IU Indianapolis ScholarWorks :: Browsing by Author "Vemuri, Gautam"

Browsing by Author "Vemuri, Gautam"

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A Computational Framework for Investigating mRNA Localization Patterns in Pancreatic Beta-Cells During Type 1 Diabetes Progression
(2024-12) Chang, Hok Wai; Petrache, Horia; Liu, Jing; Wassall, Stephen; Vemuri, Gautam; Syed, Farooq
Spatial transcriptomics improves transcriptomic studies by incorporating RNA localization information, which provides a more profound insight into cellular functions, interactions between cells, and their reactions to external stimuli. Single-molecule fluorescent in situ hybridization (smFISH) is a commonly utilized technique in spatial transcriptomics that allows for the accurate visualization of mRNA distribution in cells. This method aids in the quantitative evaluation of mRNA localization patterns by utilizing various physical properties, thereby illuminating processes such as transcription, nuclear export, and localized translation. Nevertheless, existing computational approaches for analyzing smFISH images often have constraints, concentrating primarily on cellular expression or specific biological contexts while overlooking broader physical analysis. In my PhD research, I created STProfiler, a comprehensive tool aimed at an unbiased physical examination of mRNA distribution. STProfiler includes an image analysis workflow that processes raw biological images to effectively detect mRNA and nuclei. It also employs machine learning techniques to biologically interpret mRNA spatial characteristics and categorize cells based on these features. My dissertation illustrates the use of STProfiler in multiple studies investigating the transcriptomic profiles of β-cells during the progression of type 1 diabetes (T1D), uncovering spatial transcriptomic diversity in β-cells. These investigations involve analyzing mRNA clusters and stress granules in pancreatic β-cells, measuring the physical characteristics of mRNAs linked to cellular stress and inflammation in mice developing T1D, evaluating the rise in HLA-DMB mRNA spliced variant in T1D, and exploring miRNA as a potential biomarker for T1D. Furthermore, STProfiler has also proven beneficial in tissue-wide spatial transcriptomics by creating masks for nuclei and cells from biological images and assigning mRNA transcripts to develop subcellular expression profiles. This capability allows for more thorough bioinformatic evaluations. In summary, STProfiler serves as a robust tool for both cell- and tissue-level spatial transcriptomics, offering an unbiased platform for researchers to investigate complex transcriptomic variations within cells.
Advancing super-resolution microscopy for quantitative in-vivo imaging of chromatin nanodomains
(2024-12) Seitz, Clayton; Liu, Jing; Vemuri, Gautam; Cheng, Ruihua; Wassall, Stephen; Petrache, Horia
Single molecule localization microscopy (SMLM) techniques, such as direct stochastic optical reconstruction microscopy (dSTORM), can be used to produce a pointillist representation of fluorescently-labeled biological structures at diffraction-unlimited precision. This class of techniques permits localization of fluorescent molecules in the cell with nanometer precision and thus is commonly referred to as nanoscopy. Conventional nanoscopy utilizes the deactivation of standard fluorescent tags, followed by spontaneous or photoinduced reactivation, to resolve fluorophores at distances below the diffraction limit. While powerful, this approach has limited throughput and requires localization in sparse scenes. This dissertation introduces fluorescence nanoscopy and covers its innovation and application as discussed in the following papers: Quantum enhanced localization microscopy with a single photon avalanche diode array [ 1 ] leverages recent advancements in single photon avalanche diode array technology to count fluorescent emitters using a widefield microscope. Uncertainty-aware localization microscopy by variational diffusion [ 2 ] describes a novel algorithm that applies a diffusion model in order to model a posterior distribution on high resolution localization microscopy images, given low resolution inputs. role of the BRD4 phosphoswitch in the maintenance of chromatin nanodomains via super resolution microscopy and molecular dynamics simulation. We demonstrate that BRD4 phosphorylation regulates chromatin packing and mobility in mammalian nuclei.
Beyond the Exceptional Point: Exploring the Features of Non-Hermitian PT Symmetric Systems
(2022-08) Agarwal, Kaustubh Shrikant; Joglekar, Yogesh N.; Vemuri, Gautam; Ou, Zhe “Jeff”; Petrache, Horia I.; Lukens, Joseph M.
Over the past two decades, open systems that are described by a non-Hermitian Hamiltonian have become a subject of intense research. These systems encompass classical wave systems with balanced gain and loss, semi-classical models with mode selective losses, and lossy quantum systems. The rapidly growing research on these systems has mainly focused on the wide range of novel functionalities they demonstrate. In this thesis, I intend to present some intriguing properties of a class of open systems which possess parity (P) and time-reversal (T) symmetry with a theoretical background, accompanied by the experimental platform these are realized on. These systems show distinct regions of broken and unbroken symmetries separated by a special phase boundary in the parameter space. This separating boundary is called the PT-breaking threshold or the PT transition threshold. We investigate non-Hermitian systems in two settings: tight binding lattice models, and electrical circuits, with the help of theoretical and numerical techniques. With lattice models, we explore the PT-symmetry breaking threshold in discrete realizations of systems with balanced gain and loss which is determined by the effective coupling between the gain and loss sites. In one-dimensional chains, this threshold is maximum when the two sites are closest to each other or the farthest. We investigate the fate of this threshold in the presence of parallel, strongly coupled, Hermitian (neutral) chains, and find that it is increased by a factor proportional to the number of neutral chains. These results provide a surprising way to engineer the PT threshold in experimentally accessible samples. In another example, we investigate the PT-threshold for a one-dimensional, finite Kitaev chain—a prototype for a p-wave superconductor— in the presence of a single pair of gain and loss potentials as a function of the superconducting order parameter, onsite potential, and the distance between the gain and loss sites. In addition to a robust, non-local threshold, we find a rich phase diagram for the threshold that can be qualitatively understood in terms of the band-structure of the Hermitian Kitaev model. Finally, with electrical circuits, we propose a protocol to study the properties of a PT-symmetric system in a single LC oscillator circuit which is contrary to the notion that these systems require a pair of spatially separated balanced gain and loss elements. With a dynamically tunable LC oscillator with synthetically constructed circuit elements, we demonstrate static and Floquet PT breaking transitions by tracking the energy of the circuit. Distinct from traditional mechanisms to implement gain and loss, our protocol enables parity-time symmetry in a minimal classical system.
Effect of lattice boundary on Anderson localization of nonclassical light in optical waveguide arrays
(IOP, 2023-09) Majumder, Shubradeep; Rai, Amit; Vemuri, Gautam; Physics, School of Science
We study the effect that the boundary of a one-dimensional lattice has on the Anderson localization of nonclassical light in a finite optical waveguide array in which neighboring waveguides are evanescently coupled and controlled disorder is introduced. By investigating the quantum properties of the output when nonclassical light is injected into the waveguide, we show enhancements of localization and quantum features due to the boundary.
Effects of quantum noise on the nonlinear dynamics of a semiconductor laser subject to two spectrally ltered, time-delayed optical feedbacks
(Elsevier, 2016-07) Suelzer, Joseph S.; Prasad, Awadhesh; Ghosh, Rupamanjari; Vemuri, Gautam; Department of Physics, School of Science
We report on a theoretical and computational investigation of the complex dynamics that arise in a semiconductor laser that is subject to two external, time-delayed, filtered optical feedbacks with special attention to the effect of quantum noise. In particular, we focus on the dynamics of the instantaneous optical frequency (wavelength) and its behavior for a wide range of feedback strengths and filter parameters. In the case of two intermediate filter bandwidths, the most significant results are that in the presence of noise, the feedback strengths required for the onset of chaos in a period doubling route are higher than in the absence of noise. We find that the inclusion of noise changes the dominant frequency of the wavelength oscillations, and that certain attractors do not survive in the presence of noise for a range of filter parameters. The results are interpreted by use of a combination of phase portraits, rf spectra, and first return maps.
Exceptional Points and their Consequences in Open, Minimal Quantum Systems
(2022-08) Muldoon, Jacob E.; Joglekar, Yogesh; Decca, Ricardo; Cheng, Rui; Vemuri, Gautam; Cincio, Lukasz
Open quantum systems have become a rapidly developing sector for research. Such systems present novel physical phenomena, such as topological chirality, enhanced sensitivity, and unidirectional invisibility resulting from both their non-equilibrium dynamics and the presence of exceptional points. We begin by introducing the core features of open systems governed by non-Hermitian Hamiltonians, providing the PT -dimer as an illustrative example. Proceeding, we introduce the Lindblad master equation which provides a working description of decoherence in quantum systems, and investigate its properties through the Decohering Dimer and periodic potentials. We then detail our preferred experimental apparatus governed by the Lindbladian. Finally, we introduce the Liouvillian, its relation to non-Hermitian Hamiltonians and Lindbladians, and through it investigate multiple properties of open quantum systems.
Exceptional Points in a Non-Markovian Anti-Parity-Time Symmetric System
(MDPI, 2023-12) Wilkey, Andrew; Joglekar, Yogesh N.; Vemuri, Gautam; Physics, School of Science
By studying the eigenvalues and eigenvectors of a non-Markovian anti parity-time (APT) symmetric system, we investigate the possibility of exceptional points (EPs) that may arise within it. Our work is motivated by a recently studied APT-symmetric experimental configuration consisting of a pair of time-delay coupled semiconductor lasers (SCLs). In such a system, a single time-delay represents the memory. The time-delayed coupling makes the system’s effective Hamiltonian infinite-dimensional and leads to novel features in the corresponding eigenvalues and eigenvectors. In particular, we demonstrate analytically and numerically that unlike a typical PT-symmetric dimer with zero time-delay, which has one second-order EP, our time-delayed system has parameter regimes that give rise to either one, two, or zero second-order EPs and one third-order EP, and one can select these regimes though a judicious choice of the time-delay and coupling.
Exceptional points in a time-delayed anti-parity-time symmetric system
(Optica, 2021) Wilkey, Andrew; Joglekar, Yogesh N.; Vemuri, Gautam; Physics, School of Science
We report on the experimental realization of an anti-PT symmetric system in a pair of time-delay coupled semiconductor lasers, and via numerical and analytical modeling investigate the properties of exceptional points in it.
Exceptional points in anti-PT symmetric system of delay coupled semiconductor lasers
(SPIE, 2021-08) Vemuri, Gautam; Wilkey, Andrew; Joglekar, Yogesh; Physics, School of Science
This paper will report on some features of a platform for the realization of an anti parity-time (anti-PT) symmetric system in a pair of time-delay coupled semiconductor lasers, with special emphasis on the delay induced dynamics in the system. The system is modeled by a modified Lang-Kobayashi rate equations model, augmented to include delayed coupling. The role of a phase accumulation factor that arises from the delayed coupling is elucidated. Finally, the novel exceptional point(s) behavior that is characteristic of the time-delay is investigated via numerics as well as analytically via the Lambert W function.
Imaging the Dynamics of Chromatin at Single-Nucleosome Resolution
(2024-12) Iqbal, Mohamed Fadil; Vemuri, Gautam; Liu, Jing; Petrache, Horia; Decca, Ricardo; Wassall, Stephen
DNA is organized into chromatin – a complex polymeric structure which stores information and controls gene expressions. Advancements in microscopy have enabled us to see chromatin in motion – which was previously thought to be static, and these motions contribute to various cellular functions. In my thesis I will demonstrate the molecular tools and biophysical approaches our lab has developed to uncover the mysteries of chromatin dynamics and structures at the single nucleosome resolution; I will also discuss how these new discoveries in chromatin enable us to explore its role in cell functions. This dissertation will first describe the technology advancement of live-cell image analysis; particularly, I will discuss the utilization of AI to improve the spatial and temporal resolution of chromatin imaging. Then I will show complex nature of chromatin where depending on the temporal scale of observation we see a different behavior and how computer simulations can see these differences. Following that, I will introduce our investigation on the role of chromatin motion in DNA damage and repair. Afterwards, I will discuss how the cell regulates its chromatin dynamics in response to the metabolism indicators AMPK (AMP-activated protein kinase). I will also show how chromatin motion and structure behave without the presence of key proteins such as RAD51 that aid in DNA damage. Finally I will go over future directions and improvements we can do to our current techniques to improve our understanding of chromatin’s role is various biological functions. We expect that the exploration of the spatiotemporal dynamics in live cells will facilitate the diagnosis, treatment, and prevention of cancers.

Browsing by Author "Vemuri, Gautam"

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