Radioimmunoassay of insulin and glucagon with studies on the obese hyperglycaemic syndrome in mice

Sensitive and precise radioimmunoassays for insulin and glucagon have been established. Although it was possible to employ similar precepts to the development of both hormone assays, the establishment of a reliable glucagon radioimmunoassay was complicated by the poor immunogenicity and instability of the peptide. Thus, unlike insulin antisera which were prepared by monthly injection of guinea pigs with crystalline insulin emulsified in adjuvant, the successful production of glucagon antisera was accomplished by immunisation of rabbits and guinea pigs with glucagon covalently linked to bovine plasma albumin. The conventional chloramine-T iodination with purification by gel chromatography was only suitable for the production of labelled insulin. Quality tracer for use in the glucagon radioimmunoassay was prepared by trace iodination, with subsequent purification of monoiodinated glucagon by anion exchange chromatography. Separation of free and antibody bound moieties by coated charcoal was applicable to both hormone assays, and a computerised data processing system, relying on logit-log transformation, was used to analyse all assay results. The assays were employed to evaluate the regulation of endocrine pancreatic function and the role of insulin and glucagon in the pathogenesis of the obese hyperglycaemic syndrome in mice. In the homozygous (ob/ob) condition, mice of the Birmingham strain were characterised by numerous abnormalities of glucose homeostasis, several of which were detected in heterozygous (ob/+) mice. Obese mice exhibited pancreatic alpha cell dysfunction and hyperglucagonaemia. Investigation of this defect revealed a marked insensitivity of an insulin dependent glucose sensing mechanism that inhibited glucagon secretion. Although circulating glucagon was of minor importance in the maintenance of hyperinsulinaemia, lack of suppression of alpha cell function by glucose and insulin contributed significantly to both the insulin insensitivity and the hyperglycaemia of obese mice.

Stabilisation of polypropylene using polymer-bound antioxidants

variety of hindered phenol and hindered piperidine antioxidants containing vinyl or vinylidine functional groups have been synthesised and some of these were successfully bound to Polypropylene backbone during processing operations in presence of a radical generator. Up to 20% concentrates were prepared using this technique. Commercially acceptable concentrates (MASTERBATCHES) can only be prepared with antioxidants that are only weakly chain breaking such as hindered piperidines. One of the antioxidants, AATP was found to polymrise as well as bind to Polypropylene. Bound antioxidants were found to be resistant to such channels of physical loss as solvent extraction. Temperature and concentration of the additive and radical generator were found to be important parameters in the preparation of the concentrates. The stabilising efficiences of the diluted bound antioxidants alone, and in combination (synergistic) with other antioxidants have been evaluated. Results of both thermal and photo-oxidative stabilities of the bound samples in Polypropylene show that the restriction on free mobility of the bound antioxidants in the polymer has virtually no effect on its stabilising efficiency. Bound AATP was found to generate nitroxyl radicals during the course of its stabilising activities, and in combination with a small amount of Irganox 1076, it was shown to be highly synergistic thermally. A mechanism of catalytic phenol regeneration by the resultant piperidine hydroxylamine was proposed. Although the mechanical properties of the masterbatches were affected by the transformation, this was not found to be carried over to the diluted samples. This work has shown that bound concentrates can be effectively prepared in saturated polymers for subsequent dilution to normal concentrates used in commercial stabilisation.

Kineto-elastodynamic analysis of high-speed four-bar mechanism

This thesis addresses the kineto-elastodynamic analysis of a four-bar mechanism running at high-speed where all links are assumed to be flexible. First, the mechanism, at static configurations, is considered as structure. Two methods are used to model the system, namely the finite element method (FEM) and the dynamic stiffness method. The natural frequencies and mode shapes at different positions from both methods are calculated and compared. The FEM is used to model the mechanism running at high-speed. The governing equations of motion are derived using Hamilton's principle. The equations obtained are a set of stiff ordinary differential equations with periodic coefficients. A model is developed whereby the FEM and the dynamic stiffness method are used conjointly to provide high-precision results with only one element per link. The principal concern of the mechanism designer is the behaviour of the mechanism at steady-state. Few algorithms have been developed to deliver the steady-state solution without resorting to costly time marching simulation. In this study two algorithms are developed to overcome the limitations of the existing algorithms. The superiority of the new algorithms is demonstrated. The notion of critical speeds is clarified and a distinction is drawn between "critical speeds", where stresses are at a local maximum, and "unstable bands" where the mechanism deflections will grow boundlessly. Floquet theory is used to assess the stability of the system. A simple method to locate the critical speeds is derived. It is shown that the critical speeds of the mechanism coincide with the local maxima of the eigenvalues of the transition matrix with respect to the rotational speed of the mechanism.

Design and evaluation for the future of m-interaction

Mobile technology has been one of the major growth areas in computing over recent years (Urbaczewski, Valacich, & Jessup, 2003). Mobile devices are becoming increasingly diverse and are continuing to shrink in size and weight. Although this increases the portability of such devices, their usability tends to suffer. Fuelled almost entirely by lack of usability, users report high levels of frustration regarding interaction with mobile technologies (Venkatesh, Ramesh, & Massey, 2003). This will only worsen if interaction design for mobile technologies does not continue to receive increasing research attention. For the commercial benefit of mobility and mobile commerce (m-commerce) to be fully realized, users’ interaction experiences with mobile technology cannot be negative. To ensure this, it is imperative that we design the right types of mobile interaction (m-interaction); an important prerequisite for this is ensuring that users’ experience meets both their sensory and functional needs (Venkatesh, Ramesh, & Massey, 2003). Given the resource disparity between mobile and desktop technologies, successful electronic commerce (e-commerce) interface design and evaluation does not necessarily equate to successful m-commerce design and evaluation. It is, therefore, imperative that the specific needs of m-commerce are addressed–both in terms of design and evaluation. This chapter begins by exploring the complexities of designing interaction for mobile technology, highlighting the effect of context on the use of such technology. It then goes on to discuss how interaction design for mobile devices might evolve, introducing alternative interaction modalities that are likely to affect that future evolution. It is impossible, within a single chapter, to consider each and every potential mechanism for interacting with mobile technologies; to provide a forward-looking flavor of what might be possible, this chapter focuses on some more novel methods of interaction and does not, therefore, look at the typical keyboard and visual display-based interaction which, in essence, stem from the desktop interaction design paradigm. Finally, this chapter touches on issues associated with effective evaluation of m-interaction and mobile application designs. By highlighting some of the issues and possibilities for novel m-interaction design and evaluation, we hope that future designers will be encouraged to “think out of the box” in terms of their designs and evaluation strategies.

An integrated view of data quality in earth observation

Data quality is a difficult notion to define precisely, and different communities have different views and understandings of the subject. This causes confusion, a lack of harmonization of data across communities and omission of vital quality information. For some existing data infrastructures, data quality standards cannot address the problem adequately and cannot full all user needs or cover all concepts of data quality. In this paper we discuss some philosophical issues on data quality. We identify actual user needs on data quality, review existing standards and specification on data quality, and propose an integrated model for data quality in the eld of Earth observation. We also propose a practical mechanism for applying the integrated quality information model to large number of datasets through metadata inheritance. While our data quality management approach is in the domain of Earth observation, we believe the ideas and methodologies for data quality management can be applied to wider domains and disciplines to facilitate quality-enabled scientific research.

Effect of preparation conditions on the formation of the active phase of carbon fiber catalytic systems for the low-temperature oxidation of carbon monoxide

We studied the effects of the composition of impregnating solution and heat treatment conditions on the activity of catalytic systems for the low-temperature oxidation of CO obtained by the impregnation of Busofit carbon-fiber cloth with aqueous solutions of palladium, copper, and iron salts. The formation of an active phase in the synthesized catalysts at different stages of their preparation was examined with the use of differential thermal and thermogravimetric analyses, X-ray diffraction analysis, X-ray photoelectron spectroscopy, and elemental spectral analysis. The catalytic system prepared by the impregnation of electrochemically treated Busofit with the solutions of PdCl, FeCl, CuBr, and Cu(NO ) and activated under optimum conditions ensured 100% CO conversion under a respiratory regime at both low (0.03%) and high (0.5%) carbon monoxide contents of air. It was found that the activation of a catalytic system at elevated temperatures (170-180°C) leads to the conversion of Pd(II) into Pd(I), which was predominantly localized in a near-surface layer. The promoting action of copper nitrate consists in the formation of a crystalline phase of the rhombic atacamite CuCl(OH). The catalyst surface is finally formed under the conditions of a catalytic reaction, when a joint Pd(I)-Cu(I) active site is formed. © 2014 Pleiades Publishing, Ltd.

An investigation of support effects on the Pt-catalysed selective transformation of α,β-unsaturated substrates

Pt catalyst series were prepared on mesoporous SBA-15, SBA-16, KIT-6, true liquidcrystal-templated meso-macroporous SBA-15 and a commercial, low surface area silicasupport. Support structure can be easily fabricated using surfactant templating as a mode ofstringent control on porosity, surface area and internal structure. The impact of varying Pt-support physicochemical properties was systematically studied for the selective transformation of allylic substrates under chemoselective oxidation and hydrogenation regimes, a class of reactions highly applicable to industry. Pt-based heterogeneous catalysts are well-known for their utilisation in the hydrogenation of α,β-unsaturated aldehydes,although the mode of action and lack of systematic studies in the literature fuels continuing debate into the role of Pt nanoparticles and support choice for this area. This project attempts to shed some light on several frequently asked questions in this field. Successful support synthesis and stability after Pt impregnation is confirmed through HRTEM, XRD and N2 porosimetry. Decreasing metal loading promoted dispersion values,regardless of support choice, with surface PtO2 content also showing visible enhancement.Increasing support surface area and mesoporosity exhibited the following trend on Pt dispersion augmentation; low surface area commercial silica < true liquid crystal-templated SBA-15 < SBA-15 < SBA-16 ~ KIT-6. For the selective oxidation of cinnamyl alcohol,increasing PtO2 surface population confers substantial rate enhancements, with turnover frequencies evidencing PtO2 to be the active species .In the Pt-catalysed hydrogenation of cinnamaldehyde, strong support insensitivity was observed towards catalytic activity; as turnover frequencies normalised to Pt metal reveal constant values. However, structure sensitivity to the desired unsaturated alcohol arose,evidencing the requirement of flat, extended Pt (111) facets for C=O hydrogenation. Pt/SBA-15 proved the most selective, reflecting suppressed cinnamyl alcohol hydrogenation, with DRIFTS and in-situ ATR-IR evidencing the key role of support polarity in re-orientation of cinnamaldehyde to favour di-σCO adsorption and C=O versus C=C hydrogenation. High pressures increased activity, whilst a dramatic shift in selectivity from dominant C=C (1 bar)to C=O hydrogenation (10 bar) was also observed, attributed to surface crowding and suppression of di-σCC and η4 di-σCO+πC=C cinnamaldehyde binding modes.

Stabilization of catalyst particles against sintering on oxide supports with high oxygen ion lability exemplified by Ir-catalyzed decomposition of N2O

Iridium nanoparticles deposited on a variety of surfaces exhibited thermal sintering characteristics that were very strongly correlated with the lability of lattice oxygen in the supporting oxide materials. Specifically, the higher the lability of oxygen ions in the support, the greater the resistance of the nanoparticles to sintering in an oxidative environment. Thus with γ-Al2O3 as the support, rapid and extensive sintering occurred. In striking contrast, when supported on gadolinia-ceria and alumina-ceria-zirconia composite, the Ir nanoparticles underwent negligible sintering. In keeping with this trend, the behavior found with yttria-stabilized zirconia was an intermediate between the two extremes. This resistance, or lack of resistance, to sintering is considered in terms of oxygen spillover from support to nanoparticles and discussed with respect to the alternative mechanisms of Ostwald ripening versus nanoparticle diffusion. Activity towards the decomposition of N2O, a reaction that displays pronounced sensitivity to catalyst particle size (large particles more active than small particles), was used to confirm that catalytic behavior was consistent with the independently measured sintering characteristics. It was found that the nanoparticle active phase was Ir oxide, which is metallic, possibly present as a capping layer. Moreover, observed turnover frequencies indicated that catalyst-support interactions were important in the cases of the sinter-resistant systems, an effect that may itself be linked to the phenomena that gave rise to materials with a strong resistance to nanoparticle sintering.

A hiány újratermelése (The reproduction of shortage)

Sporadic lack of consumer articles, the housing shortage, disturbances of material supply, and shortages of investment goods and of labour may be traced back to a common main cause. Shortage is constantly reproduced by specific features of the economic mechanism. The first part of the article consists of micro-analysis, mainly of the productive enterprise. Efforts to increase production may run up against ceilings of three kinds: constraints on physical resources, constraints on demand, and the budget constraint on enterprises. It is an important feature of a system which of these constraints takes effect. Resource-constrained systems can be distinguished from demand-constrained ones here. In the former, production is limited by production bottlenecks, in the latter by buyer demand. The socialist economy in its "classical" form belongs to the former type. It is related to whether the budget constraint on the enterprise is "hard" or "soft". If hard, enterprise spending is limited by its financial scope, if soft (its losses offset almost automatically) its demand becomes almost insatiable. The second part performs a macro-analysis, showing the mechanism of "suction" with the aid of a hydraulic analogy. The enterprise sector "pumps away" reserves and surpluses of the system, mainly due to the "investment hunger" that appears in the wake of expansionist efforts. Finally the article discusses briefly the interrelations between shortage and inflation.

Variables affecting the collection and preservation of human scent components through instrumental and biological evaluations

In certain European countries and the United States of America, canines have been successfully used in human scent identification. There is however, limited scientific knowledge on the composition of human scent and the detection mechanism that produces an alert from canines. This lack of information has resulted in successful legal challenges to human scent evidence in the courts of law. ^ The main objective of this research was to utilize science to validate the current practices of using human scent evidence in criminal cases. The goals of this study were to utilize Headspace Solid Phase Micro Extraction Gas Chromatography Mass Spectrometry (HS-SPME-GC/MS) to determine the optimum collection and storage conditions for human scent samples, to investigate whether the amount of DNA deposited upon contact with an object affects the alerts produced by human scent identification canines, and to create a prototype pseudo human scent which could be used for training purposes. ^ Hand odor samples which were collected on different sorbent materials and exposed to various environmental conditions showed that human scent samples should be stored without prolonged exposure to UVA/UVB light to allow minimal changes to the overall scent profile. Various methods of collecting human scent from objects were also investigated and it was determined that passive collection methods yields ten times more VOCs by mass than active collection methods. ^ Through the use of polymerase chain reaction (PCR) no correlation was found between the amount of DNA that was deposited upon contact with an object and the alerts that were produced by human scent identification canines. Preliminary studies conducted to create a prototype pseudo human scent showed that it is possible to produce fractions of a human scent sample which can be presented to the canines to determine whether specific fractions or the entire sample is needed to produce alerts by the human scent identification canines. ^

Discussion Paper: Triangulation of Methodology to Solve the Practitioner - Academic Debate Concerning the Value of Research

In support of research in the debate concerning its relevance to hospitality academics and practitioners, the author presents a discussion of how the philosophy of science impacts approaches to research, including a brief summary of empiricism, and the importance of the triangulation of research orientations. Criticism of research is the hospitality literature often focuses on the lack of an apparent philosophy of science perspective and how this perspective impacts the way in which scholars conduct and interpret research. The Validity Network Schema (VNS) presents a triangulation model for evaluating research progress in a discipline by providing a mechanism for integrating academic and practitioner research studies.

Altered Landscape or Arms Race? Making Sense of Military Spending in South America

In 2009, South American military spending reached a total of $51.8 billion, a fifty percent increased from 2000 expenditures. The five-year moving average of arms transfers to South America was 150 percent higher from 2005 to 2009 than figures for 2000 to 2004.[1] These figures and others have led some observers to conclude that Latin America is engaged in an arms race. Other reasons, however, account for Latin America’s large military expenditure. Among them: Several countries have undertaken long-prolonged modernization efforts, recently made possible by six years of consistent regional growth.[2] A generational shift is at hand. Armed Forces are beginning to shed the stigma and association with past dictatorial regimes.[3] Countries are pursuing specific individual strategies, rather than reacting to purchases made by neighbors. For example, Brazil wants to attain greater control of its Amazon rainforests and offshore territories, Colombia’s spending demonstrates a response to internal threats, and Chile is continuing a modernization process begun in the 1990s.[4] Concerns remain, however: Venezuela continues to demonstrate poor democratic governance and a lack of transparency; neighbor-state relations between Colombia and Venezuela, Peru and Chile, and Bolivia and Paraguay, must all continue to be monitored; and Brazil’s military purchases, although legitimate, will likely result in a large accumulation of equipment.[5] These concerns can be best addressed by strengthening and garnering greater participation in transparent procurement mechanism.[6] The United States can do its part by supporting Latin American efforts to embrace the transparency process. _________________ [1] Bromley, Mark, “An Arms Race in Our Hemisphere? Discussing the Trends and Implications of Military Expenditures in South America,” Brookings Institution Conference, Washington, D.C., June 3rd, 2010, Transcript Pgs. 12,13, and 16 [2] Robledo, Marcos, “The Rearmament Debate: A Chilean Perspective,” Power Point presentation, slide 18, 2010 Western Hemisphere Security Colloquium, Miami, Florida, May 25th-26th, 2010 [3] Yopo, Boris, “¿Carrera Armamentista en la Regiόn?” La Tercera, November 2nd, 2009, http://www.latercera.com/contenido/895_197084_9.shtml, accessed October 8th, 2010 [4] Walser, Ray, “An Arms Race in Our Hemisphere? Discussing the Trends and Implications of Military Expenditures in South America,” Brookings Institution Conference, Washington, D.C., June 3rd, 2010, Transcript Pgs. 49,50,53 and 54 [5] Ibid., Guevara, Iñigo, Pg. 22 [6] Ibid., Bromley, Mark, Pgs. 18 and 19

Redox Regulation of Ras Proteins in Dictyostelium discoideum

Reactive oxygen species are a normal consequence of life in an aerobic environment. However when they deviate from the narrow permissible range in cells, oxidative damage can occur. Dictyostelium discoideum is a model organism ideal for the study of cell signaling events such as those affected by oxidative stress. It was previously shown that Ras signaling in Dictyostelium is affected by genetic inactivation of the antioxidant enzyme Superoxide dismutase C (SodC) and in vitro data suggests that the NKCD motif of Ras is the redox target of superoxide. The main objective of this project was to determine the mechanism of superoxide mediated Ras regulation in vivo. To accomplish the main objective, we cloned, and in some cases, mutated different Ras proteins and later determined their activity in wild type and sodC- cells. RasC and RasD showed normal activation in sodC- cells, however RasG and RasS displayed high Ras activity. These last two Ras proteins contain the NKC118D motif inside the nucleotide binding region. A mutation of cysteine118 to alanine in RasG rendered the protein less active in sodC- than the wild type RasG protein and a mutation alanine118 to cysteine in RasD conferred redox sensitivity to this small GTPase. Additionally, the propensity of RasG to be targeted by superoxide was evident when the environment of wild type cells was manipulated to induce the internal generation of superoxide through changes in the extracellular ion levels mainly magnesium. Lack of magnesium ions increased the intracellular level of superoxide and severely hampered directional cell migration. Chemotaxis of cells expressing RasG was negatively impacted by the absence of magnesium ions; however rasG- cells did not seem to be affected in their ability to perform chemotaxis. The last experiment implies that RasG is an important mediator of cell signaling during oxidative stress, responsible for preventing cells from continuing their developmental program. Our study suggests that the cysteine residue in the NKCD motif is essential for mediating the redox sensitivity of Ras proteins in Dictyostelium and that RasG is an essential mediator of the response to oxidative stress in this organism.

A Case-Only Genome-wide Association Study of Gender- and Age-specific Risk Markers for Childhood Leukemia

Males and age group 1 to 5 years show a much higher risk for childhood acute lymphoblastic leukemia (ALL). We performed a case-only genome-wide association study (GWAS), using the Illumina Infinium HumanCoreExome Chip, to unmask gender- and age-specific risk variants in 240 non-Hispanic white children with ALL recruited at Texas Children’s Cancer Center, Houston, Texas. Besides statistically most significant results, we also considered results that yielded the highest effect sizes. Existing experimental data and bioinformatic predictions were used to complement results, and to examine the biological significance of statistical results. Our study identified novel risk variants for childhood ALL. The SNP, rs4813720 (RASSF2), showed the statistically most significant gender-specific associations (P < 2 x 10-6). Likewise, rs10505918 (SOX5) yielded the lowest P value (P < 1 x 10-5) for age-specific associations, and also showed the statistically most significant association with age-at-onset (P < 1 x 10-4). Two SNPs, rs12722042 and 12722039, from the HLA-DQA1 region yielded the highest effect sizes (odds ratio (OR) = 15.7; P = 0.002) for gender-specific results, and the SNP, rs17109582 (OR = 12.5; P = 0.006), showed the highest effect size for age-specific results. Sex chromosome variants did not appear to be involved in gender-specific associations. The HLA-DQA1 SNPs belong to DQA1*01:07and confirmed previously reported male-specific association with DQA1*01:07. Twenty one of the SNPs identified as risk markers for gender- or age-specific associations were located in the transcription factor binding sites and 56 SNPs were non-synonymous variants, likely to alter protein function. Although bioinformatic analysis did not implicate a particular mechanism for gender- and age-specific associations, RASSF2 has an estrogen receptor-alpha binding site in its promoter. The unknown mechanisms may be due to lack of interest in gender- and age-specificity in associations. These results provide a foundation for further studies to examine the gender- and age-differential in childhood ALL risk. Following replication and mechanistic studies, risk factors for one gender or age group may have a potential to be used as biomarkers for targeted intervention for prevention and maybe also for treatment.

Novel approaches for the synthesis of C-5 modified pyrimidine nucleosides

The antiviral or anticancer activities of C-5 modified pyrimidine nucleoside analogues validate the need for the development of their syntheses. In the first half of this dissertation, I explore the Pd-catalyzed cross-coupling reaction of allylphenylgermanes with aryl halides in the presence of SbF 5/TBAF to give various biaryls by transferring multiple phenyl groups, which has also been applied to the 5-halo pyrimidine nucleosides for the synthesis of 5-aryl derivatives. To avoid the use of organometallic reagents, I developed Pd-catalyzed direct arylation of 5-halo pyrimidine nucleosides. It was discovered that 5-aryl pyrimidine nucleosides could be synthesized by Pd-catalyzed direct arylation of N3-free 5-halo uracil and uracil nucleosides with simple arenes or heteroaromatics in the presence of TBAF within 1 h. Both N3-protected and N3-free uracil and uracil nucleosides could undergo base-promoted Pd-catalyzed direct arylation, but only with electron rich heteroaromatics. ^ In the second half of this dissertation, 5-acetylenic uracil and uracil nucleosides have been employed to investigate the hydrogermylation, hydrosulfonylation as well as hydroazidation for the synthesis of various functionalized 5-vinyl pyrimidine nucleosides. Hydrogermylation of 5-alkynyl uracil analogues with trialkylgermane or tris(trimethylsilyl)germane hydride gave the corresponding vinyl trialkylgermane, or tris(trimethylsilyl)germane uracil derivatives. During the hydrogermylation with triphenylgermane, besides the vinyl triphenylgermane uracil derivatives, 5-[2-(triphenylgermyl)acetyl]uracil was also isolated and characterized and the origin of the acetyl oxygen was clarified. Tris(trimethylsilyl)germane uracil derivatives were coupled to aryl halides but with decent yield. Iron-mediated regio- and stereoselective hydrosulfonylation of the 5-ethynyl pyrimidine analogues with sulfonyl chloride or sulfonyl hydrazine to give 5-(1-halo-2-tosyl)vinyluracil nucleoside derivatives has been developed. Nucleophilic substitution of the 5-(β-halovinyl)sulfonyl nucleosides with various nucleophiles have been performed to give highly functionalized 5-vinyl pyrimidine nucleosides via the addition-elimination mechanism. The 5-(β-keto)sulfonyluracil derivative has also been synthesized via the aerobic difunctionalization of 5-ethynyluracil analogue with sulfinic acid in the presence of catalytic amount of pyridine. Silver catalyzed hydroazidation of protected 2'-deoxy-5-ethynyluridine with TMSN3 in the presence of catalytic amount of water to give 5-(α-azidovinyl)uracil nucleoside derivatives was developed. Strain promoted Click reaction of the 5-(α-azidovinyl)uracil with cyclooctyne provide the corresponding fully conjugated triazole product.^