Indian Institute of Science Bangalore
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Transport and criticality in topological systems and spin models
No full textThis thesis presents work done on transport in topological insulators and graphene-based systems, and quantum criticality in one- and two-dimensional spin
models. In particular we study the following: transport on surfaces of
three-dimensional topological insulators in the presence of time-independent and
time-dependent barriers, Majorana modes in a one-dimensional topological insulator in proximity with a -wave superconductor, the phase diagram of the
Hubbard model on a triangular lattice periodically driven by an in-plane electric
field, quantum criticality of a Ising model with three-spin interactions and
a transverse field, the origin of spin-orbit coupling in a graphene-WSe heterostructure, and a prediction of edge states in trilayer graphene.
In the first chapter, we give a brief introduction to the concepts relevant to the
rest of the thesis such as topological insulators, superconductivity, Floquet theory for studying periodically driven Hamiltonians, graphene and the spin-orbit coupling terms, quantum phase transitions, and the transverse field Ising model.
In the second chapter, we consider a thin-film topological insulator (TI) in which the top and the bottom surfaces are separated by a small distance. The hybridisation
between the states on the top and bottom surfaces of this system is characterized by a coupling strength . We study the various features of transport when a potential or
magnetic barrier is applied on one of the surfaces. We find that the conductance of this system oscillates with the barrier strength with the period of oscillations
varying with the coupling strength . This gives us an indirect way of estimating the extent of hybridisation in such thin films by looking at the
conductance. The period of these oscillations changes from to as increases from zero to a value close to the energy of the incident electrons. Next we
study the effects of a magnetic barrier, and we find that the conductance reaches a
non-zero and -dependent value as the barrier strength
is increased. This is in sharp contrast to the behavior of the
conductance of a single TI surface where it approaches zero with increasing magnetic
barrier strength. We also find oscillations in the case of a magnetic barrier for
large barrier widths. The period of these oscillations depends on .
In the third chapter, we consider a similar magnetic barrier whose strength is periodically driven in time. We explore the behaviour of the conductance as a function of the driving parameters. Such a barrier can be realised by shining linearly
polarised light over a region of width on the surface of a TI.
We find that the conductance of
this system exhibits a number of interesting features like prominent peaks and dips as the parameters of the system are varied. This also paves the way to have an optical
(electromagnetic) control over the electrical current in such junctions where we can go from a high-conductance regime to a low-conductance regime or vice versa by tuning the
amplitude and frequency of the light. We also see that this system can act as a frequency detector or an optically controlled switch as a function of the incident
energy of the electron.
In the fourth chapter, we consider a model of a TI which is now constricted to a narrow and long strip running along the direction. We study what happens to the Majorana
modes when such a system is placed in proximity to an -wave superconductor. This model hosts a spin-dependent chirality and only has a right-moving spin-up and a left-moving
spin-down branch. We find that this leads to a number of unusual features, such as only one zero energy Majorana mode at each end of a finite system, a single Andreev bound
state at a Josephson junction instead of two states, and multiple Shapiro steps for particular frequencies of an AC driving.
In the fifth chapter, we study a Hubbard model on a triangular lattice at half-filling in the limit of large interaction. At half-filling, this is known to
describe a Heisenberg spin Hamiltonian with equal nearest-neighbour couplings. We study the effects of driving this system periodically with an in-plane electric field. Taking
the driving to be the perturbation, we find, using Floquet perturbation theory, that the effective Hamiltonian up to third order has two-spin Heisenberg couplings with different
magnitudes in the three different directions of the triangular lattice. We also get a three-spin interaction chiral term in the third order with its sign being opposite on
up- and down-pointing triangles.
We study the ground state phase diagram as a function of the three couplings
using exact diagonalization. We find that driving leads to new phases in the system apart from the spiral phase. We have three collinear ordered phases, one
coplanar ordered phase, and three disordered (spin-liquid) phases. These phases are distinguished by looking at the peaks of the static spin structure function in
the Brillouin zone, the ground state fidelity susceptibility, the minimum value of the correlation function in real space, and the crossings of the
energies of the ground state and first excited state.
In the sixth chapter, we consider a one-dimensional Ising model with a three-spin interaction with a transverse field of magnitude . We find that this model has
duality and a second-order phase transition at the self-dual point . We find from finite-size scaling that the correlation length exponent is
close to in this model. Having a dynamical critical exponent and a central charge , we find that the model displays weak universality and lies somewhere in
the middle of the Ashkin-Teller line of models, with the two extreme
limits of the line being the transverse field Ising and four-state Potts models.
Unlike the transverse Ising model,
our model is non-integrable, with the level spacing statistics being governed
by the Wigner-Dyson Gaussian orthogonal ensemble. We also find
that this model has a subset of zero energy states which are
rather special as they are independent of the value of
and have very low entanglement entropy compared to the states in the neighbourhood of the energy eigenvalues. These states are quantum many-body scars and they
violate the eigenstate thermalisation hypothesis (ETH).
Chapters and describe works done in collaboration with some experimental groups. In Chapter , we study the system of graphene-WSe heterostructure
where we have a strong proximity-induced spin-orbit coupling. The quantum Shubnikov-de Haas (SdH) oscillations observed experimentally show a beating implying
the presence of two closely spaced frequencies. The energy dispersion thus extracted is then studied theoretically using an effective Hamiltonian with all possible spin-orbit
couplings present. The Fermi velocity of the sample is about times that of pristine graphene. The data fitting and perturbation calculations show that the
spin-splitting
energy of nearly meV comes dominantly from the valley-Zeeman and Rashba
spin-orbit couplings in the system. In chapter , we study a system of trilayer graphene under the influence of a perpendicular electric field. The non-local
and local resistance measurements done in this system show a scaling relation given by with for a range of values of the
displacement field. The
value of is seen to be close to 1 up to temperatures around which the bulk gap closes in the system. This strongly suggests that the transport is dominated in this
sample by edge modes. We study a theoretical model for trilayer graphene with displacement fields consistent with the experiments, and show that in this regime the
valley Chern number is non-zero with a large value of for a given valley and a given spin. We also show that the system host zig-zag edge
modes for the displacement fields of interest, although they are not protected from backscattering. A simple resistor circuit model that mimics the inter-valley
scattering through dissipation then explains the linear relation between the non-local and local resistances.
At the end, we summarise our results and discuss possible future
studies in these areas of research
Characterization of Neuroprotective Reactive Astrocytes in the Aging Mammalian Brain
No full textThe brain manifests cognitive deficits in aging and becomes more vulnerable to neurodegeneration. Astrocytes play several critical roles in the brain, including synapse formation, maturation, elimination, and synaptic plasticity, and impairments in these functions have more tremendous implications for diseases and neuronal dysfunction. Astrocytes sense and respond to different pathological stimuli through a process termed astrocyte reactivity, in which astrocytes undergo molecular, cellular, and functional changes. Generally, reactive astrocytes are considered to be a beneficial partner of neurons in the CNS. However, they can adopt a detrimental state as well, depending on the nature of the stimuli. Recent studies reported that astrocytes take on an LPS-induced neuroinflammatory phenotype during aging, which may facilitate synapse elimination and predispose the brain to neurodegeneration. Our lab recently showed that astrocyte-specific deletion of the stimulus-dependent transcription factor, SRF (SrfGFAPCKO and SrfGFAP−ERCKO) resulted in reactive astrocytes, which supports normal cell counts and brain architecture, normal synapse numbers, synaptic plasticity, and spatial memory and also induced microgliosis. Interestingly, SrfGFAP−ERCKO mice confer a significant level of neuroprotection to hippocampal neurons following kainate-induced excitotoxicity and dopaminergic neuron of substantia nigra following 6-hydroxydopamine administration. In a mouse model of Alzheimer’s disease, the SRF-deficient reactive astrocytes caused a significant reduction of β-amyloid plaques in the neocortex and hippocampus. Considering the neuroprotective nature of SRF-deficient reactive astrocytes, we hypothesized that “SRF-deficient reactive astrocytes can alleviate aging-associated changes in the brain.” Here, using RNA seq profiling and different staining methods, we show that SRF deficient reactive astrocytes persisted lifelong and adopted neuroprotective phenotype during aging, which is shown by significantly protected cerebellar Purkinje neurons, and synapse number from age-associated loss, and reduced myelin loss in the hippocampal regions. Microgliosis induced by SRF-deficient reactive astrocytes also lasts throughout life. Aged SrfGFAP−ERCKO mice brains have a significantly increased number of Olig2+ cells. KEGG pathway analysis, GO analysis for biological process and gene expression analysis helped us to examine the broad range of transcriptional changes happening in aged SRF-deficient reactive astrocytes. These analyses have shown that pathways related to functions of neurons, synapses, and behavior are upregulated, whereas highlighted downregulated pathways are aging, AD, HD, and PD. We have also shown that aged SrfGFAP−ERCKO exhibited better motor coordination and balance. Together these findings demonstrate that SRF-deficient reactive astrocytes can ameliorate aging-associated changes
Beamforming and Target Tracking Methods for Active RF Phased Array Seekers
No full textThe end game guidance and control of an interceptor for neutralization of a hypersonic vehicle or a maneuvering aerial target is a challenging problem. This problem can be addressed in two ways: through faster autopilot coupled with faster lateral error correction and through the use of better on-board homing sensor. The former demands not only sophisticated control and guidance algorithms, but also faster control mechanisms such as larger control surfaces driven through faster and bigger actuators, bulky reaction control systems or thrust vector control systems. All these options lead to increase in the weight of the system, which is not only undesirable with respect to weight penalty, but also makes the vehicle performance sluggish. The latter method helps to increase the homing duration via advances in sensor technology, which will lead to less dependence on heavier control systems. This transforms to a need of a seeker with larger lock-on and tracking range in order to cater to higher closing velocities.
Active Radio Frequency Seekers are generally used as the homing sensor in long range interceptors, as they give all-weather applicability. For intercepting long range hypersonic targets, or highly manuvering aerial targets at longer ranges, Phased Array Seekers (PAS) are the promising homing sensor, as they give longer tracking ranges, even against targets with lower Radar Cross Section (RCS). Target tracking, and Line-Of-Sight (LOS) estimation through the PAS have poor efficacies, mainly due to the beam quantization, arising because of the phase angle digitization, resulting due to the use of Digital Phase Shifters (DPS). The limited space, as well as the constraint of weight, put a serious limit on the antenna aperture and the transmit power of the seeker. To achieve longer tracking ranges and better target parameter estimation, the seeker beam is required to position its boresight near to the target true LOS. This demands the placement of PAS beams in close vicinities, which is in contrast to the PAS capability, as the use of DPS limits the close placement of beams. A few papers in the existing literature propose the placement of beams in close vicinities through the use of truncated phase angles on to the PAS elements, incurring beam pointing errors. The pointing errors are proposed to be compensated through in-lab measurements and calibrations. This thesis proposes methods of high fidelity beamforming to reduce such calibration needs. We propose novel methods for reducing the beam pointing quantization in PAS, and derive their complete mathematical model. We also propose suitable strategies for effective target tracking through the PAS, which uses the proposed beamforming methods.
In the first part of the thesis, we introduce novel methods for high fidelity beamforming with reduced beam quantization. In the first set of methods, named as Phase Angle Bunching (PAB) methods, we propose bunching of DPS digitized phase angles to be assigned to PAS elements. These methods are able to achieve error-free closely spaced beam pointing. Another set of methods, named as Phase Angle Round-Off (PARO) methods, has been proposed for the purpose, which gives lower beam pointing steps by using rounding-off of phase angles. An Optimal Rounding-Off realization has been derived to minimize beam pointing errors. Another novel method, named as Composite Beamforming (CB) method, has been proposed for partially reducing the step size by forming additional beams in-between the ideal feasible beams. The mathematical formulations for the beamforming, and the monopulse characterization for the CB method have also been derived. An Off-Axis scan philosophy over the composite beams has been proposed for the Line-Of-Sight (LOS) estimation, and the electronic beam steering. The CB method gives mathematically tractable partially reduced quantized beams, which makes the implementation of Off-Axis scan based on the mathematical model feasible, relaxing the need of extensive in-lab calibrations of the physical seeker. We have employed the proposed methods on Uniform Linear Arrays (ULA) to demonstrate their efficacies. We propose unique strategies, to assign the relative phase angles to the ULA elements, for each of the proposed methods and their realizations. The implementation aspects and approaches for the proposed methods, and when they are to be used for implementation on to the seeker, have also been discussed in the thesis.
In the second part, we explore options for beam scanning and target tracking. First, the On-Axis scan method, which is in-general used in the on-board seeker, has been briefly discussed. Then, we have formalized an Off-Axis scan method based on the monopulse error characteristics of the PAS beams. We propose to use the Off-Axis scan, with the CB method, for the efficient tracking of target through the on-board PAS. The parametrization and characterization of the composite beams, for target Direction-Of-Arrival (DOA) estimation, have been carried out in the thesis. We have proposed strategies, to be used for the Off-Axis scan, to suppress the estimation noise dependent jitters, and to activate LOS dynamics depended beam switchings.
In addition, to demonstrate the target tracking efficacies, we have carried out the implementation of the proposed Composite Off-Axis scan philosophy, to engage the target during the homing phase. The Proportional Navigation (PN) guidance scheme has been used for the engagement. We have carried out extensive Monte-Carlo simulations, to demonstrate and compare the performances of the four proposed target tracking strategies, for target tracking during the homing phase and interception.
To summarize, the thesis contributes by developing high fidelity beamforming methods for forming closely spaced beams for active RF phased array seekers, and also proposes strategies for beam selection and beam switching during the target tracking
Algorithms for Achieving Fairness and Efficiency in Matching Problems
No full textMatching problems arise in numerous practical settings. Fairness and efficiency are two desirable properties in most such real world scenarios. This dissertation work presents new approaches and models for capturing and solving fairness issues in different practical settings and develops algorithms to identify fair and/or efficient matchings. The thesis is organised into two logical parts: one-sided preferences and two-sided preferences.
Part 1: One-Sided Preferences
Fair and Efficient Delivery
Motivated by the classical delivery problem, we introduce a novel model of fair division where delivery tasks must be fairly distributed among a set of agents. The delivery tasks are placed on the vertices of a given acyclic graph. The cost incurred by the agents is determined by the distance they travel from the hub where they start to service their assigned tasks. We study the existence of fair and efficient allocations of tasks to agents. We choose the fairness notions: EF1 and MMS and efficiency notions: Pareto optimality and Social optimality. We find that while all these notions can be satisfied independently, the only combination of fairness and efficiency that can always be guaranteed is MMS and PO. For the remaining combinations, we provide characterisations of the space of instances for which they can be achieved. We
find that most of the relevant problems are NP-Hard. We provide an XP-algorithm which finds the different combinations of fairness and efficiency whenever they exist.
Repeated Matchings
We propose a novel repeated matching model where the valuations of agents may change with how often they have received an item in the past. We study achieving fairness and efficiency separately as well as in conjunctions in this setting. We find that optimizing for social welfare is NP-Hard for general valuations and tractable when the valuations are monotone with time. We also prove that maximizing for social welfare over the space of EF1 repeated matchings is NP-Hard. Further, we provide algorithms and non-existence results for EF1 and EFX repeated matchings in different settings.
Part 2: Two Sided Preferences
Fairness and Stability in Many-to-One Matchings
We seek to optimize a fairness measure over the space of stable many-to-one matchings, motivated by a college admissions setting. With leximin optimality as the fairness notion, we first show the intractability of this problem. We identify a minimal set of assumptions that makes this problem solvable in polynomial time. This requires that the agents on either side have the same ordinal rankings over the agents on the other side and that these must be strict. We show that on relaxing to weak rankings, the problem becomes APX-Hard. When we remove the ranking assumption but maintain strict preferences, the problem is NP-Hard. Additionally, we show that the leximin optimal stable matching can be efficiently computed in the special case of two colleges.
Incentive Compatibility in Stable Fractional Matchings
We investigate the existence of incentive compatible mechanisms that find stable fractional matchings. We show, for general settings, that no incentive compatible mechanism can be stable. We characterise the space of instances that have a unique stable fractional matching. We prove for this set of instances that any stable matching mechanism will be incentive compatibleTata Consultancy Service
Tailoring of fields and development of multipole expansion in planar ion trap geometries
No full textIn this research work two studies have been taken up: (1) to provide a systematic method
to linearize and tailor fields in planar ion trap geometries. The proposed method is general
and is demonstrated on two trap geometries, one of which is a single-PCB (printed circuit
board) geometry and the other is a two-PCB geometry, and (2) to develop the multipole
expansion for potentials in planar trap structures. These studies have relied on numerical
simulations and analytical investigations.
The thesis is divided into six chapters.
Chapter 1 presents an introduction to planar ion traps. Following a description of
the three-dimensional (3D) ion trap mass analyzer, which includes a discussion on the
stability of ions in 3D traps as well as a brief description of the use of multipole expansion
for describing potential, it goes on to provide an overview of the planar ion traps discussed
in mass spectrometry literature. This chapter ends with a presentation of the motivation
and scope of the thesis.
Chapter 2 presents a description of computational methods used in this research. It
details the Boundary Element Method (BEM) that has been used for field calculation.
The developed method is capable of analyzing structures that comprise of both conductors
and dielectrics. Next, the method used for determination of ion trajectory and frequency
of ion motion has been discussed.
Chapter 3 takes up for investigation a single-PCB planar ion trap to gain insights into
the behaviour of planar traps. This geometry, referred to as the Test Ion Trap Geometry, is
similar to a well-known five-wire geometry discussed in literature. The studies undertaken
include the role of DC and RF potentials in trapping ions. Based on these studies, the
desired characteristics of fields in a planar ion trap have been discussed for its use as a
mass analyzer. It was concluded that for a planar trap to be used as a mass analyzer, two
features need to be ensured, namely, the need for having RF and DC field zero crossing
heights should coincide and the field in the principal direction of ion motion should be
linear.
In chapter 4, a method has been developed to linearize and tailor fields in planar trap
geometries. The proposed method has been applied to two planar trap geometries. One of
these is a single-PCB design referred to as One-Sheet Ion Trap Geometry and the other
is a two-PCB design referred to as Two-Sheet Ion Trap Geometry. In order to linearize
and tailor fields in these planar geometries, the following scheme was adopted: the central
DC electrode was split into segments. To these segmented electrodes, appropriate DC
potentials (obtained by the least squares method) were applied. This technique has been
shown to be successful in achieving linear as well as mildly superlinear fields.
Chapter 5 develops a multipole expansion to characterize potentials and fields in ar bitrary ion trap geometries. The need for this arose because planar traps do not have
any of the symmetries of the existing traps that have been discussed in literature. The
coefficients of the expansion were computed from the surface charge distribution obtained
from the BEM. From the multipole expansion, a formula has been derived to estimate the
ion oscillation frequency. The agreement between the frequencies obtained by this formula
and those obtained from numerical simulation was seen to be reasonably good for four
different ion trap geometrie
Solving The Unsolved In Multicomponent Diffusion: The Concept Of Constrained Diffusion Couple Methods
No full textQuantitative diffusion analysis in multicomponent metallic systems has been a formidable task historically and despite decades of research, most of the diffusivity estimations were limited to interdiffusion and some intrinsic diffusion coefficients in binary systems and interdiffusion coefficients in a few ternary systems until recently. The experimental complications associated with the need to intersect (n-1) serpentine diffusion paths in the n dimensional space for determining the 〖(n-1)〗^2 interdiffusion coefficients lead to various approaches like average diffusivity, square root diffusivity estimations that approximate a representative value of the diffusivity across a composition range from a single experiment. However, these values are not material constants and do not provide any information about the atomic interactions. This lack of diffusivity data in multicomponent systems has hampered the development of mobility databases essential for various simulations and physico-chemical studies of materials.
This work resolves the issues with quantitative multicomponent diffusion analysis via several newly proposed methods that solves the issue of intersecting diffusion paths through the application of special constrained diffusion paths. The equations necessary to apply these methods are derived and their application is discussed mathematically and applied experimentally to the model alloy system, the NiCoFeCr equiatomic multiprincipal element alloy to compare with available radiotracer data measured for this system.
The work first employs the pseudo-binary diffusion couple approach that develops a rectilinear diffusion path in the multicomponent space to the NiCoFeCr system to estimate the tracer coefficients from the intrinsic coefficients at the marker plane. The mathematical formulations derived for the same justify its namesake and the obtained tracer coefficients can be used to back calculate the intrinsic and interdiffusion coefficients.
The pseudo-ternary method improves on the shortcomings of the pseudo-binary diffusion couple method and enables the estimation of tracer coefficients of three components by crossing two constrained diffusion paths in a 2d plane in addition to the main and cross interdiffusion coefficients.
The body diagonal method originally proposed for determination of interdiffusion coefficients is modified here to determine the tracer coefficients of all components using only two diffusion profiles thus reducing the errors associated with crossing (n-1).paths per the original approach.
This work then explores the possibilities of crossing dissimilar constrained diffusion paths by crossing pseudo ternaries of different types. Strategically crossing a rectilinear pseudo-binary diffusion path with a serpentine conventional (body diagonal) diffusion path overcomes all the previous drawbacks of pseudo binary, pseudo ternary and body diagonal methods to determine the full set of diffusivities at any desired composition and generalizes the constrained diffusion path approach to any order multicomponent system. The obtained tracer coefficients show a good match with the diffusivities measured in radio tracer experiments.
Finally, based on the ideas from the constrained diffusion path experiments in the NiCoFeCr system, a constrained path approach is devised to measure the diffusivities in an Al based NiCoFeCr multiprincipal element alloy system which was not possible earlier due to unavailability of radio isotopes and the complexities of interdiffusion experiments in higher order systems. The obtained tracer diffusivities, show an excellent match with the trends extrapolated from lower order systems. Calculated intrinsic and interdiffusion coefficients demonstrate the importance of vacancy wind effect as well as the issues with using diffusivities having different dependent components to make predictions on diffusion trends among different elements
Characterization of XRN2-mediated microRNA turnover mechanism and its pathophysiological significance in eukaryotes
No full textMicroRNAs (miRNAs) are endogenous, small non-coding RNAs that are extensively involved in the posttranscriptional regulation of gene expression in eukaryotes. Comprehensive studies on miRNA expression and function have demonstrated a consistent link between the dysregulation of miRNA expression and various diseases, highlighting the importance of robust regulation of miRNA activity. The process of miRNA biogenesis and various regulatory mechanisms governing miRNA biogenesis are well-understood. However, molecular pathways regulating the miRNA functionality through the turnover of these small RNAs remain to be explored. Several attempts have been initiated to understand the potential of miRNA turnover pathways in maintaining miRNA homeostasis, leading to the discovery of several miRNA-degrading ribonucleases. The first report on the active turnover of miRNAs in animals demonstrated that ribonuclease XRN-2, which is known to perform vital roles in multiple RNA transaction pathways, is also involved in the degradation of several mature miRNAs, including let-7 miRNA in Caenorhabditis elegans (C. elegans). Interestingly, XRN2 and let-7 miRNAs are highly conserved throughout eukaryotic organisms. Reasonably, it raised a question of
whether the miRNA degradation activity of C. elegans XRN-2 is conserved in higher animals like human
cells.
Objective 1: Elucidating the role of XRN2 in the regulation of the microRNAs in human cell lines and its
pathophysiological significance.
Here, we demonstrate that human XRN2 directly participates in executing the turnover of mature miRNAs in multiple human cancer cell lines and is thus referred to as ‘miRNase’. Further exploration of the capability of XRN2 as a ‘miRNase’ revealed that most of the miRNAs targeted by XRN2 belong to the tumor suppressor
family of miRNAs. Substantial increase in the levels of tumor suppressor miRNAs upon XRN2 knockdown in different cancer cell lines, with a concomitant effect on the levels of their crucial target-oncogenes, is endorsed by a major impact on the tumorigenicity of the cancer cells. In vivo experiments in athymic mouse models illustrate a drastic reduction in tumor growth upon XRN2 depletion, which was more prominent in the case of glioblastoma. The clinical relevance of these observations is also verified in tumor transcriptomics data from public RNA-sequencing datasets, where XRN2 mRNA expression is inversely correlated with the levels of a large number of miRNAs, including let-7 members, and high XRN2 mRNA levels are associated with poor survival in hepatocellular carcinoma, lung adenocarcinoma, and glioblastoma. Together, our results elucidate the molecular mechanism underlying the oncogenic potential of XRN2 in relation to its ‘miRNase’ activity and thus explain the multifarious roles of XRN2 in cancer.
Objective 2: Deciphering the molecular events that facilitate the XRN2-mediated turnover of AGO-bound miRNAs in human cells.
Mature miRNAs are well protected from any enzymatic action due to their firm interactions and defined placement inside the AGO protein. Depletion of XRN2 leads to the accumulation of AGO-bound miRNAs that, in turn, downregulate their cognate targets, indicating that XRN2-mediated turnover of miRNAs occurs downstream of the process of disruption of the AGO2-miRNA complex. Ex vivo biochemical assays indicate that XRN2-mediated degradation of mature let-7 miRNAs happens upon the ‘release’ of miRNAs from AGO by proteinaceous factors without affecting AGO integrity, and these two steps are kinetically linked. Our results suggest that both the release of miRNAs from the grasp of AGO and its subsequent degradation by XRN2 occurs majorly in the nuclear compartment of the cell. Inside the nucleus, XRN2 associates with a nucleolar protein, NOP58, which functions as an RNA binding factor, thereby ensuring XRN2’s nuclease
activity to act specifically on mature miRNAs. Collectively, these results reveal that human let-7 miRNAs are regulated by a two-step turnover pathway, wherein XRN2 plays the role of a ‘miRNase’ in various tissues. We further report that the NOP58 protein is also involved in facilitating the generation of mature let-7 miRNAs by directly interacting with the pre-let-7 transcript in the nucleus.
Objective 3: Exploration of the function of miRNasome-1 complex during the larval development in Caenorhabditis elegans.
Previous studies in our lab have revealed that in C. elegans, an XRN-2 containing multiprotein complex, which is referred to as miRNasome-1, is involved in the active turnover of several mature miRNAs, including the developmentally regulated miRNA let-7. Here we report that the miRNasome-1 mediated degradation, along with the LIN-28-mediated regulation, acts simultaneously but in an independent manner to ensure the complete clearance of mature let-7 miRNAs during the early-L3 stage of C. elegans development. In summary, we propose a model for the active turnover of mature miRNAs, which is a layered process involving multiple steps in human cancer cells. We furnish the role of XRN2, and its associatory proteins, as a critical regulator of miRNA stability with a prominent impact on the physiology of cancer cells, especially their tumorigenicity. Our findings suggest that the putative ‘miRNA release factor’ and XRN2-mediated
miRNA turnover constitutes an essential pathway to regulate the stability and function of let-7 members. We also present an additional layer of regulation of functional mature let-7 during the initial development in C. elegans through the involvement of the XRN-2-mediated turnover mechanism.CSI
Energy-efficient Hardware and Algorithmic Techniques for Design of Low-power Intelligent Systems
No full textLow-power design techniques involving hardware and algorithms framework are a fundamental challenge of the modern electronic system. The internet connects devices (IoTs) with advanced capabilities in sensing and processing the data proliferated in every domain of technology adoption. Wireless IoT devices have become the backbone of the digital ecosystem, from wearable watches and intelligent health monitoring devices to earphones shaping our daily lives. The portability of electronic devices relies on the power budget it uses to operate. The low-power design techniques for electronic devices have recently received significant attention. This thesis addresses low-power design challenges, focusing on hardware and software optimization to provide low-power solutions. The first problem addressed is the design of an ultra-low-power wake-up receiver front-end with an RO-VCO combination as the mixer stage of the intermediate frequency down-conversion of the receiver front end. The novel method of the receiver front-end wake-up module is designed. This design minimizes the active power of the receiver front while optimizing noise figure and gain; it receives a gain of 14.9 dB while consuming 75 µW from a 0.75 V supply. The low noise amplifier (LNA) is designed for the LNA with an increase of 16 dB with a noise figure of 5.7 dB and input third order intercept point (IIP3) of 18.16 dBm. In the second part of the thesis, a biomedical system’s portability depends upon the medical equipment’s power and size. The size of the equipment and power budget hinders access to healthcare support in the most remote part of the world. A novel algorithmic framework for portable ultrasound imaging systems based on deep generative learning and compressed sensing has been developed. Advancement in deep learning algorithms has shown application in signal compression via gradient-based learning. One such model variation
auto-encoder is designed to learn the compressed pre-beamformed RF signal representation. This method demonstrated a significant improvement in power signal noise ratio (PSNR) and mean square error (MSE) compared to the state-of-the-art techniques. The third part presents an intelligent mechanism for audio processing based on deep learning. A single-speaker separation from the mixture of a speaker based on convolutional neural network auto-encoders is presented. The fourth contribution is developing a low-power signal conditioner, which is essential to provide various high-precision applications. The novelty of the design offers a low-power miniaturized solution that can directly interface with the processor, providing a solution for high-precision applications in industrial/medical systems. The ASIC has been implemented in 180 nm technology, consumed 285 µW of power, and takes an area of 1 mm2
Dereverberation of Speech Using Autoregressive Models of Sub-band Envelopes
No full textAutomatic speech recognition (ASR) based technologies are radically changing the way we interact with digital services and information. Most of these application leverage on hands-free speech, where talkers are able to speak at a distance from the microphones without the nuance of handheld or body-worn device. The applications like, meeting annotations, speech to text transcription in teleconferencing, hands-free interfaces for controlling consumer-products, like interactive TV, virtual assistants in mobile phones, smart speakers etc, will benefit from distant talking mode of operation. The main issues in distant talking speech recognition is the corruption of speech signals by noise and the reverberation. This thesis is focused on developing dereverberation methods for speech processing using sub-band temporal envelopes.
This thesis pursues two broad directions for addressing issues in far-field ASR. In the first part of the thesis, two methods for dereverberation are proposed. In the second part of the thesis, we develop a speech enhancement model, where the audio signal is re-synthesized using dereverberated temporal envelopes and corresponding carrier components.
In the first part of the thesis, two methods to address reverberation is developed. The first method deals with developing a 3-D Acoustic modeling framework for far-field ASR (Automatic Speech Recognition), where spatio-spectral features from all the available channels are extracted. The features that are input to the 3-D CNN are extracted by modeling the signal peaks in the spatio-spectral domain using a multi-variate autoregressive (AR) modeling approach. This AR model is efficient in capturing the channel correlations in the frequency domain of the multi-channel signal. In the second method, a neural model for speech dereverberation using the long-term sub-band envelopes of speech is developed. The neural dereverberation model estimates the envelope gain, which when applied to reverberant signals, suppresses the late reflection components in the far-field signal. The dereverberated envelopes are used for feature extraction in speech recognition.
The second part of the thesis deals with envelope-carrier based speech enhancement. Here, we investigate the effect of far-field artifacts on temporal envelopes and the corresponding carrier components. A dual path recurrent neural model is used to parallelly learn the mapping for the reverberant envelopes and the carrier signals. Further, joint learning of the speech enhancement model with the end-to-end ASR model a single neural model is proposed.
Both parts of the thesis use the frequency domain linear prediction (FDLP) based model for extracting the envelopes of the sub-band signals in long analysis windows. We show several ASR and speech quality experiments to highlight the benefits of the proposed techniques.Samsung Research India Bangalore, College of Engineering Trivandru
Differential Regulation of Calcium Dependent Phase Separation and Modular Assembly of Sap97/Hdlg Enriched Molecular Complexes
No full textRecent studies over a few decades have changed the perspective of the molecular architecture of functional zones within synapses and other cell junctions. Observations in the last decade confirm Post Synaptic Density as an assembly of segregated nanomachines than a single micromachinery. Multi-domain scaffolding molecules in the family of SAP97/hDLG form the skeleton of most of the cell-cell junctions. SAP97/hDLG, a synaptic scaffolding protein, is known for its diversity of isoforms and coordinates heterogeneity in organizing near membrane molecular complexes and differential sensitivity to second messengers like Calcium. To understand the heterogeneity in an isoform-specific organization, we used a combination of super-resolution microscopy, classical nucleation theory, pharmacology and Rank-order analysis to understand the molecular organization of SAP97/hDLG in heterologous cells and in young and matured hippocampal pyramidal neurons. In our study, we observed that SAP97/hDLG shows distinct isoform-specific nanoscale phase transitions in heterologous cells and age-specific differences in hippocampal pyramidal neurons. It opens a broader perspective to understand the molecular insights that modulate the calcium-dependent realtime-nanoscale heterogeneities in synaptic transmission and other cell-cell interfacesMOE, India; UGC