashed vehicle rate reductions for the ADS were statistically significant when compared in San Francisco and Phoenix as well as combined across all locations. The comparison in Los Angeles, which to date has low mileage and no reported events, was not statistically significant. In general, the Waymo ADS had a lower any property damage or injury rate than the human benchmarks. Given imprecision in the benchmark estimate and multiple potential sources of underreporting biasing the benchmarks, caution should be taken when interpreting the results of the any property damage or injury comparison. Together, these crash-rate results should be interpreted as a directional and continuous confidence growth indicator, together with other methodologies, in a safety case approach.

Published
2023

12. Benchmarks for Retrospective Automated Driving System Crash Rate Analysis Using Police-Reported Crash Data

Author

Scanlon, John M., Kusano, Kristofer D., Fraade-Blanar, Laura A., McMurry, Timothy L., Chen, Yin-Hsiu, Victor, Trent, Scanlon, John M., Kusano, Kristofer D., Fraade-Blanar, Laura A., McMurry, Timothy L., Chen, Yin-Hsiu, and Victor, Trent

Abstract

With fully automated driving systems (ADS; SAE level 4) ride-hailing services expanding in the US, we are now approaching an inflection point, where the process of retrospectively evaluating ADS safety impact can start to yield statistically credible conclusions. An ADS safety impact measurement requires a comparison to a "benchmark" crash rate. This study aims to address, update, and extend the existing literature by leveraging police-reported crashes to generate human crash rates for multiple geographic areas with current ADS deployments. All of the data leveraged is publicly accessible, and the benchmark determination methodology is intended to be repeatable and transparent. Generating a benchmark that is comparable to ADS crash data is associated with certain challenges, including data selection, handling underreporting and reporting thresholds, identifying the population of drivers and vehicles to compare against, choosing an appropriate severity level to assess, and matching crash and mileage exposure data. Consequently, we identify essential steps when generating benchmarks, and present our analyses amongst a backdrop of existing ADS benchmark literature. One analysis presented is the usage of established underreporting correction methodology to publicly available human driver police-reported data to improve comparability to publicly available ADS crash data. We also identify important dependencies in controlling for geographic region, road type, and vehicle type, and show how failing to control for these features can bias results. This body of work aims to contribute to the ability of the community - researchers, regulators, industry, and experts - to reach consensus on how to estimate accurate benchmarks.

Published
2023

13. From Static to Dynamic: Adapting Landmark-Aware Image Models for Facial Expression Recognition in Videos

Author

Chen, Yin, Li, Jia, Shan, Shiguang, Wang, Meng, Hong, Richang, Chen, Yin, Li, Jia, Shan, Shiguang, Wang, Meng, and Hong, Richang

Abstract

Dynamic facial expression recognition (DFER) in the wild is still hindered by data limitations, e.g., insufficient quantity and diversity of pose, occlusion and illumination, as well as the inherent ambiguity of facial expressions. In contrast, static facial expression recognition (SFER) currently shows much higher performance and can benefit from more abundant high-quality training data. Moreover, the appearance features and dynamic dependencies of DFER remain largely unexplored. To tackle these challenges, we introduce a novel Static-to-Dynamic model (S2D) that leverages existing SFER knowledge and dynamic information implicitly encoded in extracted facial landmark-aware features, thereby significantly improving DFER performance. Firstly, we build and train an image model for SFER, which incorporates a standard Vision Transformer (ViT) and Multi-View Complementary Prompters (MCPs) only. Then, we obtain our video model (i.e., S2D), for DFER, by inserting Temporal-Modeling Adapters (TMAs) into the image model. MCPs enhance facial expression features with landmark-aware features inferred by an off-the-shelf facial landmark detector. And the TMAs capture and model the relationships of dynamic changes in facial expressions, effectively extending the pre-trained image model for videos. Notably, MCPs and TMAs only increase a fraction of trainable parameters (less than +10\%) to the original image model. Moreover, we present a novel Emotion-Anchors (i.e., reference samples for each emotion category) based Self-Distillation Loss to reduce the detrimental influence of ambiguous emotion labels, further enhancing our S2D. Experiments conducted on popular SFER and DFER datasets show that we achieve the state of the art., Comment: Code will be available at: https://github.com/FER-LMC/S2D

Published
2023

14. An ultrasensitive test for profiling circulating tumor DNA using integrated comprehensive droplet digital detection.

Author

Ou, Chen-Yin, Ou, Chen-Yin, Vu, Tam, Grunwald, Jonathan T, Toledano, Michael, Zimak, Jan, Toosky, Melody, Shen, Byron, Zell, Jason A, Gratton, Enrico, Abram, Timothy J, Zhao, Weian, Ou, Chen-Yin, Ou, Chen-Yin, Vu, Tam, Grunwald, Jonathan T, Toledano, Michael, Zimak, Jan, Toosky, Melody, Shen, Byron, Zell, Jason A, Gratton, Enrico, Abram, Timothy J, and Zhao, Weian

Abstract

Current cancer detection systems lack the required sensitivity to reliably detect minimal residual disease (MRD) and recurrence at the earliest stages when treatment would be most effective. To address this issue, we present a novel liquid biopsy approach that utilizes an integrated comprehensive droplet digital detection (IC3D) digital PCR system which combines microfluidic droplet partitioning, fluorescent multiplex PCR chemistry, and our rapid 3D, large-volume droplet counting technology. The IC3D ddPCR assay can detect cancer-specific, ultra-rare genomic targets due to large sample input and high degree of partitioning. We first demonstrate our droplet digital PCR assay can robustly detect common cancer mutants including KRAS G12D spiked in wild-type genomic background or isolated from patient samples with 100% specificity. We then demonstrate that the IC3D ddPCR system can detect oncogenic KRAS G12D mutant alleles against a background of wild-type genomes at a sensitivity of 0.00125-0.005% with a false positive rate of 0% which is 50 to 1000× more sensitive than existing commercial liquid biopsy ddPCR and qPCR platforms, respectively. In addition, our technology can uniquely enable detection of circulating tumor cells using their genetic markers without a pre-enrichment step, and analysis of total tumor DNA isolated from blood samples, which will increase clinical sensitivity and specificity, and minimize inter-assay variability. Therefore, our technology holds the potential to provide clinicians with a powerful decision-making tool to monitor and treat MRD with unprecedented sensitivity for earlier stage intervention.

Published
2019

15. Distributed Lag Interaction Models with Two Pollutants.

Author

Chen, Yin-Hsiu, Chen, Yin-Hsiu, Mukherjee, Bhramar, Berrocal, Veronica J, Chen, Yin-Hsiu, Chen, Yin-Hsiu, Mukherjee, Bhramar, and Berrocal, Veronica J

Abstract

Distributed lag models (DLMs) have been widely used in environmental epidemiology to quantify the lagged effects of air pollution on a health outcome of interest such as mortality and morbidity. Most previous DLM approaches only consider one pollutant at a time. In this article, we propose distributed lag interaction model (DLIM) to characterize the joint lagged effect of two pollutants. One natural way to model the interaction surface is by assuming that the underlying basis functions are tensor products of the basis functions that generate the main-effect distributed lag functions. We extend Tukey's one-degree-of-freedom interaction structure to the two-dimensional DLM context. We also consider shrinkage versions of the two to allow departure from the specified Tukey's interaction structure and achieve bias-variance tradeoff. We derive the marginal lag effects of one pollutant when the other pollutant is fixed at certain quantiles. In a simulation study, we show that the shrinkage methods have better average performance in terms of mean squared error (MSE) across different scenarios. We illustrate the proposed methods by using the National Morbidity, Mortality, and Air Pollution Study (NMMAPS) data to model the joint effects of PM10 and O3 on mortality count in Chicago, Illinois, from 1987 to 2000.

Published
2019

16. A tough nitric oxide-eluting hydrogel coating suppresses neointimal hyperplasia on vascular stent

Author

Chen, Yin, Gao, Peng, Huang, Lu, Tan, Xing, Zhou, Ningling, Yang, Tong, Qiu, Hua, Dai, Xin, Michael, Sean, Tu, Qiufen, Huang, Nan, Guo, Zhihong, Zhou, Jianhua, Yang, Zhilu, Wu, Hongkai, Chen, Yin, Gao, Peng, Huang, Lu, Tan, Xing, Zhou, Ningling, Yang, Tong, Qiu, Hua, Dai, Xin, Michael, Sean, Tu, Qiufen, Huang, Nan, Guo, Zhihong, Zhou, Jianhua, Yang, Zhilu, and Wu, Hongkai

Abstract

Vascular stent is viewed as one of the greatest advancements in interventional cardiology. However, current approved stents suffer from in-stent restenosis associated with neointimal hyperplasia or stent thrombosis. Herein, we develop a nitric oxide-eluting (NOE) hydrogel coating for vascular stents inspired by the biological functions of nitric oxide for cardiovascular system. Our NOE hydrogel is mechanically tough and could selectively facilitate the adhesion of endothelial cells. Besides, it is non-thrombotic and capable of inhibiting smooth muscle cells. Transcriptome analysis unravels the NOE hydrogel could modulate the inflammatory response and induce the relaxation of smooth muscle cells. In vivo study further demonstrates vascular stents coated with it promote rapid restoration of native endothelium, and persistently suppress inflammation and neointimal hyperplasia in both leporine and swine models. We expect such NOE hydrogel will open an avenue to the surface engineering of vascular implants for better clinical outcomes. © 2021, The Author(s).

Published
2021

17. Classification of high-dimensional data with spiked covariance matrix structure

Author

Chen, Yin-Jen, Tang, Minh, Chen, Yin-Jen, and Tang, Minh

Abstract

We study the classification problem for high-dimensional data with $n$ observations on $p$ features where the $p \times p$ covariance matrix $\Sigma$ exhibits a spiked eigenvalues structure and the vector $\zeta$, given by the difference between the whitened mean vectors, is sparse with sparsity at most $s$. We propose an adaptive classifier (adaptive with respect to the sparsity $s$) that first performs dimension reduction on the feature vectors prior to classification in the dimensionally reduced space, i.e., the classifier whitened the data, then screen the features by keeping only those corresponding to the $s$ largest coordinates of $\zeta$ and finally apply Fisher linear discriminant on the selected features. Leveraging recent results on entrywise matrix perturbation bounds for covariance matrices, we show that the resulting classifier is Bayes optimal whenever $n \rightarrow \infty$ and $s \sqrt{n^{-1} \ln p} \rightarrow 0$. Experimental results on real and synthetic data sets indicate that the proposed classifier is competitive with existing state-of-the-art methods while also selecting a smaller number of features., Comment: 40 pages, 2 figures

Published
2021

18. The Synergistic Effects of Astragalus mongholicus and Salvia miltiorrhiza on Coronary Heart Disease Identified by Network Pharmacology and Experiment

Author

Zhang,Yun, Wang,Jie, Liu,Yong-Mei, Chen,Yin-Ying, Yang,Xiao-Chen, Duan,Lian, Zhang,Yun, Wang,Jie, Liu,Yong-Mei, Chen,Yin-Ying, Yang,Xiao-Chen, and Duan,Lian

Abstract

Yun Zhang,1 Jie Wang,2 Yong-Mei Liu,2 Yin-Ying Chen,3 Xiao-Chen Yang,4 Lian Duan2 1Department of Immunology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 2Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 3Department of the Scientific Research Office, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 4Department of Cardiology & Health Care, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of ChinaCorrespondence: Jie WangDepartment of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of ChinaTel +86 010-88001148Email wangjiedoctor2015@163.comBackground and Purpose: Two Chinese herbal medicines Huang Qi (HQ, Astragalus mongholicus) and Dan Shen (DS, Salvia miltiorrhiza) are often combined to treat coronary heart disease (CHD). The purpose of this study was to identify the underlying synergistic effects and mechanisms of HQ and DS against CHD.Methods: The active components and targets of HQ and DS, CHD-related genes, and the biological progression were analysed by network pharmacology. The myocardial infarction (MI) rat model was established by ligating the left anterior descending coronary artery. Cardiac function was detected by ultrasonic electrocardiography. The MI size, fibrosis, cardiac hypertrophy, lipid metabolism, blood viscosity, and coagulation indexes were analysed by histological staining or chemical methods, respectively.Results: A total of 170 shared and specific seed genes of HQ and DS against CHD were identified. The shared and specific biological processes of HQ and DS against CHD were obtained. The LVEF and LVFS values significantly increased, the myocardium infarct size and fibrosis significantly decreased

Published
2021

19. A Model-Based Approach to Document Software Toolchains for Supporting a Safety Analysis

Author

Baumgart, Stephan, Chen, Yin, Hamren, Rasmus, Punnekkat, Sasikumar, Baumgart, Stephan, Chen, Yin, Hamren, Rasmus, and Punnekkat, Sasikumar

Abstract

The increasing use of embedded systems to provide new functionality and customer experience requires developing the embedded systems carefully. As a new challenge, autonomous systems are developed to be working in a fleet to provide production workflows. Developing such a system-of-systems requires utilizing various software tools to manage the complexity. One task in developing safety-critical products, in general, is to analyze if the applied tools can introduce failures into the final product. Today's functional safety standards consider only single software tools for analysis. In our industrial work, we can observe a trend towards supporting product lines. A common configurable platform is developed to support a range of different products. Developing such a platform and supporting variability, a toolchain is created where software tools are glued together using scripts to support product lines and automatically generate compiled code. The current functional safety standards do not straight forward support this. This paper discusses how software tools need to support functional safety and show limitations by providing an industrial case. We provide a model-based approach to describe a toolchain and show its application to an industrial case. To analyze potential failures in the toolchain, we utilize the HAZOP method and show its application.

Published
2021
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20. How to Identify Boundary Conditions with Contrasty Metric?

Author

Luo, Weilin, Wan, Hai, Song, Xiaotong, Yang, Binhao, Zhong, Hongzhen, Chen, Yin, Luo, Weilin, Wan, Hai, Song, Xiaotong, Yang, Binhao, Zhong, Hongzhen, and Chen, Yin

Abstract

The boundary conditions (BCs) have shown great potential in requirements engineering because a BC captures the particular combination of circumstances, i.e., divergence, in which the goals of the requirement cannot be satisfied as a whole. Existing researches have attempted to automatically identify lots of BCs. Unfortunately, a large number of identified BCs make assessing and resolving divergences expensive. Existing methods adopt a coarse-grained metric, generality, to filter out less general BCs. However, the results still retain a large number of redundant BCs since a general BC potentially captures redundant circumstances that do not lead to a divergence. Furthermore, the likelihood of BC can be misled by redundant BCs resulting in costly repeatedly assessing and resolving divergences. In this paper, we present a fine-grained metric to filter out the redundant BCs. We first introduce the concept of contrasty of BC. Intuitively, if two BCs are contrastive, they capture different divergences. We argue that a set of contrastive BCs should be recommended to engineers, rather than a set of general BCs that potentially only indicates the same divergence. Then we design a post-processing framework (PPAc) to produce a set of contrastive BCs after identifying BCs. Experimental results show that the contrasty metric dramatically reduces the number of BCs recommended to engineers. Results also demonstrate that lots of BCs identified by the state-of-the-art method are redundant in most cases. Besides, to improve efficiency, we propose a joint framework (JAc) to interleave assessing based on the contrasty metric with identifying BCs. The primary intuition behind JAc is that it considers the search bias toward contrastive BCs during identifying BCs, thereby pruning the BCs capturing the same divergence. Experiments confirm the improvements of JAc in identifying contrastive BCs., Comment: to be published in ICSE21

Published
2021

21. Drug Repurposing as a Novel Treatment Approach for Medullary Thyroid Carcinoma

Author

Cherrington, Nathan, Chen, Yin, Zhang, Qing-Yu, Briehl, Margaret, Alqahtani, Tariq, Cherrington, Nathan, Chen, Yin, Zhang, Qing-Yu, Briehl, Margaret, and Alqahtani, Tariq

Abstract

Medullary thyroid carcinoma (MTC) is the most aggressive form of thyroid carcinoma with a high rate of metastasis. The gain-of-function mutation in the RET proto-oncogene has been identified as the primary cause of the development of MTC, which is a part of multiple endocrine neoplasia type 2 (MEN2) syndrome. The dominant-activating mutation in the RET proto-oncogene promotes the phosphorylation of RET receptor in a ligand independent manner. This leads to constitutive activation of downstream signaling pathways that are involved in cell growth, survival, and proliferation. Owing to their potential role in the tumor development, RET has been regarded as an exceptional molecular target for MTC treatment. Therefore, targeting RET activation with drug-like small molecules offers a potential treatment strategy for patients with MTC. Our approach included screening for potential hits utilizing a cell-based bioluminescence reporter system in which the luciferase gene expression is driven by the RET promoter. In this study, we provide three chemical drugs which effectively suppressed RET activity and can be repurposed to treat or control MTC. Each of the drugs included in this research represents a unique pathway and inhibitory mechanism, and each was successfully reduced MTC tumor growth, metastasis, invasion and survival. We believe these drugs are promising candidates for preclinical and clinical studies as mono-therapy and/or for use in combination with other agents to manage MTC.

Published
2021

22. Modular Invariants of Finite Gluing Groups

Author

Chen, Yin, Shank, R. James, Wehlau, David L., Chen, Yin, Shank, R. James, and Wehlau, David L.

Abstract

We use the gluing construction introduced by Jia Huang to explore the rings of invariants for a range of modular representations. We construct generating sets for the rings of invariants of the maximal parabolic subgroups of a finite symplectic group and their common Sylow p-subgroup. We also investigate the invariants of singular finite classical groups. We introduce parabolic gluing and use this construction to compute the invariant field of fractions for a range of representations. We use thin gluing to construct faithful representations of semidirect products and to determine the minimum dimension of a faithful representation of the semidirect product of a cyclic p-group acting on an elementary abelian p-group.

Published
2021

23. Robust distributed lag models using data adaptive shrinkage.

Author

Chen, Yin-Hsiu, Chen, Yin-Hsiu, Mukherjee, Bhramar, Adar, Sara D, Berrocal, Veronica J, Coull, Brent A, Chen, Yin-Hsiu, Chen, Yin-Hsiu, Mukherjee, Bhramar, Adar, Sara D, Berrocal, Veronica J, and Coull, Brent A

Abstract

Distributed lag models (DLMs) have been widely used in environmental epidemiology to quantify the lagged effects of air pollution on an outcome of interest such as mortality or cardiovascular events. Generally speaking, DLMs can be applied to time-series data where the current measure of an independent variable and its lagged measures collectively affect the current measure of a dependent variable. The corresponding distributed lag (DL) function represents the relationship between the lags and the coefficients of the lagged exposure variables. Common choices include polynomials and splines. On one hand, such a constrained DLM specifies the coefficients as a function of lags and reduces the number of parameters to be estimated; hence, higher efficiency can be achieved. On the other hand, under violation of the assumption about the DL function, effect estimates can be severely biased. In this article, we propose a general framework for shrinking coefficient estimates from an unconstrained DLM, that are unbiased but potentially inefficient, toward the coefficient estimates from a constrained DLM to achieve a bias-variance trade-off. The amount of shrinkage can be determined in various ways, and we explore several such methods: empirical Bayes-type shrinkage, a hierarchical Bayes approach, and generalized ridge regression. We also consider a two-stage shrinkage approach that enforces the effect estimates to approach zero as lags increase. We contrast the various methods via an extensive simulation study and show that the shrinkage methods have better average performance across different scenarios in terms of mean squared error (MSE).We illustrate the methods by using data from the National Morbidity, Mortality, and Air Pollution Study (NMMAPS) to explore the association between PM$_{10}$, O$_3$, and SO$_2$ on three types of disease event counts in Chicago, IL, from 1987 to 2000.

Published
2018

24. Combining Cloud Computing and Artificial Intelligence Scene Recognition in Real-time Environment Image Planning Walkable Area

Author

Jia-Shing Sheu, Chen-Yin Han, Jia-Shing Sheu, and Chen-Yin Han

Abstract

This study developed scene recognition and cloud computing technology for real-time environmental image-based regional planning using artificial intelligence. TensorFlow object detection functions were used for artificial intelligence technology. First, an image from the environment is transmitted to a cloud server for cloud computing, and all objects in the image are marked using a bounding box method. Obstacle detection is performed using object detection, and the associated technique algorithm is used to mark walkable areas and relative coordinates. The results of this study provide a machine vision application combined with cloud computing and artificial intelligence scene recognition that can be used to complete walking space activities planned by a cleaning robot or unmanned vehicle through real-time utilization of images from the environment.

Published
2020

25. Injectable in Situ Forming Kartogenin-Loaded Chitosan Hydrogel With Tunable Rheological Properties for Cartilage Tissue Engineering

Author

Dehghanbaniani, Dorsa, Chen, Yin, Wang, Dong, Bagheri, Reza, Solouk, Atefeh, Wu, Hongkai, Dehghanbaniani, Dorsa, Chen, Yin, Wang, Dong, Bagheri, Reza, Solouk, Atefeh, and Wu, Hongkai

Abstract

Limited regeneration capacity of cartilage can be addressed by tissue engineering approaches including localized delivery of bioactive agents using biomaterials. Although chitosan hydrogels have been considered as appropriate candidates for these purposes, however, their poor mechanical properties limit their real applications. Here, we develop in situ forming chitosan hydrogels with enhanced shear modulus by chemical modification of chitosan using N-(β-maleimidopropyloxy) succinimide ester (BMPS). Moreover, we utilize β-Glycerophosphate (β-GP) in the hydrogels for achieving thermosensitivity. We investigate the effects of BMPS, β-GP and chitosan concentration on rheological and swelling properties of the hydrogels. Accordingly, we generate significant statistical models by response surface method to predict these properties. These models provide us beneficial tools to tune the hydrogel properties depending on the cartilage defect location and properties. Finally, we incorporate a recently discovered small biomolecule, kartogenin (KGN), for promoting chondrogenesis of stem cells into the optimized hydrogel. The hydrogel's shear modulus is 78 ± 5 kPa which covers a wide range of human articular cartilage shear modulus (50–250 kPa). It can be injected to the defects non-invasively at room temperature which gels at 37 °C within minutes. Additionally, it provides a sustained KGN release for ∼40 days that may eliminate the need of multiple injections. In vitro chondrogenic results confirm enhanced chondrogenic differentiation of human adipose mesenchymal stem cells (hAMSCs) treated with KGN-loaded hydrogel, compared to pure KGN. Based on the enhanced hydrogel shear modulus, injectability, gelation behavior, long-term drug release and in vitro results, this thermosensitive hydrogel looks promising for cartilage tissue engineering. © 2020 Elsevier B.V.

Published
2020

26. Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome.

Author

Béziat, Vivien, Béziat, Vivien, Tavernier, Simon J, Chen, Yin-Huai, Ma, Cindy S, Materna, Marie, Laurence, Arian, Staal, Jens, Aschenbrenner, Dominik, Roels, Lisa, Worley, Lisa, Claes, Kathleen, Gartner, Lisa, Kohn, Lisa A, De Bruyne, Marieke, Schmitz-Abe, Klaus, Charbonnier, Louis-Marie, Keles, Sevgi, Nammour, Justine, Vladikine, Natasha, Maglorius Renkilaraj, Majistor Raj Luxman, Seeleuthner, Yoann, Migaud, Mélanie, Rosain, Jérémie, Jeljeli, Mohamed, Boisson, Bertrand, Van Braeckel, Eva, Rosenfeld, Jill A, Dai, Hongzheng, Burrage, Lindsay C, Murdock, David R, Lambrecht, Bart N, Avettand-Fenoel, Véronique, Vogel, Tiphanie P, Undiagnosed Diseases Network, Esther, Charles R, Haskologlu, Sule, Dogu, Figen, Ciznar, Peter, Boutboul, David, Ouachée-Chardin, Marie, Amourette, Jean, Lebras, Marie-Noëlle, Gauvain, Clément, Tcherakian, Colas, Ikinciogullari, Aydan, Beyaert, Rudi, Abel, Laurent, Milner, Joshua D, Grimbacher, Bodo, Couderc, Louis-Jean, Butte, Manish J, Freeman, Alexandra F, Catherinot, Émilie, Fieschi, Claire, Chatila, Talal A, Tangye, Stuart G, Uhlig, Holm H, Haerynck, Filomeen, Casanova, Jean-Laurent, Puel, Anne, Béziat, Vivien, Béziat, Vivien, Tavernier, Simon J, Chen, Yin-Huai, Ma, Cindy S, Materna, Marie, Laurence, Arian, Staal, Jens, Aschenbrenner, Dominik, Roels, Lisa, Worley, Lisa, Claes, Kathleen, Gartner, Lisa, Kohn, Lisa A, De Bruyne, Marieke, Schmitz-Abe, Klaus, Charbonnier, Louis-Marie, Keles, Sevgi, Nammour, Justine, Vladikine, Natasha, Maglorius Renkilaraj, Majistor Raj Luxman, Seeleuthner, Yoann, Migaud, Mélanie, Rosain, Jérémie, Jeljeli, Mohamed, Boisson, Bertrand, Van Braeckel, Eva, Rosenfeld, Jill A, Dai, Hongzheng, Burrage, Lindsay C, Murdock, David R, Lambrecht, Bart N, Avettand-Fenoel, Véronique, Vogel, Tiphanie P, Undiagnosed Diseases Network, Esther, Charles R, Haskologlu, Sule, Dogu, Figen, Ciznar, Peter, Boutboul, David, Ouachée-Chardin, Marie, Amourette, Jean, Lebras, Marie-Noëlle, Gauvain, Clément, Tcherakian, Colas, Ikinciogullari, Aydan, Beyaert, Rudi, Abel, Laurent, Milner, Joshua D, Grimbacher, Bodo, Couderc, Louis-Jean, Butte, Manish J, Freeman, Alexandra F, Catherinot, Émilie, Fieschi, Claire, Chatila, Talal A, Tangye, Stuart G, Uhlig, Holm H, Haerynck, Filomeen, Casanova, Jean-Laurent, and Puel, Anne

Abstract

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients' heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways.

Published
2020

27. Rapid bacterial detection and antibiotic susceptibility testing in whole blood using one-step, high throughput blood digital PCR.

Author

Abram, Timothy J, Abram, Timothy J, Cherukury, Hemanth, Ou, Chen-Yin, Vu, Tam, Toledano, Michael, Li, Yiyan, Grunwald, Jonathan T, Toosky, Melody N, Tifrea, Delia F, Slepenkin, Anatoly, Chong, Jonathan, Kong, Lingshun, Del Pozo, Domenica Vanessa, La, Kieu Thai, Labanieh, Louai, Zimak, Jan, Shen, Byron, Huang, Susan S, Gratton, Enrico, Peterson, Ellena M, Zhao, Weian, Abram, Timothy J, Abram, Timothy J, Cherukury, Hemanth, Ou, Chen-Yin, Vu, Tam, Toledano, Michael, Li, Yiyan, Grunwald, Jonathan T, Toosky, Melody N, Tifrea, Delia F, Slepenkin, Anatoly, Chong, Jonathan, Kong, Lingshun, Del Pozo, Domenica Vanessa, La, Kieu Thai, Labanieh, Louai, Zimak, Jan, Shen, Byron, Huang, Susan S, Gratton, Enrico, Peterson, Ellena M, and Zhao, Weian

Abstract

Sepsis due to antimicrobial resistant pathogens is a major health problem worldwide. The inability to rapidly detect and thus treat bacteria with appropriate agents in the early stages of infections leads to excess morbidity, mortality, and healthcare costs. Here we report a rapid diagnostic platform that integrates a novel one-step blood droplet digital PCR assay and a high throughput 3D particle counter system with potential to perform bacterial identification and antibiotic susceptibility profiling directly from whole blood specimens, without requiring culture and sample processing steps. Using CTX-M-9 family ESBLs as a model system, we demonstrated that our technology can simultaneously achieve unprecedented high sensitivity (10 CFU per ml) and rapid sample-to-answer assay time (one hour). In head-to-head studies, by contrast, real time PCR and BioRad ddPCR only exhibited a limit of detection of 1000 CFU per ml and 50-100 CFU per ml, respectively. In a blinded test inoculating clinical isolates into whole blood, we demonstrated 100% sensitivity and specificity in identifying pathogens carrying a particular resistance gene. We further demonstrated that our technology can be broadly applicable for targeted detection of a wide range of antibiotic resistant genes found in both Gram-positive (vanA, nuc, and mecA) and Gram-negative bacteria, including ESBLs (blaCTX-M-1 and blaCTX-M-2 families) and CREs (blaOXA-48 and blaKPC), as well as bacterial speciation (E. coli and Klebsiella spp.) and pan-bacterial detection, without requiring blood culture or sample processing. Our rapid diagnostic technology holds great potential in directing early, appropriate therapy and improved antibiotic stewardship in combating bloodstream infections and antibiotic resistance.

Published
2020

28. Toward a Micro-Political Theology: Revisiting Liberation Theologies from the Perspective of Michel Foucault

Author

Chen, Yin-An and Chen, Yin-An

Abstract

This dissertation attempts to explore a very significant question in the tradition of liberation theologies: 'What can the theology of liberation do if social movements and revolutions cannot maintain the fruits of freedom and liberation?' or 'What is the next stage in the development of liberation theologies?' The dissertation seeks to examine the future threshold of the theologies of liberation and proposes a new micro-political theology based on the work of Michel Foucault. In the introduction, I provided evidence to demonstrate my argument that social movements and revolutions do not bring permanent freedom and liberation to the oppressed. 'Political theology' does not help to bring about a radical change of liberation because it assumes that the church or the theological is separated from the public and political spheres. I argue that we need a micro-political theology to overcome the division between spirituality and political theology and overcome the limits of liberation theologies. Based on my reflections on this phenomenon, in Chapter one, I examined the methodology of liberation theologies, shared by Latin American liberation theology, feminist theology and womanist theology. I pointed out that liberation theologies put overemphasis on the analysis of social structure and neglect the lived-experience of the individual subject. They also lack an understanding of the project of subjectification, relying on social structure to define the groups of sufferers. In response to this situation, in Chapter two, I introduce Michel Foucault's theory of power relationships in order to rethink the exercise of power, which works not only at the level of social and political structure but on the individual's body, desire and sexuality. Foucault's theory enlarges the vision of political theology and liberation theologies to show that political resistance cannot be a limited act in the political realm. Political resistance must consider the process of subjectification, whi

Published
2020

29. Rapid bacterial detection and antibiotic susceptibility testing in whole blood using one-step, high throughput blood digital PCR.

Author

Abram, Timothy, Abram, Timothy, Cherukury, Hemanth, Ou, Chen-Yin, Vu, Tam, Toledano, Michael, Li, Yiyan, Grunwald, Jonathan, Toosky, Melody, Tifrea, Delia, Slepenkin, Anatoly, Chong, Jonathan, Kong, Lingshun, Del Pozo, Domenica, La, Kieu, Labanieh, Louai, Zimak, Jan, Shen, Byron, Peterson, Ellena, Zhao, Weian, Huang, Susan, Gratton, Enrico, Abram, Timothy, Abram, Timothy, Cherukury, Hemanth, Ou, Chen-Yin, Vu, Tam, Toledano, Michael, Li, Yiyan, Grunwald, Jonathan, Toosky, Melody, Tifrea, Delia, Slepenkin, Anatoly, Chong, Jonathan, Kong, Lingshun, Del Pozo, Domenica, La, Kieu, Labanieh, Louai, Zimak, Jan, Shen, Byron, Peterson, Ellena, Zhao, Weian, Huang, Susan, and Gratton, Enrico

Abstract

Sepsis due to antimicrobial resistant pathogens is a major health problem worldwide. The inability to rapidly detect and thus treat bacteria with appropriate agents in the early stages of infections leads to excess morbidity, mortality, and healthcare costs. Here we report a rapid diagnostic platform that integrates a novel one-step blood droplet digital PCR assay and a high throughput 3D particle counter system with potential to perform bacterial identification and antibiotic susceptibility profiling directly from whole blood specimens, without requiring culture and sample processing steps. Using CTX-M-9 family ESBLs as a model system, we demonstrated that our technology can simultaneously achieve unprecedented high sensitivity (10 CFU per ml) and rapid sample-to-answer assay time (one hour). In head-to-head studies, by contrast, real time PCR and BioRad ddPCR only exhibited a limit of detection of 1000 CFU per ml and 50-100 CFU per ml, respectively. In a blinded test inoculating clinical isolates into whole blood, we demonstrated 100% sensitivity and specificity in identifying pathogens carrying a particular resistance gene. We further demonstrated that our technology can be broadly applicable for targeted detection of a wide range of antibiotic resistant genes found in both Gram-positive (vanA, nuc, and mecA) and Gram-negative bacteria, including ESBLs (blaCTX-M-1 and blaCTX-M-2 families) and CREs (blaOXA-48 and blaKPC), as well as bacterial speciation (E. coli and Klebsiella spp.) and pan-bacterial detection, without requiring blood culture or sample processing. Our rapid diagnostic technology holds great potential in directing early, appropriate therapy and improved antibiotic stewardship in combating bloodstream infections and antibiotic resistance.

Published
2020

30. Corporate social responsibility analysed from Chinese cultural and political perspectives

Author

du Plessis Jean, Chen, Yin, du Plessis Jean, and Chen, Yin

Abstract

This study analyses Chinese corporate social responsibility from cultural and political perspectives. It integrates Chinese culturere and politics in order to reveal the corporate social responsibility in modern China. The findings pointed to corporate responsibilities to the environment, the country, and stakeholders being essential to companies in China.

Published
2019

31. The Club Cell Marker SCGB1A1 Downstream of FOXA2 is Reduced in Asthma.

Author

Zhu, Lingxiang, Zhu, Lingxiang, An, Lingling, Ran, Di, Lizarraga, Rosa, Bondy, Cheryl, Zhou, Xu, Harper, Richart W, Liao, Shu-Yi, Chen, Yin, Zhu, Lingxiang, Zhu, Lingxiang, An, Lingling, Ran, Di, Lizarraga, Rosa, Bondy, Cheryl, Zhou, Xu, Harper, Richart W, Liao, Shu-Yi, and Chen, Yin

Abstract

Human SCGB1A1 protein has been shown to be significantly reduced in BAL, sputum, and serum from humans with asthma as compared with healthy individuals. However, the mechanism of this reduction and its functional impact have not been entirely elucidated. By mining online datasets, we found that the mRNA of SCGB1A1 was significantly repressed in brushed human airway epithelial cells from individuals with asthma, and this repression appeared to be associated with reduced expression of FOXA2. Consistently, both Scgb1A1 and FoxA2 were downregulated in an ovalbumin-induced mouse model of asthma. Furthermore, compared with wild-type mice, Scgb1a1 knockout mice had increased airway hyperreactivity and inflammation when they were exposed to ovalbumin, confirming the antiinflammatory role of Scgb1a1 in protection against asthma phenotypes. To search for potential asthma-related stimuli of SCGB1A1 repression, we tested T-helper cell type 2 cytokines. Both IL-4 and IL-13 repressed epithelial expression of SCGB1A1 and FOXA2. Importantly, infection of epithelial cells with human rhinovirus similarly reduced expression of these two genes, which suggests that FOXA2 may be the common regulator of SCGB1A1. To establish the causal role of reduced FOXA2 in SCGB1A1 repression, we demonstrated that FOXA2 was required for SCGB1A1 expression at baseline. FOXA2 overexpression was sufficient to drive promoter activity and expression of SCGB1A1 and was also able to restore the repressed SCGB1A1 expression in IL-13-treated or rhinovirus-infected cells. Taken together, these findings suggest that low levels of epithelial SCGB1A1 in asthma are caused by reduced FOXA2 expression.

Published
2019

33. Chronic Exposure to Arsenite Enhances Influenza Virus Infection in Cultured Cells

Author

Smith, Catherine L., Vaillancourt, Richard R., Chen, Yin, Wondrak, Georg T., Amouzougan, Eva Alice, Smith, Catherine L., Vaillancourt, Richard R., Chen, Yin, Wondrak, Georg T., and Amouzougan, Eva Alice

Abstract

Arsenic is a ubiquitous environmental toxicant that has been associated with various human diseases. Chronic, low dose arsenic exposure has been linked to greater morbidity from cancer, cardiovascular diseases, diabetes mellitus, neurological diseases, skin lesions (keratosis), and respiratory diseases. The primary route of arsenic exposure in humans is through inhalation and ingestion. It has been reported that millions of people are exposed to arsenic in drinking water worldwide. Recent epidemiological and experimental studies show that arsenic exposure is associated with enhanced influenza virus infection in vivo. The respiratory epithelium, which is the primary target of infection, plays an important role in innate immune defense by serving as a barrier against infection. Arsenic exposure has been shown to alter the epithelial barrier function by disrupting tight junction formation. Despite the strong link between arsenic exposure and respiratory infection, there are no reports investigating the effects of arsenic exposure on influenza virus infection in vitro. Therefore, we hypothesized that the effect of arsenic exposure on epithelial cells could enhance influenza virus infection. In this study we characterized influenza A virus A/WSN/33 (H1N1) infection in arsenite-exposed Madin-Darby Canine Kidney (MDCK) epithelial cells. We also characterized influenza A virus A/Udorn/72(H3N2) infection in human bronchial epithelial cells (BEAS-2B), and adenocarcinomic human alveolar basal epithelial cells (A549) in order to uncover novel molecular mechanisms mediating arsenic enhanced influenza virus infection in vitro. We found that chronic exposure to sodium arsenite enhanced influenza A virus A/WSN/33 (H1N1) infection in MDCK cells. We observed increased viral matrix (M2) protein expression, increased viral mRNA quantity, and increased plaque area in the arsenite-exposed MDCK cells. Similarly, we also found that chronic arsenite exposure enhanced influenza A virus A/Udo

Published
2019

34. ToF-SIMS analysis of poly( l -lysine)- graft -poly(2-methyl-2-oxazoline) ultrathin adlayers

Author

Pidhatika, Bidhari, Chen, Yin, Coullerez, Geraldine, Al-Bataineh, Sameer, Textor, Marcus, Pidhatika, Bidhari, Chen, Yin, Coullerez, Geraldine, Al-Bataineh, Sameer, and Textor, Marcus

Abstract

Understanding of the interfacial chemistry of ultrathin polymeric adlayers is fundamentally important in the context of establishing quantitative design rules for the fabrication of nonfouling surfaces in various applications such as biomaterials and medical devices. In this study, seven poly(l-lysine)-graft-poly(2-methyl-2-oxazoline) (PLL-PMOXA) copolymers with grafting density (number of PMOXA chains per lysine residue) 0.09, 0.14, 0.19, 0.33, 0.43, 0.56, and 0.77, respectively, were synthesized and characterized by means of nuclear magnetic resonance spectroscopy (NMR). The copolymers were then adsorbed on Nb2O5 surfaces. Optical waveguide lightmode spectroscopy method was used to monitor the surface adsorption in situ of these copolymers and provide information on adlayer masses that were then converted into PLL and PMOXA surface densities. To investigate the relationship between copolymer bulk architecture (as shown by NMR data) and surface coverage as well as surface architecture, time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis was performed. Furthermore, ToF-SIMS method combined with principal component analysis (PCA) was used to verify the protein resistant properties of PLL-PMOXA adlayers, by thorough characterization before and after adlayer exposure to human serum. ToF-SIMS analysis revealed that the chemical composition as well as the architecture of the different PLL-PMOXA adlayers indeed reflects the copolymer bulk composition. ToF-SIMS results also indicated a heterogeneous surface coverage of PLL-PMOXA adlayers with high grafting densities higher than 0.33. In the case of protein resistant surface, PCA results showed clear differences between protein resistant and nonprotein-resistant surfaces. Therefore, ToF-SIMS results combined with PCA confirmed that the PLL-PMOXA adlayer with brush architecture resists protein adsorption. However, low increases of some amino acid signals in ToF-SIMS spectra were detected after the adlayer has

Published
2019

35. MRS-VPR: a multi-resolution sampling based global visual place recognition method

Author

Yin, Peng, Srivatsan, Rangaprasad Arun, Chen, Yin, Li, Xueqian, Zhang, Hongda, Xu, Lingyun, Li, Lu, Jia, Zhenzhong, Ji, Jianmin, He, Yuqing, Yin, Peng, Srivatsan, Rangaprasad Arun, Chen, Yin, Li, Xueqian, Zhang, Hongda, Xu, Lingyun, Li, Lu, Jia, Zhenzhong, Ji, Jianmin, and He, Yuqing

Abstract

Place recognition and loop closure detection are challenging for long-term visual navigation tasks. SeqSLAM is considered to be one of the most successful approaches to achieving long-term localization under varying environmental conditions and changing viewpoints. It depends on a brute-force, time-consuming sequential matching method. We propose MRS-VPR, a multi-resolution, sampling-based place recognition method, which can significantly improve the matching efficiency and accuracy in sequential matching. The novelty of this method lies in the coarse-to-fine searching pipeline and a particle filter-based global sampling scheme, that can balance the matching efficiency and accuracy in the long-term navigation task. Moreover, our model works much better than SeqSLAM when the testing sequence has a much smaller scale than the reference sequence. Our experiments demonstrate that the proposed method is efficient in locating short temporary trajectories within long-term reference ones without losing accuracy compared to SeqSLAM., Comment: 6 pages, 5 figures, ICRA 2019, accepted

Published
2019

36. Bio- chemical and physical characterizations of mesenchymal stromal cells along the time course of directed differentiation.

Author

Chen, Yin-Quan, Chen, Yin-Quan, Liu, Yi-Shiuan, Liu, Yu-An, Wu, Yi-Chang, Del Álamo, Juan C, Chiou, Arthur, Lee, Oscar K, Chen, Yin-Quan, Chen, Yin-Quan, Liu, Yi-Shiuan, Liu, Yu-An, Wu, Yi-Chang, Del Álamo, Juan C, Chiou, Arthur, and Lee, Oscar K

Abstract

Cellular biophysical properties are novel biomarkers of cell phenotypes which may reflect the status of differentiating stem cells. Accurate characterizations of cellular biophysical properties, in conjunction with the corresponding biochemical properties could help to distinguish stem cells from primary cells, cancer cells, and differentiated cells. However, the correlated evolution of these properties in the course of directed stem cells differentiation has not been well characterized. In this study, we applied video particle tracking microrheology (VPTM) to measure intracellular viscoelasticity of differentiating human mesenchymal stromal/stem cells (hMSCs). Our results showed that osteogenesis not only increased both elastic and viscous moduli, but also converted the intracellular viscoelasticity of differentiating hMSCs from viscous-like to elastic-like. In contrast, adipogenesis decreased both elastic and viscous moduli while hMSCs remained viscous-like during the differentiation. In conjunction with bio- chemical and physical parameters, such as gene expression profiles, cell morphology, and cytoskeleton arrangement, we demonstrated that VPTM is a unique approach to quantify, with high data throughput, the maturation level of differentiating hMSCs and to anticipate their fate decisions. This approach is well suited for time-lapsed study of the mechanobiology of differentiating stem cells especially in three dimensional physico-chemical biomimetic environments including porous scaffolds.

Published
2016

41. A Microfluidic Circulatory System Integrated with Capillary-assisted Pressure Sensors

Author

Chen, Yangfan CHEM, Chan, Ho Nam, Michael, Sean A., Shen, Yusheng, Chen, Yin, Tian, Qian, Huang, Lu, Wu, Hongkai, Chen, Yangfan CHEM, Chan, Ho Nam, Michael, Sean A., Shen, Yusheng, Chen, Yin, Tian, Qian, Huang, Lu, and Wu, Hongkai

Abstract

The human circulatory system comprises a complex network of blood vessels interconnecting biologically relevant organs and a heart driving blood recirculation throughout this system. Recreating this system in vitro would act as a bridge between organ-on-a-chip and “body-on-a-chip” and advance the development of in vitro models. Here, we present a microfluidic circulatory system integrated with an on-chip pressure sensor to closely mimic human systemic circulation in vitro. A cardiac-like on-chip pumping system is incorporated in the device. It consists of four pumping units and passive check valves, which mimic the four heart chambers and heart valves, respectively. Each pumping unit is independently controlled with adjustable pressure and pump rate, enabling users to control the mimicked blood pressure and heartbeat rate within the device. A check valve is located downstream of each pumping unit to prevent backward leakage. Pulsatile and unidirectional flow can be generated to recirculate within the device by programming the four pumping units. We also report an on-chip capillary-assisted pressure sensor to monitor the pressure inside the device. One end of the capillary was placed in the measurement region, while the other end was sealed. Time-dependent pressure changes were measured by recording the movement of the liquid-gas interface in the capillary and calculating the pressure using the ideal gas law. The sensor covered the physiologically relevant blood pressure range found in humans (0-142.5 mmHg) and could respond to 0.2 s actuation time. With the aid of the sensor, the pressure inside the device could be adjusted to the desired range. As a proof of concept, human normal left ventricular and arterial pressure profiles were mimicked inside this device. Human umbilical vein endothelial cells (HUVECs) were cultured on chip and cells can respond to mechanical forces generated by arterial-like flow patterns. © The Royal Society of Chemistry.

Published
2017

42. Applications of Smart Microfluidic Systems in Tissue Engineering

Author

Chen, Yin, Huang, Lu, Ren, Kangning, Shi, Xuetao, Wu, Hongkai, Chen, Yin, Huang, Lu, Ren, Kangning, Shi, Xuetao, and Wu, Hongkai

Abstract

In this chapter, we firstly present the concept of microfluidics and a general scope of its applications in biomedical science and engineering. Then we introduce the topic of this chapter: smart microfluidic systems in tissue engineering. Unlike conventional microfluidic devices, this sort of system possesses unique functions that are not owned by them. As a result, they are emerging as new tools in this field. In detail, we list some intriguing smart microfluidic systems and describe their applications in tissue engineering based on the type of stimuli they respond to.

Published
2017

43. A Microfluidic Circulatory System Integrated with Capillary-assisted Pressure Sensors

Author

Chen, Yangfan, Chan, Ho Nam, Michael, Sean A., Shen, Yusheng, Chen, Yin, Tian, Qian, Huang, Lu, Wu, Hongkai, Chen, Yangfan, Chan, Ho Nam, Michael, Sean A., Shen, Yusheng, Chen, Yin, Tian, Qian, Huang, Lu, and Wu, Hongkai

Abstract

The human circulatory system comprises a complex network of blood vessels interconnecting biologically relevant organs and a heart driving blood recirculation throughout this system. Recreating this system in vitro would act as a bridge between organ-on-a-chip and “body-on-a-chip” and advance the development of in vitro models. Here, we present a microfluidic circulatory system integrated with an on-chip pressure sensor to closely mimic human systemic circulation in vitro. A cardiac-like on-chip pumping system is incorporated in the device. It consists of four pumping units and passive check valves, which mimic the four heart chambers and heart valves, respectively. Each pumping unit is independently controlled with adjustable pressure and pump rate, enabling users to control the mimicked blood pressure and heartbeat rate within the device. A check valve is located downstream of each pumping unit to prevent backward leakage. Pulsatile and unidirectional flow can be generated to recirculate within the device by programming the four pumping units. We also report an on-chip capillary-assisted pressure sensor to monitor the pressure inside the device. One end of the capillary was placed in the measurement region, while the other end was sealed. Time-dependent pressure changes were measured by recording the movement of the liquid-gas interface in the capillary and calculating the pressure using the ideal gas law. The sensor covered the physiologically relevant blood pressure range found in humans (0-142.5 mmHg) and could respond to 0.2 s actuation time. With the aid of the sensor, the pressure inside the device could be adjusted to the desired range. As a proof of concept, human normal left ventricular and arterial pressure profiles were mimicked inside this device. Human umbilical vein endothelial cells (HUVECs) were cultured on chip and cells can respond to mechanical forces generated by arterial-like flow patterns. © The Royal Society of Chemistry.

Published
2017

44. INDIGO-DataCloud:A data and computing platform to facilitate seamless access to e-infrastructures

Author

Collaboration, INDIGO-DataCloud, Salomoni, Davide, Campos, Isabel, Gaido, Luciano, de Lucas, Jesus Marco, Solagna, Peter, Gomes, Jorge, Matyska, Ludek, Fuhrman, Patrick, Hardt, Marcus, Donvito, Giacinto, Dutka, Lukasz, Plociennik, Marcin, Barbera, Roberto, Blanquer, Ignacio, Ceccanti, Andrea, David, Mario, Duma, Cristina, López-García, Alvaro, Moltó, Germán, Orviz, Pablo, Sustr, Zdenek, Viljoen, Matthew, Aguilar, Fernando, Alves, Luis, Antonacci, Marica, Antonelli, Lucio Angelo, Bagnasco, Stefano, Bonvin, Alexandre M. J. J., Bruno, Riccardo, Cetinic, Eva, Chen, Yin, Chiarello, Fabrizio, Costa, Alessandro, Pra, Stefano Dal, Davidovic, Davor, Dorigo, Alvise, Ertl, Benjamin, Fanzago, Federica, Fargetta, Marco, Fiore, Sandro, Gallozzi, Stefano, Kurkcuoglu, Zeynep, Lloret, Lara, Martins, Joao, Nuzzo, Alessandra, Nassisi, Paola, Palazzo, Cosimo, Pina, Joao, Sciacca, Eva, Segatta, Matteo, Sgaravatto, Massimo, Spiga, Daniele, Taneja, Sonia, Tangaro, Marco Antonio, Urbaniak, Michal, Vallero, Sara, Verlato, Marco, Wegh, Bas, Zaccolo, Valentina, Zambelli, Federico, Zangrando, Lisa, Zani, Stefano, Zok, Tomasz, Collaboration, INDIGO-DataCloud, Salomoni, Davide, Campos, Isabel, Gaido, Luciano, de Lucas, Jesus Marco, Solagna, Peter, Gomes, Jorge, Matyska, Ludek, Fuhrman, Patrick, Hardt, Marcus, Donvito, Giacinto, Dutka, Lukasz, Plociennik, Marcin, Barbera, Roberto, Blanquer, Ignacio, Ceccanti, Andrea, David, Mario, Duma, Cristina, López-García, Alvaro, Moltó, Germán, Orviz, Pablo, Sustr, Zdenek, Viljoen, Matthew, Aguilar, Fernando, Alves, Luis, Antonacci, Marica, Antonelli, Lucio Angelo, Bagnasco, Stefano, Bonvin, Alexandre M. J. J., Bruno, Riccardo, Cetinic, Eva, Chen, Yin, Chiarello, Fabrizio, Costa, Alessandro, Pra, Stefano Dal, Davidovic, Davor, Dorigo, Alvise, Ertl, Benjamin, Fanzago, Federica, Fargetta, Marco, Fiore, Sandro, Gallozzi, Stefano, Kurkcuoglu, Zeynep, Lloret, Lara, Martins, Joao, Nuzzo, Alessandra, Nassisi, Paola, Palazzo, Cosimo, Pina, Joao, Sciacca, Eva, Segatta, Matteo, Sgaravatto, Massimo, Spiga, Daniele, Taneja, Sonia, Tangaro, Marco Antonio, Urbaniak, Michal, Vallero, Sara, Verlato, Marco, Wegh, Bas, Zaccolo, Valentina, Zambelli, Federico, Zangrando, Lisa, Zani, Stefano, and Zok, Tomasz

Abstract

This paper describes the achievements of the H2020 project INDIGO-DataCloud. The project has provided e-infrastructures with tools, applications and cloud framework enhancements to manage the demanding requirements of scientific communities, either locally or through enhanced interfaces. The middleware developed allows to federate hybrid resources, to easily write, port and run scientific applications to the cloud. In particular, we have extended existing PaaS (Platform as a Service) solutions, allowing public and private e-infrastructures, including those provided by EGI, EUDAT, and Helix Nebula, to integrate their existing services and make them available through AAI services compliant with GEANT interfederation policies, thus guaranteeing transparency and trust in the provisioning of such services. Our middleware facilitates the execution of applications using containers on Cloud and Grid based infrastructures, as well as on HPC clusters. Our developments are freely downloadable as open source components, and are already being integrated into many scientific applications., Comment: 39 pages, 15 figures.Version accepted in Journal of Grid Computing

Published
2017
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45. Freestanding 3-D Microvascular Networks Made of Alginate Hydrogel as a Universal Tool to Create Microchannels inside Hydrogels

Author

Hu, Chong, Sun, Han, Liu, Zhengzhi, Chen, Yin, Chen, Yangfan, Wu, Hongkai, Ren, Kangning, Hu, Chong, Sun, Han, Liu, Zhengzhi, Chen, Yin, Chen, Yangfan, Wu, Hongkai, and Ren, Kangning

Abstract

The diffusion of molecules such as nutrients and oxygen through densely packed cells is impeded by blockage and consumption by cells, resulting in a limited depth of penetration. This has been a major hurdle to a bulk (3-D) culture. Great efforts have been made to develop methods for generating branched microchannels inside hydrogels to support mass exchange inside a bulk culture. These previous attempts faced a common obstacle: Researchers tried to fabricate microchannels with gels already loaded with cells, but the fabrication procedures are often harmful to the embedded cells. Herein, we present a universal strategy to create microchannels in different types of hydrogels, which effectively avoids cell damage. This strategy is based on a freestanding alginate 3-D microvascular network prepared by in-situ generation of copper ions from a sacrificial copper template. This alginate network could be used as implants to create microchannels inside different types of hydrogels. This approach effectively addresses the issue of cell damage during microfabrication and made it possible to create microchannels inside different types of gels. The microvascular network produced with this method is (1) strong enough to allow handling, (2) biocompatible to allow cell culturing, and (3) appropriately permeable to allow diffusion of small molecules, while sufficiently dense to prevent blocking of channels when embedded in different types of gels. In addition, composite microtubules could be prepared by simply pre-loading other materials, e.g., particles and large biomolecules, in the hydrogel. Compared with other potential strategies to fabricate freestanding gel channel networks, our method is more rapid, low-cost and scalable due to parallel processing using an industrially massproducible template. We demonstrated the use of such vascular networks in creating microchannels in different hydrogels and composite gels, as well as with a cell culture in a nutrition gradient based on

Published
2016

46. Simple, Cost-Effective 3D Printed Microfluidic Components for Disposable, Point-of-Care Colorimetric Analysis

Author

Chan, Ho Nam, Shu, Yiwei, Xiong, Bin, Chen, Yangfan, Chen, Yin, Tian, Qian, Michael, Sean Alan, Shen Bo, Wu Hongkai, Chan, Ho Nam, Shu, Yiwei, Xiong, Bin, Chen, Yangfan, Chen, Yin, Tian, Qian, Michael, Sean Alan, Shen Bo, and Wu Hongkai

Abstract

The fabrication of microfluidic chips can be simplified and accelerated by three-dimensional (3D) printing. However, all of the current designs of 3D printed microchips require off-chip bulky equipment to operate, which hindered their applications in the point-of-care (POC) setting. In this work, we demonstrate a new class of movable 3D printed microfluidic chip components, including torque-actuated pump and valve, rotary valve, and pushing valve, which can be operated manually without any off-chip bulky equipment such as syringe pump and gas pressure source. By integrating these components, we developed a user-friendly 3D printed chip that can perform general colorimetric assays. Protein quantification was performed on artificial urine samples as a proof-of-concept model with a smartphone used as the imaging platform. The protein was quantified linearly and was within the physiologically relevant range for humans. We believe that the demonstrated components and designs can expand the functionalities and potential applications of 3D printed microfluidic chip and thus provoke more investigation on manufacturing lab-on-a-chip devices by 3D printers.

Published
2016

47. Replicating 3D Printed Structures into Hydrogels

Author

Chan, Ho Nam, Shu, Yiwei, Tian, Qian, Chen, Yangfan, Chen, Yin, Wu, Hongkai, Chan, Ho Nam, Shu, Yiwei, Tian, Qian, Chen, Yangfan, Chen, Yin, and Wu, Hongkai

Abstract

Fabricating complicated three-dimensional (3D) hydrogel structures are important in biological studies. Herein, stereolithographic printed acrylate-based masters with different complicated 3D geometry (e.g. dodecahedron and a trifurcating network) were replicated into alginate and gelatin. Alginate was further used as a sacrificial template to fabricate a perfusable microfluidic network in cell-seeded agarose to sustain the cell viability in a large slab of agarose scaffold. With the replication approach, 3D alginate (a photo-insensitive material) constructs with stereolithographic (a photolithographic technology) grade resolution and structural complexity were fabricated. © 2016 The Royal Society of Chemistry.

Published
2016

48. Fast Single-Cell Patterning for Study of Drug-Induced Phenotypic Alterations of HeLa Cells Using Time-of-Flight Secondary Ion Mass Spectrometry

Author

Huang, Lu CHEM, Chen, Yin, Weng, Lu-Tao, Leung, Mark, Xing, Xiaoxing, Fan, Zhiyong, Wu, Hongkai, Huang, Lu CHEM, Chen, Yin, Weng, Lu-Tao, Leung, Mark, Xing, Xiaoxing, Fan, Zhiyong, and Wu, Hongkai

Abstract

A facile single-cell patterning (ScP) method was developed and integrated with time-of-flight secondary ion mass spectrometry (TOF-SIMS) for the study of drug-induced cellular phenotypic alterations. Micropatterned poly-(dimethylsiloxane) (PDMS) stencil film and centrifugation assisted cell trapping were combined for the preparation of on surface single-cell microarrays, which exhibited both high site occupancy (>90%) and single-cell resolution (>97%). TOF-SIMS is a surface-sensitive mass spectrometry and is increasingly utilized in biological studies. Here we demonstrated, for the first time, its successful application in high throughput single-cell analysis. Drug-induced phenotypic alterations of HeLa cells in the early stage of apoptosis were investigated using TOF-SIMS. The major molecular sources of variations were analyzed by principle component analysis (PCA).

Published
2016

49. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Author

Klionsky, Daniel J., Abdelmohsen, Kotb, Abe, Akihisa, Abedin, Md Joynal, Abeliovich, Hagai, Arozena, Abraham Acevedo, Adachi, Hiroaki, Adams, Christopher M., Adams, Peter D., Adeli, Khosrow, Adhihetty, Peter J., Adler, Sharon G., Agam, Galila, Agarwal, Rajesh, Aghi, Manish K., Agnello, Maria, Agostinis, Patrizia, Aguilar, Patricia V., Aguirre-Ghiso, Julio, Airoldi, Edoardo M., Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akporiaye, Emmanuel T., Al-Rubeai, Mohamed, Albaiceta, Guillermo M., Albanese, Chris, Albani, Diego, Albert, Matthew L., Aldudo, Jesus, Alguel, Hana, Alirezaei, Mehrdad, Alloza, Iraide, Almasan, Alexandru, Almonte-Beceril, Maylin, Alnemri, Emad S., Alonso, Covadonga, Altan-Bonnet, Nihal, Altieri, Dario C., Alvarez, Silvia, Alvarez-Erviti, Lydia, Alves, Sandro, Amadoro, Giuseppina, Amano, Atsuo, Amantini, Consuelo, Ambrosio, Santiago, Amelio, Ivano, Amer, Amal O., Amessou, Mohamed, Amon, Angelika, An, Zhenyi, Anania, Frank A., Andersen, Stig U., Andley, Usha P., Andreadi, Catherine K., Andrieu-Abadie, Nathalie, Anel, Alberto, Ann, David K., Anoopkumar-Dukie, Shailendra, Antonioli, Manuela, Aoki, Hiroshi, Apostolova, Nadezda, Aquila, Saveria, Aquilano, Katia, Araki, Koichi, Arama, Eli, Aranda, Agustin, Araya, Jun, Arcaro, Alexandre, Arias, Esperanza, Arimoto, Hirokazu, Ariosa, Aileen R., Armstrong, Jane L., Arnould, Thierry, Arsov, Ivica, Asanuma, Katsuhiko, Askanas, Valerie, Asselin, Eric, Atarashi, Ryuichiro, Atherton, Sally S., Atkin, Julie D., Attardi, Laura D., Auberger, Patrick, Auburger, Georg, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Avantaggiati, Maria Laura, Avrahami, Limor, Awale, Suresh, Azad, Neelam, Bachetti, Tiziana, Backer, Jonathan M., Bae, Dong-Hun, Bae, Jae-Sung, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric H., Baek, Seung-Hoon, Baghdiguian, Stephen, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xue-Yuan, Bailly, Yannick, Balaji, Kithiganahalli Narayanaswamy, Balduini, Walter, Ballabio, Andrea, Balzan, Rena, Banerjee, Rajkumar, Banhegyi, Gabor, Bao, Haijun, Barbeau, Benoit, Barrachina, Maria D., Barreiro, Esther, Bartel, Bonnie, Bartolome, Alberto, Bassham, Diane C., Bassi, Maria Teresa, Bast, Robert C., Jr., Basu, Alakananda, Batista, Maria Teresa, Batoko, Henri, Battino, Maurizio, Bauckman, Kyle, Baumgarner, Bradley L., Bayer, K. Ulrich, Beale, Rupert, Beaulieu, Jean-Francois, Beck, George R., Jr., Becker, Christoph, Beckham, J. David, Bedard, Pierre-Andre, Bednarski, Patrick J., Begley, Thomas J., Behl, Christian, Behrends, Christian, Behrens, Georg M. N., Behrns, Kevin E., Bejarano, Eloy, Belaid, Amine, Belleudi, Francesca, Benard, Giovanni, Berchem, Guy, Bergamaschi, Daniele, Bergami, Matteo, Berkhout, Ben, Berliocchi, Laura, Bernard, Amelie, Bernard, Monique, Bernassola, Francesca, Bertolotti, Anne, Bess, Amanda S., Besteiro, Sebastien, Bettuzzi, Saverio, Bhalla, Savita, Bhattacharyya, Shalmoli, Bhutia, Sujit K., Biagosch, Caroline, Bianchi, Michele Wolfe, Biard-Piechaczyk, Martine, Billes, Viktor, Bincoletto, Claudia, Bingol, Baris, Bird, Sara W., Bitoun, Marc, Bjedov, Ivana, Blackstone, Craig, Blanc, Lionel, Blanco, Guillermo A., Blomhoff, Heidi Kiil, Boada-Romero, Emilio, Boeckler, Stefan, Boes, Marianne, Boesze-Battaglia, Kathleen, Boise, Lawrence H., Bolino, Alessandra, Boman, Andrea, Bonaldo, Paolo, Bordi, Matteo, Bosch, Jurgen, Botana, Luis M., Botti, Joelle, Bou, German, Bouche, Marina, Bouchecareilh, Marion, Boucher, Marie-Josee, Boulton, Michael E., Bouret, Sebastien G., Boya, Patricia, Boyer-Guittaut, Michaeel, Bozhkov, Peter V., Brady, Nathan, Braga, Vania M. M., Brancolini, Claudio, Braus, Gerhard H., Bravo-San Pedro, Jose M., Brennan, Lisa A., Bresnick, Emery H., Brest, Patrick, Bridges, Dave, Bringer, Marie-Agnes, Brini, Marisa, Brito, Glauber C., Brodin, Bertha, Brookes, Paul S., Brown, Eric J., Brown, Karen, Broxmeyer, Hal E., Bruhat, Alain, Brum, Patricia Chakur, Brumell, John H., Brunetti-Pierri, Nicola, Bryson-Richardson, Robert J., Buch, Shilpa, Buchan, Alastair M., Budak, Hikmet, Bulavin, Dmitry V., Bultman, Scott J., Bultynck, Geert, Bumbasirevic, Vladimir, Burelle, Yan, Burke, Robert E., Burmeister, Margit, Buetikofer, Peter, Caberlotto, Laura, Cadwell, Ken, Cahova, Monika, Cai, Dongsheng, Cai, Jingjing, Cai, Qian, Calatayud, Sara, Camougrand, Nadine, Campanella, Michelangelo, Campbell, Grant R., Campbell, Matthew, Campello, Silvia, Candau, Robin, Caniggia, Isabella, Cantoni, Lavinia, Cao, Lizhi, Caplan, Allan B., Caraglia, Michele, Cardinali, Claudio, Cardoso, Sandra Morais, Carew, Jennifer S., Carleton, Laura A., Carlin, Cathleen R., Carloni, Silvia, Carlsson, Sven R., Carmona-Gutierrez, Didac, Carneiro, Leticia A. M., Carnevali, Oliana, Carra, Serena, Carrier, Alice, Carroll, Bernadette, Casas, Caty, Casas, Josefina, Cassinelli, Giuliana, Castets, Perrine, Castro-Obregon, Susana, Cavallini, Gabriella, Ceccherini, Isabella, Cecconi, Francesco, Cederbaum, Arthur I., Cena, Valentin, Cenci, Simone, Cerella, Claudia, Cervia, Davide, Cetrullo, Silvia, Chaachouay, Hassan, Chae, Han-Jung, Chagin, Andrei S., Chai, Chee-Yin, Chakrabarti, Gopal, Chamilos, Georgios, Chan, Edmond Y. W., Chan, Matthew T. V., Chandra, Dhyan, Chandra, Pallavi, Chang, Chih-Peng, Chang, Raymond Chuen-Chung, Chang, Ta Yuan, Chatham, John C., Chatterjee, Saurabh, Chauhan, Santosh, Che, Yongsheng, Cheetham, Michael E., Cheluvappa, Rajkumar, Chen, Chun-Jung, Chen, Gang, Chen, Guang-Chao, Chen, Guoqiang, Chen, Hongzhuan, Chen, Jeff W., Chen, Jian-Kang, Chen, Min, Chen, Mingzhou, Chen, Peiwen, Chen, Qi, Chen, Quan, Chen, Shang-Der, Chen, Si, Chen, Steve S-L, Chen, Wei, Chen, Wei-Jung, Chen, Wen Qiang, Chen, Wenli, Chen, Xiangmei, Chen, Yau-Hung, Chen, Ye-Guang, Chen, Yin, Chen, Yingyu, Chen, Yongshun, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Yujie, Chen, Zhen, Chen, Zhong, Cheng, Alan, Cheng, Christopher H. K., Cheng, Hua, Cheong, Heesun, Cherry, Sara, Chesney, Jason, Cheung, Chun Hei Antonio, Chevet, Eric, Chi, Hsiang Cheng, Chi, Sung-Gil, Chiacchiera, Fulvio, Chiang, Hui-Ling, Chiarelli, Roberto, Chiariello, Mario, Chieppa, Marcello, Chin, Lih-Shen, Chiong, Mario, Chiu, Gigi N. C., Cho, Dong-Hyung, Cho, Ssang-Goo, Cho, William C., Cho, Yong-Yeon, Cho, Young-Seok, Choi, Augustine M. K., Choi, Eui-Ju, Choi, Eun-Kyoung, Choi, Jayoung, Choi, Mary E., Choi, Seung-Il, Chou, Tsui-Fen, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chow, Kuan-Chih, Chowdhury, Kamal, Chu, Charleen T., Chuang, Tsung-Hsien, Chun, Taehoon, Chung, Hyewon, Chung, Taijoon, Chung, Yuen-Li, Chwae, Yong-Joon, Cianfanelli, Valentina, Ciarcia, Roberto, Ciechomska, Iwona A., Ciriolo, Maria Rosa, Cirone, Mara, Claerhout, Sofie, Clague, Michael J., Claria, Joan, Clarke, Peter G. H., Clarke, Robert, Clementi, Emilio, Cleyrat, Cedric, Cnop, Miriam, Coccia, Eliana M., Cocco, Tiziana, Codogno, Patrice, Coers, Joern, Cohen, Ezra E. W., Colecchia, David, Coletto, Luisa, Coll, Nuria S., Colucci-Guyon, Emma, Comincini, Sergio, Condello, Maria, Cook, Katherine L., Coombs, Graham H., Cooper, Cynthia D., Cooper, J. Mark, Coppens, Isabelle, Corasaniti, Maria Tiziana, Corazzari, Marco, Corbalan, Ramon, Corcelle-Termeau, Elisabeth, Cordero, Mario D., Corral-Ramos, Cristina, Corti, Olga, Cossarizza, Andrea, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Cottet, Sandra, Couve, Eduardo, Covey, Lori R., Cowart, L. Ashley, Cox, Jeffery S., Coxon, Fraser P., Coyne, Carolyn B., Cragg, Mark S., Craven, Rolf J., Crepaldi, Tiziana, Crespo, Jose L., Criollo, Alfredo, Crippa, Valeria, Cruz, Maria Teresa, Cuervo, Ana Maria, Cuezva, Jose M., Cui, Taixing, Cutillas, Pedro R., Czaja, Mark J., Czyzyk-Krzeska, Maria F., Dagda, Ruben K., Dahmen, Uta, Dai, Chunsun, Dai, Wenjie, Dai, Yun, Dalby, Kevin N., Valle, Luisa Dalla, Dalmasso, Guillaume, D'Amelio, Marcello, Damme, Markus, Darfeuille-Michaud, Arlette, Dargemont, Catherine, Darley-Usmar, Victor M., Dasarathy, Srinivasan, Dasgupta, Biplab, Dash, Srikanta, Dass, Crispin R., Davey, Hazel Marie, Davids, Lester M., Davila, David, Davis, Roger J., Dawson, Ted M., Dawson, Valina L., Daza, Paula, de Belleroche, Jackie, de Figueiredo, Paul, Bressan Queiroz de Figueiredo, Regina Celia, de la Fuente, Jose, De Martino, Luisa, De Matteis, Antonella, De Meyer, Guido R. Y., De Milito, Angelo, De Santi, Mauro, de Souza, Wanderley, De Tata, Vincenzo, De Zio, Daniela, Debnath, Jayanta, Dechant, Reinhard, Decuypere, Jean-Paul, Deegan, Shane, Dehay, Benjamin, Del Bello, Barbara, Del Re, Dominic P., Delage-Mourroux, Regis, Delbridge, Lea M. D., Deldicque, Louise, Delorme-Axford, Elizabeth, Deng, Yizhen, Dengjel, Joern, Denizot, Melanie, Dent, Paul, Der, Channing J., Deretic, Vojo, Derrien, Benoit, Deutsch, Eric, Devarenne, Timothy P., Devenish, Rodney J., Di Bartolomeo, Sabrina, Di Daniele, Nicola, Di Domenico, Fabio, Di Nardo, Alessia, Di Paola, Simone, Di Pietro, Antonio, Di Renzo, Livia, DiAntonio, Aaron, Diaz-Araya, Guillermo, Diaz-Laviada, Ines, Diaz-Meco, Maria T., Diaz-Nido, Javier, Dickey, Chad A., Dickson, Robert C., Diederich, Marc, Digard, Paul, Dikic, Ivan, Dinesh-Kumar, Savithrama P., Ding, Chan, Ding, Wen-Xing, Ding, Zufeng, Dini, Luciana, Distler, Joerg H. W., Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dmytruk, Kostyantyn, Dobson, Renwick C. J., Doetsch, Volker, Dokladny, Karol, Dokudovskaya, Svetlana, Donadelli, Massimo, Dong, X. Charlie, Dong, Xiaonan, Dong, Zheng, Donohue, Terrence M., Jr., Doran, Kelly S., D'Orazi, Gabriella, Dorn, Gerald W., II, Dosenko, Victor, Dridi, Sami, Drucker, Liat, Du, Jie, Du, Li-Lin, Du, Lihuan, du Toit, Andre, Dua, Priyamvada, Duan, Lei, Duann, Pu, Dubey, Vikash Kumar, Duchen, Michael R., Duchosal, Michel A., Duez, Helene, Dugail, Isabelle, Dumit, Veronica I., Duncan, Mara C., Dunlop, Elaine A., Dunn, William A., Jr., Dupont, Nicolas, Dupuis, Luc, Duran, Raul V., Durcan, Thomas M., Duvezin-Caubet, Stephane, Duvvuri, Umamaheswar, Eapen, Vinay, Ebrahimi-Fakhari, Darius, Echard, Arnaud, Eckhart, Leopold, Edelstein, Charles L., Edinger, Aimee L., Eichinger, Ludwig, Eisenberg, Tobias, Eisenberg-Lerner, Avital, Eissa, N. Tony, El-Deiry, Wafik S., El-Khoury, Victoria, Elazar, Zvulun, Eldar-Finkelman, Hagit, Elliott, Chris J. H., Emanuele, Enzo, Emmenegger, Urban, Engedal, Nikolai, Engelbrecht, Anna-Mart, Engelender, Simone, Enserink, Jorrit M., Erdmann, Ralf, Erenpreisa, Jekaterina, Eri, Rajaraman, Eriksen, Jason L., Erman, Andreja, Escalante, Ricardo, Eskelinen, Eeva-Liisa, Espert, Lucile, Esteban-Martinez, Lorena, Evans, Thomas J., Fabri, Mario, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Faergeman, Nils J., Faggioni, Alberto, Fairlie, W. 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S., Ichihara, Atsuhiro, Imai, Yuzuru, Imbriano, Carol, Inomata, Megumi, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L., Iozzo, Renato V., Ip, Nancy Y., Irazoqui, Javier E., Iribarren, Pablo, Isaka, Yoshitaka, Isakovic, Aleksandra J., Ischiropoulos, Harry, Isenberg, Jeffrey S., Ishaq, Mohammad, Ishida, Hiroyuki, Ishii, Isao, Ishmael, Jane E., Isidoro, Ciro, Isobe, Ken-ichi, Isono, Erika, Issazadeh-Navikas, Shohreh, Itahana, Koji, Itakura, Eisuke, Ivanov, Andrei I., Iyer, Anand Krishnan V., Izquierdo, Jose M., Izumi, Yotaro, Izzo, Valentina, Jaeaettelae, Marja, Jaber, Nadia, Jackson, Daniel John, Jackson, William T., Jacob, Tony George, Jacques, Thomas S., Jagannath, Chinnaswamy, Jain, Ashish, Jana, Nihar Ranjan, Jang, Byoung Kuk, Jani, Alkesh, Janji, Bassam, Jannig, Paulo Roberto, Jansson, Patric J., Jean, Steve, Jendrach, Marina, Jeon, Ju-Hong, Jessen, Niels, Jeung, Eui-Bae, Jia, Kailiang, Jia, Lijun, Jiang, Hong, Jiang, Hongchi, Jiang, Liwen, Jiang, Teng, Jiang, Xiaoyan, Jiang, Xuejun, Jiang, Ying, Jiang, Yongjun, Jimenez, Alberto, Jin, Cheng, Jin, Hongchuan, Jin, Lei, Jin, Meiyan, Jin, Shengkan, Jinwal, Umesh Kumar, Jo, Eun-Kyeong, Johansen, Terje, Johnson, Daniel E., Johnson, Gail V. 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Hande, Ozpolat, Bulent, Pacelli, Consiglia, Paganetti, Paolo, Page, Guylene, Pages, Gilles, Pagnini, Ugo, Pajak, Beata, Pak, Stephen C., Pakos-Zebrucka, Karolina, Pakpour, Nazzy, Palkova, Zdena, Palladino, Francesca, Pallauf, Kathrin, Pallet, Nicolas, Palmieri, Marta, Paludan, Soren R., Palumbo, Camilla, Palumbo, Silvia, Pampliega, Olatz, Pan, Hongming, Pan, Wei, Panaretakis, Theocharis, Pandey, Aseem, Pantazopoulou, Areti, Papackova, Zuzana, Papademetrio, Daniela L., Papassideri, Issidora, Papini, Alessio, Parajuli, Nirmala, Pardo, Julian, Parekh, Vrajesh V., Parenti, Giancarlo, Park, Jong-In, Park, Junsoo, Park, Ohkmae K., Parker, Roy, Parlato, Rosanna, Parys, Jan B., Parzych, Katherine R., Pasquet, Jean-Max, Pasquier, Benoit, Pasumarthi, Kishore B. S., Patschan, Daniel, Patterson, Cam, Pattingre, Sophie, Pattison, Scott, Pause, Arnim, Pavenstaedt, Hermann, Pavone, Flaminia, Pedrozo, Zully, Pena, Fernando J., Penalva, Miguel A., Pende, Mario, Peng, Jianxin, Penna, Fabio, Penninger, Josef M., Pensalfini, Anna, Pepe, Salvatore, Pereira, Gustavo J. S., Pereira, Paulo C., Perez-de la Cruz, Veronica, Esther Perez-Perez, Maria, Perez-Rodriguez, Diego, Perez-Sala, Dolores, Perier, Celine, Perl, Andras, Perlmutter, David H., Perrotta, Ida, Pervaiz, Shazib, Pesonen, Maija, Pessin, Jeffrey E., Peters, Godefridus J., Petersen, Morten, Petrache, Irina, Petrof, Basil J., Petrovski, Goran, Phang, James M., Piacentini, Mauro, Pierdominici, Marina, Pierre, Philippe, Pierrefite-Carle, Valerie, Pietrocola, Federico, Pimentel-Muinos, Felipe X., Pinar, Mario, Pineda, Benjamin, Pinkas-Kramarski, Ronit, Pinti, Marcello, Pinton, Paolo, Piperdi, Bilal, Piret, James M., Platanias, Leonidas C., Platta, Harald W., Plowey, Edward D., Poggeler, Stefanie, Poirot, Marc, Polcic, Peter, Poletti, Angelo, Poon, Audrey H., Popelka, Hana, Popova, Blagovesta, Poprawa, Izabela, Poulose, Shibu M., Poulton, Joanna, Powers, Scott K., Powers, Ted, Pozuelo-Rubio, Mercedes, Prak, Krisna, Prange, Reinhild, Prescott, Mark, Priault, Muriel, Prince, Sharon, Proia, Richard L., Proikas-Cezanne, Tassula, Prokisch, Holger, Promponas, Vasilis J., Przyklenk, Karin, Puertollano, Rosa, Pugazhenthi, Subbiah, Puglielli, Luigi, Pujol, Aurora, Puyal, Julien, Pyeon, Dohun, Qi, Xin, Qian, Wen-bin, Qin, Zheng-Hong, Qiu, Yu, Qu, Ziwei, Quadrilatero, Joe, Quinn, Frederick, Raben, Nina, Rabinowich, Hannah, Radogna, Flavia, Ragusa, Michael J., Rahmani, Mohamed, Raina, Komal, Ramanadham, Sasanka, Ramesh, Rajagopal, Rami, Abdelhaq, Randall-Demllo, Sarron, Randow, Felix, Rao, Hai, Rao, V. 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N., Behrns, Kevin E., Bejarano, Eloy, Belaid, Amine, Belleudi, Francesca, Benard, Giovanni, Berchem, Guy, Bergamaschi, Daniele, Bergami, Matteo, Berkhout, Ben, Berliocchi, Laura, Bernard, Amelie, Bernard, Monique, Bernassola, Francesca, Bertolotti, Anne, Bess, Amanda S., Besteiro, Sebastien, Bettuzzi, Saverio, Bhalla, Savita, Bhattacharyya, Shalmoli, Bhutia, Sujit K., Biagosch, Caroline, Bianchi, Michele Wolfe, Biard-Piechaczyk, Martine, Billes, Viktor, Bincoletto, Claudia, Bingol, Baris, Bird, Sara W., Bitoun, Marc, Bjedov, Ivana, Blackstone, Craig, Blanc, Lionel, Blanco, Guillermo A., Blomhoff, Heidi Kiil, Boada-Romero, Emilio, Boeckler, Stefan, Boes, Marianne, Boesze-Battaglia, Kathleen, Boise, Lawrence H., Bolino, Alessandra, Boman, Andrea, Bonaldo, Paolo, Bordi, Matteo, Bosch, Jurgen, Botana, Luis M., Botti, Joelle, Bou, German, Bouche, Marina, Bouchecareilh, Marion, Boucher, Marie-Josee, Boulton, Michael E., Bouret, Sebastien G., Boya, Patricia, Boyer-Guittaut, Michaeel, Bozhkov, Peter V., Brady, Nathan, Braga, Vania M. 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V., Chandra, Dhyan, Chandra, Pallavi, Chang, Chih-Peng, Chang, Raymond Chuen-Chung, Chang, Ta Yuan, Chatham, John C., Chatterjee, Saurabh, Chauhan, Santosh, Che, Yongsheng, Cheetham, Michael E., Cheluvappa, Rajkumar, Chen, Chun-Jung, Chen, Gang, Chen, Guang-Chao, Chen, Guoqiang, Chen, Hongzhuan, Chen, Jeff W., Chen, Jian-Kang, Chen, Min, Chen, Mingzhou, Chen, Peiwen, Chen, Qi, Chen, Quan, Chen, Shang-Der, Chen, Si, Chen, Steve S-L, Chen, Wei, Chen, Wei-Jung, Chen, Wen Qiang, Chen, Wenli, Chen, Xiangmei, Chen, Yau-Hung, Chen, Ye-Guang, Chen, Yin, Chen, Yingyu, Chen, Yongshun, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Yujie, Chen, Zhen, Chen, Zhong, Cheng, Alan, Cheng, Christopher H. K., Cheng, Hua, Cheong, Heesun, Cherry, Sara, Chesney, Jason, Cheung, Chun Hei Antonio, Chevet, Eric, Chi, Hsiang Cheng, Chi, Sung-Gil, Chiacchiera, Fulvio, Chiang, Hui-Ling, Chiarelli, Roberto, Chiariello, Mario, Chieppa, Marcello, Chin, Lih-Shen, Chiong, Mario, Chiu, Gigi N. C., Cho, Dong-Hyung, Cho, Ssang-Goo, Cho, William C., Cho, Yong-Yeon, Cho, Young-Seok, Choi, Augustine M. K., Choi, Eui-Ju, Choi, Eun-Kyoung, Choi, Jayoung, Choi, Mary E., Choi, Seung-Il, Chou, Tsui-Fen, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chow, Kuan-Chih, Chowdhury, Kamal, Chu, Charleen T., Chuang, Tsung-Hsien, Chun, Taehoon, Chung, Hyewon, Chung, Taijoon, Chung, Yuen-Li, Chwae, Yong-Joon, Cianfanelli, Valentina, Ciarcia, Roberto, Ciechomska, Iwona A., Ciriolo, Maria Rosa, Cirone, Mara, Claerhout, Sofie, Clague, Michael J., Claria, Joan, Clarke, Peter G. H., Clarke, Robert, Clementi, Emilio, Cleyrat, Cedric, Cnop, Miriam, Coccia, Eliana M., Cocco, Tiziana, Codogno, Patrice, Coers, Joern, Cohen, Ezra E. W., Colecchia, David, Coletto, Luisa, Coll, Nuria S., Colucci-Guyon, Emma, Comincini, Sergio, Condello, Maria, Cook, Katherine L., Coombs, Graham H., Cooper, Cynthia D., Cooper, J. Mark, Coppens, Isabelle, Corasaniti, Maria Tiziana, Corazzari, Marco, Corbalan, Ramon, Corcelle-Termeau, Elisabeth, Cordero, Mario D., Corral-Ramos, Cristina, Corti, Olga, Cossarizza, Andrea, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Cottet, Sandra, Couve, Eduardo, Covey, Lori R., Cowart, L. 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Y., De Milito, Angelo, De Santi, Mauro, de Souza, Wanderley, De Tata, Vincenzo, De Zio, Daniela, Debnath, Jayanta, Dechant, Reinhard, Decuypere, Jean-Paul, Deegan, Shane, Dehay, Benjamin, Del Bello, Barbara, Del Re, Dominic P., Delage-Mourroux, Regis, Delbridge, Lea M. D., Deldicque, Louise, Delorme-Axford, Elizabeth, Deng, Yizhen, Dengjel, Joern, Denizot, Melanie, Dent, Paul, Der, Channing J., Deretic, Vojo, Derrien, Benoit, Deutsch, Eric, Devarenne, Timothy P., Devenish, Rodney J., Di Bartolomeo, Sabrina, Di Daniele, Nicola, Di Domenico, Fabio, Di Nardo, Alessia, Di Paola, Simone, Di Pietro, Antonio, Di Renzo, Livia, DiAntonio, Aaron, Diaz-Araya, Guillermo, Diaz-Laviada, Ines, Diaz-Meco, Maria T., Diaz-Nido, Javier, Dickey, Chad A., Dickson, Robert C., Diederich, Marc, Digard, Paul, Dikic, Ivan, Dinesh-Kumar, Savithrama P., Ding, Chan, Ding, Wen-Xing, Ding, Zufeng, Dini, Luciana, Distler, Joerg H. W., Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dmytruk, Kostyantyn, Dobson, Renwick C. J., Doetsch, Volker, Dokladny, Karol, Dokudovskaya, Svetlana, Donadelli, Massimo, Dong, X. Charlie, Dong, Xiaonan, Dong, Zheng, Donohue, Terrence M., Jr., Doran, Kelly S., D'Orazi, Gabriella, Dorn, Gerald W., II, Dosenko, Victor, Dridi, Sami, Drucker, Liat, Du, Jie, Du, Li-Lin, Du, Lihuan, du Toit, Andre, Dua, Priyamvada, Duan, Lei, Duann, Pu, Dubey, Vikash Kumar, Duchen, Michael R., Duchosal, Michel A., Duez, Helene, Dugail, Isabelle, Dumit, Veronica I., Duncan, Mara C., Dunlop, Elaine A., Dunn, William A., Jr., Dupont, Nicolas, Dupuis, Luc, Duran, Raul V., Durcan, Thomas M., Duvezin-Caubet, Stephane, Duvvuri, Umamaheswar, Eapen, Vinay, Ebrahimi-Fakhari, Darius, Echard, Arnaud, Eckhart, Leopold, Edelstein, Charles L., Edinger, Aimee L., Eichinger, Ludwig, Eisenberg, Tobias, Eisenberg-Lerner, Avital, Eissa, N. Tony, El-Deiry, Wafik S., El-Khoury, Victoria, Elazar, Zvulun, Eldar-Finkelman, Hagit, Elliott, Chris J. H., Emanuele, Enzo, Emmenegger, Urban, Engedal, Nikolai, Engelbrecht, Anna-Mart, Engelender, Simone, Enserink, Jorrit M., Erdmann, Ralf, Erenpreisa, Jekaterina, Eri, Rajaraman, Eriksen, Jason L., Erman, Andreja, Escalante, Ricardo, Eskelinen, Eeva-Liisa, Espert, Lucile, Esteban-Martinez, Lorena, Evans, Thomas J., Fabri, Mario, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Faergeman, Nils J., Faggioni, Alberto, Fairlie, W. Douglas, Fan, Chunhai, Fan, Daping, Fan, Jie, Fang, Shengyun, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Faure, Mathias, Favier, Francois B., Fearnhead, Howard, Federici, Massimo, Fei, Erkang, Felizardo, Tania C., Feng, Hua, Feng, Yibin, Feng, Yuchen, Ferguson, Thomas A., Fernandez, Alvaro F., Fernandez-Barrena, Maite G., Fernandez-Checa, Jose C., Fernandez-Lopez, Arsenio, Fernandez-Zapico, Martin E., Feron, Olivier, Ferraro, Elisabetta, Ferreira-Halder, Carmen Verissima, Fesus, Laszlo, Feuer, Ralph, Fiesel, Fabienne C., Filippi-Chiela, Eduardo C., Filomeni, Giuseppe, Fimia, Gian Maria, Fingert, John H., Finkbeiner, Steven, Finkel, Toren, Fiorito, Filomena, Fisher, Paul B., Flajolet, Marc, Flamigni, Flavio, Florey, Oliver, Florio, Salvatore, Floto, R. Andres, Folini, Marco, Follo, Carlo, Fon, Edward A., Fornai, Francesco, Fortunato, Franco, Fraldi, Alessandro, Franco, Rodrigo, Francois, Arnaud, Francois, Aurelie, Frankel, Lisa B., Fraser, Iain D. C., Frey, Norbert, Freyssenet, Damien G., Frezza, Christian, Friedman, Scott L., Frigo, Daniel E., Fu, Dongxu, Fuentes, Jose M., Fueyo, Juan, Fujitani, Yoshio, Fujiwara, Yuuki, Fujiya, Mikihiro, Fukuda, Mitsunori, Fulda, Simone, Fusco, Carmela, Gabryel, Bozena, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galadari, Sehamuddin, Galili, Gad, Galindo, Inmaculada, Galindo, Maria F., Galliciotti, Giovanna, Galluzzi, Lorenzo, Galluzzi, Luca, Galy, Vincent, Gammoh, Noor, Gandy, Sam, Ganesan, Anand K., Ganesan, Swamynathan, Ganley, Ian G., Gannage, Monique, Gao, Fen-Biao, Gao, Feng, Gao, Jian-Xin, Garcia Nannig, Lorena, Vescovi, Eleonora Garcia, Garcia-Macia, Marina, Garcia-Ruiz, Carmen, Garg, Abhishek D., Garg, Pramod Kumar, Gargini, Ricardo, Gassen, Nils Christian, Gatica, Damian, Gatti, Evelina, Gavard, Julie, Gavathiotis, Evripidis, Ge, Liang, Ge, Pengfei, Ge, Shengfang, Gean, Po-Wu, Gelmetti, Vania, Genazzani, Armando A., Geng, Jiefei, Genschik, Pascal, Gerner, Lisa, Gestwicki, Jason E., Gewirtz, David A., Ghavami, Saeid, Ghigo, Eric, Ghosh, Debabrata, Giammarioli, Anna Maria, Giampieri, Francesca, Giampietri, Claudia, Giatromanolaki, Alexandra, Gibbings, Derrick J., Gibellini, Lara, Gibson, Spencer B., Ginet, Vanessa, Giordano, Antonio, Giorgini, Flaviano, Giovannetti, Elisa, Girardin, Stephen E., Gispert, Suzana, Giuliano, Sandy, Gladson, Candece L., Glavic, Alvaro, Gleave, Martin, Godefroy, Nelly, Gogal, Robert M., Jr., Gokulan, Kuppan, Goldman, Gustavo H., Goletti, Delia, Goligorsky, Michael S., Gomes, Aldrin V., Gomes, Ligia C., Gomez, Hernando, Gomez-Manzano, Candelaria, Gomez-Sanchez, Ruben, Goncalves, Dawit A. P., Goncu, Ebru, Gong, Qingqiu, Gongora, Celine, Gonzalez, Carlos B., Gonzalez-Alegre, Pedro, Gonzalez-Cabo, Pilar, Ana Gonzalez-Polo, Rosa, Goping, Ing Swie, Gorbea, Carlos, Gorbunov, Nikolai V., Goring, Daphne R., Gorman, Adrienne M., Gorski, Sharon M., Goruppi, Sandro, Goto-Yamada, Shino, Gotor, Cecilia, Gottlieb, Roberta A., Gozes, Illana, Gozuacik, Devrim, Graba, Yacine, Graef, Martin, Granato, Giovanna E., Grant, Gary Dean, Grant, Steven, Gravina, Giovanni Luca, Green, Douglas R., Greenhough, Alexander, Greenwood, Michael T., Grimaldi, Benedetto, Gros, Frederic, Grose, Charles, Groulx, Jean-Francois, Gruber, Florian, Grumati, Paolo, Grune, Tilman, Guan, Jun-Lin, Guan, Kun-Liang, Guerra, Barbara, Guillen, Carlos, Gulshan, Kailash, Gunst, Jan, Guo, Chuanyong, Guo, Lei, Guo, Ming, Guo, Wenjie, Guo, Xu-Guang, Gust, Andrea A., Gustafsson, Asa B., Gutierrez, Elaine, Gutierrez, Maximiliano G., Gwak, Ho-Shin, Haas, Albert, Haber, James E., Hadano, Shinji, Hagedorn, Monica, Hahn, David R., Halayko, Andrew J., Hamacher-Brady, Anne, Hamada, Kozo, Hamai, Ahmed, Hamann, Andrea, Hamasaki, Maho, Hamer, Isabelle, Hamid, Qutayba, Hammond, Ester M., Han, Feng, Han, Weidong, Handa, James T., Hanover, John A., Hansen, Malene, Harada, Masaru, Harhaji-Trajkovic, Ljubica, Harper, J. 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Sue, Menna-Barreto, Rubem F. S., Menon, Manoj B., Meraz-Rios, Marco A., Merla, Giuseppe, Merlini, Luciano, Merlot, Angelica M., Meryk, Andreas, Meschini, Stefania, Meyer, Joel N., Mi, Man-Tian, Miao, Chao-Yu, Micale, Lucia, Michaeli, Simon, Michiels, Carine, Migliaccio, Anna Rita, Mihailidou, Anastasia Susie, Mijaljica, Dalibor, Mikoshiba, Katsuhiko, Milan, Enrico, Miller-Fleming, Leonor, Mills, Gordon B., Mills, Ian G., Minakaki, Georgia, Minassian, Berge A., Ming, Xiu-Fen, Minibayeva, Farida, Minina, Elena A., Mintern, Justine D., Minucci, Saverio, Miranda-Vizuete, Antonio, Mitchell, Claire H., Miyamoto, Shigeki, Miyazawa, Keisuke, Mizushima, Noboru, Mnich, Katarzyna, Mograbi, Baharia, Mohseni, Simin, Moita, Luis Ferreira, Molinari, Marco, Molinari, Maurizio, Moller, Andreas Buch, Mollereau, Bertrand, Mollinedo, Faustino, Monick, Martha M., Montagnaro, Serena, Montell, Craig, Moore, Darren J., Moore, Michael N., Mora-Rodriguez, Rodrigo, Moreira, Paula I., Morel, Etienne, Morelli, Maria Beatrice, Moreno, Sandra, Morgan, Michael J., Moris, Arnaud, Moriyasu, Yuji, Morrison, Janna L., Morrison, Lynda A., Morselli, Eugenia, Moscat, Jorge, Moseley, Pope L., Mostowy, Serge, Motori, Elisa, Mottet, Denis, Mottram, Jeremy C., Moussa, Charbel E-H, Mpakou, Vassiliki E., Mukhtar, Hasan, Levy, Jean M. 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J., Sanchez-Alcazar, Jose A., Sanchez-Prieto, Ricardo, Sandri, Marco, Sanjuan, Miguel A., Santaguida, Stefano, Santambrogio, Laura, Santoni, Giorgio, dos Santos, Claudia Nunes, and Saran, Shweta

Published
2016

50. Lipid remodelling is a widespread strategy in marine heterotrophic bacteria upon phosphorus deficiency

Author

Sebastian, Marta, Smith, Alastair, Gonzalez, Jose M., Fredricks, Helen F., Van Mooy, Benjamin A. S., Koblizek, Michal, Brandsma, Joost, Koster, Grielof, Mestre, Mireia, Mostajir, Behzad, Pitta, Paraskevi, Postle, Anthony D., Sanchez, Pablo, Gasol, Josep M., Scanlan, David J., Chen, Yin, Sebastian, Marta, Smith, Alastair, Gonzalez, Jose M., Fredricks, Helen F., Van Mooy, Benjamin A. S., Koblizek, Michal, Brandsma, Joost, Koster, Grielof, Mestre, Mireia, Mostajir, Behzad, Pitta, Paraskevi, Postle, Anthony D., Sanchez, Pablo, Gasol, Josep M., Scanlan, David J., and Chen, Yin

Abstract

© The International Society for Microbial Ecology, 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in ISME Journal 10 (2016): 968–978, doi:10.1038/ismej.2015.172., Upon phosphorus (P) deficiency, marine phytoplankton reduce their requirements for P by replacing membrane phospholipids with alternative non-phosphorus lipids. It was very recently demonstrated that a SAR11 isolate also shares this capability when phosphate starved in culture. Yet, the extent to which this process occurs in other marine heterotrophic bacteria and in the natural environment is unknown. Here, we demonstrate that the substitution of membrane phospholipids for a variety of non-phosphorus lipids is a conserved response to P deficiency among phylogenetically diverse marine heterotrophic bacteria, including members of the Alphaproteobacteria and Flavobacteria. By deletion mutagenesis and complementation in the model marine bacterium Phaeobacter sp. MED193 and heterologous expression in recombinant Escherichia coli, we confirm the roles of a phospholipase C (PlcP) and a glycosyltransferase in lipid remodelling. Analyses of the Global Ocean Sampling and Tara Oceans metagenome data sets demonstrate that PlcP is particularly abundant in areas characterized by low phosphate concentrations. Furthermore, we show that lipid remodelling occurs seasonally and responds to changing nutrient conditions in natural microbial communities from the Mediterranean Sea. Together, our results point to the key role of lipid substitution as an adaptive strategy enabling heterotrophic bacteria to thrive in the vast P-depleted areas of the ocean., This work was partially supported by grants STORM (CTM2009-09352/MAR), MALASPINA (CSD2008-00077), HOTMIX (CTM2011-30010/MAR), DOREMI (CTM2012-34294) and EcoBGM (CTM2013-48292-C3-3-R) funded by the Spanish Government, GAČR project GA13-11281S and MESOAQUA (228224) funded by the European Union Seventh Framework Program (FP7/2007-2013) and by the Natural Environment Research Council (NERC), UK (NE/M002233/1).

Published
2016

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