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Biomarkers, biologics, and bio-imaging to manage severe asthma
( Parameswaran Nair ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-
A fundamental principle in the management of severe asthma is to identify the components of the airway disease that contribute to the severity. The airway luminal inflammatory (ie bronchitic) component can be identified by applying new “omics” platforms such as proteomics, transcriptomics, or metabolomics. Simple sputum quantitative cytometry provides just as useful information that can be applied to clinical practice. The lecture will focus on the utility of biomarkers of airway inflammation (sputum cytometry and omics technology, FeNO, novel imaging including functional MRI and airway CT) to identify the inflammatory component in the airways of patients with severe asthma and how this could be applied in routine clinical practice to choose the appropriate monoclonal antibody therapy, particularly against IL-5 and IL4. The lecture will address the various predictors of success and failures of anti-IL5 therapies, including issues with inadequate dosing, the relevance of airway autoimmune responses, and the modulating effect of innate immune cells such as NK cells and macrophages on IL-5R-targeted ADCC. The utility of measurement of airway hyper-responsiveness and the assessment of the so-called non-T2 inflammation will also be discussed, and illustrated using clinical case scenarios.
Optical stimulation of cardiac cells with a polymer-supported silicon nanowire matrix
Parameswaran, Ramya,Koehler, Kelliann,Rotenberg, Menahem Y.,Burke, Michael J.,Kim, Jungkil,Jeong, Kwang-Yong,Hissa, Barbara,Paul, Michael D.,Moreno, Kiela,Sarma, Nivedina,Hayes, Thomas,Sudzilovsky, Ed National Academy of Sciences 2019 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.116 No.2
<P><B>Significance</B></P><P>Cardiac conduction disorders are potentially fatal illnesses caused by abnormalities in the heart’s electrical conduction system. Current treatments for these disorders, such as pacemakers, are effective but are bulky, rigid, and invasive. Here we develop a method to optically modulate cardiac beating frequency in primary cultured cardiomyocytes and adult rat hearts ex vivo, to a specified target frequency. Specifically, we use a low-irradiance moving laser stimulus and a biocompatible polymer–silicon nanowire composite material to achieve this modulation. This work has implications for future bioelectric studies of the cardiac conduction system as well as therapeutics for cardiac conduction disorders in the clinic.</P><P>Electronic pacemakers can treat electrical conduction disorders in hearts; however, they are invasive, bulky, and linked to increased incidence of infection at the tissue–device interface. Thus, researchers have looked to other more biocompatible methods for cardiac pacing or resynchronization, such as femtosecond infrared light pulsing, optogenetics, and polymer-based cardiac patches integrated with metal electrodes. Here we develop a biocompatible nongenetic approach for the optical modulation of cardiac cells and tissues. We demonstrate that a polymer–silicon nanowire composite mesh can be used to convert fast moving, low-radiance optical inputs into stimulatory signals in target cardiac cells. Our method allows for the stimulation of the cultured cardiomyocytes or ex vivo heart to beat at a higher target frequency.</P>
Novel insights from sputum inflammometry to manage COPD exacerbations
( Parameswaran Nair ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-
Quantitative sputum cytometry helps to assess the nature of bronchitis associated with exacerbations of COPD. This is not assessed in most clinical trials that evaluate the effectiveness of strategies to prevent or to treat exacerbations. While up to a quarter of exacerbations may be associated with raised eosinophil numbers, vast majority of exacerbations are associated with neutrophilic bronchitis that may indicate airway infections. While eosinophilia may be a predictor of response to corticosteroids (both oral and inhaled), the limited efficacy of anti-IL5 therapies would suggest that eosinophils may not directly contribute to those exacerbations. However, they may contribute to airspace enlargement in patients with COPD through various mechanisms involving IL-13 and MMP pathways. The absence of eosinophils may help to limit the unnecessary use of corticosteroids. The presence of neutrophiia could prompt an investigation for the specific pathogens in the airway. In addition, sputum measurements may also provide insights into mechanisms of susceptibility to airway infections. Iron within sputum macrophages, identified by hemosiderin staining (and by more direct quantification) may impair macrophage functions while low levels of immunoglobulins in sputum may also contribute to airway infections. Assessment of sputum at the time of exacerbations thus would help to customize treatment and treat current exacerbations and reduce the future risk of exacerbations.
Rampogu, Shailima,Parameswaran, Saravanan,Lemuel, Mary Rampogu,Lee, Keun Woo Hindawi 2018 Evidence-based Complementary and Alternative Medic Vol.2018 No.-
<P>Fenugreek (Trigonella foenum-graecum) is used as a spice throughout the world. It is known for its medicinal properties such as antidiabetic, anticarcinogenic, and immunological activities. The present study shows the properties and the nutritional quality of fenugreek seed extract and focuses on screening of active compounds in drug designing for type 2 diabetes and breast cancer. Quantitative analysis was used to calculate the percentages of protein, carbohydrates moisture, fatty acid, galactomannan, oil, and amino acid. Phytochemical analysis revealed the presence of flavonoids, terpenoids, phenols, proteins, saponins, and tannins in fenugreek seed extracts. Molecular docking and molecular dynamics simulation-based computational drug discovery methods were employed to address the role of fenugreek seed constituents against type 2 diabetes and breast cancer. The computational results reveal that the compound galactomannan can be ascribed as potential drug candidate against breast cancer and type 2 diabetes rendered by higher molecular dock scores, stable molecular dynamics (MD) simulations results, and lower binding energy calculations.</P>
Computing turbulent far-wake development behind a wind turbine with and without swirl
Hu, Yingying,Parameswaran, Siva,Tan, Jiannan,Dharmarathne, Suranga,Marathe, Neha,Chen, Zixi,Grife, Ronald,Swift, Andrew Techno-Press 2012 Wind and Structures, An International Journal (WAS Vol.15 No.1
Modeling swirling wakes is of considerable interest to wind farm designers. The present work is an attempt to develop a computational tool to understand free, far-wake development behind a single rotating wind turbine. Besides the standard momentum and continuity equations from the boundary layer theory in two dimensions, an additional equation for the conservation of angular momentum is introduced to study axisymmetric swirl effects on wake growth. Turbulence is simulated with two options: the standard ${\kappa}-{\varepsilon}$ model and the Reynolds Stress transport model. A finite volume method is used to discretize the governing equations for mean flow and turbulence quantities. A marching algorithm of expanding grids is employed to enclose the growing far-wake and to solve the equations implicitly at every axial step. Axisymmetric far-wakes with/without swirl are studied at different Reynolds numbers and swirl numbers. Wake characteristics such as wake width, half radius, velocity profiles and pressure profiles are computed. Compared with the results obtained under similar flow conditions using the computational software, FLUENT, this far-wake model shows simplicity with acceptable accuracy, covering large wake regions in far-wake study.
CERTAIN GENERALIZED THORN GRAPHS AND THEIR WIENER INDICES
Kathiresan, KM.,Parameswaran, C. The Korean Society for Computational and Applied M 2012 Journal of applied mathematics & informatics Vol.30 No.5
If G is any connected graph of order p; then the thorn graph $G_p^*$ with code ($n_1$, $n_2$, ${\cdots}$, $n_p$) is obtained by adding $n_i$ pendent vertices to each $i^{th}$ vertex of G. By treating the pendent edge of a thorn graph as $P_2$, $K_2$, $K_{1,1}$, $K_1{\circ}K_1$ or $P_1{\circ}K_1$, we generalize a thorn graph by replacing $P_2$ by $P_m$, $K_2$ by $K_m$, $K_{1,1}$ by $K_{m,n}$, $K_1{\circ}K_1$ by $K_m{\circ}K_1$ and $P_1{\circ}K_1$ by $P_m{\circ}K_1$ and their respective generalized thorn graphs are denoted by $G_P$, $G_K$, $G_B$, $G_{KK}$ and $G_{PK}$ respectively. Many chemical compounds can be treated as $G_P$, $G_K$, $G_B$, $G_{KK}$ and $G_{PK}$ of some graphs in graph theory. In this paper, we obtain the bounds of the wiener index for these generalization of thorn graphs.
In vitro Antioxidant Activities of Methanol and Aqueous Extract of Annona squamosa (L.) Fruit Pulp
Elumalai Nandhakumar,Parameswaran Indumathi 사단법인약침학회 2013 Journal of Acupuncture & Meridian Studies Vol.6 No.3
The present study evaluated the antioxidant activity of the fruit of Annona squamosa by means of in vitro studies involving two different solvent extracts: methanol and aqueous. The antioxidant properties of the extract were determined by scavenging 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH), lipid peroxidation (LPO), nitric oxide (NO), superoxide anion (O₂-), hydroxyl radical (OHㆍ), reducing power and total antioxidant. The results showed that, compared to aqueous extract, a methanolic fruit extract of A squamosa has a higher percentage of inhibition of DPPH radical scavenging activity (97.99%), LPO (94.15%), NO scavenging activity (70.96%), O₂- scavenging activity and OHㆍ scavenging activity (78.68% and 85.25%, respectively), total antioxidant activity (206 µg α-tocopherol/g) and reducing power (56.0 µg of ascorbic acid/g). The results obtained in the in vitro models clearly suggest that methanol extract has higher antioxidant activity than the aqueous extract due to a higher presence of phenolic and flavonodal constituents in the methanol extract.