Methodology Development for the Implementation ofMicrofluidic Mixers

Microfluidic platforms have been widely regarded as defining technologies for the development of chemical and biological synthesis and analysis systems, due to benefits associated with reduced reactant consumption, increases by orders of magnitude of the surface-to-volume ratios, and greatly enhanced control over reactions variables such as temperature and pressure. However, one of the bottlenecks for their wide application is the difficulty in achieving mixing, given the typical laminar flows in these systems. In this work we implement experimentally, various strategies using geometrical features to control the fluid motion and induce stirring flows. The mixers are fabricated using soft-lithography in PDMS employing replica molding. The flow structures were imaged using fluorescence confocal microscopy. In future work, the fluid flow patterns from confocal microscopy imaging, at various locations in the mixer, will be compared to theoretical predictions from computational fluid dynamics modeling.https://engagedscholarship.csuohio.edu/u_poster_2018/1064/thumbnail.jp

Methodology Development for the Implementation ofMicrofluidic Mixers

Microfluidic platforms have been widely regarded as defining technologies for the development of chemical and biological synthesis and analysis systems, due to benefits associated with reduced reactant consumption, increases by orders of magnitude of the surface-to-volume ratios, and greatly enhanced control over reactions variables such as temperature and pressure. However, one of the bottlenecks for their wide application is the difficulty in achieving mixing, given the typical laminar flows in these systems. In this work we implement experimentally, various strategies using geometrical features to control the fluid motion and induce stirring flows. The mixers are fabricated using soft-lithography in PDMS employing replica molding. The flow structures were imaged using fluorescence confocal microscopy. In future work, the fluid flow patterns from confocal microscopy imaging, at various locations in the mixer, will be compared to theoretical predictions from computational fluid dynamics modeling.https://engagedscholarship.csuohio.edu/u_poster_2018/1064/thumbnail.jp

Secure Routing Environment with Enhancing QoS in Mobile Ad-Hoc Networks

A mobile adhoc network is infrastructure-free and self configured network connected without wire. As it is infrastructure-free and no centralized control, such type of network are suitable only for conditional inter communication link. So initially maintaining Quality of Service and security aware routing is a difficult task. The main purpose of QoS aware routing is to find an optimal secure route from source to destination which will satisfy two or more QoS constrain. In this paper, we propose a net based multicasting routing scheme to discovery all possible secure path using Secure closest spot trust certification protocol (SCSTC) and the optimal link path is derived from Dolphin Echolocation algorithm (DEA). The numerical result and performance analysis clearly describe that our provided proposal routing protocol generates better packet delivery ratio, decreases packet delay reduces overhead in secured environment

Biophysical and Biomechanical Properties of Neural Progenitor Cells as Indicators of Developmental Neurotoxicity

Conventional in vitro toxicity studies have focused on identifying IC50 and the underlying mechanisms, but how toxicants influence biophysical and biomechanical changes in human cells, especially during developmental stages, remain understudied. Here, using an atomic force microscope, we characterized changes in biophysical (cell area, actin organization) and biomechanical (Young\u27s modulus, force of adhesion, tether force, membrane tension, tether radius) aspects of human fetal brain-derived neural progenitor cells (NPCs) induced by four classes of widely used toxic compounds, including rotenone, digoxin, N-arachidonoylethanolamide (AEA), and chlorpyrifos, under exposure up to 36 h. The sub-cellular mechanisms (apoptosis, mitochondria membrane potential, DNA damage, glutathione levels) by which these toxicants induced biochemical changes in NPCs were assessed. Results suggest a significant compromise in cell viability with increasing toxicant concentration (p \u3c 0.01), and biophysical and biomechanical characteristics with increasing exposure time (p \u3c 0.01) as well as toxicant concentration (p \u3c 0.01). Impairment of mitochondrial membrane potential appears to be the most sensitive mechanism of neurotoxicity for rotenone, AEA and chlorpyrifos exposure, but compromise in plasma membrane integrity for digoxin exposure. The surviving NPCs remarkably retained stemness (SOX2 expression) even at high toxicant concentrations. A negative linear correlation (R-2 = 0.92) exists between the elastic modulus of surviving cells and the number of living cells in that environment. We propose that even subtle compromise in cell mechanics could serve as a crucial marker of developmental neurotoxicity (mechanotoxicology) and therefore should be included as part of toxicology assessment repertoire to characterize as well as predict developmental outcomes

Medical students’ evaluation of competency-based and traditionaleducational environment using the Dundee Ready Education Environment Measure

Background:Competency-based medical education (CBME) was introduced in India in 2019 to transform the educational environment. Students’ perspectives are vital to incorporate positive changes and ameliorate shortcomings as important stakeholders. The authors have tried to capture these perceptions in the study. Methods: A cross-sectional study was conducted between August 2020 and May 2021 with randomly selected undergraduate student volunteers at a government medical college in Delhi, India. In all, 50 students were included from the first year enrolled in a competencybased curriculum and 50 from the second year studying a traditional curriculum. The Dundee Ready Education Environment Measure (DREEM) was used to evaluate the perceptions of the educational environments. Results: Perception of learning (PL) showed a more positive response among the first-year students (using CBME) with a mean score of 32.18±6.32 in comparison to the second-year students following the traditional curriculum with a mean score of 29.04±7.29 (P=0.04). Total score, PL, students’ perception of teachers/teaching (PT), and academic self-perception (ASP) (P=0.03,<0.01, 0.02, 0.05 respectively), were higher in day-scholars in comparison to those who stayed in college-based housing (hostellers). Overall, no gender differences were seen. Conclusion: Better PL, a reduction in problem areas, and a favorable environment in day scholars compared to hostellers were all seen in students following the CBME method. Perceptions of the two groups of students concerning support systems and other aspects such as students irritating teachers, cheating, and perceived boredom were different. This analysis of the educational environment can serve as helpful feedback to curriculum designers

Alterations in phenotype and gene expression of adult human aneurysmal smooth muscle cells by exogenous nitric oxide

International audienceAbdominal aortic aneurysms (AAA) are characterized by matrix remodeling, elastin degradation, absence of nitric oxide (NO) signaling, and inflammation, influencing smooth muscle cell (SMC) phenotype and gene expression. Little is known about the biomolecular release and intrinsic biomechanics of human AAA-SMCs. NO delivery could be an attractive therapeutic strategy to restore lost functionality of AAA-SMCs by inhibiting inflammation and cell stiffening. We aim to establish the differences in phenotype and gene expression of adult human AAA-SMCs from healthy SMCs. Based on our previous study which showed benefits of optimal NO dosage delivered via S-Nitrosoglutathione (GSNO) to healthy aortic SMCs, we tested whether such benefits would occur in AAA-SMCs. The mRNA expression of three genes involved in matrix degradation (ACE, ADAMTS5 and ADAMTS8) was significantly downregulated in AAA-SMCs. Total protein and glycosaminoglycans synthesis were higher in AAA-SMCs than healthy-SMCs (p < 0.05 for AAA-vs. healthy-SMC cultures) and was enhanced by GSNO and 3D cultures (p < 0.05 for 3D vs. 2D cultures; p < 0.05 for GSNO vs. non-GSNO cases). Elastin gene expression, synthesis and deposition, desmosine crosslinker levels, and lysyl oxidase (LOX) functional activity were lower, while cell proliferation, iNOS, LOX and fibrillin-1 gene expressions were higher in AAA-SMCs (p < 0.05 between respective cases), with differential benefits from GSNO exposure. GSNO and 3D cultures reduced MMPs −2, −9, and increased TIMP-1 release in AAA-SMC cultures (p < 0.05 for GSNO vs. non-GSNO cultures). AAA-SMCs were inherently stiffer and had smoother surface than healthy SMCs (p < 0.01 in both cases), but GSNO reduced stiffness (~25%; p < 0.01) and increased roughness (p < 0.05) of both cell types. In conclusion, exogenously-delivered NO offers an attractive strategy by providing therapeutic benefits to AAA-SMCs

Microglia Control Vascular Architecture via a TGFβ1 Dependent Paracrine Mechanism Linked to Tissue Mechanics

© 2020, The Author(s). Tissue microarchitecture and mechanics are important in development and pathologies of the Central Nervous System (CNS); however, their coordinating mechanisms are unclear. Here, we report that during colonization of the retina, microglia contacts the deep layer of high stiffness, which coincides with microglial bipolarization, reduction in TGFβ1 signaling and termination of vascular growth. Likewise, stiff substrates induce microglial bipolarization and diminish TGFβ1 expression in hydrogels. Both microglial bipolarization in vivo and the responses to stiff substrates in vitro require intracellular adaptor Kindlin3 but not microglial integrins. Lack of Kindlin3 causes high microglial contractility, dysregulation of ERK signaling, excessive TGFβ1 expression and abnormally-patterned vasculature with severe malformations in the area of photoreceptors. Both excessive TGFβ1 signaling and vascular defects caused by Kindlin3-deficient microglia are rescued by either microglial depletion or microglial knockout of TGFβ1 in vivo. This mechanism underlies an interplay between microglia, vascular patterning and tissue mechanics within the CNS

Human surfactant protein D alters oxidative stress and HMGA1 expression to induce p53 apoptotic pathway in eosinophil leukemic cell line

This article is made available through the Brunel Open Access Publishing Fund. Copyright: © 2013 Mahajan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant protein D (SP-D), an innate immune molecule, has an indispensable role in host defense and regulation of inflammation. Immune related functions regulated by SP-D include agglutination of pathogens, phagocytosis, oxidative burst, antigen presentation, T lymphocyte proliferation, cytokine secretion, induction of apoptosis and clearance of apoptotic cells. The present study unravels a novel ability of SP-D to reduce the viability of leukemic cells (eosinophilic leukemic cell line, AML14.3D10; acute myeloid leukemia cell line, THP-1; acute lymphoid leukemia cell lines, Jurkat, Raji; and human breast epithelial cell line, MCF-7), and explains the underlying mechanisms. SP-D and a recombinant fragment of human SP-D (rhSP-D) induced G2/M phase cell cycle arrest, and dose and timedependent apoptosis in the AML14.3D10 eosinophilic leukemia cell line. Levels of various apoptotic markers viz. activated p53, cleaved caspase-9 and PARP, along with G2/M checkpoints (p21 and Tyr15 phosphorylation of cdc2) showed significant increase in these cells. We further attempted to elucidate the underlying mechanisms of rhSP-D induced apoptosis using proteomic analysis. This approach identified large scale molecular changes initiated by SPD in a human cell for the first time. Among others, the proteomics analysis highlighted a decreased expression of survival related proteins such as HMGA1, overexpression of proteins to protect the cells from oxidative burst, while a drastic decrease in mitochondrial antioxidant defense system. rhSP-D mediated enhanced oxidative burst in AML14.3D10 cells was confirmed, while antioxidant, N-acetyl-L-cysteine, abrogated the rhSP-D induced apoptosis. The rhSP-D mediated reduced viability was specific to the cancer cell lines and viability of human PBMCs from healthy controls was not affected. The study suggests involvement of SP-D in host’s immunosurveillance and therapeutic potential of rhSP-D in the eosinophilic leukemia and cancers of other origins.Department of Biotechnology, Indi

Host Biomarkers Reflect Prognosis in Patients Presenting With Moderate Coronavirus Disease 2019: A Prospective Cohort Study

Efficient resource allocation is essential for effective pandemic response. We measured host biomarkers in 420 patients presenting with moderate coronavirus disease 2019 and found that different biomarkers predict distinct clinical outcomes. Interleukin (IL)-1ra, IL-6, IL-10, and IL-8 exhibit dose-response relationships with subsequent disease progression and could potentially be useful for multiple use-cases