Reliability Abstracts and Technical Reviews January-December 1968

No abstract availabl

A unified state variable analysis of repetitively pulsed recombination lasers

A unified state-space model of a high repetition rate electrical discharge in a helium-strontium mixture is presented. The atomic (number density of particles in a particular state), optical (number density of photons), thermodynamic (local particle temperature and pressure) and electrical (voltage and current) internal states of the system are the state variables. A generalised circuit analysis program (GCAP) provides a description of the excitation circuit used to power the strontium laser. Rate equations describing the time evolution of the state variables are simultaneously numerically integrated to provide a description of the laser system during the discharge of a capacitor through the laser load and in the immediate afterglow. The effects of parametric variation of the circuit on strontium laser performance are examined. The model predicts that Sr++ ions are formed during the discharge current pulse by step-wise excitation from SrII states lying lower in energy. A population inversion is achieved on the 62S1/2-52P3/2 transition in SrII (lambda=430.5nm) in the current pulse afterglow by rapid three-body recombination of Sr++ ions. A strong recombination flux is established on rapid termination of the discharge current pulse. Impedance matching of excitation circuit to load is essential for stimulated emission under recombination conditions. The results of the state variable analysis are validated by experiment. The operating characteristics of a discharge-heated strontium vapour laser are presented. An average power of 0.3W is obtained in a high heat-loss configuration. The fall-time of the discharge current pulse is reduced by means of a saturable inductor placed in parallel with the laser load. The circuit generates current pulses with peak amplitudes up to 300A and fall-times of less than 70ns. GCAP is used to estimate the theoretical limits on the fall-time of the laser current by state variable analysis of a flux-controlled model of the saturable inductor

A portability assistant for Fortran applications

This thesis addresses the issues of porting software from one machine environment to another. Some general observations are made about the definition of Portability and the design and portability of programs written in high level programming languages, in particular Fortran. Two areas of portability are considered in detail: (i) Portability Criteria and Measures - The main criteria affecting the portability of Fortran applications are identified and possible measures of the effects of these criteria considered. A Portability Function is defined for obtaining a measure of the percentage portability of Fortran programs. (ii) Portability Assistant - The use of existing analysis tools to obtain measures of the criteria affecting the portability of Fortran programs is considered. A portability assistant is provided in the form of an Ingres Relational Database, which holds die data obtained from these measures, enables the portability function to be applied to the application and assists in the porting of the application. The methods of measuring the criteria affecting Fortran programs and the use of an Ingres database as a portability assistant is then applied to a particular example, the porting of NOMIS, a large manpower database

Design and verification of Guidance, Navigation and Control systems for space applications

In the last decades, systems have strongly increased their complexity in terms of number of functions that can be performed and quantity of relationships between functions and hardware as well as interactions of elements and disciplines concurring to the definition of the system. The growing complexity remarks the importance of defining methods and tools that improve the design, verification and validation of the system process: effectiveness and costs reduction without loss of confidence in the final product are the objectives that have to be pursued. Within the System Engineering context, the modern Model and Simulation based approach seems to be a promising strategy to meet the goals, because it reduces the wasted resources with respect to the traditional methods, saving money and tedious works. Model Based System Engineering (MBSE) starts from the idea that it is possible at any moment to verify, through simulation sessions and according to the phase of the life cycle, the feasibility, the capabilities and the performances of the system. Simulation is used during the engineering process and can be classified from fully numerical (i.e. all the equipment and conditions are reproduced as virtual model) to fully integrated hardware simulation (where the system is represented by real hardware and software modules in their operational environment). Within this range of simulations, a few important stages can be defined: algorithm in the loop (AIL), software in the loop (SIL), controller in the loop (CIL), hardware in the loop (HIL), and hybrid configurations among those. The research activity, in which this thesis is inserted, aims at defining and validating an iterative methodology (based on Model and Simulation approach) in support of engineering teams and devoted to improve the effectiveness of the design and verification of a space system with particular interest in Guidance Navigation and Control (GNC) subsystem. The choice of focusing on GNC derives from the common interest and background of the groups involved in this research program (ASSET at Politecnico di Torino and AvioSpace, an EADS company). Moreover, GNC system is sufficiently complex (demanding both specialist knowledge and system engineer skills) and vital for whatever spacecraft and, last but not least the verification of its behavior is difficult on ground because strong limitations on dynamics and environment reproduction arise. Considering that the verification should be performed along the entire product life cycle, a tool and a facility, a simulator, independent from the complexity level of the test and the stage of the project, is needed. This thesis deals with the design of the simulator, called StarSim, which is the real heart of the proposed methodology. It has been entirely designed and developed from the requirements definition to the software implementation and hardware construction, up to the assembly, integration and verification of the first simulator release. In addition, the development of this technology met the modern standards on software development and project management. StarSim is a unique and self-contained platform: this feature allows to mitigate the risk of incompatibility, misunderstandings and loss of information that may arise using different software, simulation tools and facilities along the various phases. Modularity, flexibility, speed, connectivity, real time operation, fidelity with real world, ease of data management, effectiveness and congruence of the outputs with respect to the inputs are the sought-after features in the StarSim design. For every iteration of the methodology, StarSim guarantees the possibility to verify the behavior of the system under test thanks to the permanent availability of virtual models, that substitute all those elements not yet available and all the non-reproducible dynamics and environmental conditions. StarSim provides a furnished and user friendly database of models and interfaces that cover different levels of detail and fidelity, and supports the updating of the database allowing the user to create custom models (following few, simple rules). Progressively, pieces of the on board software and hardware can be introduced without stopping the process of design and verification, avoiding delays and loss of resources. StarSim has been used for the first time with the CubeSats belonging to the e-st@r program. It is an educational project carried out by students and researchers of the “CubeSat Team Polito” in which StarSim has been mainly used for the payload development, an Active Attitude Determination and Control System, but StarSim’s capabilities have also been updated to evaluate functionalities, operations and performances of the entire satellite. AIL, SIL, CIL, HIL simulations have been performed along all the phases of the project, successfully verifying a great number of functional and operational requirements. In particular, attitude determination algorithms, control laws, modes of operation have been selected and verified; software has been developed step by step and the bugs-free executable files have been loaded on the micro-controller. All the interfaces and protocols as well as data and commands handling have been verified. Actuators, logic and electrical circuits have been designed, built and tested and sensors calibration has been performed. Problems such as real time and synchronization have been solved and a complete hardware in the loop simulation test campaign both for A-ADCS standalone and for the entire satellite has been performed, verifying the satisfaction of a great number of CubeSat functional and operational requirements. The case study represents the first validation of the methodology with the first release of StarSim. It has been proven that the methodology is effective in demonstrating that improving the design and verification activities is a key point to increase the confidence level in the success of a space mission

A study of the superficial deposits in upper Weardale

The geomorphology of the upper reaches of the River Wear Valley has been based on Individual assessments of the complex topography of the area. Evaluation of the superficial deposits as a method of understanding the area, has so far been limited to subjective assessment. In this study a technique recently developed in sedimentary petrology is applied to samples of the suite of deposits existing in Upper Weardale. Two samples are considered, one, a purposive sample chosen to "represent" the deposits of the region for an initial evaluation of the technique, the other sample, a random sample, to permit general conclusions about the nature of the deposits existing in that area. Analysis of the particle-size distribution of the sediments obtained in each sample gives a basis for conclusions about the representative nature of both purposive and random samples. Factor Analysis of the particle-size data gives similar results for each body of data and the Factor analyses of all data as a single unit demonstrates an equal consistency. Consideration of the nature of the four factors produced in this way leads to their tentative identification as the products of glacial action, water-washing processes, rock decomposition and gelifluction. This tentative identification is reinforced by the statistically significant trend surface patterns which emerge from further data analysis. In the final section all other evidence is considered together with the results obtained from data analysis. The conclusions about the geomorphological history are compatible with the evidence considered by previous workers, although the conclusion that the whole area was over-ridden by ice is a departure from the commonly-held view. Conclusions of a methodological nature concerning the wider application of these techniques to complex suites of deposits are also formulated

Systemorientierte Analysen von hepatischen 13C-Markierungs- und Stoffwechseldynamiken

In this thesis a data-driven model-based approach was undertaken to analyze the liver central metabolism at the systems-level. The work focused on the model-assisted interpretation of metabolome and fluxome data. Experimental observations of stationary and non-stationary 13C-labeling and metabolite data enabled the identification of metabolic fluxes, metabolite dynamics, and patterns of metabolic control by means of transient 13C-flux analysis, dynamic modeling, and metabolic control analysis. The major goals of this contribution were (i) to establish an experimental set-up and a computational framework for acquiring and analyzing transient 13C-mass fraction data in mammalian cells and to use it to identify metabolic fluxes in HepG2 cells, (ii) to apply transient 13C-flux analysis to quantify the effects of a therapeutic dose of the hypolipidemic drug atorvastatin on the cholesterol pathway and central metabolism in primary rat hepatocytes, and (iii) to provide systems-level analyses of the dynamics and control of the central carbon metabolism in hepatoma cells. The experimental observation of the isotopic transient offers the temporal resolution needed to identify intracellular flux maps in mammalian cells from 13C-labeling experiments. To enable the estimation of metabolic fluxes from non-stationary 13C-labeling data in slow- and non-growing mammalian cell batch and fed-batch cultures, reliable means were provided for simultaneous quenching of metabolism and extraction of intracellular intermediates. The developed sampling procedures and chemical analyses were used to quantify metabolite levels and mass fractions in a dynamic labeling experiment with HepG2 cells using 13C-labeled glucose as substrate. In glycolysis and the pentose-phosphate pathway (PPP), isotopic steady state was reached within 30 min, whereas in the tricarboxylic acid (TCA) cycle isotopic steady state was not attained within 120 min. The experimental data were used to estimate the corresponding flux map. In order to identify the flux distribution, a computational framework was developed. The flux estimation was based on a large-scale stoichiometric model, which was used to estimate effluxes into the biomass, and an isotopomer model of glycolysis, the pentose-phosphate pathway, and the tricarboxylic acid cycle. The split ratio between glycolysis and the pentose-phosphate pathway was determined to 57 % and 43 %. It is worth noting that this was the first time metabolic fluxes were estimated in a mammalian system from a transient 13C-labeling experiment. The effects of a therapeutic concentration of the hypolipidemic drug atorvastatin on cholesterol biosynthesis and central metabolism were determined in primary rat hepatocytes using 13C-labeled glutamine and transient 13C flux analysis. Isotopic steady state was observed within 4 h in the central metabolism but not in the cholesterol pathway, regardless of whether the hypolipidemic agent was administered or not. The flux through the cholesterol pathway was found to drop from 0.27 to 0.08 mmol/(lcv h) in response to the administration of the statin. Only minor differences were determined in the central carbon fluxes between cells treated with 50 nM atorvastatin and untreated cells. The flux control coefficient of the HMG-CoA reductase over the cholesterol synthesis flux was determined to 0.46, i.e. cholesterol biosynthesis is not completely controlled by the HMG-CoA reductase. This means that other reaction steps may be also potent targets for lowering blood cholesterol levels. A dynamic liver central carbon metabolism model was developed from metabolite time-series and applied to break down the control hierarchy in hepatoma cells. The dynamic metabolite data were collected from HepG2 cells in a stimulus response experiment in which the cells had been deprived of extracellular glucose. The enzyme kinetics were described with the canonical linlog formalism, which had been reported previously to yield a good approximation quality, while only requiring the determination of comparatively few parameters. The in silico metabolite time-series data were in accordance with the experimentally determined metabolite dynamics. To unravel the internal control structure of the hepatoma central carbon metabolism, concentration and flux control coefficients, partial flux control coefficients, and internal response coefficients were deduced. The control patterns found support the hypotheses that the glucose-6-phosphate dehydrogenase reaction and the Warburg effect (cancer cells have an increased glycolytic flux in the presence of an adequate oxygen supply) are promising targets for tumor treatment.In dieser Arbeit wurde ein datengetriebener modellbasierter Ansatz verfolgt, um den zentralen hepatischen Metabolismus auf Systemebene zu analysieren. Der Schwerpunkt lag dabei auf der modellgestützten Interpretation von Metabolome- und Fluxome-Daten. Die experimentelle Bestimmung von stationären und instationären Markierungs- und Metabolitdaten ermöglichte die Identifizierung von metabolischen Flüssen, Stoffwechsel-Dynamiken und metabolischen Kontrollprinzipien auf Basis von transienter 13C-Stoffflussanalyse, dynamischer Modellierung und metabolischer Kontrollanalyse. Die Hauptziele dieser Arbeite waren (i) die Etablierung eines experimentellen Set-ups und eines rechenbasierten Auswertungsrahmenwerks zur Erhebung und Analyse transienter Massenisotopomerdaten in Säugetierzellen und deren Einsatz zur Identifizierung metabolischer Flüsse in HepG2-Zellen, (ii) die Anwendung der instationären 13C Stoffflussanalyse zur Quantifizierung der Effekte einer therapeutischen Dosis des cholesterinsenkenden Medikaments Atorvastatin auf die Cholesterol-Synthese und den Zentralstoffwechsel in primären Rattenhepatozyten und (iii) die Untersuchung der Dynamik und Kontrolle des zentralen Kohlenstoffwechsels in Hepatoma-Zellen auf Systemebene. Die experimentelle Beobachtung der Markierungsdynamik bietet die erforderliche zeitliche Auflösung, um intrazelluläre Flussverteilungen auch in Säugetierzellen auf Grundlage von Markierungsexperimenten bestimmen zu können. Um die tracerbasierte Schätzung metabolischer Flüsse auch in Batch und Fed-Batch Fermentationen von langsam und nicht wachsenden Säugetierzellen zu ermöglichen, wurden zunächst geeignete Techniken zum gleichzeitigen Quenching des Metabolismus und zur Extraktion intrazellulärer Metabolite etabliert. Die entwickelte Probenahmetechniken und Analytikmethoden wurden dann verwendet, um Metabolitkonzentrationen und Massenfraktionen in HepG2-Zellen in einem dynamischen Markierungsexperiment mit 13C-gelabelter Glucose zu bestimmen. Zur Flussschätzung wurde ein rechenbasiertes Auswertungsrahmenwerk entwickelt. In diesem Rahmenwerk ist es möglich, metabolische Flüsse und Konzentrationen aus stationären und instationären Markierungsdaten zu schätzen. Im Rahmen der Flussschätzung wurde ein großskaliges stöchiometrisches Modell entworfen und dazu verwendet, Abflüsse in die Biomasse zu schätzen. Zur Auswertung der Markierungsdaten wurde ein Isotopomerenmodell der Glykolyse, des Pentosephosphatwegs und des Tricarbonzyklus eingesetzt. Das Verhältnis zwischen dem Fluss in die Glykolyse und in den Pentosephosphatweg wurde zu 57 % und 43 % bestimmt. Basierend auf einem Markierungsversuch mit 13C-gelabeltem Glutamine und instationärer 13C Stoffflussanalyse wurden die Effekte einer therapeutischen Konzentration des Medikaments Atorvastatin auf die Cholesterol-Biosynthese und den Zentrallstoffwechsel von primären Rattenhepatozyten quantifiziert. Unabhängig von der Anwendung des Medikaments stellte sich isotopische Stationarität im Zentralkohlenstoffwechsel innerhalb von 4 h ein, jedoch nicht im Cholesterolstoffwechsel. Als Reaktion auf die Gabe des Medikaments sank der Fluss durch den Cholesterolweg von 0,27 auf 0,08 mmol/(lcv h). Nur unwesentliche Unterschiede wurden im zentralen Kohlenstoffwechsel zwischen Zellen festgestellt, die in 50 nM Atorvastatin kultiviert worden waren, und unbehandelten Zellen. Der Flusskontrollkoeffizient der HMG-CoA Reduktase über den Cholesterol-Synthesefluss wurde zu 0,46 bestimmt, d.h. die Cholesterol-Biosynthese wird nicht ausschließlich durch die HMG-CoA Reduktase kontrolliert. Daraus ergibt sich, dass evtl. auch andere Reaktionsschritte interessante Eingriffsmöglichkeiten zur Senkung der Blutcholesterolwerte bieten. Ein dynamisches Model des zentralen Leberstoffwechsels wurde ausgehend von Metabolitzeitreihen entwickelt und dazu verwendet die Kontrollhierarchie in Hepatoma-Zellen aufzuklären. Die Metabolitdaten wurden in einem Stimulus-Response Experiment mit HepG2-Zellen erhoben, bei dem der Stoffwechsel durch Wegnahme der extrazellulären Glucose ausgelenkt wurde. Die Enzymkinetiken wurden durch den kanonischen Linlog-Ansatz beschrieben, der durch ein gutes Approximationsvermögen bei gleichzeitig verhältnismäßig wenig zu schätzenden Parametern charakterisiert ist. Die in silico Zeitreihen stimmten gut mit den experimentell beobachteten Stoffwechsel-Dynamiken überein. Um die interne Kontrollstruktur des zentralen Kohlenstoffwechsels in Hepatoma-Zellen aufzuklären, wurden Konzentrations- und Flusskontrollkoeffizienten sowie partielle Flusskontrollkoeffizienten und partielle interne Responsekoeffizienten bestimmt. Die gefundenen Kontrollmuster unterstützen Hypothesen nach denen sich die Glucose-6-Phosphate Dehydrogenase und der Warburg-Effekt (Krebszellen haben einen erhöhten glycolytischen Fluss bei ausreichender Sauerstoffversorgung) als Targets zur Tumortherapie eignen

Vision 2040: A Roadmap for Integrated, Multiscale Modeling and Simulation of Materials and Systems

Over the last few decades, advances in high-performance computing, new materials characterization methods, and, more recently, an emphasis on integrated computational materials engineering (ICME) and additive manufacturing have been a catalyst for multiscale modeling and simulation-based design of materials and structures in the aerospace industry. While these advances have driven significant progress in the development of aerospace components and systems, that progress has been limited by persistent technology and infrastructure challenges that must be overcome to realize the full potential of integrated materials and systems design and simulation modeling throughout the supply chain. As a result, NASA's Transformational Tools and Technology (TTT) Project sponsored a study (performed by a diverse team led by Pratt & Whitney) to define the potential 25-year future state required for integrated multiscale modeling of materials and systems (e.g., load-bearing structures) to accelerate the pace and reduce the expense of innovation in future aerospace and aeronautical systems. This report describes the findings of this 2040 Vision study (e.g., the 2040 vision state; the required interdependent core technical work areas, Key Element (KE); identified gaps and actions to close those gaps; and major recommendations) which constitutes a community consensus document as it is a result of over 450 professionals input obtain via: 1) four society workshops (AIAA, NAFEMS, and two TMS), 2) community-wide survey, and 3) the establishment of 9 expert panels (one per KE) consisting on average of 10 non-team members from academia, government and industry to review, update content, and prioritize gaps and actions. The study envisions the development of a cyber-physical-social ecosystem comprised of experimentally verified and validated computational models, tools, and techniques, along with the associated digital tapestry, that impacts the entire supply chain to enable cost-effective, rapid, and revolutionary design of fit-for-purpose materials, components, and systems. Although the vision focused on aeronautics and space applications, it is believed that other engineering communities (e.g., automotive, biomedical, etc.) can benefit as well from the proposed framework with only minor modifications. Finally, it is TTT's hope and desire that this vision provides the strategic guidance to both public and private research and development decision makers to make the proposed 2040 vision state a reality and thereby provide a significant advancement in the United States global competitiveness

In vitro and in vivo diversity of HIV-1 subtype C envelope proteins and correlation with changes in biological properties of viral isolates.

Student Number : 0114163J - PhD thesis - Faculty of Health SciencesHIV-1 gains entry into host cells by binding to CD4 and a coreceptor, predominantly CCR5 or CXCR4. Viruses that use CCR5 are termed R5, those able to use CXCR4 are termed X4 while viruses able to use both coreceptors are referred to as R5X4. Accelerated CD4 decline and disease progression within an infected HIV-1 subtype B infected individual is often associated with the emergence of viruses able to use CXCR4. However, CXCR4 coreceptor usage appears to occur less frequently among HIV-1 subtype C viruses, the most predominant strain circulating globally, including South Africa. The aim of this study was to investigate the genetic determinants of CXCR4 usage in HIV-1 subtype C isolates. The V3 region of the envelope glycoprotein is the major determinant of coreceptor usage. In Chapter 2, 32 subtype C isolates with known phenotypes (16 R5, 8 R5X4 and 8 X4 isolates) were assessed using a subtype C specific V3-heteroduplex tracking assay. Results indicated that there were sufficient genetic differences to discriminate between R5 viruses and those able to use CXCR4 (both R5X4 and X4). In general, R5 isolates had a mobility ratio >0.9 whereas CXCR4-using isolates were usually <0.9. Sequence analysis of the V3 region showed that CXCR4-using viruses were often associated with an increased positive amino acid charge, insertions and loss of a glycosylation site, similar to HIV-1 subtype B. In contrast, where subtype B consensus V3 has a GPGR crown motif irrespective of coreceptor usage, all 16 subtype C R5 viruses had a conserved GPGQ sequence at the tip of the loop, while 12 of the 16 (75%) CXCR4-using viruses had substitutions in this motif, most commonly arginine (R). Thus, the rare occurrence of CXCR4-using viruses in subtype C may be due to the highly conserved nature of the GPGQ crown that may limit the potential for the development of X4 viruses. The usefulness of available genotype-based methods for predicting viral phenotypes in subtype C was explored in Chapter 3. Results indicated that commonly used prediction methods could detect R5 viruses, but were not very sensitive at identifying X4 viruses. We therefore developed a subtype C specific predictor based on position specific scoring matrices (PSSM). Similar methodology, as used in developing the subtype B PSSM, was applied on a training set of 280 subtype C sequences of known phenotype (229 NSI/CCR5 and 51 SI/CXCR4). The C-PSSM had a specificity of 94% (C.I. [92%-96%]) and sensitivity of 75% (C.I. [68%-82%]), indicating that the C-PSSM had improved sensitivity in predicting CXCR4 usage. This method also highlighted amino acid positions within V3 that could contribute differentially to phenotype prediction in subtypes B and C. A reliable phenotype prediction method, such as the C-PSSM, could provide a rapid and less expensive approach to identifying CXCR4 variants, and thus increase our knowledge of subtype C coreceptor usage. In Chapter 4 we examined the genetic changes in full-length gp160 envelope genes of 23 sequential isolates from 5 patients followed for two to three years. Three of the patients' isolates used CCR5 at all time points while 2 patients underwent a coreceptor switch with disease progression. The genetic changes observed over time indicated changes in length of variable loops particularly the V1, V4 and V5 and shifting N-glycosylation sites, particularly in the 2 patients that used CXCR4. Changes in the V3 were only noted in the 2 patients’ that used CXCR4 which included substitutions of specific amino acids including those in the crown and increased amino acid charge in the V3 region. Both of these patients were dually infected suggesting that recombination may contribute to the rapid emergence of X4 viruses. The in vitro and in vivo development of CXCR4 usage was analysed in a pediatric patient that experienced a coreceptor switch during disease progression (Chapter 5). Biological and molecular clones were generated and the V1-V5 regions sequenced. Analyses of the V3 region indicated that the evolution to CXCR4 usage happens in a step-wise manner that included increased charge and changes in the crown motif. The intermediate variants with predicted dualtropism were also associated with increased V1-V2 lengths, suggesting that other regions may contribute to coreceptor switching. Furthermore, the development of CXCR4 usage within this patient was due to two mutational pathways, in which one resulted in R5X4 viruses and the other X4 variants. In Chapter 6, the impact and treatment of acute TB on HIV-1 diversity in co-infected patients was investigated, specifically to determine the genetic characteristics of the viral populations present before, during and after TB treatment. Plasma samples from 18 HIV-1 infected patients were analysed using the C2V3 region, six of whom showed a high degree of variation using a V3-HTA and were selected for further analyses. All patients were predicted as R5 with no evidence of coreceptor switching over time. There was no correlation between the degree of genetic diversity and viral load, although both showed fluctuations over time. Phylogenetic and pairwise genetic distance analysis indicated that there was amplification of existing variants in 3 patients while in the other 3 patients there were dramatic shifts in viral populations suggesting selection of viral sub-populations over time. Thus in some co-infected patients, TB can affect HIV-1 genetic heterogeneity although there was no evidence of a shift towards CXCR4 usage despite the presence of an AIDS defining illness. Observations in this study have shown that the V3 region is the major determinant of coreceptor usage within HIV-1 subtype C, similar to HIV-1 subtype B. Characteristics such as increased charge length variability of the V3 region and loss of the glycosylation site within this region are associated with CXCR4 usage. The limited number of X4 viruses in subtype C does suggest some restricting mechanisms for CXCR4 usage. In this study we looked at genetic determinants and found that the rare occurrence of CXCR4-using viruses in subtype C, may be due to the highly conserved nature of the GPGQ crown that may limit the potential for the development of subtype C X4 viruses. Furthermore, the development of CXCR4 usage happened in a step-wise manner, with R5X4 viruses intermediates, in which an increased V1-V2 was observed suggesting that other regions within the envelope protein do contribute to coreceptor usage. Thus, regions such as V1-V2 and V4-V5 did contribute to coreceptor usage, but the V3 region remained the most important determinant of coreceptor usage in HIV-1 subtype C isolates. Collectively these findings have provided important data on the genetic determinants of CXCR4 usage in HIV-1 subtype C and an understanding of how they might evolve within a patient

Taurine: An Indispensable Ingredient in the Development of Sustainable Aquafeeds

Aquaculture as a global industry is at a crossroad; increased production cannot rely on the unsustainable harvest of forage fish for feed production. The use of fishmeal and fish oil as components in feeds for aquaculture, most notably for high value marine carnivores must be reduced or eliminated. The most promising and sustainable sources of replacement feed must be plant derived, such as soybean meal, wheat flour, and corn gluten along with dozens of other plant derived sources. Likewise for fish oil the most promising sources are plant oils such as soybean and canola oil supplemented with necessary omega-3 fatty acids. This work was undertaken to examine the effects of switching marine carnivores from fishmeal-based feeds to fishmeal-free, plant-based diets. The majority of this research has been conducted with cobia, Rachycentron canadum, a promising species for intensive aquaculture due to its rapid growth rates, high disease resistance, and lack of a major commercial fishery as competition. A variety of plant proteins, plant protein blends and alternative lipid sources were examined for digestibility and efficacy as fishmeal replacement sources in regards to their effects on growth rates, feed conversion, and a range of physiological characteristics. This work has explored the hypothesis that marine carnivores have lost the ability to synthesize taurine, a non-protein amino acid, in sufficient quantities and must therefore be supplied through the diet, and should be considered essential for all marine carnivores. By measurement of gene expression of the genes in taurine biosynthesis, this work shows that cobia do not possess the ability to regulate taurine biosynthesis confirming taurine must be supplied through the diet. Overall, this work has developed multiple plant protein-based feeds that perform equivalently or better than commercial and commercial-like diets. Taurine has been shown to be an essential ingredient when seeking to reduce or preferably, eliminate fishmeal and thereby making aquaculture sustainable in providing protein to meet the world's growing population

The oxidative degradation of organic contaminants using a manganese oxide-containing mine waste

Manganese oxide tailings material, a waste product generated during Mn ore extraction processes in South Africa, has been assessed in terms of its potential to oxidatively breakdown organic contaminants. Azo dyes and polycyclic aromatic hydrocarbons (anthracene) show oxidative interactions with the tailings, resulting in the formation of products which are more environmentally favourable than the parent compound. Tailings samples from five mines were characterised to establish the redox reactivity of the material. Based on chemical and mineralogical data the tailings were grouped into the carbonate-rich Mamatwan type (MT) tailings (Mamatwan and Gloria mines), the Mn oxide- enriched Wessels type (WT) tailings (Wessels and Nchwaning mines) and the Mn oxide enriched Hotazel type (HT) tailings (Hotazel mine). The tailings are net-alkaline and non acid generating with a point of zero charge below pH 4. The average Mn oxidation state of the three tailings types ranges from 1.2 to 1.5 in the order HT>WT>MT. Despite a low surface area (1.5 to 6.4 m(^2) .g(^-1)) the tailings show a substantial (0.5 to 3.0%) 'easily' reducible, reactive Mn phase as well as a large pool of more recalcitrant dithionite-extractable Mn. Thus the tailings material displays both 'quick and slow release' oxidative capacity. The oxidative decolorisation of acid azo dyes acid orange 7 (AO 7) and acid yellow 36 (AY 36) by the Mn tailings is highly pH dependent, with increased oxidation occurring at lower pH. The reaction mechanism for the oxidation of AO 7 by the tailings has many similarities to enzymatic degradation of the dye observed with white rot fungi. The reaction, initiated on the phenolic group, occurs via successive one electron transfers from the dye molecule to the Mn oxide. A series of radical reactions occur resulting m the asymmetrical cleavage of the azo bond and the generation of terminal reaction products 1,2 naphthoquinone and 4- hydroxybenzenesulfonate. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) demonstrated that initial sorption of AO 7 is pH dependent and outer-sphere. A pronounced lag phase exists between the initial sorption of the dye to a Mn oxide surface and the initiation of oxidation. This lag phase can indicate that either the transfer of the initial electron is rate limiting or that correct orientation followed by inner- sphere complexation is necessary before oxidation can take place. The reaction mechanism proposed for the oxidation of AY 36 is initiated at the amino moiety and proceeds via successive, one electron transfers from the dye to the Mn tailings. The reaction pathway involves the formation of a number of colourless intermediate products, some of which hydrolyse in a Mn oxide-independent step. The terminal oxidation products were observed to bep-benzoquinone and 3-hydroxybenzenesulfonate.Light, both UV and ambient, and auxiliary compounds such as acetate buffer and salts did not reduce the decolorisation capacity of the tailings. Increased buffer strength enhanced decolorisation and addition of Na(_2)S0(_4) in the presence of buffer increased the initial oxidation of AO 7. The decolorisation capacity of the Mn tailings showed durability with 90% colour removal observed 60 days after daily dye replenishment. Drying anthracene-spiked Mn tailings, synthetic Mn oxide and calcite water slurries resulted in anthracene oxidation to anthraquinone (6-30% oxidation). Small but significant (4%) anthracene oxidation was also observed when anthracene spiked water was evaporated from quartz and a clean glass surface. No anthracene oxidation was apparent without the evaporation of water at pH > 5. The HT tailings oxidised up to 30% anthracene when dried, the most substantial oxidation took place below 5% gravimetric water content. Evaporation of anthracene-spiked cyclohexane slurries resulted in the same observed oxidation from both Mn tailings and calcite. It could not be established whether elecfron transfer was occurring between the Mn oxide phase of the tailings and the anthracene or whether the transformation was solely a surface mediated phenomenon with oxygen being used as the elecfron acceptor. Under fully hydrated conditions the Mn oxide tailings oxidised 75% of anthracene to anthraquinone at pH values less than 4.5. This would suggest that the Mn tailings can oxidise anthracene and sufficient mineral-contaminant contact can be achieved despite the low water solubility of the compound