Indian Institute of Science Bangalore
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Optical and Electrical Studies of Hybrid Nanomaterial Composites Based on Noble Metal Nanostructures
No full textLocalized surface plasmon resonance (LSPR) in noble metal nanoparticles like gold (Au) and silver
(Ag) results in enhancements in optical absorption and scattering by the nanoparticles, accompanied by
a dramatic amplification and localization of electric fields to sub-wavelength regions. These
enhancements, especially the confinement of light to such small scales, pave the way for applications
like surface-enhanced Raman spectroscopy (SERS), chemical sensing, and subwavelength guiding and
can be impactful to quantum technologies, especially on-chip light-driven devices.
In this thesis, we discuss in detail the effects of the sub-wavelength confinement of enhanced electric
fields by the plasmonic nanocavities on the optical response of two-dimensional materials (2D) like
Molybdenum disulphide (MoS2 )and Tungsten diselenide (WSe2) for development of new optical
functionalities with scope towards quantum applications. We also briefly discuss the electrical response
of Au-Ag nanostructures fabricated using chemical and physical methods.
At the heart of this work is fabricating the Au-Ag plasmonic nanocavities with sub-nm separation. We,
therefore, engineer an easy-to-fabricate technique to form such nanostructures on demand. Monolayer
MoS2 with a thickness of 0.7 nm is used as a spacer layer for the sub-nm cavity, and the design of the
cavity is chosen based on numerical simulations. We exploit the enhanced absorption of light by the
Au-Ag nanostructures upon resonant illumination and the low thermal conductivity of MoS2 to
collectively localize heat at specific locations resulting in the fabrication of metal nanocavities on
demand. The Raman signal of MoS2 is seen to increase by 40 times, making it a perfect candidate for
SERS applications and other optoelectronic applications. Estimating a temperature rise of ~ 250 ℃ in
the system using AI-enabled pattern recognition further corroborates the desired nanostructuring.
We focus on the effect of similar plasmonic cavities on the optical response of 2D materials toward
applications. We select monolayer WSe2 as our material of choice owing to its tremendous optical and
mechanical properties discussed later. We aim to understand the effect of mechanical strain and
plasmonic cavity on the optical and mechanical properties of WSe2, and optical characterizations of PL
and Raman show a definite effect of the same. A strain of about 0.3% and p-type doping is estimated
for WSe2 embedded in an Au-Ag cavity. While conventional electrical measurements establish the
nature of doping well, these require a different device fabrication strategy. The non-invasive nature of
the PL and the Raman characterizations used here ensures that more complicated electrical device
structures can be avoided.
After identifying the nature of doping and the amount of strain by the cavity over WSe2, we emphasize
the class of interaction between the two entities governing its application scope. Here we describe the
interaction type between WSe2 and Au-Ag nanocavity using a custom-built darkfield setup and provide
evidence that the coupling between them lies in a strong regime, implying the formation of hybrid states.
These have scope for new optical phenomena with non-linearities and device applications, such as low threshold lasers. We explain in detail the features of our plasmonic cavity that help achieve this strong
coupling with a monolayer WSe2 and the energy dispersion of the hybrid states, which shows a very
large Rabi splitting of 170 meV.
We further use the Au-Ag plasmonic cavity to engineer a new geometry to generate efficient single
photon emitters in monolayer WSe2. We show that embedding WSe2 in the plasmonic cavity increases
its exciton emission by atleast five times. A comparison with bare WSe2 and other control samples
shows that our geometry undeniably reduces the line widths of emission with a minimum line width of
120 eV. While we discuss in detail the implications of excitation wavelength, cavity type, temperature,
etc., on these sharp emissions, our results add another device geometry parameter to improve single exciton physics and quantum optics with atomically thin semiconductors. We show that the signal can
be improved further by spectrally filtering individual emitters.
Finally, we describe preliminary experiments on the electrical and optical properties of Au-Ag
nanostructures fabricated using chemical and physical techniques. The anomalous non-metallic features
seen in the electrical response may be relevant to recent reports of superconductivity seen in similar
Ag-Au nanostructures. A detailed investigation is carried out to study the effect of sample composition
and external factors on anomalous response
High-Level Synthesis of Geant4 Particle Transport Application for FPGA
No full textGeant4 is a software toolkit that simulates particle transport in matter and is widely used in high energy, nuclear, and medical physics applications. The toolkit offers a wide range of physics models and geometry configurations to describe particle interactions and tracking in detail. As applications become complex and time-critical, there arises a need to explore custom hardware implementations of the code to reduce simulation times while maintaining high levels of precision. In this thesis, we present the implementation of a Geant4 application on FPGA to explore its acceleration benefits and identify the challenges in porting the code on hardware.
Since the toolkit is written in C++ and uses floating-point algorithms, targeting a hand-coded RTL implementation is not feasible. We use the High-level synthesis technique to synthesize the untimed C++ code to hardware. We present the methodology used to synthesize and optimize the class-based design highlighting the challenges faced in the source-to-source transformation of the code. We also present techniques used to optimize the floating-point operations in the design and their effect on the generated hardware.
Finally, we implement a photon transport application on the Xilinx Alveo U250 FPGA card to analyze the energy deposited by a monoenergetic photon beam in water and compare the implementation with the software for functionality and performance. We also present the successive effect of optimizations on the generated hardware in terms of speed and area and use it to discuss the future directions for improving the simulation performance
Studies on Δ40p53 mediated regulation of specific coding and non-coding RNAs: Consequences on cellular processes
No full textp53 is a crucial transcriptional regulator which influences almost every possible pathway that impinges on the life of a cell. As expected of such an instrumental protein, the molecular network of p53 is as diverse as it is intense. Our laboratory has been working on the only known translational isoform of p53, Δ40p53. Δ40p53 isoform controls the folding, oligomerization and post-translational modifications of p53 complexes, thereby regulating the transcriptional and growth suppressive effects of p53. p53 has been intricately integrated into the non-coding RNA network of the cell through rigorous research over the last decade. Several non-coding RNAs that p53 regulates have been identified over the past few years of extensive studies. However, the role of Δ40p53 in regulating non-coding RNAs either via co-regulation through hetero-tetramerization with full-length p53 (FLp53) or via direct regulatory mechanisms has remained largely unexplored. p53, in consistence with its effect as the guardian angel of cells, is inhibitory to the development and survival of cancer stem cells. Δ40p53 has proven to be different from its "big brother," FLp53. It has been implicated in anti-aging, maintenance of hematopoietic stem cells and developmental programs. Against this anomalous functional behavior of Δ40p53, a pertinent question is whether this isoform plays a role in developing and maintaining cancer stem cells or stem-like cells.
To explore the direct regulatory mechanisms of ∆40p53, we have studied its role in regulating non-coding RNAs and its possible consequences on cellular processes. Moreover, we have also studied the atypical function of Δ40p53 in the biogenesis of stem-like cells.
Therefore, the specific objectives are as follows:
1. To study the mechanism and implications of lncRNA regulation by ∆40p53.
2. To elucidate the specific role of ∆40p53 in modulating the expression of miRNAs and their downstream mRNA targets.
3. To investigate the definite effect of ∆40p53 on the biogenesis of cancer stem-like cells mediated by regulation of cellular mRNAs
Objective 1: To study the mechanism and implications of lncRNA regulation by ∆40p53
To study the lncRNAs that are influenced differentially by ∆40p53 and FLp53, an RNA microarray was earlier performed in our laboratory by overexpression of ∆40p53 and FLp53 in H1299 cells (p53 null adenocarcinoma cell line). From the same data set, we validated the lncRNAs, of which many were uncharacterized in the literature. Among the lncRNAs, we selected LINC00176 for further detailed investigation due to its known function of miRNA regulation and differential effect on cellular processes. Upon validation, LINC00176 levels were affected predominantly by the overexpression and knockdown of ∆40p53. Further, under DNA damage, ER stress, and glucose deprivation, LINC00176 was upregulated in HCT116 p53-/- cells (harboring only ∆40p53) compared to HCT116 p53+/+ cells. To understand the mechanism of regulation of the lncRNA, ChIP, RNA Stability and UV-Crosslinking Assays were performed. It revealed that Δ40p53 (and not FLp53) could transactivate LINC00176 transcriptionally and regulate its stability. Results suggest that the increased abundance of LINC00176 in the presence of ∆40p53 compared to p53 could be due to its dual regulation at the genome and transcriptome level. LINC00176 was ectopically overexpressed and partially silenced in HCT116-/- cells to determine the direct cellular effect. Results indicate that LINC00176 increases epithelial cell markers while reducing cell viability and proliferation. Interestingly, RNA pulldown also revealed that LINC00176 sequesters several putative miRNA targets (miR-761, miR-184, miR-508, miR-138, miR-15b-5p) to regulate the cellular processes. Results provide essential insights into the pivotal role of ∆40p53 in regulating the novel LINC00176 RNA-microRNA-mRNA axis independent of FLp53 and in maintaining cellular homeostasis.
Objective 2: To elucidate the specific role of ∆40p53 in modulating the expression of miRNAs and their downstream mRNA targets.
We previously demonstrated that Δ40p53 independently regulates miR-186-5p-YY1 to reduce cell proliferation, implying that it may have broader effects on the expression of other micro RNAs. In this study, we performed small RNA sequencing to identify the pool of miRNAs differentially regulated by ∆40p53 and FLp53. We report that the expression of specific miRNAs is regulated explicitly by ∆40p53. miR-4671-5p, miR-548ae-5p, miR-301b-5p, and miR-34a-5p were shortlisted for further studies based on their significance and differential fold changes obtained in the sequencing. Preliminary results suggested that miR-4671-5p gets differentially regulated, with a significant decrease in its levels upon ∆40p53 overexpression and no change with FLp53 overexpression. miR-4671-5p abundance changed according to the ratios of FLp53 to ∆40p53, indicating the physiological relevance of its regulation by both isoforms. We performed bioinformatic analysis and selected N-sulfoglucosamine sulfohydrolase (SGSH), cyclin-dependent kinases (CDK) 11B and CDK5 regulatory subunit 1 (CDK5R1) as the potential targets of miR-4671-5p, all of which are involved in driving cell cycle progression. To check if miR-4671-5p directly binds to the potential targets, wild-type and mutant target 3'UTRs were cloned. Luciferase assay with the wild type and mutant 3'UTRs in the presence of miR-4671-5p depicted CDK5R1 and SGSH as direct targets of miR-4671-5p. SGSH gene expression levels have potential prognostic relevance on survival that trends in the opposite direction of miR-4671-5p levels associated with the same cancer types, supporting a possible physiological relevance of the interaction. Overexpression of miR-4671-5p directly inhibited SGSH and triggered intra-S-phase cell cycle arrest. ∆40p53-miR-4671-5p-SGSH axis emerges as a novel axis capable of regulating cell cycle progression. These results enhance understanding of ∆40p53 functions mediated by miRNAs that help to maintain metabolic and cellular homeostasis independently of FLp53.
Objective 3: To investigate the role of ∆40p53 in the biogenesis of cancer stem-like cells
Cancer stem cells are a specific subpopulation of cells in a cancerous background, which enjoy the ability of self-renewal and the enhanced capability to generate tumors. p53 is known to inhibit the survival and maintenance of cancer stem cells. However, in this context, Δ40p53 has proven to be different from its "big brother." In a different context, Δ40p53 has been integrated into various development programs and is involved in the maintenance of stemness. It has also been shown to inhibit aging. The molecular factors causing such ∆40p53-mediated consequences are largely unexplored. To characterize the differences in cancer stem-like cell propagation in the presence of p53 and ∆40p53, we have investigated Cancer Stem Cell phenotypic profiles in HCT116-/- and HCT116+/+ cell lines and evaluated their correlation with several CSC functional properties, including spheroid formation ability, side population (SP) phenotype, cell surface marker expression and sensitivity to anticancer compounds.
A higher percentage of cancer stem-like cells (side population cells) was observed in ∆40p53 (in HCT116-/-) than in HCT116+/+. Further, chemosensitivity assays, analysis of stem cell markers, and sphere formation assay with HCT116-/- and HCT116+/+ elucidated new insights into our understanding of the ∆40p53 function. HCT116-/- showed chemoresistance with an increased dosage of 5-FU (5-Fluorouracil) compared to HCT116+/+, which was sensitive under the same drug conditions. We also observed large irregular spheroids for HCT116-/- compared to smaller ones in HCT116+/+. The differential phenotypes observed in the two cell lines indicated that various molecular players could drive them. Therefore, a total RNA sequencing was performed with HCT116-/- and HCT116+/+. We found 206 significantly differentially expressed mRNAs between the two cell lines confirming molecular level changes contributing to the above phenotypes. Further, some of the significant genes were validated, correlating to our above observations and enhancing our understanding of ∆40p53-mediated functions.
Taken together, we have investigated the exclusive role of ∆40p53 on non-coding RNAs (miRNAs and lncRNAs) and their consequences on cellular processes. Parallelly, we have also investigated the atypical role of ∆40p53 (taking p53 as a reference point) in maintaining cancer stem-like cells driving cancer progression.IISc-MHR
Structural and Thermoelectric Studies of Sb2Te3 and Bi2Te3 Based Chalcogenide Alloys and Nanocomposites
No full textThermoelectricity is one of the potential solutions for the rapidly increasing energy demand. Thermoelectric generators can turn waste heat into usable energy. Due to their effectiveness in the 300 K to 500 K temperature range, Sb2Te3 and Bi2Te3 are two of the most researched thermoelectric materials. These thermoelectric materials that operate at room temperature can have their thermoelectric performance improved through doping, nanostructuring, orientation engineering, and nanocomposites, among other techniques. Due to their capacity to lower thermal conductivity (κ) while maintaining a high-power factor (PF=S2σ), nanocomposites and doping techniques have garnered the most attention among them. The rate of melt solidification has recently been demonstrated to have the ability to dramatically adjust the thermoelectric characteristics to a greater extent.
The thermoelectric characteristics of Sb2Te3/Te nanocomposites and Bi2Te3 alloy were examined in the first section of this thesis. This work has shown that the rate of melt solidification has a substantial impact on the structural and thermoelectric properties. It has been demonstrated that the optimum way to get better thermoelectric performances is with moderate melt quenching rates (normal water and ice water quenching).
The thermoelectric properties of nanocomposites made by combining Sb2Te3 and poly methyl methacrylate (PMMA) have been studied in the second section of the thesis. For polymer nanocomposites, thermal conductivity was found to be significantly reduced. A 30% reduction in thermal conductivity has been seen with 5% polymer composites.
In the last part of the thesis, the effect of Zn doping on Sb2Te3 has been studied. The prepared powder samples were sintered by spark plasma sintering (SPS). An increase in Zn doping increased the power factor considerably because Zn+2 doping in place of Sb+3 in Sb2Te3 acts as an acceptor. It increases p-type carrier concentration and thereby enhances the electrical conductivity. The thermoelectric figure of merit was found to increase by 12 % for the Zn-doped Sb2Te3. The zT of the SPS sintered Zn-doped Sb2Te3 is increased by 80% compared to the as-prepared Sb2Te3 ingot. The results presented in this thesis demonstrate that the zT of thermoelectric materials can be modulated by using different melt solidification rates, doping, and by forming nanocomposites
Improved Methods for Filtration, Drainage and Structural Evaluations With and Without Geocomposites for Subsurface Drainage of Pavements
No full textPavements are continuously exposed to the environment leading to ingress of water from multiple sources that structurally weakens the pavement materials. The conventional solution for drainage requires granular material of a minimum thickness of 250 mm, reflecting a massive demand for suitable quality aggregates. The potential alternative to reduce the demand is incorporating a drainage geocomposite in pavements. In this thesis, improved methods for filtration, drainage, and structural evaluations with and without geocomposites are developed. The unbounded granular materials are required to be internally stable to perform self-filtration. This study investigates the practical utility of Cu and Cc in evaluating the internal stability of soils. A theoretical approach for predicting critical hydraulic gradients is developed based on the notion of differential void states of fine fraction of internally unstable soils. Granular and geotextile filters are provided in the subsurface drainage systems to limit soil erosion and allow unimpeded water seepage. In this thesis, improved design criteria are developed for the filter requirements of soil retention, hydraulic conductivity, and clogging. Further, a new approach based on the demand-capacity model is developed for the hydraulic design of granular and granular-cum-geocomposite drainage layers in pavements. Lastly, the influence of the granular filter characteristics and geocomposite on the modulus of the subgrade-subbase interface is investigated based on the Resilient Modulus tests of composite samples. Improvements to current codal provisions and specifications for subsurface drainage of pavements are suggested and illustrated
Unravelling the kinematics, dynamics and structure of galaxies using H I - 21cm observation
No full textThe advent of the multi-wavelength observations of galaxies in this recent era gives us the opportunity to study the details of the different pivotal facets of galactic astrophysics. Among the observations in different wavelengths, the H I interferometric observations are of immense importance and useful. Several extensive H I 21cm interferometric observations of nearby galaxies have been performed in the last few decades, and they comprise a large number of data sets. It has now become essential to appraise the existing archival data so that this large sample volume can be used to examine the completion and coverage of sources. To explore the potential of these archival data, we constructed a sample from all the galaxies observed in 21cm by the Giant Meter wave Radio Telescope (GMRT). This results in a total of 515 galaxies, the largest sample to date. We intend to analyse all this data uniformly and carry out different exciting science cases. In this regard, We have started carrying out this exercise of GMRT ARChIve Atomic gas survey (GARCIA) (Biswas et al. 2022) with a pilot sample of eleven galaxies and explored different science cases. As a first step in this regard, we use the data products of this pilot sample to identify the warm and cold phases of the interstellar medium (ISM) using Multi-Gaussian decomposition method. For all our galaxies, we observe a bimodality in the distribution of widths of the decomposed Gaussians of the spectra, indicating the two neutral phases of the ISM. Most of the previous studies of distinguishing these two phases were limited to spectra with a signal-to-noise ratio (SNR) of 10 or above. However, our method successfully distinguishes these two phases at a much lower SNR of 5, resulting in the detection of more cold gases inside these galaxies. We found that the outskirts are dominated by cold gas for most of our galaxies, whereas warm gas dominates the central region. This could happen because in the central region, star formation activity is higher, and hence, there exists an increased amount of turbulence.
To comprehend the fundamental aspects of galaxy structures, dynamics, composition, formation and evolution; it is important to have proper understanding of the kinematics and distribution of different components of the galaxies. In this regard, we present the 3D kinematical models of these galaxies by fitting the Tilted-ring model to 3-dimensional data cubes and discuss the importance of doing 3D kinematic modelling over 2D kinematical modelling (fitting the Tilted-ring model to the 2D velocity field). Equipped with the rotation curve from 3D kinematical modelling, we build a robust technique for galaxy mass modelling. We model this observed H I rotation curve using 3.6 μm infrared data and SDSS r-band data for stellar contribution, H I surface density profile for gas, and Navarro-Frenk-White (NFW) profile (Navarro et al. 1996) for dark matter halo. We employ the Markov Chain Monte Carlo (MCMC) optimisation method for parameter estimation and model the rotation curve. This is for the first time when the 3D modelled rotation curve; stellar kinematics derived using the Multi-Gaussian Expansion (MGE) (Cappellari 2002) technique and Jeans Anisotropic Modelling (JAM) (Cappellari 2008); along with the contribution of gas derived from our own developed method that does not assume any profile beforehand; have been put together for doing the mass modelling of galaxies via MCMC optimisation method. Further, to validate our analysis, we compare the parameters derived from our method of 3D kinematic modelling and mass modelling with important scaling relations, i.e., the Mgas -Mstar, Mstar -Mhalo and Mgas -Mhalo relations and found that they are in good agreement with these relations.
Further, it has been well observed that there exists a global non-axisymmetric lopsided mass distribution in approximately 30% of late-type galaxies within the nearby Universe (Varela-Lavin et al. 2022). The recent observations from Spitzer survey (Sheth et al. 2010) and studies with the disk galaxies from TNG50 simulation (Varela-Lavin et al.2022), it has been anticipated that lopsidedness is a generic trait of galaxies and does not typically depend on a rare event such as interactions or mergers. This phenomenon puts additional constraints on the existing galaxy formation and evolution models. Hence it is important to understand the origin of this lopsidedness. In this regard, we investigate both the kinematic and morphological lopsidedness of the galaxies from the GARCIA pilot sample. Through a theoretical consideration, Jog (2002) showed that both the kinematic lopsidedness and morphological lopsidedness can be explained by the response of a galactic disk to a lopsided halo potential. Previous studies by van Eymeren et al. (2011) showed that the values of the halo perturbation parameter found kinematically and morphologically by the Fourier decomposition method differ from each other depending upon the type of differences in rotation curves from both arms. However, we found that irrespective of the nature of differences in the rotation curves of the two arms, the halo perturbation parameter found kinematically and morphologically are both in the same range. Our results suggest that the perturbation parameter found kinematically and morphologically are consistent with the prediction from Jog(2002).
Moreover, our robust techniques of 3D kinematic modelling and mass modelling are further applied for an extended number of sources from the CALIFA survey (Calar Alto Legacy Integral Field Area survey, Sánchez et al. 2012, 2016). We have observed a sample of 15 of the CALIFA galaxies, which are at different stages of quenching, through uGMRT, as a part of the MasQue (Mass Modelling and Star-formation Quenching of Nearby Galaxies) (Kalinova et al. 2021) project. Acceptable fits for the mass modelling were obtained for seven sources in this sample. The parameters found in the 3D kinematic modelling and mass modelling of GARCIA and CALIFA sources are used to revisit one of the most important scaling relations in Astrophysics, i.e., the Baryonic Tully-Fisher relation (BTFR). Most of the previous studies of this relation are based on the velocity widths from the single-dish spectra corrected for the optical inclinations (e.g, McGaugh et al. 2000) or with rotation velocity from 2D kinematic modelling (Lelli et al. 2019). As there are discrepancies in inclination and velocity found in 3D and 2D kinematic modelling, we revisit this relation with parameters from 3D kinematic modelling and compare the results with the existing literature. Although our sample size is moderate, our study shows the importance of revisiting this relation with the 3D kinematic data and with a larger sample of galaxies.
To conclude, through our studies, we have shown the potential of archival data to extract various science cases; presented the robust method and the details of the kinematic and mass modelling for a number of 18 sources; showed the importance of revisiting BTFR through 3D kinematically modelled data and found that kinematic lopsidedness and morphological lopsidedness are comparable irrespective of the nature of the difference in the rotation curve. Though these studies are currently limited to the pilot sample of the GARCIA galaxies, the same will be done with the analysed data products of the next and successive batches of GARCIA. Besides that, in the upcoming era of big interferometers such as Square Kilometer Array (SKA), where the data will be saved in the image domain, these apprised archival saved in the visibility domain will be helpful to revisit the raw data and apply improved calibration techniques or investigating the instrumental and environmental effects or processing new algorithms as they become available
Structure-Property Correlation in Additively Manufactured High-Temperature Materials: Insights from Nickel-Based Superalloy IN718 & Nickel-Based Eutectic High Entropy Alloy AlCoCrFeNi2.1
No full textHigh-temperature alloys are technically very important materials that possess higher resistance toward mechanical and chemical degradation at 0.4-0.6 TM for a constant/cyclic load. These attributes make them candidate materials for aerospace and energy generation systems that require harsh operating conditions. The most popularly used high-temperature alloys are the Nickel-base superalloys, and among various Ni-base alloys, Inconel 718 (IN 718) is the most used material. The currently used superalloys are already exploited to very high operating temperatures near their solidus or the precipitate solvus temperatures. Any further increase in Carnot efficiency is only possible through design improvements and enhanced turbine cooling efficiency, which the Additive Manufacturing (AM) technique can address. However, the adoption of AM processes for aerospace/mission-critical components is impeded due to microstructural heterogeneities and spontaneous defects observed in AM-produced parts. It is, therefore, necessary to develop processes that head to minimum porosity and design suitable heat treatments, and to evaluate the relevant mechanical properties post-heat treatment. A further approach could be to develop some new alloys that could be additively manufactured and exhibit the desirable properties.
The work carried out in the present thesis is aimed at addressing both these issues. In the first part of the thesis, attempts have been made to develop suitable heat treatments that would lead to desirable microstructures for tailoring relevant optimal mechanical properties that could render the material for the desired applications. Both the most commonly used routes of powder bed additive manufacturing have been used, namely the Electron Beam Melting (EBM) and the Selective Laser Melting (SLM). Heat treatment schedules have been designed for both the so-obtained materials, and the microstructure, texture, and mechanical behavior of the as-built and heat-treated AM materials have been investigated. In the case of IN718, the specially designed heat treatment was aimed at optimizing the volume fraction of coherent and incoherent precipitates, and their role in the mechanical response has been explored in greater depth. In the second part, the present work will be substantiated with another class of high-temperature material, Ni-base eutectic high entropy alloy (EHEA) AlCoCrFeNi2.1 has been produced by additive manufacturing which has shown better mechanical response than the conventional Ni-Al system. A comprehensive understanding of room and high temperature mechanical properties has been developed
Insights into life-cycle stage transition of Trichomonas vaginalis and advancement in its diagnosis
No full textTrichomonas vaginalis is a protozoan parasite and the causative agent of the most common non-viral, sexually transmitted disease (STD) in humans known as trichomoniasis. WHO estimates more than 270 million cases of trichomoniasis worldwide throughout the year. There is a lack in the understanding about its life cycle and mode of transmission. There are a few reports where non-sexual transmission is also observed, but the mechanism remains unclear. T. vaginalis is mostly prevalent in women in their reproductive age. Thus, the parasite must deal with changes in vaginal epithelium, cervical mucus, pH, redox potential, and overall modulation of the vaginal microbiome that occurs during the menstrual cycle. The survival and success of the parasite requires a robust and specialized machinery to tackle these stresses. The only drug of choice for trichomoniasis is metronidazole and drug-resistance are on the rise. There is also a lack of accurate diagnosis for the detection of T. vaginalis infection as the current diagnosis is mostly based on the clinical presentation of symptoms and is inaccurate.
The life cycle of Trichomonas vaginalis possess a trophozoite form which is transmitted sexually. In our study, we demonstrated the presence of Cyst-like structures (CLS) in the life cycle of T. vaginalis and characterized it under different stress conditions. This CLS form can survive in unfavourable conditions such as osmotic imbalance and presence of detergents and possess a thick cell membrane. This CLS stage can convert back to trophozoite form when favourable conditions return. The CLS form was observed to co-exist with trophozoite form in vivo in patient’s vaginal swab samples, indicating that CLS can also be infective. To understand the mechanism of formation of CLS, we have performed 2DGE and mass spectrometry based in-depth proteomics by using label free approach. We observed that the morphological transformation from trophozoite to CLS is coupled to less metabolic activity and alterations in proteins of adhesion and cytoskeletal reorganization. We also observed metronidazole resistance in CLS which is in range of the drug resistance observed in trophozoite forms of resistant strains.
In addition, we have biochemically characterized an important organelle present in Trichomonas known as hydrogenosome. Using mass spectrometry, we performed an exhaustive proteomics analysis to classify the identified proteins into their functional pathways. The study allows understanding of this ill-explored organelle present in an early branching eukaryote. We have developed a point-of-care diagnostic test for the detection of antibodies against the T. vaginalis infection in humans, which can be used in healthcare settings for accurate diagnosis.
Altogether, our study establishes a transmissible stage in the life cycle of T. vaginalis which can be transmitted non-sexually. In addition, the study highlights metabolic characterization, emergence of drug resistance and development of its point-of-care diagnostic tool for its infection
A Fundamental Investigation Of Discrete Liquid, Gas And Fines Flow In A Random Packed Bed Along With Applications
No full textThe discontinuous nature of liquid flow in a random packed bed is observed in many chemical engineering and metallurgical applications like blast furnace and heap leaching. So, to model the liquid flow in these systems, the discrete nature of the liquid flow should be taken into consideration. Moreover, the effect of gas flow on the particles and liquid phase of the packed bed, taking into account the random nature of the bed and the discrete nature of the liquid, is lacking. Therefore, fundamental understanding of the liquid-solid-gas interactions in a random bed is important to improve the processes.
To understand the effect of gas-solid interaction, a slow-moving packed bed, inside the reactor, has been considered. Particles are discharged from the bottom and gas is injected laterally. The gas flow has been modelled using continuum-based fluid flow equations. It is found that gas flow is not symmetric inside the reactor due to significant variation in void sizes inside the bed. This along with gas variation also affects the residence time of each particle inside the bed.
This work is extended to the liquid flow in random bed using Discrete Liquid Flow (DLF) theory. A novel graph-based recursive Depth First Search (DFS) algorithm is developed to find the shape and size of voids in the random bed. The liquid flow behaviour has been studied in various conditions, like changing the packing size and bed height. This study confirms that the bed topology plays an important role in dictating the liquid flow behavior in a randomly packed bed. Using the DLF, DFS, the various phenomena, which occur in a multiphase flow packed bed, such as rupturing of rivulets, liquid hysteresis have been understood and explained fundamentally.
The study is further extended to heap leaching process, where the liquid flows as droplets and rivulets due to very low liquid flow rates. The liquid flow behaviour is studied in terms of tortuosity, liquid distribution, breakthrough time, contact angle etc. The study shows that heap leaching processes can be modelled in more accurate and deterministic way using DLF theory along with DFS algorithm by avoiding the uncertain experimental parameters (like bed permeability etc).
Finally, the flow behaviour of the liquid phase in a random packed bed is studied, taking into account the movement of particles due to the lateral gas and fines injection. The deviation of the liquid path due to the gas and fines drag is also captured. It is found that the deviation of the liquid path is higher for the larger particle sizes
Micro-carriers mediated bacteriophage delivery for targeting intracellular Mycobacterium tuberculosis infection and TB prevention
No full textTuberculosis (TB) is a debilitating infectious disease that afflicts 10 million people every year. Treatment is particularly challenging due to prolonged treatment duration (4-6 months) consisting of an oral regimen of 4 antibiotics. Discontinuation of treatment due to patient non-compliance often results in a relapse of infection and increased antibiotic resistance. Multidrug resistant TB (MDR-TB) is an alarming global health issue, with a prevailing incidence of 450 000 cases and an estimated 200,000 deaths in 2021. There is a clinical need to find effective treatments against drug-resistant strains and develop a patient-compliant method of drug delivery. In this work, we have used polymeric microparticles to establish an inhalation-based platform for delivering TB drugs. We also focus on bacteriophages, which are bactericidal even against antibiotic-resistant strains. We work towards developing microparticle-based approaches to improve their access to intracellular niches and deposition in lungs.
Mycobacterium tuberculosis (Mtb) infects host macrophages and continues to survive and grow intracellularly. To target this intracellular reservoir in macrophages, first, we engineered polylactic-co-glycolic acid (PLGA) microparticles. Positively charged poly-l-lysine-conjugated micron-sized particles demonstrated remarkable internalization by Mtb-infected THP-1 macrophages and primary bone marrow-derived macrophages. Cationic microparticles also exhibited higher uptake in all immune cells and alveolar macrophages upon intra-tracheal delivery in vivo. We then proceeded to extend the application of this platform to deliver bacteriophages within infected macrophages.
Bacteriophages have limited penetration within mammalian cells and cannot efficiently interact with intracellular bacteria. Cationic microparticles served as excellent phage-carriers as they delivered two log-fold higher phages intracellularly compared to non-modified particles. Intracellular Mtb can reside within several intracellular compartments, such as endosomes, lysosomes, or cytosol. To improve the colocalization of microparticles with Mtb, we chemically conjugated Transferrin (Tf), which is known to be recruited by intracellular bacteria. Tf-coated cationic microparticles exhibited enhanced interaction with the mycobacterial phagosome.
Due to the high prevalence of the disease, especially in high-risk populations such as HIV patients, healthcare workers, and family members of TB patients, we envisioned an inhalable formulation that can be administered regularly to prevent the development of infection. We tested if bacteriophages can be used as prophylactic agents for TB and observed significant protective effect. We also synthesized 5-7 µm PLGA porous particles to improve phage delivery.
Bacteriophages are subjected to several biological barriers during in vivo administration which limits their application especially for lung-associated intracellular infections. Biomaterial-based approaches can be applied to improve phage pharmacokinetics and efficiency. Local delivery to infection sites is most preferred as phages require direct contact with bacteria for their action. In this work, we have developed PLGA microparticles to enable bacteriophage internalization within infected cells and bacteriophage deposition in lungs upon intra-tracheal delivery. This work opens doors for further development of inhalable carriers for bacteriophages.Department of Biotechnology (DBT-JRF