42 research outputs found
A study of the dynamics and genetics of COVID-19 through machine learning
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Previous issue date: 2020-07-22COrona VIrus Disease (COVID-19), a disease caused due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) resulted in over 12 million infections and over 560,000 deaths in a worldwide pandemic. Countries all over the world carried out mitigation measures to curb the pandemic in forms of lockdowns, disinfection measures, and social distancing. We aim to study the dynamics of this disease by using a machine learning based approach using Long Short-Term Memory (LSTM) in order to evaluate the degree to which the virus spread. Our model is trained on accumulated COVID-19 cases and deaths. Parameters in our model can be adjusted to obtain predictions as required. Results have been obtained at both the country and county levels for the United States of America and some globally affected areas. We show predictions up to three different points of time – May 11, June 10, and June 30. We have also carried out a quantitative evaluation of mitigation measures in eight different counties in the United States depending on the rate of difference between a short and long window parameter based on the proposed LSTM model. The proposed LSTM model provides useful insights and can be a useful aid for various places planning strategies for mitigation and reopening. We aim to study the genetics of COVID-19 using a Multi-Layer Perceptron (MLP) model to recognize and classify COVID-19 genetic sequences at various taxonomic levels. Our model is an alignment-free method based on machine learning and natural language processing techniques that achieves reasonable performance in terms of cross-validation accuracy and time compared to the baseline model. The results from this work could potentially contribute to society during the current global concern.Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2020-10-02 without embargo termsThe student, Sayantani Basu, accepted the attached license on 2020-07-22 at 08:43.The student, Sayantani Basu, submitted this Thesis for approval on 2020-07-22 at 09:30.This Thesis was approved for publication on 2020-07-22 at 11:54.DSpace SAF Submission Ingestion Package generated from Vireo submission #15720 on 2020-10-02 at 15:15:1
Self-healing DNA-based injectable hydrogels with reversible covalent linkages for controlled drug delivery
No full textInjectable hydrogels represent a valuable tool for the delivery of therapeutic molecules aimed to restore the functionality of damaged tissues. In this study, we report the design of a nanocomposite DNA-based hydrogel crosslinked with oxidized alginate (OA) via the formation of reversible imine linkages. The formulated hydrogel functioned as an injectable carrier for the sustained delivery of a small molecule drug, simvastatin. The degree of oxidation of alginate and the concentration of silicate-based nanoparticles (nSi) were varied to modulate the rheological properties of the hydrogels. Specifically, the formulations consisting of OA with higher degree of oxidation displayed the highest value of storage moduli, yield stress, yield strain, and rapid recovery after removal of cyclic stress. The hydrogel formulations exhibited self-healing and shear-thinning properties due to the reversible nature of the covalent imine bonds formed between the aldehyde groups of OA and the amine groups present in the DNA nucleotides. Moreover, the incorporation of charged nSi further enhanced the shear strength of the formulated hydrogels by establishing electrostatic interactions with the phosphate groups of the DNA network. The optimized hydrogel was able to promote the sustained release of simvastatin for more than a week. The bioactivity of the released drug was confirmed by testing its ability to induce osteogenic differentiation and migration of human adipose-derived stem cells in vitro. Overall, the results obtained from this study demonstrate that DNA could be used as a natural biopolymer to fabricate self-healing injectable hydrogels with sustained release properties for minimally invasive therapeutic approaches.Statement of significanceDynamic covalent chemistry, especially Schiff base reactions have emerged as a promising route for the formation of injectable hydrogels. Our study demonstrated the development of a DNA-based self-healing hydrogel formed via Schiff base reaction occurring at physiological conditions. The hydrogels functioned as sustained delivery vehicles for the hydrophobic drug simvastatin, which requires a polymeric carrier for controlled delivery of therapeutic concentrations of the drug without exhibiting cytotoxic effects. Presently available hydrogel-based drug delivery systems encounter major challenges for the delivery of hydrophobic drugs due to the hydrophilic nature of the base matrix. Our strategy presents a platform technology for the design of minimally invasive approaches for the sustained delivery of hydrophobic drugs similar to simvastatin. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved
Nucleic Acid-Based Dual Cross-Linked Hydrogels for in Situ Tissue Repair via Directional Stem Cell Migration
No full textIn situ tissue repair holds great potential as a cell-free regenerative strategy. A critical aspect of this approach is the selection of cell instructive materials that can efficiently regulate the defect microenvironment via the release of chemoattractant factors to mobilize and recruit endogenous stem cells toward the site of implantation. Here we report the design of a DNA-based hydrogel as a drug delivery platform for the sustained release of a promising chemoattractant, SDF-1 alpha. The hydrogel is composed of chemically cross-linked DNA strands, which are bridged via silicate nanodisks (nSi). Silicate nanodisks electrostatically interact with the negatively charged DNA backbone resulting in the formation of a dual cross-linked nanocomposite hydrogel with a combination of chemical and physical cross-link points. The formulated nanocomposites display enhanced elasticity and mechanical toughness as compared to their nonsilicate containing counterparts. Moreover, the electrostatic interaction between nSi and SDF-1 alpha leads to sustained release of the chemokine from the hydrogels. The in vitro bioactivity assays confirm the retention of chemotactic properties of the protein after its release. Overall, the dual cross-linked DNA-based hydrogel platform could be potentially used as a cell-instructive material for the recruitment of host stem cells to guide the process of in situ tissue repair
Multifunctional mesoporous and nanostructured catalysts: exploring novel synthetic methods, properties and applications
No full textNovel multifunctional mesoporous and nanostructured catalysts containing two or more different types of judiciously chosen functional / catalytic groups were developed and their unique and cooperative catalytic activities in various useful organic reactions were explored. First, mesoporous silica material containing tertiary amine/silanol groups was synthesized by simple postgrafting synthetic method. The material was found to exhibit efficient cooperative acid/base bifunctional catalytic activity towards Michael addition reactions between trans-β-nitrostyrene and various active methylene compounds such as malononitrile, acetylacetone and dimethylmalonate. Besides serving as a solid base catalyst, such organoamine-functionalized mesoporous silica materials can be utilized as effective support materials for catalytically active organometallic complexes. This was demonstrated by immobilizing ethylenediamine onto mesoporous silica via postgrafting synthetic method and then complexing Fe(III) onto the supported ethylenediamine groups. This yielded a bifunctional Fe(III)/silanol-based heterogeneous catalyst that showed efficient catalytic activity towards epoxide ring opening reactions. Next, the potential of these types of organic-functionalized mesoporous silicas for immobilization of metallic nanoparticle catalysts was investigated. Specifically, mercaptopropyl-functionalized mesoporous silica was synthesized and the material was then supported with ultrasmall Aun nanoclusters. The catalytic properties of the resulting materials in styrene oxidation were studied. Furthermore, the effect of the removal of the thiol groups from around the surfaces of the gold nanoclusters on catalytic activities of the mesoporous silica-supported nanoparticles was investigated. As mesoporous silica have some limitations of crowding in their pores and poor mass transport for reactants when they are functionalized with larger groups such as nanoparticles, a new strategy was developed, where such catalytic groups were immobilized on the outer surface of silica microspheres. These supported nanoparticle catalytic groups on the silica nanospheres were further coated with a porous silica shell in order to overcome their possible aggregation, sintering and loss of catalytic activities. The resulting nanomaterials, dubbed produced SiO2-Au-pSiO2 core-shell-shell microspheres, were then used as efficient and recyclable nanocatalysts for styrene epoxidation. This strategy was further extended to core-shell-shell microspheres containing the metal (e.g., Pd) nanoparticles within G4 PAMAM dendrimers that are supported on silica nanosphere cores and coated by nanoporous silica shells. These nanomaterials, denoted as SiO2-Pd/PAMAM-pSiO2 core-shell-shell microspheres, were shown to serve not only as efficient and recyclable catalysts but also as selective catalysts for specific functional groups in hydrogenation reaction of various substrates.Ph. D.Includes bibliographical referencesby Sayantani Da
Controlling Adult Stem Cell Behavior Using Nanodiamond-Reinforced Hydrogel: Implication in Bone Regeneration Therapy
No full textAbstractNanodiamonds (NDs) have attracted considerable attention as drug delivery nanocarriers due to their low cytotoxicity and facile surface functionalization. Given these features, NDs have been recently investigated for the fabrication of nanocomposite hydrogels for tissue engineering. Here we report the synthesis of a hydrogel using photocrosslinkable gelatin methacrylamide (GelMA) and NDs as a three-dimensional scaffold for drug delivery and stem cell-guided bone regeneration. We investigated the effect of different concentration of NDs on the physical and mechanical properties of the GelMA hydrogel network. The inclusion of NDs increased the network stiffness, which in turn augmented the traction forces generated by human adipose stem cells (hASCs). We also tested the ability of NDs to adsorb and modulate the release of a model drug dexamethasone (Dex) to promote the osteogenic differentiation of hASCs. The ND-Dex complexes modulated gene expression, cell area, and focal adhesion number in hASCs. Moreover, the integration of the ND-Dex complex within GelMA hydrogels allowed a higher retention of Dex over time, resulting in significantly increased alkaline phosphatase activity and calcium deposition of encapsulated hASCs. These results suggest that conventional GelMA hydrogels can be coupled with conjugated NDs to develop a novel platform for bone tissue engineering.</jats:p
Strategies to develop endogenous stem cell-recruiting bioactive materials for tissue repair and regeneration
No full textA leading strategy in tissue engineering is the design of biomimetic scaffolds that stimulate the body's repair mechanisms through the recruitment of endogenous stem cells to sites of injury. Approaches that employ the use of chemoattractant gradients to guide tissue regeneration without external cell sources are favored over traditional cell-based therapies that have limited potential for clinical translation. Following this concept, bioactive scaffolds can be engineered to provide a temporally and spatially controlled release of biological cues, with the possibility to mimic the complex signaling patterns of endogenous tissue regeneration. Another effective way to regulate stem cell activity is to leverage the inherent chemotactic properties of extracellular matrix (ECM)-based materials to build versatile cell-instructive platforms. This review introduces the concept of endogenous stem cell recruitment, and provides a comprehensive overview of the strategies available to achieve effective cardiovascular and bone tissue regeneration. © 2017 Elsevier B.V
Répartition des crossovers méiotiques : hétérogénéité, modélisation de l'interférence, interaction entre voies de formation
No full textFor most organisms, crossovers forming during meiosis exhibit crossover interference – nearby crossovers are rare. This phenomenon was studied in great detail in Arabidopsis thaliana using a large backcross population for male and female meiosis. We used the gamma two-pathway model by superposing proportion (1- p) of interfering crossovers with p of non-interfering crossovers. It was observed that female meiosis shows higher interference but lower proportion of non-interfering crossovers than male meiosis. Further intra-chromosomal interference comparisons conclude that there are variations between (a) left and right arms, and (b) the central versus distal regions of a chromosome. Then statistical tests revealed heterogeneities in the non-interfering crossover proportion along chromosomes. Thereafter various statistical tools developed to examine a very novel wild-type tomato data annotating crossover positions from both pathways provided evidence for ‘cross-talk’ between the two pathways of crossover formation as opposed to being independent. Finally a model named Pathway-Specific Landscapes Gamma-Sprinkling (PSL-GS) incorporating chromosomal non-uniformity in the individual pathways has been proposed to extend present state-of-the-art interference modeling which consider both pathways to be uniform along chromosomes.Dans la plupart des organismes, les crossovers se formant au cours de la méiose sont interférérents : deux crossovers sont rarement à proximité. Nous avons étudié ce phénomène en détail dans la plante modèle Arabidopsis thaliana en utilisant une grande population de rétro-croisements, en méiose mâle et en méiose femelle. Nous avons utilisé le modèle Gamma à deux voies, superposant à la voie interférente une proportion p de crossovers d'une deuxième voie non interférente. La méiose femelle montre une interférence plus élevée et une proportion p plus faible que la méiose mâle. Par ailleurs nos comparaisons intra-chromosomiques concluent qu'il existe des variations d'interférence entre le bras gauche et le bras droit d'une part et entre la partie centrale et les régions distales d'autre part. Nous avons ensuite développé des tests statistiques qui ont révélé des hétérogénéités dans la proportion p le long des chromosomes. De telles variations ont ensuite été trouvées dans un jeu de données de tomate où notre analyse statistique nous a permis de montrer pour la première fois sur un organisme «sauvage» que la deuxième voie était très peu interférente et qu'en fait les deux voies avaient un peu de « cross-talk ». Vu que la limitation la plus sévère des modèles utilisés jusqu'à présent est l'hypothèse de constance du paramètre p, nous avons développé un modèle généralisé où les deux voies peuvent avoir des paysages de recombinaison différents. Ce modèle nommé PSL-GS a été implémenté en logiciel et testé sur des données simulées et sur trois jeux de données de plantes. L'utilisation du critère BIC suggère que tout comme chez la tomate, les paysages de recombinaison d'Arabidopsis et du maïs sont différents entre les 2 voies
Distribution of meiotic crossovers : heterogeneity, modeling interference, inter-pathway crosstalk
No full textDans la plupart des organismes, les crossovers se formant au cours de la méiose sont interférérents : deux crossovers sont rarement à proximité. Nous avons étudié ce phénomène en détail dans la plante modèle Arabidopsis thaliana en utilisant une grande population de rétro-croisements, en méiose mâle et en méiose femelle. Nous avons utilisé le modèle Gamma à deux voies, superposant à la voie interférente une proportion p de crossovers d'une deuxième voie non interférente. La méiose femelle montre une interférence plus élevée et une proportion p plus faible que la méiose mâle. Par ailleurs nos comparaisons intra-chromosomiques concluent qu'il existe des variations d'interférence entre le bras gauche et le bras droit d'une part et entre la partie centrale et les régions distales d'autre part. Nous avons ensuite développé des tests statistiques qui ont révélé des hétérogénéités dans la proportion p le long des chromosomes. De telles variations ont ensuite été trouvées dans un jeu de données de tomate où notre analyse statistique nous a permis de montrer pour la première fois sur un organisme «sauvage» que la deuxième voie était très peu interférente et qu'en fait les deux voies avaient un peu de « cross-talk ». Vu que la limitation la plus sévère des modèles utilisés jusqu'à présent est l'hypothèse de constance du paramètre p, nous avons développé un modèle généralisé où les deux voies peuvent avoir des paysages de recombinaison différents. Ce modèle nommé PSL-GS a été implémenté en logiciel et testé sur des données simulées et sur trois jeux de données de plantes. L'utilisation du critère BIC suggère que tout comme chez la tomate, les paysages de recombinaison d'Arabidopsis et du maïs sont différents entre les 2 voies.For most organisms, crossovers forming during meiosis exhibit crossover interference – nearby crossovers are rare. This phenomenon was studied in great detail in Arabidopsis thaliana using a large backcross population for male and female meiosis. We used the gamma two-pathway model by superposing proportion (1- p) of interfering crossovers with p of non-interfering crossovers. It was observed that female meiosis shows higher interference but lower proportion of non-interfering crossovers than male meiosis. Further intra-chromosomal interference comparisons conclude that there are variations between (a) left and right arms, and (b) the central versus distal regions of a chromosome. Then statistical tests revealed heterogeneities in the non-interfering crossover proportion along chromosomes. Thereafter various statistical tools developed to examine a very novel wild-type tomato data annotating crossover positions from both pathways provided evidence for ‘cross-talk’ between the two pathways of crossover formation as opposed to being independent. Finally a model named Pathway-Specific Landscapes Gamma-Sprinkling (PSL-GS) incorporating chromosomal non-uniformity in the individual pathways has been proposed to extend present state-of-the-art interference modeling which consider both pathways to be uniform along chromosomes
Répartition des crossovers méiotiques : hétérogénéité, modélisation de l'interférence, interaction entre voies de formation
No full textFor most organisms, crossovers forming during meiosis exhibit crossover interference – nearby crossovers are rare. This phenomenon was studied in great detail in Arabidopsis thaliana using a large backcross population for male and female meiosis. We used the gamma two-pathway model by superposing proportion (1- p) of interfering crossovers with p of non-interfering crossovers. It was observed that female meiosis shows higher interference but lower proportion of non-interfering crossovers than male meiosis. Further intra-chromosomal interference comparisons conclude that there are variations between (a) left and right arms, and (b) the central versus distal regions of a chromosome. Then statistical tests revealed heterogeneities in the non-interfering crossover proportion along chromosomes. Thereafter various statistical tools developed to examine a very novel wild-type tomato data annotating crossover positions from both pathways provided evidence for ‘cross-talk’ between the two pathways of crossover formation as opposed to being independent. Finally a model named Pathway-Specific Landscapes Gamma-Sprinkling (PSL-GS) incorporating chromosomal non-uniformity in the individual pathways has been proposed to extend present state-of-the-art interference modeling which consider both pathways to be uniform along chromosomes.Dans la plupart des organismes, les crossovers se formant au cours de la méiose sont interférérents : deux crossovers sont rarement à proximité. Nous avons étudié ce phénomène en détail dans la plante modèle Arabidopsis thaliana en utilisant une grande population de rétro-croisements, en méiose mâle et en méiose femelle. Nous avons utilisé le modèle Gamma à deux voies, superposant à la voie interférente une proportion p de crossovers d'une deuxième voie non interférente. La méiose femelle montre une interférence plus élevée et une proportion p plus faible que la méiose mâle. Par ailleurs nos comparaisons intra-chromosomiques concluent qu'il existe des variations d'interférence entre le bras gauche et le bras droit d'une part et entre la partie centrale et les régions distales d'autre part. Nous avons ensuite développé des tests statistiques qui ont révélé des hétérogénéités dans la proportion p le long des chromosomes. De telles variations ont ensuite été trouvées dans un jeu de données de tomate où notre analyse statistique nous a permis de montrer pour la première fois sur un organisme «sauvage» que la deuxième voie était très peu interférente et qu'en fait les deux voies avaient un peu de « cross-talk ». Vu que la limitation la plus sévère des modèles utilisés jusqu'à présent est l'hypothèse de constance du paramètre p, nous avons développé un modèle généralisé où les deux voies peuvent avoir des paysages de recombinaison différents. Ce modèle nommé PSL-GS a été implémenté en logiciel et testé sur des données simulées et sur trois jeux de données de plantes. L'utilisation du critère BIC suggère que tout comme chez la tomate, les paysages de recombinaison d'Arabidopsis et du maïs sont différents entre les 2 voies
