Creation dependencies of evolutionary artefact and design process knowledge

As design progresses, artefact and process knowledge often evolve together. However, there is very limited knowledge on the true nature of the dependencies between these two elements of knowledge. This paper presents the first attempt to clearly define 'creation' dependencies, which cause a change in design knowledge. Three data analyses were used to identify the dependencies: two were in-depth protocol analyses of a single student product design project and a senior ship designer’s daily work, and a third was a quantitative questionnaire analysis involving seven experienced complex system designers from industry. The analyses revealed a set of 52 previously unknown creation dependencies between artefact and design process knowledge with commonality found in only 5, with additional dependencies being identified that were specific to the design being studied. Different frequencies of dependency occurrence and particular dependency loops were identified. In addition, the importance and role of domain knowledge were explicitly revealed. The described research highlights the need for further work to provide a more comprehensive definition of the nature of evolutionary artefact and design process knowledge dependencies. Identification of these dependencies offers a significant opportunity to develop tools and techniques with an enhanced ability to support 'what–if' analyses during design

Tortured words : the first Soviet Writers Congress, Moscow 1934 : socialist realism and Soviet reality in Stalin's Russia 1934-1939

Both the academic and the fiction element of the thesis concerns events in the Soviet Union and elsewhere in Europe in the 1930s. The first element informs the second. The academic portion is based on the first Soviet Writers Congress of 1934, the only such gathering allowed by Stalin in his lifetime and an event following which many of its delegates were murdered. Primary research sources include the stenographic verbatim record of the Congress itself and an addendum consisting of biographical material published by the Writers Union of the USSR in 1990 as Russian Communism tottered towards its end. This part of the thesis examines aspects of Soviet reality against the background of the Purges, and includes consideration of the writer’s world, the significance of the Red Army to literary life, the position of foreigners and the doctrine of Socialist Realism, officially sanctified at the Congress. Other sources include memoir, histories of the period and material from the Thirties Soviet press. The fiction element comprises an excerpt from a novel, The Eastern Bow, which takes its title from Auden’s poem A Summer Night. It is a story of espionage set in Moscow, Paris and London from 1937 to 1939. The plot involves the writing of a book in Russia by an unknown writer of genius who tells the truth about Stalin, the Purges and what the Revolution has become –a perversion of its earlier ideals. The secret police, the NKVD, hunt for the book, its author and all connected with it. This sub-plot combines with another centred in London and Paris in which a Soviet spy within MI6 is also being sought by elements within British intelligence. The two strands combine in France at the climax of the novel

Synthesis of chiral cage annulated macrocycles.

Master of Science in Chemistry. University of KwaZulu-Natal, Durban 2006.Chiral crown ethers have recently been shown to be useful asymmetric catalysts in many carbon-carbon bond forming reactions. The design and synthesis of new chiral macrocycles and ligands for use in asymmetric catalysis is of great interest in the field of synthetic chemistry. Catalytic asymmetric Michael additions have been studied using chiral crown ethers as phase transfer catalysts. Many chiral crown ethers have been synthesised and tested in asymmetric catalysis but the design of these systems is still an area of much interest. The attempted synthesis of a new class of novel macrocycles such as 1 is described (chapter 2). The synthesis of a new class of chiral cage annulated macrocycles such as 2 is reported (chapter 3). The testing of these macrocycles as catalysts in the Michael addition of 2-nitropropane to chalcone was carried out with poor enantioselectivity being observed Recognition events in chemistry occur on a molecular scale that is difficult to monitor without the use of molecular devices. Photoinduced Electron Transfer (PET) systems have been the subject of much research over the past three decades. The attempted synthesis of the first chiral PET sensor 3 is described (chapter 4).Could not copy diagrams from abstract

Synthesis of camphor derived ligands for applications in asymmetric catalysis.

Thesis (Ph.D.)-University of KwaZulu-Natal, 2009.Chiral monoterpenes such as camphor have been widely used in the development of asymmetric catalysts with varying degrees of success. Pyridyl N-donor ligands derived from camphor have been extensively studied and have proven to be very successful. C3 pendant pyridyl alcohol ligands have been neglected until this study. Herein the synthesis of a series of six novel C3 pendant ligands is described. The ligands were synthesised in six steps (seven for ligand 4) using R-(+)-camphor as the starting material. Two alternative methods for the synthesis were investigated with the second method (Method B) proving to be superior. Several difficulties with regards to regioisomers and diastereomers were overcome in establishing the procedure for the synthesis of the ligands. The final compounds were successfully synthesised in moderate yields with absolute regio- and stereo-control. The ligands were evaluated as chiral catalysts in a series of different reactions. The first of these was the alkylation of a series of aldehydes using diethylzinc. This reaction was investigated in order to compare the efficacy of the novel compounds to previous camphor derived pyridyl alcohol ligands. All previous molecules of this type have been evaluated as catalysts in this reaction with varying degrees of success. The novel ligands successfully catalysed this reaction with moderate to good enantioselectivity (up to 85% ee). The results obtained showed these compounds to be significantly superior to a previous analogous C2 pendant β-amino alcohol reported in literature. The results were also comparable to other camphor derived pyridyl alcohol ligands reported previously. The synthesis of ligands 1-4 as well as their evaluation as catalysts in the alkylation of aldehydes with diethylzinc is discussed in detail in chapter 2 (Paper 1). The second reaction in which the ligands were evaluated was the Henry (Nitroaldol) reaction. This reaction has not seen many camphor derived ligands applied as catalysts. Two additional derivatives (5-6) were synthesized and all the compounds were screened as catalysts in this reaction. The ligands successfully catalyzed the reaction with good to excellent yields but only moderate selectivity (up to 56% ee). The details of this evaluation are discussed in chapter 3 (Paper 2). The final reaction in which the ligands were evaluated was the Diels-Alder reaction of 2- acrolyloxazolidinone with cyclopentadiene. The reaction was again successfully catalysed in moderate to good yields with good endo:exo selectivity but fairly poor stereoselectivity (up to 43% ee). Computational models of the proposed complexes were developed in order to explain the poor observed selectivity. The details of this study are reported in chapter 4 (Paper 3). Chapter 5 (Paper 4) involves a NMR and computational investigation of some of the ligands. Complete NMR elucidation using 2D NMR techniques were carried out for the selected ligands. Optimisation of the ligands using high level DFT calculations was carried out in order to aid in the visualisation of potential through space interactions within each molecule

Synthesis of camphor derived ligands for applications in asymmetric catalysis.

Thesis (M.Sc.)-University of KwaZulu-Natal, Durban, 2006.Chiral crown ethers have recently been shown to be useful asymmetric catalysts in many carbon-carbon bond forming reactions. The design and synthesis of new chiral macrocycles and ligands for use in asymmetric catalysis is of great interest in the field of synthetic chemistry. Catalytic asymmetric Michael additions have been studied using chiral crown ethers as phase transfer catalysts. Many chiral crown ethers have been synthesised and tested in asymmetric catalysis but the design of these systems is still an area of much interest. The attempted synthesis of a new class of novel macrocycles such as 1 is described (chapter 2). The synthesis of a new class of chiral cage annulated macrocycles such as 2 is reported (chapter 3). The testing of these macrocycles as catalysts in the Michael addition of 2-nitropropane to chalcone was carried out with poor enantioselectivity being observed Recognition events in chemistry occur on a molecular scale that is difficult to monitor without the use of molecular devices. Photoinduced Electron Transfer (PET) systems have been the subject of much research over the past three decades. The attempted synthesis of the first chiral PET sensor 3 is described (chapter 4)

Intra-session and inter-day reliability of the Myon 320 electromyography system during sub-maximal contractions

Electromyography systems are widely used within the field of scientific and clinical practices. The reliability of these systems are paramount when conducting research. The reliability of Myon 320 Surface Electromyography System is yet to be determined. This study aims to determine the intra-session and inter-day reliability of the Myon 320 Surface Electromyography System. Muscle activity from fifteen participants was measured at the anterior deltoid muscle during a bilateral front raise exercise, the vastus lateralis muscle during a squat exercise and the extensor carpi radialis brevis (ECRB) muscle during an isometric handgrip task. Intra-session and inter-day reliability was calculated by intraclass correlation coefficient, standard error of measurement and coefficient of variation (CV). The normalized root mean squared (RMS) surface electromyographic signals produced good intra-session and inter-day testing intraclass correlation coefficient values (range: 0.63-0.97) together with low standard error of measurement (range: 1.49-2.32) and CV (range: 95% Confidence Interval = 0.36-12.71) measures for the dynamic-and-isometric contractions. The findings indicate that the Myon 320 Surface Electromyography System produces good to fair reliability when examining intra-session and inter-day reliability. Findings of the study provide evidence of the reliability of electromyography between trials which is essential during clinical testing.</p

Building capacity for clinical research in developing countries: the INDOX cancer research network experience

Transnational Organisations increasingly prioritise the need to support local research capacity in low and middle income countries in order that local priorities are addressed with due consideration of contextual issues. There remains limited evidence on the best way in which this should be done or the ways in which external agencies can support this process

Next-generation sequencing (NGS) in the microbiological world : how to make the most of your money

The Sanger sequencing method produces relatively long DNA sequences of unmatched quality and has been considered for long time as the gold standard for sequencing DNA. Many improvements of the Sanger method that culminated with fluorescent dyes coupled with automated capillary electrophoresis enabled the sequencing of the first genomes. Nevertheless, using this technology to sequence whole genomes was costly, laborious and time consuming even for genomes that are relatively small in size. A major technological advance was the introduction of next-generation sequencing (NGS) pioneered by 454 Life Sciences in the early part of the 21th century. NGS allowed scientists to sequence thousands to millions of DNA molecules in a single machine run. Since then, new NGS technologies have emerged and existing NGS platforms have been improved, enabling the production of genome sequences at an unprecedented rate as well as broadening the spectrum of NGS applications. The current affordability of generating genomic information, especially with microbial samples, has resulted in a false sense of simplicity that belies the fact that many researchers still consider these technologies a black box. In this review, our objective is to identify and discuss four steps that we consider crucial to the success of any NGS-related project. These steps are: (1) the definition of the research objectives beyond sequencing and appropriate experimental planning, (2) library preparation, (3) sequencing and (4) data analysis. The goal of this review is to give an overview of the process, from sample to analysis, and discuss how to optimize your resources to achieve the most from your NGS-based research. Regardless of the evolution and improvement of the sequencing technologies, these four steps will remain relevant

Identification of Novel Imprinted Differentially Methylated Regions by Global Analysis of Human-Parthenogenetic-Induced Pluripotent Stem Cells

Parental imprinting is an epigenetic phenomenon by which genes are expressed in a monoallelic fashion, according to their parent of origin. DNA methylation is considered the hallmark mechanism regulating parental imprinting. To identify imprinted differentially methylated regions (DMRs), we compared the DNA methylation status between multiple normal and parthenogenetic human pluripotent stem cells (PSCs) by performing reduced representation bisulfite sequencing. Our analysis identified over 20 previously unknown imprinted DMRs in addition to the known DMRs. These include DMRs in loci associated with human disorders, and a class of intergenic DMRs that do not seem to be related to gene expression. Furthermore, the study showed some DMRs to be unstable, liable to differentiation or reprogramming. A comprehensive comparison between mouse and human DMRs identified almost half of the imprinted DMRs to be species specific. Taken together, our data map novel DMRs in the human genome, their evolutionary conservation, and relation to gene expression

SNARE mimic peptide triggered membrane fusion kinetics revealed using single particle techniques

Membrane fusion is an essential part of the proper functioning of life. As such it is not only important that organisms carefully regulate the process, but also that it is well understood. One way to facilitate and study membrane fusion is to use artificial, minimalist, fusion peptides. In this study the efficiency and kinetics of two fusion peptides, denoted CPE and CPK, were studied using single-particle TIRF microscopy. CPE and CPK are helical peptides which interact with each other, forming a coiled-coil motif. The peptides can be inserted into a lipid membrane using a lipid anchor, and if these peptides are anchored in opposing lipid membranes, then the coiled-coil interaction can provide the mechanical force necessary to overcome the energy barrier to initiate fusion, much in the same way the SNARE complex does. In this study we find that the fusogenic facilitation of CPE and CPK in liposomes is, at least partially, dependent on the size of the particle. In addition, under certain fusogenic conditions such as when using small liposomes of ∼60 nm in diameter, CPK alone is enough to facilitate membrane fusion in both bulk and single-particle studies. We show this using bulk lipid mixing assays utilizing FRET and single-particle TIRF, making use of dequenching fluorophores to indicate fusion. This provides us with new insights into the mechanisms of peptide-mediated membrane fusion and illuminates both challenges as well as opportunities when designing drug delivery systems.</p