Targeted Stimuli-Responsive Dextran Conjugates for Doxorubicin Delivery to Hepatocytes

A targeted, stimuli-responsive, polymeric drug delivery vehicle is being developed in our lab to help alleviate severe side-effects caused by narrow therapeutic window drugs. Targeting specific cell types or organs via proteins, specifically, lectin-mediated targeting holds potential due to the high specificity and affinity of receptor-ligand interactions, rapid internalization, and relative ease of processing. Dextran, a commercially available, biodegradable polymer has been conjugated to doxorubicin and galactosamine to target hepatocytes in a three-step, one-pot synthesis. The loading of doxorubicin and galactose on the conjugates was determined by absorbance at 485 nm and elemental analysis, respectively. Conjugation efficiency based on the amount loaded of each reactant varies from 20% to 50% for doxorubicin and from 2% to 20% for galactosamine. Doxorubicin has also been attached to dextran through an acid-labile hydrazide bond. Doxorubicin acts by intercalating with DNA in the nuclei of cells. The fluorescence of doxorubicin is quenched when it binds to DNA. This allows a fluorescence-based cell-free assay to evaluate the efficacy of the polymer conjugates where we measure the fluorescence of doxorubicin and the conjugates in increasing concentrations of calf thymus DNA. Fluorescence quenching indicates that our conjugates can bind to DNA. The degree of binding increases with polymer molecular weight and substitution of doxorubicin. In cell culture experiments with hepatocytes, the relative uptake of polymer conjugates was evaluated using flow cytometry, and the killing efficiency was determined using the MTT cell proliferation assay. We have found that conjugate uptake is much lower than that of free doxorubicin. Lower uptake of conjugates may increase the maximum dose of drug tolerated by the body. Also, non-galactosylated conjugate uptake is lower than that of the galactosylated conjugate. Microscopy indicates that doxorubicin localizes almost exclusively at the nucleus, whereas the conjugates are present throughout the cell. Doxorubicin linked to dextran through a hydrazide bond was used to achieve improved killing efficiency. Following uptake, the doxorubicin dissociates from the polymer in an endosomal compartment and diffuses to the nucleus. The LC₅₀ of covalently linked doxorubicin is 7.4 μg/mL, whereas that of hydrazide linked doxorubicin is 4.4 μg/mL.

VLSI architecture for an Underwater Robot Vision System

It is well known that image processing requires a huge amount of computation, mainly at low level processing where the algorithms are dealing with a great number of data-pixel. One of the solutions to estimate motions involves detection of the correspondences between two images. For normalised correlation criteria, previous experiments shown that the result is not altered in presence of nonuniform illumination. Usually, hardware for motion estimation has been limited to simple correlation criteria. The main goal of this paper is to propose a VLSI architecture for motion estimation using a matching criteria more complex than Sum of Absolute Differences (SAD) criteria. Today hardware devices provide many facilities for the integration of more and more complex designs as well as the possibility to easily communicate with general purpose processors

Proposal of a parallel architecture for a motion detection algorithm

This paper proposes a parallel architecture for estimation of the motion of an underwater robot. It is well known that image processing requires a huge amount of computation, mainly at low-level processing where the algorithms are dealing with a great number of data. In a motion estimation algorithm, correspondences between two images have to be solved at the low level. In the underwater imaging, normalised correlation can be a solution in the presence of non-uniform illumination. Due to its regular processing scheme, parallel implementation of the correspondence problem can be an adequate approach to reduce the computation time. Taking into consideration the complexity of the normalised correlation criteria, a new approach using parallel organisation of every processor from the architecture is proposed

On AUV control architecture

This paper surveys control architectures proposed in the literature and describes a control architecture that is being developed for a semi-autonomous underwater vehicle for intervention missions (SAUVIM) at the University of Hawaii. Conceived as hybrid, this architecture has been organized in three layers: planning, control and execution. The mission is planned with a sequence of subgoals. Each subgoal has a related task supervisor responsible for arranging a set of pre-programmed task modules in order to achieve the subgoal. Task modules are the key concept of the architecture. They are the main building blocks and can be dynamically re-arranged by the task supervisor. In our architecture, deliberation takes place at the planning layer while reaction is dealt through the parallel execution of the task modules. Hence, the system presents both a hierarchical and an heterarchical decomposition, being able to show a predictable response while keeping rapid reactivity to the dynamic environment

All-Optical Label Stacking: Easing the Trade-offs Between Routing and Architecture Cost in All-Optical Packet Switching

All-optical label swapping (AOLS) forms a key technology towards the implementation of all-optical packet switching nodes (AOPS) for the future optical Internet. The capital expenditures of the deployment of AOLS increases with the size of the label spaces (i.e. the number of used labels), since a special optical device is needed for each recognized label on every node. Label space sizes are affected by the way in which demands are routed. For instance, while shortest-path routing leads to the usage of fewer labels but high link utilization, minimum interference routing leads to the opposite. This paper studies all-optical label stacking (AOLStack), which is an extension of the AOLS architecture. AOLStack aims at reducing label spaces while easing the compromise with link utilization. In this paper, an integer lineal program is proposed with the objective of analyzing the softening of the aforementioned trade-off due to AOLStack. Furthermore, a heuristic aiming at finding good solutions in polynomial-time is proposed as well. Simulation results show that AOLStack either a) reduces the label spaces with a low increase in the link utilization or, similarly, b) uses better the residual bandwidth to decrease the number of labels even more

What is the Web? The Web Architecture

The Introductory Lecture is a discussion about "What is the Web". It involves lots of calling out TLAs and writing them on the blackboard, dividing things into servers, clients, protocols, formats, and the punchline is that the one unique and novel thing about the web is the hypertext link. This follows naturally into the Web architecture - the answer to the question "what is the web".

COMP6218 Web Architecture - Web Content Formats

Plain Text - ASCII, Unicode, UTF-8 Content Formats - XML-based formats (RSS, MathML, SVG, Office) + PDF Text based data formats: CSV, JSON

Enterprise Architecture notes/white papers

A collection of notes and white papers regarding Enterprise Architecture

WAIS seminar: Application Performance Monitoring and Architecture Discovery with Kieker

Wednesday 23rd April 2014 Speaker(s): Willi Hasselbring Organiser: Leslie Carr Time: 23/04/2014 14:00-15:00 Location: B32/3077 File size: 802Mb Abstract The internal behavior of large-scale software systems cannot be determined on the basis of static (e.g., source code) analysis alone. Kieker provides complementary dynamic analysis capabilities, i.e., monitoring/profiling and analyzing a software system's runtime behavior. Application Performance Monitoring is concerned with continuously observing a software system's performance-specific runtime behavior, including analyses like assessing service level compliance or detecting and diagnosing performance problems. Architecture Discovery is concerned with extracting architectural information from an existing software system, including both structural and behavioral aspects like identifying architectural entities (e.g., components and classes) and their interactions (e.g., local or remote procedure calls). In addition to the Architecture Discovery of Java systems, Kieker supports Architecture Discovery for other platforms, including legacy systems, for instance, inplemented in C#, C++, Visual Basic 6, COBOL or Perl. Thanks to Kieker's extensible architecture it is easy to implement and use custom extensions and plugins. Kieker was designed for continuous monitoring in production systems inducing only a very low overhead, which has been evaluated in extensive benchmark experiments. Please, refer to http://kieker-monitoring.net/ for more information.

Web Architecture: HTML Practical

Resources from the HTML session on 6th October 2015

Web Architecture: HTTP Practical

A summary of the HTTP calls we made during the tutorial session.