Indian Institute of Science Bangalore
etd@IISc Electronic Theses and Dissertations at Indian Institute of ScienceNot a member yet
6204 research outputs found
Sort by
Ageing associated altered host response to bacterial infection
No full textChapters in which I have elucidated and elaborately described how senescence alters the cellular response to infection, here I demonstrate how senescence in multiple tissues simultaneously contribute to pathogen spread and colonization. The relevance of our in vitro observations of senescent cells being less conducive for bacterial proliferation was extended in vivo using the naturally aged mouse model. In this in vivo model of infection also we find lesser bacterial burden in aged animals and evidence from cell infection data suggests that the accumulation of senescent cells in these organs could perhaps be a major contributing factor. Hence, for the first time we demonstrate an alternate advantage of senescent cell presence and persistence in the system besides its well described contribution to wound healing (Demaria et al, 2014). Ageing associated persistent inflammation and oxidative stress reflect innate immune system preparedness to fight impending infections which is beneficial to an organism witnessing a decline in adaptive immune responses as is associated with the elderly. However, inability to manage these responses beyond its intended control of infection results in excessive damage to the host and subsequent mortality.
In summary, this Chapter presents senescence or ageing associated oxidative stress and inflammation as a Goldilocks situation and highlights the need for identification of senotherapeutic agents that can decrease aggravated systemic inflammation without perturbing other host favourable factors like anti-microbial responses for use as adjunct therapy in infected aged individuals
Understanding the Mechanism of Noncanonical Functions of RAGs in Lymphoid Cancer and Glioblastoma
No full textRecombination activating genes (RAGs) composed of RAG1 and RAG2, are the endonuclease involved in V(D)J recombination, which is critical for adaptive immunity in mammals. Activation-induced cytidine deaminase (AID), expressed in germinal B cells, deaminates CpG/ methylated CpG, generating single nucleotide mismatch of either U/G or T/G. Several studies suggest that RAGs and AID are the key players responsible for the generation of chromosomal translocations.
In summary, noncanonical functions of RAGs were explored in the present study. In the first part, we investigated whether a combination of RAG and AID activities can explain mechanism of uncharacterized fragile regions associated with several lymphoid cancers. Through combination of in silico and biochemical assays, we propose a novel mechanism of generation of chromosomal rearrangements in lymphoid cancers, mediated by both AID and RAGs, where RAGs bind to nonamer and cleave at adjacent mismatch generated due to deamination of meCpG or unmethylated cytosines.
In the second part of the thesis, the expression and functional relevance of RAGs in glioblastoma was explored. The present study showed RAGs expression in majority of human glioblastoma cell lines. We show that RAG contributes to recombination events involved in chromosomal aberrations seen in high grade glioma. Our data suggests the potential role of RAGs in chromosomal rearrangements associated with glioblastoma
The Effect of Gamma Radiation on Protein Structure and Dynamics
No full textGamma radiation being the most energetic form of electromagnetic radiation has applications in number of different fields such as in medicine for treating cancer, food sterilization and in astronomy for studying phenomenon like gamma ray bursts. However, the mechanism of action or the residue wise information of the effects of gamma radiation is lacking. Also, most of the research in this direction has been to study the effects on DNA. But cells contain other biomolecules also and so we took up protein molecule for our study. The study on the effect of gamma radiation on proteins could form an essential part in our understanding of how it changes the structure of these biomolecules which could help us in explaining how it is able to cure cancer or could provide answers to questions like how life originated on earth and the possibility of existence of extraterrestrial life.
In this thesis, with this objective, we have tried in unraveling some of the effects of gamma radiation on proteins with the spectroscopic techniques of NMR and Mass. The first chapter gives a brief overview of the gamma radiation overall and explains some of the research work done previously by others along with introducing the techniques of NMR Spectroscopy and Mass Spectrometry which we have used for the first time to perform the studies. NMR being one of the most sensitive techniques in providing atomic level details in proteins has been used extensively to study the effects. The second chapter deals with the effect of gamma radiation on one such protein Ubiquitin. Since, Ubiquitin is a very stable protein and also it is involved in the cancer metabolic pathway, the effect of gamma radiation on Ubiquitin was taken up for the study.
The outcome of the study is that gamma radiation has a dosage and sample dependent effect on the protein. Ubiquitin as a globular protein in its pure form in showed no observable effect at low dosage of irradiation that is being used for cancer treatment. However, at higher dosage of radiation, there were substantial changes in the structural and dynamical properties of the protein which is discussed in details in the thesis
Investigation of Thin Films for Frequency Selective Surface Based Radar Absorbing Structures
No full textModern day stealth aircraft uses microwave absorbers for absorption of incident Radar signals transmitted by rival aircraft. Recently, several attempts were made to fabricate radar absorbing structures (RAS) of various configurations and embedding frequency selective surfaces (FSS), in the form of periodic 2-D patterns, is one of the approaches. The FSS is fabricated from resistive thin films which are usually coated on a dielectric substate. The use of thin films with optimum properties is essential for achieving broadband microwave absorption. For stealth aircraft structures, there exists a need to synthesize and investigate resistive thin films having properties ranging from good optical transparency, electrical conductivity coupled with good mechanical properties and structural integrity. In this work, sputter coating of thin films of Gold, Indium Tin Oxide (ITO), Silver Nanowire were attempted on Polymethyl Methacrylate (PMMA), a difficult substrate (PMMA) to process in vacuum, and characterized for their optical & electrical properties and environmental stability. Thin film of ITO emerged as the suitable candidate and the film properties were further tailored such that it can be employed as top FSS layer and backplane of the optically transparent RAS. The RAS was designed using CST microwave studio by employing Jerusalem Cross as FSS element. The absorber configuration was optimized for wide bandwidth performance, good angular stability and polarization insensitiveness. Similarly, Nickel thin films were deposited on E-Glass fabric and electromagnetic and mechanical properties were characterized to examine their suitability for load bearing structural members. Integral RAS for both optically transparent and structural applications were fabricated for the optimized configurations. The optically transparent microwave absorber was shown to exhibit polarization independent absorptivity with a bandwidth of 8.5 GHz and good angular stability up to 45o. The absorber for structural applications was shown to possess good absorptivity with a bandwidth of 6.5 GHz in comparison to the bandwidth of 4.5 GHz exhibited by a conventional particle loaded absorber which was also fabricated in this wor
Optimal Redundancy in Distributed Systems for Latency and Repair
No full textDistributed systems are employed in many modern storage and computing architecture for greater reliability and cost-efficiency. There are several important considerations in the design and implementation of such distributed systems, such as latency, availability, storage cost, among others. We look into the interplay between redundancy and the parameters, latency and repair for the design of such systems.
Data is replicated and stored redundantly over multiple servers for availability in distributed databases. In this thesis, we first study the impact of redundancy on system latency in distributed databases. We focus on databases with frequent reads and writes, where both read and write latencies are important. This is in contrast to databases designed primarily for either read or write applications. Redundancy has contrasting effects on read and write latency. Read latency can be reduced by potential parallel access from multiple servers, whereas write latency increases as a larger number of replicas have to be updated. We quantify this tradeoff between read and write latency as a function of redundancy and provide a closed-form approximation when the request arrival is Poisson and the service is memoryless. We empirically show that this approximation is tight across all ranges of system parameters. Thus, we provide guidelines for redundancy selection in distributed databases. Further, we demonstrate the existence of optimal redundancy even in systems with non-memoryless service through simulations and experiments on practical systems.
Secondly, we propose a redundant scheme that introduces repair locality in distributed computation. In contrast to the previous model, we consider performing computations other than simple read and write across the distributed system. In distributed computing, a computation job is split into multiple tasks, and the tasks are executed over multiple nodes. In such a setting, slow compute nodes, referred to as stragglers, pose a bottleneck on the job computation time. For distributed computing of multivariate polynomials, Lagrange coded computing (LCC) proposed in literature tolerates an optimal number of stragglers while providing security against adversaries. Introducing repair locality in this setting reduces the number of worker nodes contacted to recover a particular computation and allows clients/intermediate nodes to compute individual function outputs. We propose a distributed polynomial computing scheme, where data is encoded using Tamo-Barg codes with carefully chosen parameters. We show that the scheme tolerates a larger number of stragglers when compared to the repeated LCC and Product Lagrange coded schemes for certain parameters. Furthermore, we provide an alternate proof for the optimality of LCC for multilinear functions based on properties of multivariate polynomial interpolation
Simulation and Characterization of Streamflow Time Series
No full textStreamflow can be partitioned into distinct time scales to better understand the underlying governing processes: fast flow, representing surface runoff controlled mainly by meteorological processes that operate over relatively shorter time scales and slow flow, representing the baseflow through groundwater flow and subsurface flow that occur at a slower rate. Because of the significant differences between fast and slow process controls, each may be used to explain streamflow variability independently. The thesis considers this concept by including seasonal (timing) streamflow variability in a regional context. In order to isolate the effects of these drivers on the observed Flow Duration Curves (FDCs), a modeling framework is developed that comprises of partitioning streamflow in multiple ways: seasons/months in the time domain, east-west/north-south directions in the space domain, fast/slow flows in the process domain, and small to large catchments to account for the size of the catchment in a basin. This modeling framework is demonstrated through the Peninsular Indian river system, in which the hydrology is primarily governed by the monsoon rains. The framework of stratifying streamflow variability consists of three independent elements: (i) process partitioning: partitioning of the total streamflow into the fast flow and slow flow, each of which is impacted differently by climate and landscape properties, (ii) time scale partitioning: stratifying the temporal streamflow variability into distinct seasons namely-South-West monsoon, North-East monsoon, and Non-monsoon, and (iii) investigating the directional aspects of west-east and north-south gradients in the space domain. Findings of the study showed that South-West monsoon and fast flows are the major contributors to mean annual flow and total flow respectively, in these river systems. The spatially increasing mean rainfall towards the northern part and favourable geology compounded by seasonal rainfall pattern in the southern parts of the Peninsular region control the directional variation of fast and slow flow contributions to total flow respectively. The rainfall variability due to monsoons and mountain ranges, and regional geology, are dominant climatic and landscape drivers of streamflow variability across the region. Moreover, the seasonal rainfall patterns and subsurface flows regulate the combined influence of time scale and process controls on total flow.
Synthetic daily streamflow generation requires a critical understanding of the underlying dynamics resulting from the inherent time irreversibility in the rising and falling limbs of the hydrograph. Most models in literature considering the time irreversibility deal with single site streamflow simulation. Addressing intersite dependencies is, however, crucial for interconnected stream networks. The thesis presents a multisite streamflow generating framework to simulate concurrent streamflow sequences. This framework explicitly takes into account the spatial correlation and time irreversible dynamics of streamflow. A few streamflow gauging stations in the Godavari River Basin, located in Southern India, are considered to demonstrate the applicability of the framework. Through this work, the thesis contributes to the methodological development of streamflow simulation by capturing temporal asymmetry hydrograph and spatio-temporal dependency structure among multiple stations. The modeling procedure consists of the following steps: (i) fitting statistical models to the ascension and recession limbs of the hydrographs in the historical streamflow time series, (ii) constructing a set of correlated streamflow states through a nonparametric approach to address the dependence characteristics of streamflow across multiple stations, and (iii) simulating the multisite streamflow sequences that are consistent with the asymmetry of the ascension and recession limbs of the hydrograph. The proposed framework shows the ability to adequately generate multisite simulations capturing at-site statistics as well as intersite correlations for the case study. Furthermore, the approach ensures that the simulated flow values are not merely resampled from the historical data but uses the physical features of the hydrograph and shows variability beyond that observed in the historical sequence. Such a rich variety of streamflow sequences can help water managers to investigate how existing water resources systems on interconnected stream networks will operate in scenarios which have not been observed in the historical record.
The thesis further deals with streamflow indices for large sample hydrology that take into consideration the time asymmetry. The study aims to provide flow descriptors on larger catchment scales and use these metrics to examine the driving forces of catchment attributes governing rising and falling limbs. The indices related to hydrograph limbs are primarily associated with distinct catchment attributes, forming a relationship between indices and catchment attributes to demarcate the governing drivers in corresponding hydrograph segments. The study presents a collection of streamflow indices with temporal asymmetry for 671 catchments in the United States. The regional variations across catchments are discussed using the spatial maps of streamflow indices. The flow metrics considering temporal asymmetry of hydrographs offer an alternative technique for determining the driving forces of streamflow hydrographs and opening up new possibilities to explore how the interaction of topography, soil, climate, vegetation, and geology defines the hydrological behavior of catchment.
In summary, the main research contribution of this thesis is on developing novel statistical approaches towards providing an understanding of streamflow dynamics and demonstrate their applicability in different hydrological settings
Proton kinetic energy anomaly, Kauzmann temperature for nanoconfined water and design of nanoscale membrane for water desalination.
No full textStructure, dynamics and thermodynamics of water molecules con fined inside the nanopores
of various geometries are of fundamental interest owing to their potential applications
in various nanofluidic devices, such as ion-selective channels, ionic transistor, sensing,
molecular sieving, desalination, and blue energy harvesting. Strongly confi ned water
shows strong quantum effect and others testing ground for many interesting physics not
commonly found in bulk system. In this thesis, we have studied various aspects of the
structure, dynamics and thermodynamics of water con fined inside nanopore of carbon
nanotube (CNTs), and graphene slit-pore using atomistic molecular dynamics (MD) simulation.
In particular, we have studied proton kinetic energy anomaly and anisotropy
of the kinetic energy tensor, Kauzmann temperature for bulk and con ned water to
understand its dimensionality dependence. Based on our current understanding of the
dynamics of con fined fluid, we have also proposed design of new nanoscale membrane for
desalination
Exploring Topological Phases of Matter using Density Functional Theory and Machine Learning Approaches
No full textTopological phases of matter such as topological insulator (TI), quantum anomalous Hall insulator (QAHI), nodal line semimetal (NLSM), and triple point metal (TPM) can be realized by manipulating the spin-orbit coupling (SOC) and symmetry present in the crystalline solids. To understand many of these phases in novel materials, we attempted to develop symmetry-based methods using the density functional theory in combination with the high-throughput (HT) and machine learning (ML) approaches. To take advantages of crystalline symmetry in preserving triply degenerated band crossing in the Brillouin zone, we first studied a new set of semimetals X2YZ (X = {Cu, Rh, Pd, Ag, Au, Hg}, Y = {Li, Na, Sc, Zn, Y, Zr, Hf, La, Pr, Pm, Sm, Tb, Dy, Ho, Tm} and Z = {Mg, Al, Zn, Ga, Y, Ag, Cd, In, Sn, Ta, Sm}), which show the existence of multiple topological triple point fermions along four independent C3 axes in this cubic lattice. Next, we report the topological phases of the hydrogenated group 13 monolayers (aluminane, gallenane, indinane, and thallinane), where time-reversal (TRS), inversion (IS), and mirror symmetry (MS) protect the topological NLSM state. Interestingly, under 2.6% tensile strain along the x-direction, gallenane evolves to TI, which could be promising for spintronics applications. On the other hand, TRS and IS breaking with strong SOC effect in the hexagonal lattices produce valley-polarized QAH effect, having potential applications in dissipation-less valleytronics devices. To explore large search space of VP-QAH insulators, a HT method has been developed, and applied to “aNANt” MXene database, which resulted in 14 MXenes exhibiting the VP-QAH effect. These screened MXenes have non-zero Berry curvature at the Brillouin-zone corner and a single chiral edge state connecting from valence to conduction band within the bulk bandgap, resulting in a valley-dependent dissipation-less current flow. The strong spin-orbit coupling effect in the 2D buckled inversion asymmetric crystal could provide another important striking phenomenon Rashba effect, where the orbital momentum is locked with the spin. By employing HT-based computational screening method, we extract 206 Rashba semiconductors, among which 20 have Rashba constant greater than 1eVÅ. These could have promising applications in spin-based field effect transistors. Predicting existence of all these phases via DFT is a time and resource extensive process, which hinders the accelerated search. Therefore, we have developed ML based models in imbalanced dataset that can classify and predict new magnetic nodal line semimetals and Rashba materials. The classification and regression models to predict MNLSMs, and corresponding nodal positions use only the basic elemental features. With an excellent classification accuracy of 94% to predict NLMSMs, the regression model predicts the nodal line positions (N1 and N2) having R2 of 0.96 and 0.92, respectively. Similarly, the classification model classifies the Rashba materials with 89% accuracy. The symmetry analysis-based HT and ML approaches developed here could be utilized to search for novel materials having these exotic properties in an accelerated manner
Roles of Drosophila Beadex and CG9650 in the development and functioning of the larval neuromuscular junctions
No full textIn eukaryotes, all voluntary and involuntary actions like, cognition, learning & memory, voluntary
movements, feeding, etc., are coordinated by the employment of neuronal circuitry that transmits
the signal from the source (in the central nervous system) to an effector (another neuron, tissue or
organ). Neurotransmission, a process in which neurotransmitters released by axon terminals of a
neuron binds to receptors on dendrites of another neuron, or other effector tissue or organ, is
indispensably responsible for these actions. Many voluntary actions, like locomotion, result from
chemical synapses that are formed between a motor neuron and a skeletal muscle, which are also
known as neuromuscular junctions (NMJ).
Along with appropriate growth and accurate organization, a functional NMJ demands a well balanced expression of molecular effectors for robust synaptic transmission. Several signaling
pathways, including the Wnt pathway, BMP pathway, MAPK pathway, and Syt4 underly the
formation and maintenance of a functional NMJ. Many of the signaling molecules involved in
these pathways regulate various morphological features of the NMJ like the span area, branch
length, bouton numbers & size, as well as the physiology at the synapse. Drosophila larval neurons
have been used extensively as a model to identify new molecular players and decode neuronal
circuits involved. Extensive work in Drosophila larval NMJ led to the identification of major
molecular players and their developmental and functional roles, like endocytosis e.g. by studies on
shibire (dynamin), exocytosis by studies on cacophony (calcium ion channel), SNARE proteins
(for synaptic vesicle fusion), etc., regulators of NMJ morphology, like highwire, futsch, TDP-43,
Rae1, Dishelved, LIMK1, etc., active zone assembly players BRP, Syd-1 (RhoGAP100F), Lipirin-α., etc. Though these studies have proven to be valuable paradigms to study the mammalian
synapses, many new molecular candidates whose function and interactions at the NMJ remain
uncovered. Additionally, even though several pathways have been elucidated, the mechanism of
action and genetic interaction between different molecular players is yet not clear.
Our lab had previously identified two such players - Beadex (Bx), the Drosophila homolog of
Human LMOs; and CG9650, the Drosophila homolog of Human BCL11A and BCL11B, that affect
the NMJ morphology of the Drosophila third instar larvae. The mutant of Bx (Bx7
) and RNAi-mediated neuronal knockdown of both Bx and CG9650 exhibited defects in larval locomotion. In
the present study, using a combination of techniques from behavioral assays, Drosophila genetics,
to imaging studies, we show that while Bx regulates NMJ span area, CG9650 governs the bouton morphology. Subsequent electrophysiological recordings revealed that both were important for
maintaining the normal spontaneous firing of the neurons. To deduce their mechanism of action at
NMJs, we performed a microarray analysis, in the case of Bx and discovered its plausible
involvement in the retrograde BMP pathway via the LIMK signaling. On the other hand, an
mRNA-sequencing analysis for CG9650 suggested its roles in the regulation of c-fos, the
component of the AP1 transcription complex, that works along the JNK pathway at the NMJ.UGC, DBT, DST, IIS
Tailoring excitonic complexes in layered materials
No full textLayered transition metal dichalcogenides (TMDCs) host a variety of strongly bound
exciton complexes that control the optical properties in these materials. Apart from
spin and valley, layer index provides an additional degree of freedom in a few-layer-thick
lm. While in the 1H monolayer TMD inversion symmetry is broken, and the reflection
symmetry is maintained but, in the bilayer, it is reversed. Trions are excitonic species
with a positive or negative charge, and thus, unlike neutral excitons, the
flow of trions can
generate a net detectable charge current. Trions under favourable doping conditions can
be created in a coherent manner using resonant excitation. The neutral biexciton (bound
state of two excitons) can assemble further to create a charged state with another electron
or hole. Generally, in W-based TMDs these ve-particle quinton states dominate the
population density and this can also be engineered to produce photocurrent at cryogenic
temperature.
In the firrst work, we show that in a few-layer TMDC lm, the wave functions of the
conduction and valence-band-edge states contributing to the K(K0) valley are spatially
con ned in the alternate layers - giving rise to direct (quasi-)intralayer bright exciton and
lower-energy interlayer dark excitons. Depending on the spin and valley con figuration,
the bright-exciton state is further found to be a coherent superposition of two layer-
induced states, one (E type) distributed in the even layers and the other (O type) in the
odd layers. The intralayer nature of the bright exciton manifests as a relatively weak
dependence of the exciton binding energy on the thickness of the few-layer lm, and
the binding energy is maintained up to 50 meV in the bulk limit - which is an order of
magnitude higher than conventional semiconductors. Fast Stokes energy transfer from
the intralayer bright state to the interlayer dark states provides a clear signature in
the layer-dependent broadening of the photoluminescence peak and plays a key role in
the suppression of the photoluminescence intensity observed in TMDCs with thickness
beyond a monolayer.
In the second work, we show that bilayer WS2 exhibits a quantum con ned Stark
effect (QCSE) that is linear with the applied out-of-plane electric field, in contrast to a
quadratic one for a monolayer because of the contrasting symmetries between monolayer
and bilayer. The interplay between the unique layer degree of freedom in the bilayer
and the field-driven partial interconversion between intralayer and interlayer excitons
generates a giant tunability of the exciton oscillator strength. This makes bilayer WS2 a
promising candidate for an atomically thin, tuneable electro-absorption modulator at the
exciton resonance, particularly when stacked on top of a graphene layer that provides
an ultrafast nonradiative relaxation channel. By tweaking the biasing confi guration,
we further show that the excitonic response can be largely tuned through electrostatic
doping, by efficiently transferring the oscillator strength from neutral to charged exciton.
In the third and fourth work, we demonstrate interlayer charge transport from top
few-layer graphene to bottom monolayer graphene, mediated by a coherently formed
trion state using a few-layer graphene/monolayer WS2/monolayer graphene vertical het-
erojunction. This is achieved by using a resonant excitation and varying the sample
temperature. The resulting change in the WS2 bandgap allows us to scan the excitation
around the exciton-trion spectral overlap with high spectral resolution. By correlating
the vertical photocurrent and in situ photoluminescence features at the heterojunction as
a function of the spectral position of the excitation, we show that (1) trions are anoma-
lously stable at the junction even up to 463 K due to enhanced doping, and (2) the
photocurrent results from the ultrafast formation of a trion through exciton-trion coher-
ent coupling, followed by its fast interlayer transport. Further, the resonant photocurrent
thus generated can be effectively controlled by a back gate voltage applied through the
incomplete screening of the bottom monolayer graphene, and the photocurrent strongly
correlates with the gate dependent trion intensity, while the non-resonant photocurrent exhibits only a weak gate dependence. We estimate a sub-100 fs switching time of the
device.
In the final work, we have used the pulsed laser excitation to create the quinton
states in monolayer WS2 while resonantly exciting the exciton and trion states at low
temperature. Strong light absorption by the charged biexciton under spectral resonance,
coupled with its charged nature, makes it intriguing for photodetection - an area that is
hitherto unexplored. Using the high built-in vertical electric eld in an asymmetrically
designed few-layer graphene encapsulated 1L-WS2 heterostructure, here we report, for
the rst time, a large, highly nonlinear photocurrent arising from the strong absorption
by two charged biexciton species under zero external bias (self-powered mode). Time-
resolved measurement reveals that the photoresponse is ultra-fast, on the order of sub-5
ps. By using single- and two-color photoluminescence excitation spectroscopy, we show
that the two biexcitonic peaks originate from bright-dark and bright-bright exciton-trion
combinations.
The possibility of electrical manipulation and detection of a charged exciton (trion)
before its radiative recombination makes it promising for excitonic devices. The demon-
stration of coherent formation, high stabilization, vertical transportation, and electrical
detection of trions marks a step toward room-temperature trionics. Following the same
the ve-particle charged quinton can also be efficiently generated and electrically de-
tected. They can be used in electrical detection of constituting bright and dark states
and quantum manipulation of the coupled spin-valley physics. Such innate nonlinearity
in the photocurrent due to its biexcitonic origin, coupled with the ultra-fast response
due to swift inter-layer charge transfer exempli fies the promise of manipulating many-
body effects in monolayers. Also, the findings are prospective toward highly tunable,
atomically thin, compact, and light on chip, re-confi gurable components and promising
for several applications such as higher harmonics generation of the modulating signal,
receiver design in microwave photonics and visible light communication, square-law cir-
cuits, and also in nonlinear next generation optoelectronics