Freshwater prawn fry production and delivery process: key to sustainable aquaculture development for Bangladesh

This study was conducted to identify a functioning fingerlings production and delivery system for a sustainable aquaculture development. Data were collected from 234 respondents randomly sampled from a population of 600 fish farmers. Results indicated that farmer-to-farmer was the major source of fingerlings production and distribution system. Although this source accessed disadvantaged groups like the rural based, resource poor, less educated and women, it lacked knowledge on how to produce good quality fingerlings. These results suggest that a decentralized and privatized fingerlings production and delivery system should be promoted. For this system to operate effectively the aquaculture department should first identify potential zones for aquaculture growth and profit motivated fingerlings producers and distributors. Furthermore, the institutional mechanism through which farmer-to-farmer will operate should be identified and strengthened through short and long term training programmes. The government should support the system by providing guidelines for good quality fingerlings management; maintain brood stock parents and technical training in Bangladesh.

Introduction to LVFRP Technical Document 9

As stated in the title, this is an introduction to all the reports contained in this technical document and related to the various workshops on Participatory Rural Appraisal (PRA) held in all the riparian countries around Lake Victoria within the LVFRP.

Delivery of Targeted Nanoparticles Across the Blood-Brain Barrier Using a Detachable Targeting Ligand

Chronic diseases of the central nervous system are poorly treated due to the inability of most therapeutics to cross the blood-brain barrier. The blood-brain barrier is an anatomical and physiological barrier that severely restricts solute influx, including most drugs, from the blood to the brain. One promising method to overcome this obstacle is to use endogenous solute influx systems at the blood-brain barrier to transport drugs. Therapeutics designed to enter the brain through transcytosis by binding the transferrin receptor, however, are restricted within endothelial cells. The focus of this work was to develop a method to increase uptake of transferrin-containing nanoparticles into the brain by overcoming these restrictive processes.

To accomplish this goal, nanoparticles were prepared with surface transferrin molecules bound through various liable chemical bonds. These nanoparticles were designed to shed the targeting molecule during transcytosis to allow increased accumulation of nanoparticles within the brain.

Transferrin was added to the surface of nanoparticles through either redox or pH sensitive chemistry. First, nanoparticles with transferrin bound through disulfide bonds were prepared. These nanoparticles showed decreased avidity for the transferrin receptor after exposure to reducing agents and increased ability to enter the brain in vivo compared to those lacking the disulfide link.

Next, transferrin was attached through a chemical bond that cleaves at mildly acidic pH. Nanoparticles containing a cleavable link between transferrin and gold nanoparticle cores were found to both cross an in vitro model of the blood-brain barrier and accumulate within the brain in significantly higher numbers than similar nanoparticles lacking the cleavable bond. Also, this increased accumulation was not seen when using this same strategy with an antibody to transferrin receptor, indicating that behavior of nanoparticles at the blood-brain barrier varies depending on what type of targeting ligand is used.

Finally, polymeric nanoparticles loaded with dopamine and utilizing a superior acid-cleavable targeting chemistry were investigated as a potential treatment for Parkinson’s disease. These nanoparticles were capable of increasing dopamine quantities in the brains of healthy mice, highlighting the therapeutic potential of this design. Overall, this work describes a novel method to increase targeted nanoparticle accumulation in the brain.

Development of a Cationic Mucic Acid Polymer-Based Nanoparticle siRNA Delivery System

Cancer chemotherapy has advanced from highly toxic drugs to more targeted treatments in the last 70 years. Chapter 1 opens with an introduction to targeted therapy for cancer. The benefits of using a nanoparticle to deliver therapeutics are discussed. We move on to siRNA in particular, and why it would be advantageous as a therapy. Specific to siRNA delivery are some challenges, such as nuclease degradation, quick clearance from circulation, needing to enter cells, and getting to the cytosol. We propose the development of a nanoparticle delivery system to tackle these challenges so that siRNA can be effective.

Chapter 2 of this thesis discusses the synthesis and analysis of a cationic mucic acid polymer (cMAP) which condenses siRNA to form a nanoparticle. Various methods to add polyethylene glycol (PEG) for stabilizing the nanoparticle in physiologic solutions, including using a boronic acid binding to diols on mucic acid, forming a copolymer of cMAP with PEG, and creating a triblock with mPEG on both ends of cMAP. The goal of these various pegylation strategies was to increase the circulation time of the siRNA nanoparticle in the bloodstream to allow more of the nanoparticle to reach tumor tissue by the enhanced permeation and retention effect. We found that the triblock mPEG-cMAP-PEGm polymer condensed siRNA to form very stable 30-40 nm particles that circulated for the longest time – almost 10% of the formulation remained in the bloodstream of mice 1 h after intravenous injection.

Chapter 3 explores the use of an antibody as a targeting agent for nanoparticles. Some antibodies of the IgG1 subtype are able to recruit natural killer cells that effect antibody dependent cellular cytotoxicity (ADCC) to kill the targeted cell to which the antibody is bound. There is evidence that the ADCC effect remains in antibody-drug conjugates, so we wanted to know whether the ADCC effect is preserved when the antibody is bound to a nanoparticle, which is a much larger and complex entity. We utilized antibodies against epidermal growth factor receptor with similar binding and pharmacokinetics, cetuximab and panitumumab, which differ in that cetuximab is an IgG1 and panitumumab is an IgG2 (which does not cause ADCC). Although a natural killer cell culture model showed that gold nanoparticles with a full antibody targeting agent can elicit target cell lysis, we found that this effect was not preserved in vivo. Whether this is due to the antibody not being accessible to immune cells or whether the natural killer cells are inactivated in a tumor xenograft remains unknown. It is possible that using a full antibody still has value if there are immune functions which are altered in a complex in vivo environment that are intact in an in vitro system, so the value of using a full antibody as a targeting agent versus using an antibody fragment or a protein such as transferrin is still open to further exploration.

In chapter 4, nanoparticle targeting and endosomal escape are further discussed with respect to the cMAP nanoparticle system. A diboronic acid entity, which gives an order of magnitude greater binding (than boronic acid) to cMAP due to the vicinal diols in mucic acid, was synthesized, attached to 5kD or 10kD PEG, and conjugated to either transferrin or cetuximab. A histidine was incorporated into the triblock polymer between cMAP and the PEG blocks to allow for siRNA endosomal escape. Nanoparticle size remained 30-40 nm with a slightly negative ca. -3 mV zeta potential with the triblock polymer containing histidine and when targeting agents were added. Greater mRNA knockdown was seen with the endosomal escape mechanism than without. The nanoparticle formulations were able to knock down the targeted mRNA in vitro. Mixed effects suggesting function were seen in vivo.

Chapter 5 summarizes the project and provides an outlook on siRNA delivery as well as targeted combination therapies for the future of personalized medicine in cancer treatment.

Improving Content Delivery Efficiency through Multi-Layer Mobile Edge Adaptation

This paper presents a novel architecture for optimizing the HTTP-based multimedia delivery in multi-user mobile networks. This proposal combines the usual client-driven dynamic adaptation scheme DASH-3GPP with network-assisted adaptation capabilities, in order to maximize the overall Quality of Experience. The foundation of this combined adaptation scheme is based on two state of the art technologies. On one hand, adaptive HTTP streaming with multi-layer encoding allows efficient media delivery and improves the experienced media quality in highly dynamic channels. Additionally, it enables the possibility to implement network-level adaptations for better coping with multi-user scenarios. On the other hand, mobile edge computing facilitates the deployment of mobile services close to the user. This approach brings new possibilities in modern and future mobile networks, such as close to zero delays and awareness of the radio status. The proposal in this paper introduces a novel element, denoted as Mobile Edge-DASH Adaptation Function, which combines all these advantages to support efficient media delivery in mobile multi-user scenarios. Furthermore, we evaluate the performance enhancements of this content- and user context-aware scheme through simulations of a mobile multimedia scenario.

Biofunctionalization of alginate microcapsules: advances in cell-based drug delivery systems

172 p.

Low Molecular Weight Chitosan (LMWC)-based Polyplexes for pDNA Delivery: From Bench to Bedside

Non-viral gene delivery vectors are emerging as a safer alternative to viral vectors. Among natural polymers, chitosan (Ch) is the most studied one, and low molecular weight Ch, specifically, presents a wide range of advantages for non-viral pDNA delivery. It is crucial to determine the best process for the formation of Low Molecular Weight Chitosan (LMWC)-pDNA complexes and to characterize their physicochemical properties to better understand their behavior once the polyplexes are administered. The transfection efficiency of Ch based polyplexes is relatively low. Therefore, it is essential to understand all the transfection process, including the cellular uptake, endosomal escape and nuclear import, together with the parameters involved in the process to improve the design and development of the non-viral vectors. The aim of this review is to describe the formation and characterization of LMWC based polyplexes, the in vitro transfection process and finally, the in vivo applications of LMWC based polyplexes for gene therapy purposes.

The Lune catchment abstraction management strategy. Consultation document September 2003

This consultation document sets out the proposed future licensing strategy for the Lune Catchment Abstraction Management Strategy (CAMS) area. Following the three month consultation period, the Environment Agency will determine the final licensing strategy and publish it in the CAMS document. The strategy will provide an indication of whether new abstraction licences are likely to be available and the conditions that should be expected on licences. Water plays a vital role in the Lune catchment, providing water for public supply, supporting recreation, such as angling and canoeing, and providing sustainable flows to preserve numerous designated sites. There is minimal abstraction throughout much of the catchment, apart from the lower reaches of the River Lune. The document is split into five sections relating to the CAMS process. Sections 1 to 4 outline the CAMS process, and Section 5 outlines the proposed licensing strategy for the Lune CAMS areas. It is important to note that this strategy deals with groundwater and surface water abstractions separately; Sections 4 and 5 are split to differentiate between the surface water and groundwater results and strategy.

Summary document of the work being done in 1992-1993 regarding the migratory salmonid fisheries of the River Ribble catchment

This document lists the work on salmonid fisheries in the River Ribble catchment in the north west of England which was done in 1992-93. The document includes the following: analysis of historical catch data from the River Ribble covering 1937-1991; Ribble and Hodder stock assessment surveys 1992-93 including Swanside Beck; Ribble catch data from game angling log books 1993; results of salmon scale sampling 1993; results of microtagging programme in Hodder and Ribble 1993; Waddow Weir dish counter data 1993; Winkley Hall (Hodder), Locks Weir and Waddow Hall (Ribble) fish counter data 1993; number of fish and ova from Witcherwell Hatchery 1993.