326 research outputs found
Cross-Talk Between Inflammation and Barrier Framework at Mucosal Surfaces in the Lung: Implications for Infections and Pathology
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
Transcriptional Landscape Of FOXP3+ Regulatory T Cells Under Mitochondrial Oxidative Stress: Implications For Inflammaging
No full textThis thesis explores the intricate relationship between mitochondrial oxidative stress and the function of FOXP3+ regulatory T cells (Tregs), highlighting their essential roles in the aging immune system and the development of age-related diseases. The study delves into how mitochondrial impairments within Tregs contribute to widespread inflammation leading to pathological aging. One key analysis shows that mitochondrial oxidative stress undermines Treg functionality, intensifying inflammatory responses and increasing frailty in older adults. This dysfunction is associated with elevated inflammatory markers and presents a potential target for therapeutic interventions aimed at restoring mitochondrial health to alleviate these impacts. Another significant discovery connects the dysfunction of CD4 Foxp3 Tregs in cerebrospinal fluid with the worsening of Alzheimer\u27s pathologies. The study finds that mitochondrial deterioration within Tregs is crucial in regulating neuroinflammation, thereby affecting the progression of Alzheimer\u27s disease. Enhancing mitochondrial function is identified as a possible approach to diminish inflammatory signals and the buildup of amyloid in the brain. A Foxp3-specific TFAM conditional knockout mouse model reveals that the absence of mitochondrial transcription factor A (TFAM) in Tregs leads to a shift in the CD4 T cell landscape toward more pathogenic profiles, characterized by increased cellular senescence, plasticity, and systemic inflammation. These findings highlight the potential of targeting mitochondrial function in Tregs as a novel therapeutic strategy to influence immune aging. The thesis underscores that boosting mitochondrial biogenesis or curtailing mitochondrial oxidative stress could stabilize Treg function, thus reducing inflammaging and its associated health risks. This research offers a thorough examination of the role of Tregs under mitochondrial oxidative stress, substantially enhancing our understanding of immune regulation in aging and its implications for treating age-related diseases. By outlining the links between mitochondrial dysfunction and immune regulation, this thesis enriches the field of geroscience, proposing viable interventions to improve health span and reduce the burdens faced by aging population
Book Ends & Odd Books : Publications Refuting Conventional Form from the Banff Centre Library Collection
No full textMathur explains how he "unselected" nearly 200 works for this exhibition of unconventional publications by international artists and authors, recognizing the influence of Ulises Carrion's article "The New Art of Making Books." The author reflects upon the roles of language and poetics, the distinction between book and text, and how politics and power affect the making and reception of these works. 2 bibl. ref
A Computational And Experimental Framework For Investigating Mitochondrial Dysfunction In Neuroinflammation And Neurodegeneration
No full textNeurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease (AD), are characterized by progressive neuronal loss and functional decline, driven by chronic neuroinflammation and oxidative stress. ALS primarily affects motor neurons, leading to muscle weakness and paralysis, while AD results in cognitive decline due to widespread neuronal degeneration. Microglia, the brain’s resident immune cells, maintain neuronal health but can become excessively reactive under mitochondrial dysfunction, exacerbating neuroinflammatory responses. Mitochondrial Transcription Factor A (TFAM), essential for mitochondrial DNA (mtDNA) stability and function, is critical for mitochondrial maintenance. Its dysfunction in microglia leads to impaired mitochondrial function, excessive reactive oxygen species (ROS) production, oxidative stress, and inflammatory signaling, all of which contribute to disease progression. However, the molecular mechanisms linking TFAM dysfunction to neuroinflammation remain poorly understood. This dissertation investigates these mechanisms using genetically engineered mouse models with microglial-specific TFAM deletion (Cre-loxP system) to mimic mitochondrial dysfunction. Single-cell RNA sequencing, proteomics analysis, and ontology-driven gene interaction networks were leveraged to identify transcription factors, pathways, and gene interactions involved in oxidative stress and neuroinflammation. Experimental validation using immunohistochemistry and quantitative PCR (qPCR) further assessed mitochondrial integrity and microglial activation. This study aims to uncover novel molecular interactions linking TFAM loss to mitochondrial damage and neuroinflammatory signaling, providing insights into potential therapeutic targets. By integrating computational and experimental approaches, this research advances the understanding of mitochondrial dysfunction and neuroinflammation, offering new strategies to mitigate oxidative stress and reduceinflammation
Book review: paper tiger: law, bureaucracy and the developmental state in Himalayan India by Nayanika Mathur
No full textFollowing eighteen months of intensive fieldwork, in Paper Tiger: Law, Bureaucracy and the Developmental State in Himalayan India author Nayanika Mathur details the everyday absurdities of bureaucracy in the Himalayan borderlands, showing the frequent gulf between ‘real life’ and the abstract workings of the law. Elisabetta Iob highly recommends this accessible, witty and vividly written book as an outstanding and essential example of ethnographic research
FINANCING COMMUNITY FACILITIES: A CASE STUDY OF THE PARKS AND RECREATIONAL GENERAL OBLIGATION BOND MEASURE OF SAN JOSE, CALIFORNIA
No full textThis study of the City of San Jose’s Parks and Recreation General Obligation (GO) Bond Measure seeks to identify the politics-, management-, and planning-related lessons learned by the City as it developed its community facilities using the GO bonds proceeds. The study finds that these lessons include: be conservative in what you promise the residents; be prepared for changes in economic environment by identifying supplementary funding sources should the primary source not yield adequate funds; make sure that the jurisdiction is organizationally capable of handling the increased workload; and prepare detailed project plans prior to the bond issuance.Community Infrastructure and Services; Municipal Bonds; Public Finance
An Analytical Criterion for Centrifugal Instability in Non-Axisymmetric Vortices
No full textNon-axisymmetric vortices are ubiquitous in nature; examples include polar vortices in planets, the giant red spot in Jupiter, tornadoes and cyclones on Earth, mesoscale eddies in the ocean. Turbulent flows are furthermore known to be dominated by small- and large-scale vortex structures. Owing to the wide range of applications, knowledge of conditions under which a given vortex becomes unstable is beneficial. Here, the centrifugal instability of two-dimensional, non-axisymmetric vortices in the presence of an axial flow and a background rotation is studied using the local stability approach. The local stability approach, based on geometric optics and similar in formulation to the rapid distortion theory \cite{bib:godeferd2001}, considers the evolution of shortwavelength perturbations along streamlines in the base flow. This approach, developed by Lifschitz Hameiri \cite{bib:lifschitz1991}, is particularly useful for base flows for which a global stability analysis is computationally expensive. A sufficient criterion for centrifugal instability in an axisymmetric vortex with and is first derived by analytically solving the local stability equations for wave vectors that are periodic upon evolution around a closed streamline. This criterion is then heuristically extended to non-axisymmetric vortices and written in terms of integral quantities on a streamline. The criterion is then shown to be accurate in describing centrifugal instability over a reasonably large range of parameters that specify Stuart vortices and Taylor-Green vortices
An Interactive Dialogue for the Creation, Maintenance and Querying of a Data Base Representative of the Anatomy of an Administrative System
No full textTitle: An Interactive Dialogue for the Creation, Maintenance and Querying of a Data Base Representative of the Anatomy of an Administrative System, Author: Pratima Mathur, Location: ThodeThe logical structure of a database is given, and is
representative of the anatomy of an administrative system,
and of the personnel organization by which it is operated.
This project will adopt an appropriate host computer,
terminal, and physical representation of the database, for
the main purpose of developing a user-terminal dialogue by
which the database can be created and maintained. The
dialogue should be as easy and flexible to use by an audit
analyst as is possible, while at the same time imposing a
systematic and disciplined approach to the task.ThesisMaster of Science (MS
Uncovering a novel role for FXR-SHP axis in liver physiology, diseases and beyond
No full textLiver performs a multitude of functions ranging from detoxification, metabolism and digestion. To execute these tasks, one of the mechanisms that the liver utilizes is nuclear receptor signaling, which in turn can transcriptionally regulate gene networks. My doctoral thesis focuses on studying the role of two nuclear receptors, FXR and SHP in maintaining liver function. Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP) are well-known regulators of glucose, fat and bile acid homeostasis. Here, I uncover novel roles for FXR-SHP axis not only in the liver but also in extrahepatic organs, like heart. In Chapter 2, I discuss how hepatic loss of FXR and SHP results in increased glycosylation of liver proteins and structural defects in Golgi apparatus, and ultimately liver cancer. Chapter 3 focuses on comprehending how FXR-SHP ablation results in increased drug metabolic capacity of the liver. Finally, chapter 4 discusses how liver dysfunction, caused by loss of FXR and SHP, can induce metabolic and functional defects in heart. Taken together, these projects will help understand some of the FXR and SHP transcriptional networks under different physiological and pathological contexts and may open avenues for pharmacological manipulation to treat various diseases.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-08-01The student, Bhoomika Mathur, accepted the attached license on 2019-07-04 at 01:18.The student, Bhoomika Mathur, submitted this Dissertation for approval on 2019-07-04 at 01:31.This Dissertation was approved for publication on 2019-07-09 at 15:41.DSpace SAF Submission Ingestion Package generated from Vireo submission #14170 on 2019-11-26 at 13:04:27Made available in DSpace on 2019-11-26T20:49:21Z (GMT). No. of bitstreams: 3
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Algorithmic advances in dynamic analysis for detecting concurrency bugs
No full textConcurrency is an indispensable programming paradigm and multi-threaded programs form the bedrock of most modern software applications. Multi-threaded programs, however, are also the most tricky to get right. Despite rigorous in-house testing, concurrency issues like data races, race conditions, deadlocks and atomicity violations incessantly find there way into production-level software. In the past, errors arising due to complex concurrency bugs in software have led to catastrophic loss of human lives and money. Tackling concurrency bugs, and in particular, efficiently detecting such bugs, has, therefore, been the center of attention in computer science research for several decades now.
Dynamic analysis techniques, in particular, have emerged as the de facto standard for detecting concurrency bugs. Such techniques, examine execution traces of programs, with an aim to detect concurrency bugs at runtime. This thesis advances the state-of-the art in dynamic analysis for detecting concurrency bugs. We propose several algorithms for improving the precision, recall and efficiency of existing techniques for dynamically detecting concurrency bugs like data races and atomicity violations. We also investigate several complexity-theoretic questions establishing precise complexity bounds on several questions arising in dynamic concurrency bug detection.
We first consider the problem of detecting data races dynamically. Most popular techniques for dynamic race detection are either based on a principle of lockset violations, or on the happens-before partial order. While these techniques are usually employed at runtime, for detecting data races on-the-fly, there are many scenarios when executions can be, or need to be analyzed for concurrency bugs in an offline setting. Since executions can be extremely large, they are often stored in a compressed format to ease their warehousing. In this thesis, we study the problem of detecting data races when the analysis needs to be performed over an execution that has been compressed using a grammar-based compression scheme. We show how to detect data races efficiently in such a setting, without needing to decompress the (potentially) exponentially succinct compressed format.
We next study the problem of dynamic race prediction, which asks if one can infer the presence of data races beyond those present in a single trace observed by monitoring a program while it is executing. Existing race detectors report false alarms, miss a lot of real races, or do not scale beyond small execution traces. We propose several algorithms that offer a good balance of scalability and predictive power, while being sound (no false positives). We also study the problem from a complexity-theoretic point of view and identify upper and lower bounds, both in the general setting and in settings when the observed execution trace satisfies special properties.
Next, we consider the problem of dynamically detecting atomicity violations. This thesis proposes a linear time vector-clock algorithm for a well-studied notion of atomicity, called conflict serializability, for which the only known algorithms ran in cubic time.
The algorithms proposed in this thesis have been implemented and evaluated against large benchmark suites to evaluate their effectiveness. The techniques developed in this thesis are backed by strong theoretical foundations that ensure that our algorithms are scalable, sound and have high predictive power, making them applicable for analyzing modern software systems.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-12-01The student, Umang Mathur, accepted the attached license on 2021-07-16 at 17:21.The student, Umang Mathur, submitted this Dissertation for approval on 2021-07-16 at 17:26.This Dissertation was approved for publication on 2021-07-19 at 11:23.DSpace SAF Submission Ingestion Package generated from Vireo submission #16995 on 2022-04-06 at 17:16:10Made available in DSpace on 2022-04-29T21:41:39Z (GMT). No. of bitstreams: 2
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