496 research outputs found
Simulated Stochastic Approximation Annealing for Global Optimization With a Square-Root Cooling Schedule
No full textSimulated annealing has been widely used in the solution of optimization problems. As known by many researchers, the global optima cannot be guaranteed to be located by simulated annealing unless a logarithmic cooling schedule is used. However, the logarithmic cooling schedule is so slow that no one can afford to use this much CPU time. This article proposes a new stochastic optimization algorithm, the so-called simulated stochastic approximation annealing algorithm, which is a combination of simulated annealing and the stochastic approximation Monte Carlo algorithm. Under the framework of stochastic approximation, it is shown that the new algorithm can work with a cooling schedule in which the temperature can decrease much faster than in the logarithmic cooling schedule, for example, a square-root cooling schedule, while guaranteeing the global optima to be reached when the temperature tends to zero. The new algorithm has been tested on a few benchmark optimization problems, including feed-forward neural network training and protein-folding. The numerical results indicate that the new algorithm can significantly outperform simulated annealing and other competitors. Supplementary materials for this article are available online.Faming Liang is Professor (E-mail: [email protected]), and Yichen Cheng is Graduate Student (E-mail: [email protected]), Department of Statistics, Texas A&M University, College Station, TX 77843. Guang Lin is Research Scientist, Pacific Northwest National Laboratory, 902 Battelle Boulevard, P.O. Box 999, MSIN K7-90, Richland, WA 99352 (E-mail: [email protected]). Liang's research was partially supported by grants from the National Science Foundation (DMS-1106494 and DMS-1317131) and the award (KUS-C1-016-04) made by King Abdullah University of Science and Technology (KAUST). The authors thank the editor, associate editor, and three referees for their constructive comments, which have led to significant improvement of this article
Modeling Dengue Virus-Hepatic Cell Interactions Using Human Pluripotent Stem Cell-Derived Hepatocyte-like Cells
No full textSummaryThe development of dengue antivirals and vaccine has been hampered by the incomplete understanding of molecular mechanisms of dengue virus (DENV) infection and pathology, partly due to the limited suitable cell culture or animal models that can capture the comprehensive cellular changes induced by DENV. In this study, we differentiated human pluripotent stem cells (hPSCs) into hepatocytes, one of the target cells of DENV, to investigate various aspects of DENV-hepatocyte interaction. hPSC-derived hepatocyte-like cells (HLCs) supported persistent and productive DENV infection. The activation of interferon pathways by DENV protected bystander cells from infection and protected the infected cells from massive apoptosis. Furthermore, DENV infection activated the NF-κB pathway, which led to production of proinflammatory cytokines and downregulated many liver-specific genes such as albumin and coagulation factor V. Our study demonstrates the utility of hPSC-derived hepatocytes as an in vitro model for DENV infection and reveals important aspects of DENV-host interactions
Abstract 2015: Mesenchymal stem cell correlates oral leukoplakia malignant transformation through regulate T cell response
No full textAbstract
Introduction
Leukoplakia is one of the most common clinically presented oral potential malignant disorders (OPMD). Detailed understanding of leukoplakia-associated molecular or cellular changes would help us better undertand about the progress of leukoplakia malignant transformation. In this study, we examined the potential involvement of MSC in this very progress, and demonstrated lesion resident MSCs may favour leukoplakia malignant transformation through its strong immunoregulation on T cell.
Methods
Eighteen six-week-old female Sprague-Dawley rats (180-220g) were given 0.05g/L 4NQO in drinking water for 22 weeks for development of lesions. Lesions classfied by histological HE stainnig. MSCs were obtained from single cell suspesion of lesions, and cultured with splenocyte to study its immunoregulate ability.
Results
1. MSC-like cells are enriched in carcinogen induced leukoplakia and cancers. Representative results showing the lesions on tongue of rats. And relative proportion of MSC phenotype marker (CD29+, CD31-, CD45-, CD90+) in oral lesions (OMSC) were counted by flow cytometry.
2. Leukoplakia-derived MSC (L-OMSC), cancer-derived MSC (C-OMSC), and the normal mucosa-derived MSC (N-OMSC) share the similar stemness properties.
3. Cancer lesion have less infiltrating T cells (quantified by IHC and FCM of CD3 ). Cancer-derived MSCs suppress T cell proliferation, but not promote T cell apoptosis and inhibit T cell migration to the lesions.
4. Higher number of lesion derived MSCs associates with higher celluar proliferation in the lesions.
Summary
Our study demonstrated MSCs could migrate to pre-malignant leukoplakia lesions prior to tumor establishment. Further, MSCs play an important role in leukoplakia malignant transformation induced by chemicals, which via its strong immunomodulatory activities.
Citation Format: Yichen Chen, Bailin He, Da Ma, Jingjing Song, Xi Wang, Bin Cheng, Zhi Wang. Mesenchymal stem cell correlates oral leukoplakia malignant transformation through regulate T cell response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2015. doi:10.1158/1538-7445.AM2017-2015</jats:p
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DNA Methylation and Human Diseases: Applied and Methodological Studies
No full textDNA methylation plays important roles in regulating gene expression and chromosome integrity via addition of methyl groups to cytosine residues. A growing number of human diseases have been found to be associated with aberrant DNA methylation. DNA methylation also provides potential cancer biomarkers and therapeutic targets.
Lung cancer remains the leading cause of cancer-related mortality worldwide, with an estimated 224,390 new cases and 158,080 deaths in the U.S. alone in 2016. In Chapter 1, the association between overall survival and DNA methylation of a tumor-suppressor gene named LRRC3B was investigated in 1,230 early-stage non-small cell lung cancer patients. It provides evidence of plausibility for building biomarkers on DNA methylation of LRRC3B for overall survival of early-stage non-small cell lung cancer, thus filling a gap between previous in vitro studies and clinical applications.
Acute respiratory distress syndrome (ARDS) is a severe lung disease with a mortality rate of over 40% among moderate-to-severe patients. In Chapter 2, we conducted an epigenome-wide association study (EWAS) between DNA methylation and 28-day survival time in 185 moderate-to-severe ARDS patients from intensive care units (ICUs). We identified four CpG sites that were significantly associated with ARDS survival in two independent cohorts. By integrating all four statistically significant methylation sites, we built a methylation risk score for each patient. Patients with a higher methylation risk score had a significantly higher hazard of death within 28 days.
As the next generation sequencing (NGS) technology becomes more and more affordable, sequencing-based methylation measurements would become popular in epigenetic studies. But it also presents challenge in data analysis, including co-methylation network analysis. In Chapter 3, we showed that while standard sequencing-based methylation measurement provides an unbiased estimate for the methylation level, it leads to a biased estimate for correlation between methylation sites. In Chapter 4, we also showed that sequencing-based methylation measure also leads to biased estimates for linear regression coefficients. We proposed a new method to obtain unbiased estimate for methylation correlation and linear coefficients based on bisulfite sequencing data. We demonstrated its performance using various simulation settings as well as real data generated using bisulfite sequencing technique.DNA methylation; lung cancer; ARDS; bisulfite sequencin
Raw Data for "On-demand cell-autonomous gene therapy for brain circuit disorders", Qiu et al. 2022 Science
No full textRaw Data for Qui et al. 2022 10.1126/science.abq6656
On-demand cell-autonomous gene therapy for brain circuit disorders
Yichen Qiu, Nathanael O’Neill, Benito Maffei, Clara Zourray, Amanda Almacellas Barbanoj, Jenna C. Carpenter,Steffan P. Jones, Marco Leite, Thomas J. Turner, Francisco C. Moreira, Albert Snowball, Tawfeeq Shekh-Ahmad, Vincent Magloire, Serena Barral, Manju A. Kurian, Matthew C. Walker, Stephanie Schorge, Dimitri M. Kullmann, Gabriele Lignani
Content:
EEG
MEA
Immuno
Patch Clamp Electrophysiology
All data are in a open source format. MEA files can be analysed using the MATLAB-based developed by Prof Michela Chiappalone and requests should be direct to:
Michela Chiappalone [email protected]
Ilaria Colombi [email protected]
EEG files are .zip with different transmitters. See EEG_Keys.xlxs for whcih virus was used in each animal.
MEA files are divided in 2 separate .zip: 1. Fig2 and Fig S3 and S7. 2. Fig S6.
Immuno: all the raw images are in the .zip file seprated by Figure #
Patch Clamp Electrophysiology: all the raw .abf files are in the .zip file separated by Figure #
For more info or to request materials please contact the corrsponding author Gabriele Lignani [email protected]
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Stochastic Approximation and Its Application in MCMC
No full textStochastic approximation has been widely used since first proposed by Herbert Robbins and Sutton Monro in 1951. It is an iterative stochastic method that attempts to find the zeros of functions that cannot be computed directly. In this thesis, we used the technique in several different aspects. It was used in the analysis of large geostatistical data, in the improvement of simulated annealing algorithm also, as well as for NMR protein structure determination.
1. We proposed a resampling based Stochastic approximation method for the analysis of large geostatistical data. The main difficulty that lies in the analysis of geostatistical data is the computation time is extremely long when the sample size becomes large. Our proposed method only use a small portion of the data at each iteration. Each time, we update our estimators based on a randomly selected subset of the data using stochastic approximation. In this way, we use the information from the whole data set while keep the computation time almost irrelevant to the sample size. We proved the consistency of our estimator and showed by simulation study that the computation time is much reduced compared to other existing methods.
2. Simulated Annealing algorithm has been widely used for optimization problems. However, it can not guarantee the global optima to be located unless a logarithmic cooling schedule is used. However, the logarithm rate is so slow that no one can afford such a long cpu time. We proposed a new stochastic optimization algorithm, the so-called simulated stochastic approximation annealing (SAA) algorithm, which is a combination of simulated annealing and the stochastic approximation Monte Carlo (SAMC) algorithm. It is shown that the new algorithm can work with a cooling schedule that decreases much faster than in the logarithmic cooling schedule while guarantee the global optima to be reached when temperature tends to zero.
3. Protein Structure determination is a very important topic in computational biology. It aims to determine different conformations for each protein, which helps to understand biological functions such as protein-protein interactions, protein-DNA interactions and so on. Protein structure determination consists of a series of steps and peak picking is a very important step. It is the prerequisite for all other steps. Manually pick the peaks is very time consuming. To automate this process, several methods have been proposed. However, due to the complexity of NMR spectra, the existing method is hard to distinguish false peaks and true peaks perfectly. The main difficulty lies in identifying true peaks with low intensity and overlapping peaks.
We propose to model the spectrum as a mixture of bivariate Gaussian densities and used stochastic approximation Monte Carlo (SAMC) method as the computational approach to solve this problem. Essentially, by putting the peak picking problem into a Bayesian framework, we turned it into a model selection problem. Because Bayesian method will automatically penalize including too much component into the model, our model will distinguish true peaks from noises without pre-process of the data
Současné změny v zahraniční politice Tchaj-wanu
No full textThe preliminary scope of work of this thesis, following the neo-classical realisms methodology of analyzing, we intend to find out Taiwans foreign policy trajectory. We want to know under what circumstances and domestic situation, Taiwan chooses to follow what foreign policies. Through the analysis of objective power (which includes economy, technology, military, and International relations), and with internal political situation (which is mainly focused on elites perceptionsof the country) , we hope to find out the patterns of the foreign policy and possibly contribute to future foreign policy insight. The thesis found out that due to Taiwans constitutional type which is a semi-presidential system, Taiwans foreign policies are heavily aligned with the leaders perceptions and interpretations under the unified government. The leaders view, on the other hand, is still heavily influenced by their traditional party's stands and the goals for both two parties in recent years after democratization are always seeking more visibility in international relations and reduce the threats. The different methods and approaches applied by the leaders resulted in completely different outcomes of the objective power of Taiwan and also the changes in the opinions of citizens over the years. The results could help us...Department of International RelationsKatedra mezinárodních vztahuFakulta sociálních vědFaculty of Social Science
Recent Changes of Taiwan's Foreign Policy
No full textThe preliminary scope of work of this thesis, following the neo-classical realisms methodology of analyzing, we intend to find out Taiwans foreign policy trajectory. We want to know under what circumstances and domestic situation, Taiwan chooses to follow what foreign policies. Through the analysis of objective power (which includes economy, technology, military, and International relations), and with internal political situation (which is mainly focused on elites perceptionsof the country) , we hope to find out the patterns of the foreign policy and possibly contribute to future foreign policy insight. The thesis found out that due to Taiwans constitutional type which is a semi-presidential system, Taiwans foreign policies are heavily aligned with the leaders perceptions and interpretations under the unified government. The leaders view, on the other hand, is still heavily influenced by their traditional party's stands and the goals for both two parties in recent years after democratization are always seeking more visibility in international relations and reduce the threats. The different methods and approaches applied by the leaders resulted in completely different outcomes of the objective power of Taiwan and also the changes in the opinions of citizens over the years. The results could help us..
What Is an Author's Role in the AI Era? Demystifying the Black Box of Human-AI Collaborative Creation Through an "Aesthetic Judgment" Study of the novel Solid Reference Frame Manuscript
No full textThis project repository establishes a permanent timestamp for a study that rethinks Roland Barthes' proclamation of the "death of the author" for the AI era. It engages with Michel Foucault's concept of "author-function" to propose "Aesthetic Judgment" as a new theoretical framework for human-AI collaborative creation. This framework reconceptualizes AI as a "critical partner"—a source of provocation and challenge. The human author, in turn, exercises decisive curatorial power through four key operations: 1) The Right to Question, 2) The Right to Select, 3) The Right to Arbitrate, and 4) The Right to Integrate.
Employing a "Process-Tracing" methodology, the research analyzes the complete manuscript of the novel Solid Reference Frame to demystify the creative "black box." This empirical study aims to demonstrate how the human author's role is transformed from a solitary genius into a systemic architect of meaning, thereby asserting a new, viable author-function for the digital age
Tailored family adaptation to living in a zero-energy house: Occupant’s crises and conflicts with a heat pump-based system
No full textBackgroundThis project belongs to the IEBB project, which advocates for the renovation of ‘zero energy houses’ (ZEH) that synergize insulation and heat pump systems for energy conservation. The ZEH’s energy-saving efficiency depends on user behaviour. From a systems perspective, improper human interactions hinder energy saving, while occupants may find system responses that conflict with their preferences. This study delves into these conflicts and crises, highlighting the variance in post-occupancy adaptation influenced by individual perceptions and familial interplay. The project’s zenith aim is to tailor adaptation, ensuring co-performance between the heat pumpsystem and households. Key InsightIn researching residents’ responses to the ‘routine crisis’ introduced by a new system, I discovered that these ‘crises’ could be productive, stimulating household engagement and fostering harmonious interactions with ZEH systems. This insight gave rise to the concept of the ‘enacted interface’ - a distinctive bridge between residents and their automated homes that supports the adaptation process. Through analysis, I identified elements that amplify residents’ engagement with ‘crises’ and observed the influence of family diversity on individual perceptions and responses to them. The results are manifested in two interrelated frameworks: one describing the ubiquity of ‘crises’ and another characterising the classification and impact of different elements.DesignThis design aims to make households curious about ‘crises’ and guide them towards tailored adaptations to new tech. The ‘Clock’ thermostat provides a consistent interface for temperature adjustments, while the ‘Feeling Message Board’ suggests lifestyle tips based on the user’s emotional input and changing scenarios. Both reinforce the system’s ability to communicate contextual and real-time status, motivating users to actively engage with its functions. Additionally, the design stimulates family discussions about the indoor environment and promotes collaborative responses to ‘crises’. Through co-performance of the system’s dynamic feedback and the household’s proactive exploration, the aim is to facilitate tailored adaptation.IEBB projectIntegrated Product Desig
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