25 research outputs found

    Inhibition of Mitogen-Activated Protein Kinase Erk1/2 Promotes Protein Degradation of ATP Binding Cassette Transporters A1 and G1 in CHO and in HuH7 cells.

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    Signal transduction modulates expression and activity of cholesterol transporters. We recently demonstrated that the Ras/mitogen-activated protein kinase (MAPK) signaling cascade regulates protein stability of Scavenger Receptor BI (SR-BI) through Proliferator Activator Receptor (PPARα) -dependent degradation pathways. In addition, MAPK (Mek/Erk 1/2) inhibition has been shown to influence liver X receptor (LXR) -inducible ATP Binding Cassette (ABC) transporter ABCA1 expression in macrophages. Here we investigated if Ras/MAPK signaling could alter expression and activity of ABCA1 and ABCG1 in steroidogenic and hepatic cell lines. We demonstrate that in Chinese Hamster Ovary (CHO) cells and human hepatic HuH7 cells, extracellular signal-regulated kinase 1/2 (Erk1/2) inhibition reduces PPARα-inducible ABCA1 protein levels, while ectopic expression of constitutively active H-Ras, K-Ras and MAPK/Erk kinase 1 (Mek1) increases ABCA1 protein expression, respectively. Furthermore, Mek1/2 inhibitors reduce ABCG1 protein levels in ABCG1 overexpressing CHO cells (CHO-ABCG1) and human embryonic kidney 293 (HEK293) cells treated with LXR agonist. This correlates with Mek1/2 inhibition reducing ABCG1 cell surface expression and decreasing cholesterol efflux onto High Density Lipoproteins (HDL). Real Time reverse transcriptase polymerase chain reaction (RT-PCR) and protein turnover studies reveal that Mek1/2 inhibitors do not target transcriptional regulation of ABCA1 and ABCG1, but promote ABCA1 and ABCG1 protein degradation in HuH7 and CHO cells, respectively. In line with published data from mouse macrophages, blocking Mek1/2 activity upregulates ABCA1 and ABCG1 protein levels in human THP1 macrophages, indicating opposite roles for the Ras/MAPK pathway in the regulation of ABC transporter activity in macrophages compared to steroidogenic and hepatic cell types. In summary, this study suggests that Ras/MAPK signaling modulates PPARα- and LXR-dependent protein degradation pathways in a cell-specific manner to regulate the expression levels of ABCA1 and ABCG1 transporters

    Nano- and Microparticle-Induced Cell Death, Inflammation and Immune Responses

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    This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac

    Evaluation of ultra-wide band technology for social distancing awareness in an office environment towards reducing spread of COVID-19

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    The thesis aims at establishing a proof of concept for the implementation of Ultra-wideband (UWB) technology for social distancing awareness among people in an office environment. As people get vaccinated and offices open, it is imperative to have an awareness mechanism for employee safety. UWB presents itself as a monumental upgrade over other short-range technologies in terms of accuracy and scalability. This thesis aims to highlight UWB-based devices as an effective, accurate solution for social distancing needs, particularly in high-density areas (offices, banks, etc.), required by the COVID-19 pandemic. The research used a test scenario of 2 users in an office room, where they were instructed to maintain 6 feet distance (CDC Guideline) for a working day. The results showed that the average daily contact time was 29 minutes given social awareness, self-correcting behavior, and accurate measurements from UWB devices. For enhancing the test scenario, a feedback mechanism was deployed in the office room which alerted the users of their time in contact and the behavior of the users was observed. The results showed an improvement, with the average daily contact time being 13 minutes between the users. The contact time exceeded no longer than 15 minutes (CDC Guideline) collectively between the users for a working day highlighting the intuitive sound-based feedback mechanism and the accurate UWB measurements. Finally, the conducted research shows that as UWB becomes ubiquitous, social awareness can be scaled for not only employees, but visitors as well using mobile applications. As new variants keep popping up in the world, it is imperative to have a scalable, yet flexible system and the thesis showcases such a system.M.S.Includes bibliographical reference

    Annexin A6—Linking Ca2+ signaling with cholesterol transport

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    AbstractAnnexin A6 (AnxA6) belongs to a conserved family of Ca2+-dependent membrane-binding proteins. Like other annexins, the function of AnxA6 is linked to its ability to bind phospholipids in cellular membranes in a dynamic and reversible fashion, in particular during the regulation of endocytic and exocytic pathways. High amounts of AnxA6 sequester cholesterol in late endosomes, thereby lowering the levels of cholesterol in the Golgi and the plasma membrane. These AnxA6-dependent redistributions of cellular cholesterol pools give rise to reduced cytoplasmic phospholipase A2 (cPLA2) activity, retention of caveolin in the Golgi apparatus and a reduced number of caveolae at the cell surface. In addition to regulating cholesterol and caveolin distribution, AnxA6 acts as a scaffold/targeting protein for several signaling proteins, the best characterized being the Ca2+-dependent membrane targeting of p120GAP to downregulate Ras activity. AnxA6 also stimulates the Ca2+-inducible involvement of PKC in the regulation of HRas and possibly EGFR signal transduction pathways. The ability of AnxA6 to recruit regulators of the EGFR/Ras pathway is likely potentiated by AnxA6-induced actin remodeling. Accordingly, AnxA6 may function as an organizer of membrane domains (i) to modulate intracellular cholesterol homeostasis, (ii) to create a scaffold for the formation of multifactorial signaling complexes, and (iii) to regulate transient membrane–actin interactions during endocytic and exocytic transport. This article is part of a Special Issue entitled: 11th European Symposium on Calcium

    Analysis of Chinese patents associated with incremental clustering algorithms: A review / Archana Chaudhari

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    With the advent of Internet-of-Things (IoT) and overall Information-Technology world, an enormous amount of data is getting generated dynamically and in real-time mode, in almost all domains of research and application systems. Such huge data has embedded patterns and hidden information to extract and learn. This learning is incremental in nature for all involved entities and users, as the data is growing exponentially in real-time. To achieve learning from such dynamic data sources, incremental clustering algorithms are used mandatorily. This mandate has given rise to increased patents related to incremental clustering concept, which is primarily a significant part of Machine Learning field. In this paper, we contribute to the in-progress discussion on the use of intellectual property resources, particularly patents related to machine learning, incremental clustering, incremental learning with a special focus to country China. Due consideration of the prior art search, the author found that China the country of registration of the application extensively contributes to the intellectual property related to incremental clustering domain hence felt the need to undertake this detailed patent analysis about this topic. We hope all readers, research scholars will be benefited with the latest research presented in this paper pertaining to various patents in the advanced areas of computer engineering

    Analysis of Chinese Patents associated with Incremental Clustering Algorithms: A Review

    No full text
    With the advent of Internet-of-Things (IoT) and overall Information-Technology world, an enormous amount of data is getting generated dynamically and in real-time mode, in almost all domains of research and application systems. Such huge data has embedded patterns and hidden information to extract and learn. This learning is incremental in nature for all involved entities and users, as the data is growing exponentially in real-time. To achieve learning from such dynamic data sources, incremental clustering algorithms are used mandatorily. This mandate has given rise to increased patents related to incremental clustering concept, which is primarily a significant part of Machine Learning field. In this paper, we contribute to the in-progress discussion on the use of intellectual property resources, particularly patents related to machine learning, incremental clustering, incremental learning with a special focus to country China. Due consideration of the prior art search, the author found that China the country of registration of the application extensively contributes to the intellectual property related to incremental clustering domain hence felt the need to undertake this detailed patent analysis about this topic. We hope all readers, research scholars will be benefited with the latest research presented in this paper pertaining to various patents in the advanced areas of computer engineering

    Analysis of Chinese Patents associated with Incremental Clustering Algorithms: A Review

    No full text
    With the advent of Internet-of-Things (IoT) and overall Information-Technology world, an enormous amount of data is getting generated dynamically and in real-time mode, in almost all domains of research and application systems. Such huge data has embedded patterns and hidden information to extract and learn. This learning is incremental in nature for all involved entities and users, as the data is growing exponentially in real-time. To achieve learning from such dynamic data sources, incremental clustering algorithms are used mandatorily. This mandate has given rise to increased patents related to incremental clustering concept, which is primarily a significant part of Machine Learning field. In this paper, we contribute to the in-progress discussion on the use of intellectual property resources, particularly patents related to machine learning, incremental clustering, incremental learning with a special focus to country China. Due consideration of the prior art search, the author found that China the country of registration of the application extensively contributes to the intellectual property related to incremental clustering domain hence felt the need to undertake this detailed patent analysis about this topic. We hope all readers, research scholars will be benefited with the latest research presented in this paper pertaining to various patents in the advanced areas of computer engineering

    Adapting RGB pose estimation to new domains

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    2019 Spring.Includes bibliographical references.Many multi-modal human computer interaction (HCI) systems interact with users in real-time by estimating the user's pose. Generally, they estimate human poses using depth sensors such as the Microsoft Kinect.For multi-modal HCI interfaces to gain traction in the real world, however, it would be better for pose estimation to be based on data from RGB cameras, which are more common and less expensive than depth sensors. This has motivated research into pose estimation from RGB images. Convolutional Neural Networks (CNNs) represent the state-of-the-art in this literature, for example [1–5], and [6]. These systems estimate 2D human poses from RGB images. A problem with current CNN-based pose estimators is that they require large amounts of labeled data for training. If the goal is to train an RGB pose estimator for a new domain, the cost of collecting and more importantly labeling data can be prohibitive. A common solution is to train on publicly available pose data sets, but then the trained system is not tailored to the domain. We propose using RGB+D sensors to collect domain-specific data in the lab, and then training the RGB pose estimator using skeletons automatically extracted from the RGB+D data. This paper presents a case study of adapting the RMPE pose estimation network [4] to the domain of the DARPA Communicating with Computers (CWC) program [7], as represented by the EGGNOG data set [8]. We chose RMPE because it predicts both joint locations and Part Affinity Fields (PAFs) in real-time. Our adaptation of RMPE trained on automatically-labeled data outperforms the original RMPE on the EGGNOG data set
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