Engineering multiple levels of specificity in an RNA viral vector

Synthetic molecular circuits could provide powerful therapeutic capabilities, but delivering them to specific cell types and controlling them remains challenging. An ideal "smart" viral delivery system would enable controlled release of viral vectors from "sender" cells, conditional entry into target cells based on cell-surface proteins, conditional replication specifically in target cells based on their intracellular protein content, and an evolutionarily robust system that allows viral elimination with drugs. Here, combining diverse technologies and components, including pseudotyping, engineered bridge proteins, degrons, and proteases, we demonstrate each of these control modes in a model system based on the rabies virus. This work shows how viral and protein engineering can enable delivery systems with multiple levels of control to maximize therapeutic specificity

Using rapid assessment techniques in development of WSPs

This paper explains the important contribution that rapid assessment techniques (RATs) can make to the development of generic WSPs and associated programmes (for example sanitation promotion programmes) in a region or country, by assisting in identifying potential risks associated with individual water source types or supply technologies, from chemicals, or from management practices. The techniques are equally applicable to all types of water supply – from spring sources and hand-dug wells, through community-based boreholes, with hand or mechanised pumps, to large urban utility supplies, but especially in developing countries

Information systems - a methodology for capturing user requirements.

Systems development has been a topic of discussion for many years, with the growth of the Information Technology (IT) industry. Many organisations use systems to allow them to have more control over the processes that are carried out on a daily basis. The Systems Development Life Cycle (SDLC) has had a major impact on the way that systems are developed. It provides a structure that begins with identifying the feasibility of the project to be completed, and guides the project through implementation and maintenance of the system. It has been suggested that the lack of user involvement during this development process is a major cause of this failure in the systems that are developed. This research addresses this problem by reviewing the most popular methods and examining the concept of user involvement. An industrial perspective also assists in generating key issues in systems development. These, together with the lessons learned during the literature review form the basis of the development of a new approach. The new approach proposed in this thesis (URCAM, User requirements Capturing Method) comprises a set of stages and phases that a developer can use to carry out the process of capturing user requirements. While learning from the weaknesses of the existing methods, the proposed method considers their strengths. URCAM was evaluated during a systems development project at BICC General Cables. The results of the evaluation suggested that the method would produce higher quality information than verbal communication. However, the major strengths of the method are that it offers the developer a guide that they could follow from identifying the types of users who would be involved, to the sign-off, of the final specification. URCAM forms are also presented, which offer the user an opportunity to write down information. The results suggest that this method helps the user to feel more involved and increases their willingness to use the implemented system.PhD in the School of Applied Science

Using abuse frames to bound the scope of security problems

Security problems arise from the concern for protecting assets from security threats. In a systems development process, the security protection of a system is specified by security requirements, identified from the analysis of the threats to the system. However, as it is often not possible to obtain a full system description until late in the RE process, a security problem often has to be described in the context of a bounded scope, that is, one containing only the domains relevant to some part of the functionality of the full system. By binding the scope of a security problem, it can be described more explicitly and precisely, thereby facilitating the identification and analysis of threats, which in turn drive the elicitation and elaboration of security requirements. In this poster, we elaborate on an approach we developed based on abuse frames and suggest how it can provide a means for structuring and bounding the scope security problems

A new complimentary web-based tool for manual analysis of microcirculation videos: validation of the capillary mapper against the current gold standard AVA 3.2

OBJECTIVE: The aim of the current study was to compare a newly developed web-based freely accessible software program for manual analysis of the microcirculation, the Capillary Mapper (CM), with AVA 3.2 software (AVA; MicroVision Medical B.V., Amsterdam, The Netherlands), which is the current gold standard for analysis of microcirculation videos. METHODS: A web-based software program was developed, which enables manual analysis of videos of the microcirculation to be carried out according to recommendations of the 2018 consensus conference. A set of 50 high quality microcirculation videos was analyzed with AVA and CM with respect to total vessel density, perfused vessel density, proportion of perfused vessels, and the microvascular flow index. RESULTS: Comparison of the mean values derived from manual analysis with CM and AVA revealed no significant differences in microcirculatory variables. Analysis according to Bland and Altman revealed an acceptable bias between manual analysis with the CM and AVA for all variables tested with sufficient limits of agreement. The analysis of intraclass correlation showed "excellent" agreement for all microcirculatory variables analyzed. CONCLUSIONS: The newly developed CM was successfully validated for manual analyses of microcirculation videos against the current gold standard, the software AVA 3.2

Rapid assessment of drinking water quality: a handbook for implementation

Water is a basic human right as recently re-clarified in General Comment 15 of the Committee on Economic, Social and Cultural Rights. The importance of water for health and development has been reflected in international policy initiatives since the International Decade for Water Supply and Sanitation Development (the 1980s). This was further emphasised by the Millennium Declaration Goal to halve the proportion of the World's population that lacks access to water supply and most recently the identification of water and sanitation as a highest priority issue by the Commission for Sustainable Development. Since the 1960s, WHO has periodically reported on the development of the access to safe drinking-water sources; this is now implemented as a joint programme of work with UNICEF through the WHO/UNICEF Joint Monitoring Programme (JMP) for Water Supply and Sanitation. In recent reviews and evaluations the need for JMP to progressively address new and emerging priorities has been highlighted. As part of the ongoing plan of work of JMP, a major initiative to more comprehensively take account of water quality issues has been initiated. This handbook has been developed as a resource to support the systematic evaluation of drinking-water quality status at country and local levels. It is hoped that it will be useful to those interested in describing and understanding drinking-water quality status in the context of JMP at national/state levels and on a project basis

Quasi-doubly periodic solutions to a generalized Lame equation

We consider the algebraic form of a generalized Lame equation with five free parameters. By introducing a generalization of Jacobi's elliptic functions we transform this equation to a 1-dim time-independent Schroedinger equation with (quasi-doubly) periodic potential. We show that only for a finite set of integral values for the five parameters quasi-doubly periodic eigenfunctions expressible in terms of generalized Jacobi functions exist. For this purpose we also establish a relation to the generalized Ince equation.Comment: 15 pages,1 table, accepted for publication in Journal of Physics

On Approximation of the Eigenvalues of Perturbed Periodic Schrodinger Operators

This paper addresses the problem of computing the eigenvalues lying in the gaps of the essential spectrum of a periodic Schrodinger operator perturbed by a fast decreasing potential. We use a recently developed technique, the so called quadratic projection method, in order to achieve convergence free from spectral pollution. We describe the theoretical foundations of the method in detail, and illustrate its effectiveness by several examples.Comment: 17 pages, 2 tables and 2 figure

Rapid asssessment of drinking-water quality: a handbook for implementation

The JMP Rapid assessment of drinking-water quality (RADWQ) was conceived by WHO and UNICEF to explore the quality of drinking-water from "improved" sources. Results in five pilot countries showed a wide range of conditions, from full compliance with the WHO Drinking-water Quality Guidelines to specific sources in a given country only meeting standards in 34% of the samples. Further efforts along the lines of RADWQ will take global water quality testing out of the strict sphere of monitoring into the broader field of capacity development. The RADWQ handbook describes the methods and procedures applied by WHO and UNICEF in the five countries, for adoption by any authority or institution that wants to prepare a snapshot of the quality of "improved" sources of drinking-water, as a first step towards strengthening drinking-water quality regulations

Microcirculation

The microcirculation is the part of the circulation where oxygen, nutrients, hormones, and waste products are exchanged between circulating blood and parenchymal cells.The microcirculation includes not only all the vessels with a diameter <100 μm but also the interactions between blood components (circulating cells, coagulation factors), the vessels lined by the endothelium, and the glycocalyx.Facultad de Ciencias Médica