Design and synthesis of biofunctional magnetic/fluorescent glyco-nanoparticles and quantum dots and their application as specific molecular imaging probes

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Unnatural amino acids in the synthesis and semisynthesis of metalloprotein motifs

The design, synthesis, and characterization of two novel metalloprotein motifs is presented. The first project involved the design and construction of a protein motif which was programmed to form a tetradentate metal complex upon the addition of metal cations. The overall structure of the motif was based on a ββ super-secondary structure consisting of a flexible peptide sequence flanked by metal binding regions located at the carboxy and amino termini. The metal binding region near the amino terminus was constructed from a reverse turn motif with two metal ligating residues, (2R, 3R)-β-methyl-cysteine and histidine. Selection of the peptide sequence for this region was based on the conformational analysis of a series of tetrapeptides designed to form reverse turns in solution.

The stereospecific syntheses of a series of novel bipyridyl- and phenanthrolylsubstituted amino acids was carried out to provide ligands for the carboxy terminus metal binding region. These residues were incorporated into peptide sequences using solid phase peptide synthesis protocols, and metal binding studies indicated that the metal binding properties of these ligands was dictated by the specific regioisomer of the heteroaromatic ring and the peptide primary sequence.

Finally, a peptide containing optimized components for the metal binding regions was prepared to test the ability of the compound to form the desired intramolecular peptide:metal cation complexes. Metal binding studies demonstrated that the peptide formed monomeric complexes with very high metal cation binding affinities and that the two metal binding regions act cooperatively in the metal binding process. The use of these systems in the design of proteins capable of regulating naturally occurring proteins is discussed.

The second project involved the semisynthesis of two horse heart cytochrome c mutants incorporating the bipyridyl-amino acids at position 72 of the protein sequence. Structural studies on the proteins indicated that the bipyridyl amino acids had a neglible effect on the protein structure. One of the mutants was modified with Ru(bpy)_2^(+2) to form a redox-active protein, and the modified protein was found to have enhanced electron transfer properties between the heme and the introduced metal site.

Structure-Guided Design and Biophysical Characterization of Novel Anti-HIV Reagents

Despite over 30 years of effort, an HIV-1 vaccine that elicits protective antibodies still does not exist. Recent clinical studies have identified that during natural infection about 20% of the population is capable of mounting a potent and protective antibody response. Closer inspection of these individuals reveal that a subset of these antibodies, recently termed potent VRC01-like (PVL), derive exclusively from a single human germline heavy chain gene. Induced clonal expansion of the B cell encoding this gene is the first step through which PVL antibodies may be elicited. Unfortunately, naturally occurring HIV gp120s fail to bind to this germline, and as a result cannot be used as the initial prime for a vaccine regimen. We have determined the crystal structure of an important germline antibody that is a promising target for vaccine design efforts, and have set out to engineer a more likely candidate using computationally-guided rational design.

In addition to prevention efforts on the side of vaccine design, recently characterized broadly neutralizing anti-HIV antibodies have excellent potential for use in gene therapy and passive immunotherapy. The separation distance between functional Fabs on an antibody is important due to the sparse distribution of envelop spikes on HIV compared to other viruses. We set out to build and characterize novel antibody architectures by incorporating structured linkers into the hinge region of an anti-HIV antibody b12. The goal was to observe whether these linkers increased the arm-span of the IgG dimer. When incorporated, flexible Gly4Ser repeats did not result in detectable extensions of the IgG antigen binding domains, by contrast to linkers including more rigid domains such as β2-microglobulin, Zn-α2-glycoprotein, and tetratricopeptide repeats (TPRs). This study adds an additional set of linkers with varying lengths and rigidities to the available linker repertoire, which may be useful for the modification and construction of antibodies and other fusion proteins.

Fish pass design - criteria for the design and approval of fish passes and other structures to facilitate the passage of migratory fish in rivers

Many of British rivers hold stocks of salmon (Salmo salar L.) and sea trout (Salmo trutta L.) and during most of the year some of the adult fish migrate upstream to the head waters where, with the advent of winter, they will eventually spawn. For a variety of reasons, including the generation of power for milling, improving navigation and measuring water flow, man has put obstacles in the way of migratory fish which have added to those already provided by nature in the shape of rapids and waterfalls. While both salmon and sea trout, particularly the former, are capable of spectacular leaps the movement of fish over man-made and natural obstacles can be helped, or even made possible, by the judicious use of fish passes. These are designed to give the fish an easier route over or round an obstacle by allowing it to overcome the water head difference in a series of stages ('pool and traverse' fish pass) or by reducing the water velocity in a sloping channel (Denil fish pass). Salmon and sea trout make their spawning runs at different flow conditions, salmon preferring much higher water flows than sea trout. Hence the design of fish passes requires an understanding of the swimming ability of fish (speed and endurance) and the effect of water temperature on this ability. Also the unique features of each site must be appreciated to enable the pass to be positioned so that its entrance is readily located. As well as salmon and sea trout, rivers often have stocks of coarse fish and eels. Coarse fish migrations are generally local in character and although some obstructions such as weirs may allow downstream passages only, they do not cause a significant problem. Eels, like salmon and sea trout, travel both up and down river during the course of their life histories. However, the climbing power of elvers is legendary and it is not normally necessary to offer them help, while adult silver eels migrate at times of high water flow when downstream movement is comparatively easy: for these reasons neither coarse fish nor eels are considered further. The provision of fish passes is, in many instances, mandatory under the Salmon and Freshwater Fisheries Act 1975. This report is intended for those involved in the planning, siting, construction and operation of fish passes and is written to clarify the hydraulic problems for the biologist and the biological problems for the engineer. It is also intended to explain the criteria by which the design of an individual pass is assessed for Ministerial Approval.

Design and implementation of fishery modules in integrated household surveys in developing countries

Fish and other aquatic animals contribute to the food security of citizens of developing countries, both as a source of income and as a component of healthy diets, yet fishing is not currently captured in most integrated household surveys. This sourcebook provides essential technical guidance on the design of statistical modules and questionnaires aimed at collecting fishery data at the household level. Background on the main policies important to the fishery sector, information on the data needed to analyze issues of policy relevance, and methodology on the construction of survey questions to collect necessary data are also provided. The document is organized to provide essential technical guidance on how to design statistical modules and questionnaires aimed at collecting fishery data at the household level. It includes an overview of the main technical and statistical challenges related to sampling fishery-dependent households. The document starts with an introductory section identifying the potential reasons why fisheries and in particular small-scale fisheries have not been adequately included in national statistical systems in a large number of countries. The report then proposes a succinct review of what is known (and what remains unknown) about small-scale fisheries and their contribution to the livelihoods of households in sub-Saharan Africa. It also provides readers with background on the main policies that are important to the fishery sector, information on the data needed to analyze issues of policy relevance, and methodology on the construction of survey questions to collect necessary data.

Trapped charge dynamics in a sol-gel based TiO(2) high- k gate dielectric silicon metal-oxide-semiconductor field effect transistor.

We have studied the response of a sol-gel based TiO(2), high k dielectric field effect transistor structure to microwave radiation. Under fixed bias conditions the transistor shows frequency dependent current fluctuations when exposed to continuous wave microwave radiation. Some of these fluctuations take the form of high Q resonances. The time dependent characteristics of these responses were studied by modulating the microwaves with a pulse signal. The measurements show that there is a shift in the centre frequency of these high Q resonances when the pulse time is varied. The measured lifetime of these resonances is high enough to be useful for non-classical information processing.

The design and implementation of dialogue control in voice operated database inquiry systems

This paper describes work performed as part of the U.K. Alvey sponsored Voice Operated Database Inquiry System (VODIS) project in the area of intelligent dialogue control. The principal aims of the work were to develop a habitable interface for the untrained user; to investigate the degree to which dialogue control can be used to compensate for deficiencies in recognition performance; and to examine the requirements on dialogue control for generating natural speech output. A data-driven methodology is described based on the use of frames in which dialogue topics are organized hierarchically. The concept of a dynamically adjustable scope is introduced to permit adaptation to recognizer performance and the use of historical and hierarchical contexts are described to facilitate the construction of contextually relevant output messages. © 1989.

Unified modelling in support of organization design and change

The aim of this research is to provide a unified modelling-based method to help with the evaluation of organization design and change decisions. Relevant literature regarding model-driven organization design and change is described. This helps identify the requirements for a new modelling methodology. Such a methodology is developed and described. The three phases of the developed method include the following. First, the use of CIMOSA-based multi-perspective enterprise modelling to understand and capture the most enduring characteristics of process-oriented organizations and externalize various types of requirement knowledge about any target organization. Second, the use of causal loop diagrams to identify dynamic causal impacts and effects related to the issues and constraints on the organization under study. Third, the use of simulation modelling to quantify the effects of each issue in terms of organizational performance. The design and case study application of a unified modelling method based on CIMOSA (computer integrated manufacturing open systems architecture) enterprise modelling, causal loop diagrams, and simulation modelling, is explored to illustrate its potential to support systematic organization design and change. Further application of the proposed methodology in various company and industry sectors, especially in manufacturing sectors, would be helpful to illustrate complementary uses and relative benefits and drawbacks of the methodology in different types of organization. The proposed unified modelling-based method provides a systematic way of enabling key aspects of organization design and change. The case company, its relevant data, and developed models help to explore and validate the proposed method. The application of CIMOSA-based unified modelling method and integrated application of these three modelling techniques within a single solution space constitutes an advance on previous best practice. Also, the purpose and application domain of the proposed method offers an addition to knowledge. © IMechE 2009.

Design and simulation of SMES system using YBCO tapes for direct drive wave energy converters

The ocean represents a huge energy reservoir since waves can be exploited to generate clean and renewable electricity; however, a hybrid energy storage system is needed to smooth the fluctuation. In this paper a hybrid energy storage system using a superconducting magnetic energy system (SMES) and Li-ion battery is proposed. The SMES is designed using Yttrium Barium Copper Oxide (YBCO) tapes, which store 60 kJ electrical energy. The magnet component of the SMES is designed using global optimization algorithm. Mechanical stress, coupled with electromagnetic field, is calculated using COMSOL and Matlab. A cooling system is presented and a suitable refrigerator is chosen to maintain a cold working temperature taking into account four heat sources. Then a microgrid system of direct drive linear wave energy converters is designed. The interface circuit connecting the generator and storage system is given. The result reveals that the fluctuated power from direct drive linear wave energy converters is smoothed by the hybrid energy storage system. The maximum power of the wave energy converter is 10 kW. © 2012 IEEE.

SOI CMOS integrated zinc oxide nanowire for toluene detection

The paper reports on the in-situ growth of zinc oxide nanowires (ZnONWs) on a complementary metal oxide semiconductor (CMOS) substrate, and their performance as a sensing element for ppm (parts per million) levels of toluene vapour in 3000 ppm humid air. Zinc oxide NWs were grown using a low temperature (only 90°C) hydrothermal method. The ZnONWs were first characterised both electrically and through scanning electron microscopy. Then the response of the on-chip ZnONWs to different concentrations of toluene (400-2600ppm) was observed in air at 300°C. Finally, their gas sensitivity was determined and found to lie between 0.1% and 0.3% per ppm. © 2013 IEEE.

Transparent oxide semiconductors for advanced display applications

The article discusses the progress and issues related to transparent oxide semiconductor (TOS) TFTs for advanced display and imaging applications. Amorphous oxide semiconductors continue to spark new technological developments in transparent electronics on a multitude of non-conventional substrates. Applications range from high-frame-rate interactive displays with embedded imaging to flexible electronics, where speed and transparency are essential requirements. TOS TFTs exhibit high transparency as well as high electron mobility even when fabricated at room temperature. Compared to conventional a-Si TFT technology, TOS TFTs have higher mobility and sufficiently good uniformity over large areas, similar in many ways to LTPS TFTs. Moreover, because the amorphous oxide semiconductor has higher mobility compared to that of conventional a-Si TFT technology, this allows higher-frame-rate display operation. This would greatly benefit OLED displays in particular because of the need for lower-cost higher-mobility analog circuits at every subpixel.