219 research outputs found
Exploring the fundamentals of nanomaterials design for biomolecular sensing and cancer imaging
No full textSubmission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-12-01The student, Subhendu Pandit, accepted the attached license on 2022-08-15 at 22:15.The student, Subhendu Pandit, submitted this Dissertation for approval on 2022-08-15 at 22:47.This Dissertation was approved for publication on 2022-08-23 at 16:05.DSpace SAF Submission Ingestion Package generated from Vireo submission #17887 on 2023-04-12 at 11:33:57Over the last few decades despite significant improvements in chemotherapy, radiation therapy, and other traditional drug-based therapies for cancer treatment, surgical resection is still one of the best ways of removing solid cancer tumors. If a cancer tumor can be precisely resected, without leaving any positive cancer margin behind and without unnecessary removal of healthy tissues, it can lead to remission and good quality of life for the patient. Currently, in operating rooms, surgeons primarily rely on their visual and tactile senses to resect a cancer tumor. This often leads to imprecise resection, especially in irregular tumors and non-palpable tumors, leading to multiple follow-up surgeries and often relapse of cancer. Pre-operative imaging modalities like CT/MRI/PET images provide rough guidance for the surgeons to locate cancer tumors but due to deformation of tissues, real-time intra-operative image-guidance guidance is required to perform precision surgeries. Optical fluorescence imaging in the near-infrared window with appropriate contrast agents and imaging devices could be used for real-time image guidance for cancer surgery. Optical fluorescence-based molecular imaging holds the promise to bridge pre-operative imaging with intra-operative reality.
Currently, there are only three FDA-approved near-infrared (NIR) fluorescent agents, indocyanine green, methylene blue, and OTL38. Indocyanine green and methylene blue are blood pool agents, which have been repurposed to be used in image-guided surgery because of their FDA approval. OTL38, on the other hand, is a folate-receptor-targeted NIR dye developed specifically for image-guided surgery applications. To push the forefront of optical fluorescence image-guided surgery, new biocompatible NIR-fluorescent contrast agents with desired pharmacokinetic properties need to be developed specifically for image-guided surgery. Here we have explored three nanomaterials, carbon dots, semiconductor polymeric nanoparticles, and albumin-based probes, for their potential application in image-guided surgery.
Carbon dots (CDs) are a class of fluorescent nanomaterials that are biocompatible, biodegradable, easy to synthesize, and have bright and stable fluorescence. Most importantly, carbon dots contain no heavy metal, which is a long-term toxicity concern for most inorganic fluorescent nanoparticles. If CDs could be tuned to have NIR emission and can be effectively targeted to be delivered to cancer tumors, CDs could be an excellent contrast agent for image-guided surgery. However, the emission mechanism and electronic structure of CDs are poorly understood. In this thesis, we have explored various surface modifications of CDs to tune their optical properties and understand how those alter their emission behavior. We have shown that crosslinking the surface carboxylic acids of CDs with bisamines leads to a blue shift of fluorescence emission and changes their cellular uptake properties. We have also studied how surface modification of CDs with electron-donating or electron-accepting groups changes their photophysical properties in bulk and at the single-particle level. We also observed a probable near-infrared emitting aggregated state in CDs at very high concentrations and tried to capture the aggregated state with polymeric encapsulation and with lipid nanoparticles but both the approaches did not work. Finally, we have conducted scanning tunneling microscopy (STM) studies on phenylenediamine-derived multi-color CDs to understand the origin of their multi-color emission. We have imaged the ground state electronic band structure of these materials at a sub-single-particle resolution to understand their possible fluorescence mechanism. All these studies provide us with insight into the fluorescence mechanism of CDs to tune them for various biomedical and energy applications. The fluorescence emission of CDs is heavily influenced by the chemical environment around it. The surface defects in CDs are believed to be the main emission center of CDs, and the electronic structure of those groups is influenced by the pH, solvent, and other external factors. CDs change their emission behavior with non-covalent interactions (electrostatic, π-π, H-bonding, hydrophobic interaction, etc.) with the surrounding environment. We used this property of CDs to make multiple array-based sensors for detecting proteins and metal ions. We developed a surface-functionalized CD-array for sensing proteins in the buffer and human serum. We also developed another array-based sensor with the crosslinked CDs to detect proteins. We showed metal ion sensing with the crosslinked CD array and with an associated CD structure array.
Next, we have explored a nanoformulation of semiconductor polymeric nanoparticles (SPNs) for their potential use in image-guided surgery. SPNs have emerged as a promising class of nanoparticles that are comprised of optically active semiconducting polymers (SPs). As SPs are organic and biologically inert, SPNs essentially circumvent the issue of heavy metal ion-induced toxicity to living organisms and thereby possess good biocompatibility. We developed a nanoformulation of fluorescent SPNs by coating them with targeting ligand-modified red blood cell membranes (RBCm). With different ligand modifications on RBCm coating (folate and cRGD insertions) we could target different receptors, folate receptors and αVβ3 integrins, on cancer cells. With our biomimetic coating, we could achieve enhanced blood circulation, precise tumor targeting, and reduced macrophage uptake. We also chose two SPNs for our nanoformulations in such a way that both of them can be excited with a single laser excitation but the fluorescence emission signal could be separated. Being able to target two biomarkers together, with multiplexed imaging agents, helps us better image heterogeneous tumors and leads to better resection. The single laser excitation helps further reduce the instrumentation clutter in operating rooms. These nanoformulations provide us with a platform to develop biomimetic nanoparticles, particularly for image-guided surgery applications.
Optical fluorescence guidance has been the primary modality for intra-operative imaging, but it suffers from the problem of poor penetration depth. Radio guidance, together with optical fluorescence guidance can address the penetration depth problem of unimodal optical probes. Here we have developed an albumin-based probe for bimodal fluorescence and PET imaging. We have done the synthesis and characterization of the albumin-based probes to understand how albumin can be modified to incorporate two imaging modalities together. We have looked at the cellular uptake of the probes and their in vivo biodistribution to determine the feasibility of clinical translation. The PET images reveal that, unlike the unimodal probes, our bimodal probe gets heavily stuck in the liver like most other nanoparticles and raises the long-term toxicity problem. Our bimodal albumin-based probes could still be useful for IGS because of their ability to target gp60 proteins to actively transcytose into cancer tumors but that needs further careful evaluation for conclusive evidence.
In summary, we have studied CDs, biomimetic SPNs, and albumin-based fluorescence-PET probes to determine their potential in clinical translation as an IGS probe. For CDs, we have done mainly fundamental studies to understand their emission properties to be able to eventually tune CDs to have NIR emission for IGS applications. We have shown that we could build array-based sensors with surface-functionalized CDs for biomolecular detection. For biomimetic SPNs, we have done in vitro and in vivo studies to show their enhanced blood circulation, precise tumor targeting, reduced macrophage uptake, and multiplexing ability for targeting multiple biomarkers at the same time for potential application in IGS. We have also developed an albumin-based bi-modal probe for a fluorescence-PET signal for radio guidance along with fluorescence guidance for IGS
Atlanto-occipital fusion: A case report
No full textThe atlas is the first cervical vertebra. In the history of anatomy, due to its primary function of supporting the skull, it has been innumerably compared with Atlas the Greek God, who holds the globe of the earth on his shoulders. This vertebra is devoid of a body and has two prominent lateral masses bearing a pair of superior concave facets and inferior smooth facets each. Atlanto-occipital fusion may be unilateral or bilateral, complete or incomplete and symptomatic or asymptomatic. In our, case atlanto-occipital fusion was observed in the skull of a male cadaver. Our study will be of significance to clinicians in the specialties of radiodiagnosis, orthopedics, neurosurgery and anesthesiology. Because of a lack of knowledge of developmental malformation in the craniocervical region, sudden death can occur during clinical manipulation. Head and neck surgeons must keep in mind that such anomaly can exist without any prior symptoms. The specimen seen represents a case of congenital fusion. The articular processes of the specimen are fused between the occipital and the atlas bones. Atlanto-occipital fusion decreases the diameter of the foramen magnum and produce neurovascular symptoms
Spinodal decomposition in the inverse cascade of two-dimensional, binary-fluid turbulence
No full textWe study spinodal decomposition in the inverse-cascade regime of two dimensional turbulence in symmetric, binary fluid mixtures. We show that turbulence leads to break up of domains whose size, in the inverse cascade regime, is proportional to the Hinze scale. Even more strikingly, we show that the inverse cascade of energy is blocked by the formation of domains
Particles and Fields in Superfluids: Insights from the Two-dimensional Gross-Pitaevskii Equation
No full textWe study the dynamics of active particles in two-dimensional superfluids at temperature , for a variety of initial configurations, by carrying out extensive direct-numerical-simulations of the two-dimensional, Galerkin-truncated Gross-Pitaevskii equation. Our study elucidates the interplay of particles and fields, in both simple and turbulent flows. We show that particle collisions can be inelastic, if the repulsive interactions between particles is weak, and elastic otherwise. We show that assemblies of many particles and vortices yield turbulent spatiotemporal evolutions
Multifractal Droplet Dynamics in Two-Dimensional, binary-fluid turbulence
No full textWe present the most extensive direct numerical simulations, attempted so far, of statistically steady, homogeneous, isotropic turbulence in two-dimensional, binary-fluid mixtures with air-drag-induced friction. We model this mixture by using the Cahn-Hilliard-Navier-Stokes equations and choose parameters, e.g., the surface tension, such that we have a droplet of the minority phase moving inside a turbulent background of the majority phase. Our study reveals that a single droplet, whose mean radius lies in the inertial range of scales, (a) enhances the the forward-cascade part of the energy spectrum of two-dimensional turbulence and (b) stretches the tails of the PDF of the Okubo-Weiss parameter . We show that the dynamics of the droplet is affected significantly by the turbulence in the fluid. In particular, the PDFs of the components of the acceleration shows wide, non-Guassian tails. We characterize the time dependence of the deformation of the droplet and show that it exhibits multifractality
Real-space Manifestations of Bottlenecks in Turbulence Spectra
No full textAn energy-spectrum bottleneck, a bump in the turbulence spectrum between the inertial and dissipation ranges, is shown to occur in the non-turbulent, one-dimensional, hyperviscous Burgers equation and found to be the Fourier-space signature of oscillations in the real-space velocity, which are explained by boundary-layer-expansion techniques. Pseudospectral simulations are used to show that such oscillations occur in velocity correlation functions in one- and three-dimensional hyperviscous hydrodynamical equations that display genuine turbulence
Universal Statistical Properties of Inertial-particle Trajectories in Three-dimensional, Homogeneous, Isotropic, Fluid Turbulence
No full textWe obtain new universal statistical properties of heavy-particle trajectories in three-dimensional, statistically steady, homogeneous, and isotropic turbulent flows by direct numerical simulations. We show that the probability distribution functions (PDFs) P(Φ), of the angle Φ between the Eulerian velocity u and the particle velocity v, at a point and time, scales as P(Φ) ∼Φ−, with a new universal exponent ≃ 4
Mutual-Friction Coefficients in Two-Dimensional Superfluids: From the Gross-Pitaevskii equation to the Hall-Vinen-Bekharevich-Khalatnikov Two-fluid Model
No full textWe start from the two-dimensional Gross-Pitaevskii equation (GPE) and develop algorithms for the ab-initio determination of the temperature (T) dependence of the mutual-friction coefficients, α and α, and the normal-fluid density Pn, which appear as parameters in the Hall-Vinen-Bekharevich-Khalatnikov (HVBK) two-fluid model for a superfluid. In the second part of our study, we elucidate the statistical properties of two-dimensional, homogeneous, isotropic superfluid turbulence in the simplified HVBK model, with values for the mutual-friction coefficients that are comparable to those we obtain from the first part of our study
How does trade impact agricultural productivity?
No full textThe student, Akshay Pandit, submitted this Thesis for approval on 2020-07-22 at 15:29.This Thesis was approved for publication on 2020-07-23 at 10:50.DSpace SAF Submission Ingestion Package generated from Vireo submission #15729 on 2020-10-02 at 15:34:07Made available in DSpace on 2020-10-07T22:44:48Z (GMT). No. of bitstreams: 2
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Previous issue date: 2020-07-23"Agricultural production has faced increased demands over the last half century from an expanding economy and population. We live in a globalized world, in which agriculture is deeply intertwined in international markets and trade. In this paper, we address the overarching research question: ""What is the impact of trade on agricultural productivity?''. To this end, we present a comprehensive statistical and econometric analysis on the relationship between international trade and agricultural production. We use national-scale data on crop yield, area harvested, production, and trade for the last half century (1961-2016) from the Food and Agricultural Organization of the United Nations. We introduce novel weighting and decomposition analyses to explore the relationship between trade and crop productivity. To determine the causal impact of trade on agriculture we implement instrumental variable (IV) econometric methods. We find that trade has led to an increase in global agricultural productivity over time (e.g. through increased productivity, the intensive margin). Global productivity gains have accrued primarily through the participation of more countries in global trade (e.g. expanding the area of contribution, the extensive margin). Additionally, we find that trade has enabled global crop consumption to increase. These findings indicate that trade openness leads to greater productivity in agriculture in general. This work highlights that trade can help to achieve productivity gains in agriculture and potentially help the world to address remaining yield gaps."Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2022-08-01The student, Akshay Pandit, accepted the attached license on 2020-07-22 at 15:28.Embargo set by: Seth Robbins for item 116267
Lift date: 2022-10-07T22:44:53Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Onl
لڑکون کا کهیل / راج بہادر
No full textapplication/pdfبار 17Collection of essays on various topics written by the author in his youth / by Raj Bahadur, Pandit
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