Synthesis and evaluation of asperlicin analogues as non-peptidal cholecystokinin-antagonists

The SAR of Asperlicin analogues is reported, leading to bioactive 1,4-benzodiazepine-2-ones, which were prepared in a 3 step reaction sequence. The Asperlicin substructure was built up using Tryptophan and readily available 2-amino-acetophenones. This template, containing a 1,4-benzodiazepin-2-one moiety with a 3-indolmethyl side chain, was transformed into mono- and di-substituted 3-indol-3 '-yl-methyl-1,4-benzodi-azepine-2-ones by selective alkylation and acylation reactions. The SAR optimization of the 1,4-benzodiazepine scaffold has included variations at the 5-, 7-, 8-position, at the N1, N-indole nitrogen and the configuration of the C3-position. The most active Asperlicin analogue, having an IC50 of 1.6 microM on the CCKA receptor subtype, was obtained from Tryptophan in only 3 steps in an overall yield of 48%.

Learning for life:educational provision at Cadbury, 1831-1981

Cadbury showed concern for the welfare of its labour force in a variety of ways and not least in the provision of educational and educative-recreational facilities. The firm regarded the education of employees as having a positive effect on the efficiency of the business at the same time as being of benefit to the individual, the local community and the nation. The life-long education of people was seen as essential for personal fulfilament, social improvement, economic competitiveness and the proper functioning of democratic procedures. The educational system built up at Cadbury, and the philosophy on which it was founded, acquired both a domestic and international reputation. Its main components were the day continuation education of juniors; the Bournville Works Evening Institute; vocational and non-vocational scholarships; emphasis on the primary importance of general education as a basis for life, work and technical training; stress on equality of educational opportunity for females; and leisure and sporting amenities which the firm felt to be educative in the sense that they contributed to personal psychological and physical development and social skills. The system was primarily shaped and constructed in the first three decades of the twentieth century and went into decline and eventual demise in the 1960's and 1970's as a result of economic pressures, social changes, enhanced state arrangements for education, shifts in Cadbury management thinking and the merger with Schweppes in 1969.

Web strength of rolled steel joists

This work is concerned with the behaviour of thin webbed rolled steel joists or universal beams when they are subjected to concentrated loads applied to the flanges. The prime concern is the effect of high direct stresses causing web failure in a small region of the beam. The review shows that although many tests have been carried out on rolled steel beams and built up girders, no series of tests has restricted the number of variables involved to enable firm conclusions to be drawn. The results of 100 tests on several different rolled steel universal beam sections having various types of loading conditions are presented. The majority of the beams are tested by loading with two opposite loads, thus eliminating the effects of bending and shear, except for a small number of beams which are tested simply supported on varying spans. The test results are first compared with the present design standard (BS 449) and it is shown that the British Standard is very conservative for most of the loading conditions included in the tests but is unsafe for others. Three possible failure modes are then considered, overall elastic buckling of the web, flexural yielding of the web due to large out of plane deflexions and local crushing of the material at the junction of the web and the root fillets. Each mode is considered theoretically and developed to establish the main variables, thus enabling a comparison to be made with the test results. It is shown that all three failure modes have a particular relevance for individual loading conditions, but that determining the failure load given the beam size and the loading conditions is very difficult in certain instances. Finally it is shown that there are some empirical relationships between the failure loads and the type of loading for various beam serial sizes.

The structural properties of glassfibre reinforced plastics

The research work described in this thesis is concerned with the development of glassfibre reinforced plastics for structural uses in Civil Engineering construction. The first stage was primarily concerned with the design of GRP lamintes with structura1 properties and method of manufacture suitable for use with relatively large structural components. A cold setting, pressure moulding technique was developed which proved to be efficient in reducing the void content in the composite and minimising the exothermic effect due to curing. The effect of fibre content and fibre arrangement on strength and stiffness of the cornposite was studied and the maximum amount of' fibre content that could be reached by the adopted type of moulding technique was determined. The second stage of the project was concerned with the introduction of steel-wire "sheets" into the GRP cornposites, to take advantage of the high modulus of steel wire to improve the GRP stiffness and to reduce deformation. The experimental observations agreed reasonably well with theoretical predictions in both first and second stages of the work. The third stage was concerned with studying the stability of GRP flat rectangular plates subjected to uniaxial compression or pure shear, to simulate compression flanges or shear webs respectively. The investigation was concentrated on the effect of fibre arrangement in the plate on buckling load. The effect of the introduction of steel-wire sheets on the plate stability in compression was also investigated. The boundary conditions were chosen to be close to those usually assumed in built-up box-sections for both compression flanges and webs. The orthotropic plate and the mid-plane symmetric were used successfully in predicting the buckling load theoretically. In determining the buckling load experimentally, two methods were used. The Southwell plot method and electrical strain gauge method. The latter proved to be more reliable in predicting the buckling load than the former, especially for plates under uniaxial compression. Sample design charts for GRP plates that yield and buckle simultaneously under compression are also presented in the thesis. The final stage of the work dealt with the design and test of GRP beams. The investigation began by finding the optimum cross-section for a GRP beam. The cross-section which was developed was a thin walled corrugated section which showed higher stiffness than other cross-sections for the same cross-sectional area (i.e. box, I, and rectangular sections). A cold setting, hand layings technique was used in manufacturing these beams wbich were of nine types depending on the type of glass reinforcement employed and the arrangement of layers in the beam. The simple bending theory was used in the beam design and proved to be satisfactory in predicting the stresses and deflections. A factor of safety of 4 was chosen for design purposes and considered to be suitable for long term use under static load. Because of its relatively low modulus, GRP beams allowable deflection was limited to 1/120th of the span which was found to be adequate for design purposes. A general discussion of the behaviour of GRP composites and their place relative to the more conventional structural material was also presented in the thesis.

The appraisal and management of multi-storey dwelling blocks using large concrete panel systems

This exploratory study is concerned with the integrated appraisal of multi-storey dwelling blocks which incorporate large concrete panel systems (LPS). The first step was to look at U.K. multi-storey dwelling stock in general, and under the management of Birmingham City Council in particular. The information has been taken from the databases of three departments in the City of Birmingham, and rearranged in a new database using a suite of PC software called `PROXIMA' for clarity and analysis. One hundred of their stock were built large concrete panel system. Thirteen LPS blocks were chosen for the purpose of this study as case-studies depending mainly on the height and age factors of the block. A new integrated appraisal technique has been created for the LPS dwelling blocks, which takes into account the most physical and social factors affecting the condition and acceptability of these blocks. This appraisal technique is built up in a hierarchical form moving from the general approach to particular elements (a tree model). It comprises two main approaches; physical and social. In the physical approach, the building is viewed as a series of manageable elements and sub-elements to cover every single physical or environmental factor of the block, in which the condition of the block is analysed. A quality score system has been developed which depends mainly on the qualitative and quantitative conditions of each category in the appraisal tree model, and leads to physical ranking order of the study blocks. In the social appraisal approach, the residents' satisfaction and attitude toward their multi-storey dwelling block was analysed in relation to: a. biographical and housing related characteristics; and b. social, physical and environmental factors associated with this sort of dwelling, block and estate in general.The random sample consisted of 268 residents living in the 13 case study blocks. Data collected was analysed using frequency counts, percentages, means, standard deviations, Kendall's tue, r-correlation coefficients, t-test, analysis of variance (ANOVA) and multiple regression analysis. The analysis showed a marginally positive satisfaction and attitude towards living in the block. The five most significant factors associated with the residents' satisfaction and attitude in descending order were: the estate, in general; the service categories in the block, including heating system and lift services; vandalism; the neighbours; and the security system of the block. An important attribute of this method, is that it is relatively inexpensive to implement, especially when compared to alternatives adopted by some local authorities and the BRE. It is designed to save time, money and effort, to aid decision making, and to provide ranked priority to the multi-storey dwelling stock, in addition to many other advantages. A series of solution options to the problems of the block was sought for selection and testing before implementation. The traditional solutions have usually resulted in either demolition or costly physical maintenance and social improvement of the blocks. However, a new solution has now emerged, which is particularly suited to structurally sound units. The solution of `re-cycling' might incorporate the reuse of an entire block or part of it, by removing panels, slabs and so forth from the upper floors in order to reconstruct them as low-rise accommodations.

The sedimentology and diagenesis of the Pendleside limestone group in the Craven Basin of Northern England. Available in 2 volumes.

This thesis describes the stratigraphy, sedimentology and diagenesis of the Pendleside Limestone (Asbian age), a sequence of limestones, shales and dolostones in the Clitheroe area of N. W. England. Field study of 19 measured sections indicates that it was deposited in a rhythmically subsiding basin (Craven Basin) because of movements on the Mid-Craven Fault which was active in Dinantian times. The sequence is up to 190m thick and consists mostly of distal turbidite deposits which have been reworked at horizons when sediment accumulation built up to the wave base. The original depositional fabric and mineralogy of the Pendleside Limestone Group has been extensively modified by diagenetic processes including cementation, authi­genesis, dolomitization and silicification. These processes have been studied using a wide variety of laboratory techniques. The carbonate cements of the PendIeside Limestone consist predominantly of ferroan calcite and non-ferroan calcite with microdolomite incIusions. The former is probably a stable replacement of original-high-magnesian calcite. Cementation was accompanied by the formation of authigenic albite and quartz. Much of the upper part of the Pendleside Limestone has been extensively dolomitized and chertified. Several distinct zones of dolomitization are found which increase in thickness and intensity towards the top of the Pendleside Limestone Group. The dolostone horizons correspond to coarser-grained lithologies deposited during periods of shallow water sedimentation. The composition of the dolomites changes from ferroan dolomite in the lower part of the Group to non-ferroan dolomite in the upper part. The low strontium and sodium content of the dolostones in association with the other evidence suggests that the dolomitization was brought about in an open system by the mixing of marine and fresh water in phreatic lens which were established at periodic intervals. The dolomitization was closely associated with chertification although this was initiated by the dissolution of siliceous spicules which provided the necessary source of silica.

Sparse signal representation by adaptive non-uniform B-spline dictionaries on a compact interval

Non-uniform B-spline dictionaries on a compact interval are discussed in the context of sparse signal representation. For each given partition, dictionaries of B-spline functions for the corresponding spline space are built up by dividing the partition into subpartitions and joining together the bases for the concomitant subspaces. The resulting slightly redundant dictionaries are composed of B-spline functions of broader support than those corresponding to the B-spline basis for the identical space. Such dictionaries are meant to assist in the construction of adaptive sparse signal representation through a combination of stepwise optimal greedy techniques.

FREADMAN, AnneThe Livres-Souvenirs of Colette Genre and the Telling of Time Oxford: Legenda, August 2012200 pp., £40.00, ISBN: 978-1-906540-93-7

Full text: The title of the book gives us a major clue on the innovative approach developed by Anne Freadman in her analysis of a particular Colette corpus, the one devoted to auto-biographical writing: Les Vrilles de la vigne, Mes apprentissages, La Maison de Claudine, Sido ,L’E ́toile Vesper and Le Fanal bleu. Freadman follows the powerful lure of Rimbaldianvieilles vieilleries and its echoes with Colette’s fondness for collecting objects, people and memories. To this must be added a technical aspect, that of the study of the genre of Colette’s writing. Freadman argues that, by largely avoiding the autobiographical form, the writer achieves a new way of ‘telling time’, collecting anecdotes and detail taken from the quotidian and setting them within an all-encompassing preoccupation with time. This provides the second part of the title.The sonata form directs the sequence of the book, orchestrated into five parts,from ‘exposition’ to ‘first subject’ to‘bridge’ to ‘second subject’ to ‘recapitulation’. This has the advantage of enabling Freadman to move and progress between distinct themes—autobiography first,then alternative forms—with grace,whilst preserving within her own writing what she sees as the essence of Colette’s relationship to time in her ‘Livres-Souvenirs’, the telling of time. This‘telling of time’ is itself therefore cleverly subjected to the time constraints and freedoms of musical composition. Freadman’s ‘Exposition’ takes us through a discussion of the autobiographical genre, analysing the texts against anumber of theorists, from Lejeune to Benjamin and Ricoeur, before launching into ‘Colette and Autobiography’. It argues pertinently that Colette did not write a ‘sustained’ autobiography, even inthe most autobiographical of her writings, Mes apprentissages. Measured against Goodwin’s three sources for autobiography, confession, apologia and memoirs, Colette’s autobiographical writings appear to be at odds with all of them. Freadman then goes on in Part II of her argument, to persuasively uncover a project that rejects self-scrutiny and with no autobiographical strategy. In ‘Collecting Time’, despite claims of continuity, narrative logic and causality areabandoned in favour of a collection offragments, family stories that are built up generation after generation into familylegends. A close and fruitful analysis of Sidoleads us to a study of ‘The Art of Ending’, concentrating on L’E ́toile Vesperandle Fanal Bleu. The closing chapter gives a fascinating reading of La Naissance du jouras an exemplar of the way in which the two subjects developed in Freadman’s volume are cast together:Colette’s own working through the autobiographical genre, and her refusal to write memoirs, in favour of collecting memories, and the strategies she uses for her purpose. In ‘Recapitulation’, her concluding chapter, Freadman adroitlyen capsulates her analysis in a fetching title: ‘Fables of Time’. Indeed, the wholepremise of her book is to move away from autobiographical genre, having acknowledged the links and debt the corpus owes to it, and into a study of the multiple and fruitful ways in which Colette tells time.The rich and varied readings of thematerial, competently informed by theoretical input, together with acute sensitivity to the corpus, mark out this study as incontournable for Colette scholars.