43 research outputs found

    Potential effects of triterpenoids in osteoarthritis model systems

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    Osteoarthritis, a degenerative joint disease, is one of the most common rheumatic disorders and the leading cause of chronic disability in the United States. Currently there are many pharmacologic and non-pharmacologic therapies for osteoarthritis however; these therapies do not appear to concomitantly affect disease symptoms and structure. Here, we have investigated the effects of synthetic oleanane triterpenoids, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), and its analogs CDDO-imidazolide (CDDOIm) and CDDO-ethyl amide (CDDO-EA) in the anabolic as well as catabolic pathways of osteoarthritis using two different osteoarthritis model systems. We found that CDDO-Im and CDDO-EA, at concentrations as low as 200 nM, induce chondrogenesis in organ cultures of new born mouse calvaria in a time and dose dependant manner. The cartilage phenotype was measured histologically with metachromatic toluidine blue staining for proteoglycans and by immunohistochemical staining for type II collagen. Real time PCR analysis using mRNA from calvaria after a 7day treatment with CDDO-Im and CDDO-EA showed upregulation of SOX9 and collagen type 2 and well as other cartilage markers. We also found that LG100268, a rexinoid, downregulates the expression of primary cartilage markers in mouse calvaria suggesting a possible role for rexinoids in chondrogenesis. Vitamin D (1α 25(OH)2 D3) did not show any significant effects at the dose tested. With respect to the catabolic pathway, we established that CDDO-EA and CDDO-Im are involved in suppression of tumor necrosis factor-α (TNF-α) and interleukin 1-β (IL-1β) induced matrix metalloproteinase (MMP) expression in SW1353 chondrosarcoma cells. These results suggest that synthetic triterpenoids CDDO-Im and CDDO-EA can be considered as potentially useful agents for the treatment of osteoarthritis.M.S.Includes bibliographical referencesby Noopur Snehal Sha

    Correction to: Polymer Nanocomposites in Biomedical Engineering

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    In the original version of the book, the following belated corrections have been incorporated: The co-editor names ''Basheer Ahmed'' has been changed to ''M. Basheer Ahamed'' and ''Al-Maadeed Mariam Ali S A'' has been changed to ''Mariam Ali S A Al-Maadeed''. In chapter ''Silver Nanoparticles and Its Polymer Nanocomposites Synthesis, Optimization, Biomedical Usage, and Its Various Applications'', the author name ''Snehal Kargirwar Bramhe'' has been changed to ''Snehal Kargirwar Brahme'' and the affiliations of authors ''Snehal Kargirwar Brahme'' and ''Subhash Kondawar'' were swapped. The correction book has been updated with the changes.Scopu

    A Modified NK Cell Degranulation Assay Applicable for Routine Evaluation of NK Cell Function

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    Natural killer (NK) cells play important role in innate immunity against tumors and viral infections. Studies show that lysosome-associated membrane protein-1 (LAMP-1, CD107a) is a marker for degranulation of NK and cytotoxic T cells and its expression is a sensitive marker for the cytotoxic activity determination. The conventional methods of determination of CD107a on NK cells involve use of peripheral blood mononuclear cells (PBMC) or pure NK cells and K562 cells as stimulants. Thus, it requires large volume of blood sample which is usually difficult to obtain in pediatric patients and patients with cytopenia and also requires specialized laboratory for maintaining cell line. We have designed a flow cytometric assay to determine CD107a on NK cells using whole blood, eliminating the need for isolation of PBMC or isolate NK cells. This assay uses phorbol-12-myristate-13-acetate (PMA) and calcium ionophore (Ca2+-ionophore) instead of K562 cells for stimulation and thus does not require specialized cell culture laboratory. CD107a expression on NK cells using modified NK cell degranulation assay compared to the conventional assay was significantly elevated (p<0.0001). It was also validated by testing patients diagnosed with familial hemophagocytic lymphohistiocytosis (FHL) with defect in exocytosis. This assay is rapid, cost effective, and reproducible and requires significantly less volume of blood which is important for clinical evaluation of NK cells

    A New Perspective on the Origin of DNA Double-Strand Breaks and Its Implications for Ageing

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    It is estimated that 10&ndash;50 DNA double-strand breaks (DSBs) occur in a nucleated human cell per cell cycle. We reviewed the present state of knowledge and hypothesized that the currently accepted mechanisms cannot explain such high frequency of DSBs occurring daily under normal physiological conditions. We propose an alternative model that implicates illegitimate genomic integration into healthy cells of cell-free chromatin (cfCh) particles released from the billions of cells that die in the body every day. Repeated genomic integration of cfCh may have catastrophic consequences for the cell, such as DSBs, their faulty repair by nonhomologous end joining (NHEJ) followed by apoptosis with release of more cfCh which would integrate into genomes of surrounding cells. This can creates a vicious cycle of cfCh integration, DSBs, NHEJ, and more apoptosis, thereby providing a potential explanation as to why so many billions of cells die in the body on a daily basis. We also recount the recent observation that cfCh integration and the resulting DSBs activate inflammatory cytokines. This leads us to propose that concurrent DSBs and induction of inflammation occurring throughout life may be the underlying cause of ageing, degenerative disorders, and cancer. Finally, we discuss the prospect that agents that can inactivate/degrade cfCh may hold the key to making healthy ageing a realizable goal

    Interactive Learning in State-space: Enabling robots to learn from non-expert humans

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    Imitation Learning is a technique that enables programming the behavior of agents through demonstration, as opposed to manually engineering behavior. However, Imitation Learning methods require demonstration data (in the form of state-action labels) and in many scenarios, the demonstrations can be expensive to obtain or too complex for a demonstrator to execute. This lack or sub-optimality of demonstrations limits the applicability and performance of many Imitation Learning methods. Advancements in Interactive Imitation Learning techniques however, have made it easier for demonstrators to train agents and improve their performance. These techniques involve demonstrators interacting with and guiding the agent as it performs the requisite task. This guidance is typically in the form of corrections or feedback on the current actions being executed by the agent. In this thesis, a novel Interactive Learning technique is proposed that uses human corrective feedback in state-space to train and improve agent behavior. This technique is beneficial since providing guidance to the agent in terms of `changing its state' is often easier or more intuitive for the human demonstrator (as opposed to changing the actions being executed). For instance, in manipulation tasks using a robotic arm, it is easier for the demonstrator to provide state information such as the Cartesian position of the end-effector rather than low-level action information such as joint angles. Keeping such scenarios in mind, we propose our method titled: Teaching Imitative Policies in State-space (TIPS). We evaluate the performance of TIPS for various control tasks as part of the OpenAI Gym toolkit as well as for a manipulation task using a KUKA LBR iiwa robotic arm. We show that through continuous improvement via feedback, agents trained using TIPS outperform the demonstrator and in-turn outperform conventional Imitation Learning agents.Electrical Engineering | Embedded System

    Development of Protein Rich Ready-to-Use Chapati/Roti Flour.

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    This Dissertation / Report is the outcome of investigation carried out by the creator(s) / author(s) at the department/division of Central Food Technological Research Institute (CFTRI), Mysore mentioned below in this page

    Seismic Damage in Shear Wall-Slab Junction in RC Buildings

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    AbstractNonlinear time history analyses, under different levels of recorded earthquake ground motion, are carried out using the computer program ABAQUS to study the seismic damage in shear wall – slab junction of an RC wall-frame building. The beams, columns, shear walls and slabs are discretized with eight-noded solid elements. The incurred cumulative damage is determined at various locations for all the three models. It is observed that the damage gets primarily concentrated at the wall – slab junction region with increasing levels of ground motion
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