152 research outputs found
Spatially mapped gene expression analysis from tissue
"Spatial gene expression analysis platforms have been widely used for a variety of applications ranging from pathogen detection to the analysis of spatial variation of an mRNA in a tissue section. Traditionally, this is accomplished by using in situ polymerase chain reaction (in situ PCR) or in situ hybridization (ISH). In addition, laser capture microdissection (LCM) followed by RT-qPCR of the locally captured tissue has also been used to study these spatial variations at a molecular level. But, all of the above techniques are plagued with different issues such as low sensitivity in the case of ISH, low reproducibility and long experimental run time for in situ PCR, and long sample acquisition and purification times for the LCM based techniques. This calls for a method that can reliably, rapidly and with high sensitivity perform spatial gene expression analysis starting from a tissue sample. We present a novel approach that combine microfabrication techniques with reverse transcription-loop mediated isothermal amplification (RT-LAMP) to achieve this goal. This novel technique uses a micro-fabricated chip with an array of micro-wells with knife-like sharp well edges to assist in division of a tissue cryosection into small pieces in a process we call ""tissue pixelation"". The array consists of over five thousand 100um (side length) pyramidal wells with a volume of ~ 175pL each. Following the above tissue transfer step, reagents are loaded onto the chip into the individual wells using a parallel loading process and independent picoliter volume RT-LAMP reactions are performed in each well. Towards this end, we have completed and characterized the chip fabrication, tissue pixelation and picoliter volume reagent loading on chip steps. In addition to this, we have also designed and characterized a novel RT-LAMP reaction for topoisomerase II alpha (TOP2A) mRNA biomarker for LNCaP prostate cancer cells."Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2018-05-01The student, Anurup Ganguli, accepted the attached license on 2016-04-28 at 12:57.The student, Anurup Ganguli, submitted this Thesis for approval on 2016-04-28 at 13:05.This Thesis was approved for publication on 2016-04-29 at 15:13.DSpace SAF Submission Ingestion Package generated from Vireo submission #9572 on 2016-07-07 at 14:18:11Made available in DSpace on 2016-07-07T21:18:12Z (GMT). No. of bitstreams: 6
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Previous issue date: 2016-04-29Embargo set by: Seth Robbins for item 93329
Lift date: 2018-07-07T21:18:16Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 93329 on 2018-07-08T09:15:20Z
Effect of growth parameters in controlling the growth direction of In2O3 micro/nanowires
Study on structural and optical properties of α-(AlxCr1-x)2O3 (0 ≤ x ≤ 1) solid solutions
Investigation of composition dependence of the nanowire samples grown on brass on synthesis conditions
Essays on international trade, protectionism and financial flows
This dissertation brings together three essays investigating the changing dynamics of international trade, protection and financial flows since the mid-1980s, a period marked by the beginning of sharp increases in the worldwide flows of goods and capital. In the first essay, I study empirically the effect of Indian Antidumping (AD) cases on trade flows from other countries. India files the highest number of AD cases in the world, with an outstanding majority of such cases resulting in protection for the domestic firms. I also look at the effect of AD cases on trade diversion from countries subject to or "named" in AD investigations to non-subject or "non-named" countries and conclude that Indian AD policy is effective. I use a unique dataset combining AD data from the WTO with trade data from Comtrade. The empirical model is estimated via the Arellano-Bond procedure.
The second essay builds on the first one. Here, I use a capital market event study to empirically analyze the effects of the huge level and extent of Indian AD protection; in efficient capital markets such gains should be immediately capitalized in the protected firms' stock prices. I also perform cross-section regressions to study the influence of key firm variables on market reaction. I use a unique dataset combining AD data from the WTO with firm level stock price data from the Bombay Stock Exchange. Results indicate that there is no perceptible response from the Indian stock market to AD protection. The cross-section results corroborate this evidence.
Finally, the third essay looks at the remarkable upsurge in global capital flows since the mid-1980's and associated issues in the current account and net external position of countries. The growing divergence between the current account and changes in the net international investment position of countries is looked at empirically and investigated with the aid of a model of BoP accounting. I estimate a Probit model of currency crises using annual BoP data for a panel of 84 countries and conclude that the identity between the current account and changes in the net international investment position holds only in theory.Ph.D.Includes bibliographical references (p. 86-89)
Study of structural, magnetic and electronic properties of Ni-Fe-Ga based ferromagnetic shape memory alloys
Micro-nano scale diagnostics and therapeutic platforms for personalized medicine
Limited Restriction Lifted for Item 113065 on 2021-11-27T10:15:20Z.Personalized medicine can be defined as the use of the combined knowledge (molecular analysis and symptoms) about an individual to predict disease susceptibility, disease prognosis, or treatment response and thereby improve that person's health. The goal is to perform specific analyses of the patient’s sample and other conventionally used indicators for creating an individualized treatment response for the patient that would yield better outcomes.
In cancer, the approach of personalized medicine is to analyze the patient’s tumor biopsy for genetic mutations and gene expression alterations and use this data to provide targeted drugs specifically for that patient’s alterations. However, there are a significant number of cases where genomic analysis currently fails to identify effective drugs or applicable clinical trials. Towards this, intratumor heterogeneity represents a major obstacle to effective cancer treatment and personalized medicine as currently, cancer diagnosis is performed on biopsies of a small region of a tumor, which may not necessarily provide representative biological information for the tumor as a whole. Therefore, there is a need for platforms that can provide insights into this intratumor heterogeneity in a clinical setting and elucidate the spatial sub-clonal architecture within a tumor at a molecular level. In this thesis, we present a platform that performs spatial gene expression analysis on a tumor tissue section using a microchip and provides the spatial map of target mRNA biomarker in less than 2 hours. The microchip allows for on-chip picoliter real-time reverse transcriptase loop mediated isothermal amplification (RT-LAMP) reactions on a histological tissue section without any analyte purification while preserving the native spatial location of the nucleic acid molecules. A major challenge towards this goal was to perform automated microdissection of the tissue on the microchip while preserving the spatial orientation. This was solved by engineering the chip design to have knife-like individual well edges and developing a novel tissue pixelation protocol.
In the other subset of cases, where the molecular analysis of tumor biopsy does identify targetable genomic alterations, patients do not always respond to therapy. For such cases, strategies to confirm therapeutic efficacy of drug candidates or identify additional drug options would be beneficial to both clinicians and patients. In these cases, the approach of personalized medicine is to use the patient’s tumor biopsy sample to form and culture tumor organoids using a compatible three-dimensional culture platform and downstream perform empirical drug testing on these organoids to yield the best possible drug candidate for the patient. In this thesis, we also present a high throughput hanging drop 3D culture platform, performed on a microchip, with potential applications in cancer drug screening.
We also explore the utility of other micro-nano scale biosensing and diagnostic platforms in enabling personalized medicine. Towards this, we demonstrate a label free ion-sensitive field effect transistor (ISFET) based microRNA sensing platform where we show robust detection of Let 7b microRNA, which is a biomarker for human lung, breast and prostate cancer, using a million transistors on a single chip. We have also explored the application of biosensing platforms for personalized medicine in infectious diseases. In this thesis, we demonstrate a point-of-care biosensing platform that can detect zika virus directly from a whole blood sample using real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) and a smartphone-based imaging setup.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2021-08-01The student, Anurup Ganguli, accepted the attached license on 2019-07-09 at 18:02.The student, Anurup Ganguli, submitted this Dissertation for approval on 2019-07-09 at 18:12.This Dissertation was approved for publication on 2019-07-11 at 09:33.DSpace SAF Submission Ingestion Package generated from Vireo submission #14230 on 2019-11-26 at 14:01:59Made available in DSpace on 2019-11-26T20:59:37Z (GMT). No. of bitstreams: 3
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Previous issue date: 2019-07-11Embargo set by: Seth Robbins for item 113065
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Evaluation of the atomization-based cutting fluid spray system in milling of titanium alloy
Titanium alloys are considered difficult to machine materials because of poor thermal conductivity and long elongation to break ratio, which makes it difficult to dissipate heat generated during cutting process. Therefore, effective cooling and lubrication effects are vital during machining of these alloys. Recently, it has been shown that an atomization-based cutting fluid (ACF) spray system can effectively cool and lubricate the cutting zone during turning of Ti-6Al-4V, leading to significant improvement in machinability of titanium alloys. However, the efficacy of the ACF spray system is yet to be tested for other machining operations that are different from turning, like milling. The droplet impingement dynamics in milling are different than that in turning because of the presence of a rotating cutting tool as opposed to a stationary single point cutting tool in turning. Also, milling is an intermittent cutting process that gets affected by thermal shock caused by cutting fluid.
The research presented in this thesis investigates the effectiveness of the ACF spray system in end-milling of a titanium alloy, Ti-6Al-4V. To accomplish this, an experimental study has been conducted in two phases. During the first phase, the experiments are conducted to study the role of various combinations of spray parameters on cutting forces and select the one that has the least cutting forces. In the second phase, machining experiments are conducted, using the spray parameters selected in phase one, to assess the machinability of titanium alloy for different cutting fluid application methods,viz., ACF system, flood cooling and dry cutting, and evaluate the effectiveness of ACF spray system for different machining conditions.
It is concluded from Phase 1 experiments that the cutting forces are the least for those spray parameters for which the velocity of the droplets is well within the spreading regime. Furthermore, a numerical model, based on Discrete Phase Modeling approach and Eulerian Wall Film model, of an ACF spray system has been developed and used to simulate the liquid film formation on a rotating cylindrical surface, to explain the variation in the experimentally observed cutting forces for different combinations of spray parameters.
The end-milling experiments show that the presence of carbon dioxide in the droplet carrier gas is responsible for cooling the cutting zone more effectively in milling than what could be achieved in its absence. As a result, tool life increases by 50% when the droplet carrier gas is a mixture of air and carbon dioxide as compared to the case where droplet carrier gas has only air. Tool life experiments show that the ACF spray system outperforms other cutting methods, in three areas critical to access machinability, namely cutting forces, surface roughness and tool wear. Using the ACF spray system leads to uniform tool flank wear, which results in lower cutting forces and higher surface finish, and the tool life extends upto 75% over flood cooling. Additionally, chip morphology analysis reveals that using ACF spray system leads to the formation of shorter and thinner chips, as compared to that when flood cooling is used.Submission published under a 24 month embargo labeled 'U of I only', the embargo will last until 2017-08-01The student, Surojit Ganguli, accepted the attached license on 2015-07-23 at 16:36.The student, Surojit Ganguli, submitted this Thesis for approval on 2015-07-23 at 16:45.This Thesis was approved for publication on 2015-07-23 at 17:13.DSpace SAF Submission Ingestion Package generated from Vireo submission #8637 on 2015-09-29 at 15:00:59Made available in DSpace on 2015-09-29T20:50:26Z (GMT). No. of bitstreams: 2
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Previous issue date: 2015-07-23Embargo set by: Seth Robbins for item 89512
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Structural evolution and the kinetics of Cu clustering in the amorphous phase of Fe-Cu-Nb-Si-B alloy
An attempt has been made to investigate the evolution of the structure of the amorphous phase of Fe-73.9 Cu-0.9 Nb-3.1 Si-13.2 B-8.9 (finemet) alloy by a combination of wide-angle x-ray scattering, small angle x-ray scattering (SAXS), Mossbauer spectroscopy and X-ray absorption near edge spectroscopy on the supposition that they would provide complementary information. Before the onset of nanocrystallization, the amorphous phase undergoes a structural relaxation resulting in small increase in the hyperfine field and a decrease in the width of the first diffraction maxima. There is an increase in the topological ordering in the system, though chemical inhomogeneity sets-in due to the clustering of Cu atoms in the pure amorphous state of this alloy. Annealing at 400 degrees C (well below the crystallization temperature) for different time durations results in occurrence of Cu clusters having fcc structure. Kinetics of Cu clustering is studied using SAXS. The incubation time for the clustering at 400 degrees C is similar to 120 min. With further annealing, the average cluster size gradually increases from the initial value of similar to 0.4 nm, reaching a value of similar to 0.6 nm after annealing for 720 min. Cluster size exhibits a t(1/2) dependence, suggesting a diffusion controlled growt
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