A combinatorial approach to the chemical synthesis and biological evaluation of 3,4,5-trisubstiituted furan-2(5H)-ones

Many important natural products contain the furan-2(5H)-one structure. The structure of this molecule lends itself to manipulation using combinatorial techniques due to the presence of more than one site for the attachment of different suhstituents. By developing different reaction schemes at the three sites available for attachment on the furan-2(5H)-one scaffold, combinatorial chemistry techniques can be employed to assemble libraries of novel furan 2(5H)-ones. These libraries can then be entered into various biological screening programmes. This approach will enable a vast diversity or compounds to be examined, in the hope or finding new biologically active Iead structures. The work in this thesis has investigated the potential that combinatorial chemistry has in the quest for new biologically active lead structures based on the furan-2(5H)-one structure. Different reactions were investigated with respect to their suitability for inclusion in a library. Once sets of reactions at the various sites had been established, the viability of these reactions in the assembly of combinatorial libraries was investigated. Purification methods were developed, and the purified products entered into suitable biological screening tests. Results from some of these tests were optimised using structure activity relationships, and the resulting products re-screened. The screening tests performed were for anticancer and antimicrobial activity, cholecystokinin (CCK-B) antagonism and anti-inflammatory activity (in the quest for novel cyclo-oxygenase (COX-2) selective non-steroidal anti-inflammatory drugs). It has been shown that many reactions undergone by the furan-2(5H)-one structure are suitable for the assembly of a combinatorial library. Investigation into the assembly of different libraries has been carried out with initial screening results included. From this work, further investigation into combinatorial library assembly and structure activity relationships of screened reaction products can be undertaken.

Evaluation of public housing strategies in Mexico City : an exploratory goal programming approach

This thesis describes the development and use of a goal programming methodology for the evaluation of public housjng strategies in Mexico City, The methodology responds to the need to incorporate the location, size and densities of housing projects on the one hand, and "external" constraints such as the ability of low income families to pay for housing, and the amounts of capital and land available, on the other. The provision of low cost housing by public housing agencies in Mexico City is becoming increasingly difficult because there are so many constraints to be met and overcome, the most important of which is the ability of families to pay for housing. Other important limiting factors are the availability of capital and of land plots of the right size in desired locations. The location of public housing projects is significant because it determines the cost and pattern of work trips, which in a metropolitan area such as Mexico City are of considerable importance to both planners and potential. house owners. In addition, since the price of land is closely related to its location, the last factor is also significant in determining the price of the total housing package. Consequently there is a major trade-off between a housing strategy based on the provision of housing at locations close to employment, and the opposite one based on the provjsion of housjng at locations where employment accessibility is poorer but housing can be provided at a lower price. The goal programming evaluation methodology presented in this thesis was developed to aid housing planners to evaluate housing strategies which incorporate the issues raised above,

Reflection and reflexivity in reviewing and evaluating CDIO:an empirical approach to evaluation

Facilitated by an Engineer and a Social Scientist, both of whom have expertise in Engineering Education Research and Evaluation (EERE), this interactive workshop is divided into three main sections, each one focusing on a different area of evaluation. It will build on research conducted at Aston University School of Engineering and Applied Science to explore and critique the value of introducing CDIO across the first year undergraduate curriculum. Participants will be invited to consider the pedagogical and engineering related challenges of evaluating the academic and practical value of CDIO as a strategy for learning and teaching in the discipline. An empirical approach to evaluation developed by the researchers to provide empirically grounded evidence of the pedagogical and vocational value of CDIO will form the theoretical and conceptual basis of the workshop. This approach is distinctive in that it encapsulates both engineering and social science methods of evaluation. It is also contemporaneous in nature, with the researchers acting as a ‘fly on the wall’ capturing data as the programme unfolds. Through facilitated discussion and participation, the workshop will provide colleagues with the opportunity to develop a cross-disciplinary, empirically grounded research proposal specifically for the purposes of critically evaluating CDIO. It is anticipated that during the workshop, colleagues will work together in small groups. Suitable pedagogical approaches and tools will be suggested and a purposefully developed Engineering Education Research Guide, written by the workshop facilitators, will be given to all participants to inform and support the Workshop approach.

Evaluation efficiency of large-scale data set with negative data:an artificial neural network approach

Data envelopment analysis (DEA) is the most widely used methods for measuring the efficiency and productivity of decision-making units (DMUs). The need for huge computer resources in terms of memory and CPU time in DEA is inevitable for a large-scale data set, especially with negative measures. In recent years, wide ranges of studies have been conducted in the area of artificial neural network and DEA combined methods. In this study, a supervised feed-forward neural network is proposed to evaluate the efficiency and productivity of large-scale data sets with negative values in contrast to the corresponding DEA method. Results indicate that the proposed network has some computational advantages over the corresponding DEA models; therefore, it can be considered as a useful tool for measuring the efficiency of DMUs with (large-scale) negative data.

Development and psychometric evaluation of a new team effectiveness scale for all types of community adult mental health teams:a mixed-methods approach

Defining 'effectiveness' in the context of community mental health teams (CMHTs) has become increasingly difficult under the current pattern of provision required in National Health Service mental health services in England. The aim of this study was to establish the characteristics of multi-professional team working effectiveness in adult CMHTs to develop a new measure of CMHT effectiveness. The study was conducted between May and November 2010 and comprised two stages. Stage 1 used a formative evaluative approach based on the Productivity Measurement and Enhancement System to develop the scale with multiple stakeholder groups over a series of qualitative workshops held in various locations across England. Stage 2 analysed responses from a cross-sectional survey of 1500 members in 135 CMHTs from 11 Mental Health Trusts in England to determine the scale's psychometric properties. Based on an analysis of its structural validity and reliability, the resultant 20-item scale demonstrated good psychometric properties and captured one overall latent factor of CMHT effectiveness comprising seven dimensions: improved service user well-being, creative problem-solving, continuous care, inter-team working, respect between professionals, engagement with carers and therapeutic relationships with service users. The scale will be of significant value to CMHTs and healthcare commissioners both nationally and internationally for monitoring, evaluating and improving team functioning in practice.

A pragmatic approach for engineering porous mannitol and mechanistic evaluation of particle performance

The importance of mannitol has increased recently as an emerging diluent for orodispersible dosage forms. The study aims to prepare spray dried mannitol retaining high porosity and mechanical strength for the development of orally disintegrating tablets (ODTs). Aqueous feed of d-mannitol (10% w/v) comprising ammonium bicarbonate, NH4HCO3 (5% w/v) as pore former was spray dried at inlet temperature of 110-170°C. Compacts were prepared at 151MPa and characterized for porosity, hardness and disintegration time. Particle morphology and drying mechanisms were studied using thermal (HSM, DSC and TGA) and polymorphic (XRD) methods. Tablet porosity increased from 0.20±0.002 for pure mannitol to 0.53±0.03 using fabricated porous mannitol. Disintegration time dropped by 50-77% from 135±5.29s for pure mannitol to 75.33±2.52-31.67±1.53s for mannitol 110-170°C. Hardness increased by 150% at 110°C (258.67±28.89N) and 30% at 150°C (152.70±10.58N) compared to pure mannitol tablets (104.17±1.70N). Increasing inlet temperature resulted in reducing tablet hardness due to generation of 'micro-sponge'-like particles exhibiting significant elastic recovery. Impact of mannitol polymorphism on plasticity/elasticity cannot be ruled out as a mixture of α and β polymorphs formed upon spray drying.

Assessing an experimental approach to industrial policy evaluation:Applying RCT+ to the case of Creative Credits

Experimental methods of policy evaluation are well-established in social policy and development eco-nomics but are rare in industrial and innovation policy. In this paper, we consider the arguments forapplying experimental methods to industrial policy measures, and propose an experimental policy eval-uation approach (which we call RCT+). This approach combines the randomised assignment of firmsto treatment and control groups with a longitudinal data collection strategy incorporating quantitativeand qualitative data (so-called mixed methods). The RCT+ approach is designed to provide a causativerather than purely summative evaluation, i.e. to assess both ‘whether’ and ‘how’ programme outcomesare achieved. In this paper, we assess the RCT+ approach through an evaluation of Creative Credits – aUK business-to-business innovation voucher initiative intended to promote new innovation partnershipsbetween SMEs and creative service providers. The results suggest the potential value of the RCT+ approachto industrial policy evaluation, and the benefits of mixed methods and longitudinal data collection.

Towards asphalt mixture morphology evaluation with the virtual specimen approach

The morphology of asphalt mixture can be defined as a set of parameters describing the geometrical characteristics of its constituent materials, their relative proportions as well as spatial arrangement in the mixture. The present study is carried out to investigate the effect of the morphology on its meso- and macro-mechanical response. An analysis approach is used for the meso-structural characterisation based on the X-ray computed tomography (CT) data. Image processing techniques are used to systematically vary the internal structure to obtain different morphology structures. A morphology framework is used to characterise the average mastic coating thickness around the main load carrying structure in the structures. The uniaxial tension simulation shows that the mixtures with the lowest coating thickness exhibit better inter-particle interaction with more continuous load distribution chains between adjacent aggregate particles, less stress concentrations and less strain localisation in the mastic phase.

An Approach for a more Objective Evaluation of Practical Projects, Used in the Training Process

Well–prepared, adaptive and sustainably developing specialists are an important competitive advantage, but also one of the main challenges for businesses. One option of the education system for creation and development of staff adequate to the needs is the development of pro jects with topics from real economy ("Practical Projects"). The objective assessment is an essential driver and motivator, and is based on a system of well-chosen, well-defined and specific criteria and indicators. An approach to a more objective evaluation of practical projects is finding more objective weights of the criteria. A natural and reasonable approach is the accumulation of opinions of proven experts and subsequent bringing out the weights from the accumulated data. The preparation and conduction of a survey among recognized experts in the field of project-based learning in mathematics, informatics and information technologies is described. The processing of the data accumulated by applying AHP, allowed us to objectively determine weights of evaluation criteria and hence to achieve the desired objectiveness. ACM Computing Classification System (1998): K.3.2.

A joint approach to treating dental phobia:a re-evaluation of a collaboration between community dental services and specialist psychotherapy services ten years on

Objective To audit the records of a group of patients who had previously benefited from cognitive behavioural therapy (CBT) for dental phobia.Aim To ascertain if they had returned to the use of intravenous (IV) sedation to facilitate dental treatment. Ten years ago these patients were routinely requiring IV sedation to facilitate dental treatment due to severe dental phobia.Method Sixty patients entered the original pilot project. Of those, 30 were offered CBT and 21 attended. Twenty of those patients (95.2%) were subsequently able to have dental treatment without IV sedation. In this follow-up study the electronic records of 19 of the 20 patients who had originally been successful with CBT were re-audited. Our purpose was to see if there was any record of subsequent IV sedation administration in the intervening ten years.Results Of the 19 successful CBT patients available to follow-up, 100% had not received IV sedation since the study ten years ago. This may suggest the initial benefit of CBT has endured over the ten-year period.Conclusion This study indicates that the use of CBT for patients with dental phobia proves beneficial not only in the initial treatment but that the benefits may endure over time. This results in a significant reduction in health risks to the patient from repeated IV sedation. It may also translate into significant financial savings for dental care providers. Our evidence for CBT as treatment for dental phobia suggests dental services should be implementing this approach now rather than pursuing further research. © 2011 Macmillan Publishers Limited. All rights reserved.

Knowledge representation and evaluation an ontology-based knowledge management approach

Competition between Higher Education Institutions is increasing at an alarming rate, while changes of the surrounding environment and demands of labour market are frequent and substantial. Universities must meet the requirements of both the national and European legislation environment. The Bologna Declaration aims at providing guidelines and solutions for these problems and challenges of European Higher Education. One of its main goals is the introduction of a common framework of transparent and comparable degrees that ensures the recognition of knowledge and qualifications of citizens all across the European Union. This paper will discuss a knowledge management approach that highlights the importance of such knowledge representation tools as ontologies. The discussed ontology-based model supports the creation of transparent curricula content (Educational Ontology) and the promotion of reliable knowledge testing (Adaptive Knowledge Testing System).

Evaluation of wind-induced internal pressure in low-rise buildings: A multi scale experimental and numerical approach

Hurricane is one of the most destructive and costly natural hazard to the built environment and its impact on low-rise buildings, particularity, is beyond acceptable. The major objective of this research was to perform a parametric evaluation of internal pressure (IP) for wind-resistant design of low-rise buildings and wind-driven natural ventilation applications. For this purpose, a multi-scale experimental, i.e. full-scale at Wall of Wind (WoW) and small-scale at Boundary Layer Wind Tunnel (BLWT), and a Computational Fluid Dynamics (CFD) approach was adopted. This provided new capability to assess wind pressures realistically on internal volumes ranging from small spaces formed between roof tiles and its deck to attic to room partitions. Effects of sudden breaching, existing dominant openings on building envelopes as well as compartmentalization of building interior on the IP were systematically investigated. Results of this research indicated: (i) for sudden breaching of dominant openings, the transient overshooting response was lower than the subsequent steady state peak IP and internal volume correction for low-wind-speed testing facilities was necessary. For example a building without volume correction experienced a response four times faster and exhibited 30–40% lower mean and peak IP; (ii) for existing openings, vent openings uniformly distributed along the roof alleviated, whereas one sided openings aggravated the IP; (iii) larger dominant openings exhibited a higher IP on the building envelope, and an off-center opening on the wall exhibited (30–40%) higher IP than center located openings; (iv) compartmentalization amplified the intensity of IP and; (v) significant underneath pressure was measured for field tiles, warranting its consideration during net pressure evaluations. The study aimed at wind driven natural ventilation indicated: (i) the IP due to cross ventilation was 1.5 to 2.5 times higher for Ainlet/Aoutlet>1 compared to cases where Ainlet/Aoutlet<1, this in effect reduced the mixing of air inside the building and hence the ventilation effectiveness; (ii) the presence of multi-room partitioning increased the pressure differential and consequently the air exchange rate. Overall good agreement was found between the observed large-scale, small-scale and CFD based IP responses. Comparisons with ASCE 7-10 consistently demonstrated that the code underestimated peak positive and suction IP.

Application and evaluation of an Institute of Medicine approach to dietary assessment and planning in long -term care

The primary purpose of these studies was to determine the effect of planning menus using the Institute of Medicine's (IOMs) Simple Nutrient Density Approach on nutrient intakes of long-term care (LTC) residents. In the first study, nutrient intakes of 72 subjects were assessed using Dietary Reference Intakes (DRIs) and IOM methodology. The intake distributions were used to set intake and menu planning goals. In the second study, the facility's regular menus were modified to meet the intake goals for vitamin E, magnesium, zinc, vitamin D and calcium. An experiment was used to test whether the modified menu resulted in intakes of micronutrients sufficient to achieve a low prevalence (<3%) of nutrient inadequacies. Three-day weighed food intakes for 35 females were adjusted for day-to-day variations in order to obtain an estimate of long-term average intake and to estimate the proportion of residents with inadequate nutrient intakes. ^ In the first study, the prevalence of inadequate intakes was determined to be between 65-99% for magnesium, vitamin E, and zinc. Mean usual intakes of Vitamin D and calcium were far below the Adequate Intakes (AIs). In the experimental study, the prevalence of inadequacies was reduced to <3% for zinc and vitamin E but not magnesium. The groups' mean usual intake from the modified menu met or exceeded the AI for calcium but fell short for vitamin D. Alternatively, it was determined that addition of a multivitamin and mineral (MVM) supplement to intakes of the regular menu could be used to achieve goals for vitamin E, zinc and vitamin D but not calcium and magnesium. ^ A combination of menu modification and MVM supplementation may be necessary to achieve a low prevalence of micronutrient inadequacies among LTC residents. Menus should be planned to optimize intakes of those nutrients that are low in an MVM, such as calcium, magnesium, and potassium. A MVM supplement should be provided to fill the gap for nutrients not provided in sufficient amounts by the diet, such as vitamin E and vitamin D. ^