Polymeric Nanocarriers for Delivery of Small Molecules and miRNAs for the Treatment of Liver Fibrosis and Pancreatic Cancer

The aim of this thesis is to develop combination therapy of small molecules and miRNAs for treating liver fibrosis and pancreatic cancer. New amphiphilic biodegradable polymers capable of carrying small hydrophobic molecules and hydrophilic anionic nucleic acids were synthesized, characterized and evaluated in vitro and in vivo liver fibrosis and pancreatic cancer mouse models. In Chapter 1, an overview of liver fibrosis, current treatments and the role of miRNAs in liver fibrosis as well as the design of their delivery systems is given. Further, a general introduction to pancreatic cancer and role of miRNAs in pancreatic cancer is given. In Chapter 2, small molecules GDC-0449 and rosiglitazone were encapsulated into nanoparticles prepared using a biodegradable copolymer mPEG-b-p(CB-co-LA) and used for the treatment of common bile duct ligation (CBDL) induced liver-fibrotic rats. GDC-0449 and rosiglitazone loaded nanoparticles could reverse early stage liver fibrosis by reducing ECM deposition in the liver and inhibiting Hh signaling pathway. Chapter 3 reports the design of a cationic biodegradable copolymer methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonate-graft-dodecanol-graft-tetraethylene-pentamine) (mPEG-b-PCC-g-DC-g-TEPA) for encapsulation of GDC-0449 into the micelle core and complexation of miR-let7b via electrostatic interaction with TEPA. These micelles were characterized for particle size, surface morphology, drug loading, cytotoxicity and transfection efficiency in vitro. Micelles containing both these drugs were evaluated in a subcutaneous pancreatic tumor model. The combination therapy effectively inhibited tumor growth compared to micelles carrying either GDC-0449 or miR-let7b. Immunohistochemical analysis of tumor sections revealed decreased tumor cell proliferation and increased apoptosis of tumor cells of the animals treated with miR-let7b and GDC-0449 combination. Chapter 4 describes the use of mPEG-b-PCC-g-DC-g-TEPA copolymer for delivery of miR-29b1 and GDC-0449 in CBDL mice. Systemic administration of these micelles into CBDL liver fibrotic mice resulted in high concentrations of GDC-0449 and miR-29b1 to the liver cells as determined by in situ liver perfusion. We observed a significant decrease in collagen deposition in the liver and serum injury markers, leading to improvement in liver morphology and disease condition. Combination therapy was effective in providing hepatoprotection, lowering liver injury related serum enzyme levels and reducing fibrotic protein markers such as collagen, α-SMA, FN-1 and p-AKT compared to monotherapy. Finally, Chapter 5 summarizes the results of this thesis and gives suggestions for future research

Behaviour of Market Arrivals and Prices of Selected Vegetable Crops: A Study of Four Metropolitan Markets

This study has been undertaken with the twin objectives of examining the variability pattern of market arrivals and prices of selected vegetable crops (cabbage, cauliflower, tomato and peas) in metropolitan markets of Delhi, Mumbai, Bangalore and Kolkata and analysing the relationship between market arrivals and prices. The study is based on market arrivals and wholesale prices of different vegetable crops collected from the Azadpur market of Delhi and Agricultural and Processed Food Products Export Development Authority (APEDA), New Delhi, for the period 1990-2001. The study has shown that the extent of variability in the arrivals of cabbage was lower in Bangalore and higher in Mumbai. The prices were relatively stable in Mumbai but were more volatile in Bangalore. There was broadly a similar pattern in the price variability across different months in Kolkata and Delhi markets. For cauliflower, the variability in the market arrivals was more pronounced in Kolkata than the remaining three markets. The price variability was, however, more marked in Delhi. The extent of variability in the market arrivals of tomato across different months was very high in all the four markets. Likewise, while the maximum variability in the prices of peas was noted for Delhi, these were relatively less marked in Bangalore. The results of the study have confirmed the negative relationship between market arrivals and prices in terms of correlation coefficients over the years and across months in all the four metropolitan markets, though there were several instances of positive relationship.Agricultural and Food Policy,

Changing Consumer Preferences From Unorganized Retailing Towards Organized Retailing: A Study in Jammu

The retail industry in India is emerging as a one of the largest industries estimated to account for more than 10 per cent of the country’s GDP and around 8 per cent of the employment.This present study was conducted with a purpose of understanding the changes taking place in the minds of consumers towards modern retail formats and traditional retailers. It was observed that due to the changing demographics, increase in DINKS families, urbanization, and awareness due to electronic media especially internet the customers have multiple options to choose from modern retail outlets to neighborhood shops. Majority of the consumers are visiting organized formats for variety, easy availability, cleanliness with additional facility of entertainment for children and convenient parking facility and restaurant etc. In case of unorganized outlets immediacy of the store, credit and bargaining facility balance the tilt. Unlike higher age groups who prefer to visit Kirana stores, the younger generation has more inclination towards organized retail. Families with annual income less than 4.0 Lakh and having a single bread earner prefer shopping with nearby mom-n-pop stores. Both organized as well as unorganized retailers need to add value added services to make the shopping experience more comfortable and value oriented

Monitoring paneer for Listeria monocytogenes- A high risk food pathogen by multiplex PCR

A multiplex polymerase chain reaction (PCR) assay was developed and applied to spiked and natural paneer samples to detect Listeria monocytogenes, a high risk food pathogen. The sensitivity of the assay on L. monocytogenes spiked paneer samples was 104 cells prior to enrichment, was improved to 103 cells after 4 h enrichment and one to 10 cells after 6 h enrichment as indicated by the amplification of 1.2 kb and 713 bp PCR products. The multiplex PCR assay when applied to 10 randomly sampled natural paneer products did not reveal any amplification products, indicating the absence of this organism from these samples.Key words: Listeria monocytogenes, multiplex PCR, 16S rRNA, hemolysin, paneer products

Project success and critical success factors of construction projects: project practitioners’ perspectives

Project management is primarily practitioneroriented and loaded with many critical success factors (CSFs), and although these are well-evidenced in theory, they do not deliver as efficiently as factors of interest to project professionals during execution. The present study explores the perceptions of senior project managers (PMs) about project success, CSFs and complexity in large construction projects. Data from project practitioners were collected through semi-structured interviews and analysed using content analysis. The participants were selected with convenience sampling method given the complex understanding of the domain and included highly experienced PMs from the global community with expertise in project management. PMs perceive a small number of CSFs in contrast to the large exhaustive CSFs listed in the questionnaire surveys. Though important, traditional constraints of the Iron Triangle are considered inadequate in defining project success. Project professionals are seen as relying more on other performance indicators for defining a project as a success. They perceive complex construction projects in terms of a large number of interfaces, complex working systems and uncertainty. The findings of this paper suggest that project practitioners perceive differently about the CSFs and project success

The physiological and performance responses with a water cooled hood in a heat stress environment while doing creative mental work

Call number: LD2668 .T4 1969 G78Master of Scienc

Impact of Nuclear Deformation on Neutron Dripline Prediction: A Study of Mg Isotopes

We have employed the relativistic Hartree-Bogoliubov (RHB) model with density-dependent meson-exchange interaction and separable pairing to investigate neutron dripline mechanisms for heavy Mg isotopes. In the present study, 40Mg is predicted to be dripline nuclei. The calculations are carried out by taking axial deformation into account. An investigation of shape transition is also done for even-even 32-42Mg isotopes. Our prediction for neutron dripline for 40Mg is consistent with some recent studies

Rehabilitation of Maxillary defect using Removable Maxillary Cast Partial Denture Hollow Prosthesis for managing Mucomycosis patient: A Clinical Case Report

  Introduction: Mucormycosis is the fungal infection which especially affects immunocompromised patients. Case Report: In this case report, prosthetic rehabilitation of maxillary defect due to past mucormycosis in an uncontrolled diabetic patient was discussed by means of lightweight prosthesis by attaching a hollow occlusal shim to cast partial denture framework as absence of alveolar ridge on the defect side tends to increase the weight of the prosthesis which would have compromised the retention of the prosthesis. Conclusion: This technique is simple, economical and less time-consuming

Enhanced photocatalytic and disinfection activities of silver loaded ordered mesoporous titanium dioxide for water treatment

In the present paper ordered mesoporous titanium dioxide (TiO2) has been synthesized by using the nanocasting method with SBA-15 as a hard template and titanium alkoxide as the precursor. The silver has been loaded onto the obtained ordered mesoporous TiO2 using photoreduction method. The physicochemical properties of as-prepared and calcined silver loaded mesoporous titanium dioxide (SMTO) have been characterized by various techniques. The XRD pattern confirms the existence of tetragonal anatase-rutile mixed phases of TiO2 with a crystallite size of the range of 12-15 nm. SEM and TEM images show that the aggregation of nanocrystalline phase results in the formation of nanometer sized mesoporous TiO2 with a well-defined spherical morphology and retained ordered structure. The as-obtained samples exhibit good photocatalytic degradation of rhodamine B, Congo red and methyl orange dyes as model water contaminant at room temperature with UV light irradiation. The samples under study also show substantial disinfection properties against E. coli & S. aureus used as a model strain. The significant enhancement of the photocatalytic and disinfection activities of the SMTO materials is mainly attributed to their absorbed more photons and reduced electron-hole pair recombination due to synergic effect of porosity of the ordered structure and Ag-impregnated nanoparticles, respectively